阅读说明：本技术 具有可拆卸贴片和监测的医疗流体注射设备和方法 (Medical fluid injection device and method with detachable patch and monitoring ) 是由 迈克尔·D·霍芬 马修·J·赫德尔斯顿 大卫·斯特凡奇克 罗温·康弗斯 科里·冈纳森 J· 于 2019-12-31 设计创作，主要内容包括：本文提供用于监测受试者的一个或多个健康或生理参数的系统和方法。所述系统和方法可以包含耦合到注射器的贴片。数据可以被传输到移动装置或远程服务器,在所述移动装置或远程服务器那里所述数据可以被处理。处理后的数据可以用于告知受试者健康或生理状况。(Provided herein are systems and methods for monitoring one or more health or physiological parameters of a subject. The systems and methods may include a patch coupled to a syringe. The data may be transmitted to a mobile device or a remote server where it may be processed. The processed data can be used to inform the subject of a health or physiological condition.)

1. A system for measuring a health or physiological parameter of a subject, comprising:

a patch comprising a first housing having a sensor configured to: (i) measuring the health or physiological parameter from the subject when the patch is secured to the body of the subject, and (ii) providing one or more outputs corresponding to the health or physiological parameter from the subject, wherein the first housing comprises an opening; and

a syringe having a second housing comprising a cannula in fluid communication with a fluid flow path, wherein the second housing is coupled to the first housing such that, when the patch is secured to the body, the cannula is directed through the opening and into contact with the body of the subject, wherein the syringe is configured to (i) direct a substance from a reservoir to the fluid flow path in fluid communication with the reservoir, and (ii) direct the substance from the fluid flow path through the cannula to the subject.

2. The system of claim 1, further comprising a pump integrated with the cannula, wherein the pump is configured to direct the substance from the fluid flow path through the cannula to the subject.

3. The system of claim 1, wherein the cannula is configured to extend toward or retract away from the body of the subject.

4. The system of claim 1, wherein the opening comprises a pierceable membrane.

5. The system of claim 4, wherein the pierceable membrane is pierced by the cannula to create the opening.

6. The system of claim 1, wherein the reservoir is secured to the syringe.

7. The system of claim 6, wherein the reservoir is removable from the syringe.

8. The system of claim 6, wherein the reservoir is part of the syringe.

9. The system of claim 1, wherein the substance is a drug.

10. The system of claim 9, wherein the medicament is for treating one or more diseases selected from the group consisting of: cardiovascular diseases, musculoskeletal diseases, gastrointestinal diseases, skin diseases, immune diseases, ophthalmic diseases, hematological diseases, neurological diseases, neoplastic diseases, endocrine diseases, metabolic diseases, and respiratory diseases.

11. The system of claim 1, wherein the syringe comprises the reservoir, wherein the reservoir is configured to hold a formulation with the substance.

12. The system of claim 1, wherein the first housing is removably coupled to the second housing.

13. The system of claim 1, wherein the patch includes a communication interface for transmitting data corresponding to the health or physiological parameter to an electronic device in communication with the communication interface.

14. The system of claim 13, wherein the communication interface comprises a wireless communication interface.

15. The system of claim 14, wherein the communication interface comprises a WiFi interface.

16. The system of claim 14, wherein the communication interface comprises a near field communication interface.

17. The system of claim 14, wherein the communication interface comprises a bluetooth interface.

18. The system of claim 14, wherein the wireless communication interface comprises an optical wireless interface.

19. The system of claim 13, wherein the communication interface comprises a wired communication interface.

20. The system of claim 1, wherein the sensor is selected from the group consisting of: conductivity sensors, impedance sensors, capacitance sensors, charge sensors, humidity sensors, temperature sensors, heart rate sensors, gap pressure sensors, resistance sensors, optical sensors, expansion sensors, acoustic sensors, vibration sensors, blood pressure sensors, color sensors, chemical sensors, and substance tracking sensors.

21. The system of claim 20, further comprising a second sensor, wherein the second sensor is configured to measure one or more device parameters selected from the group consisting of: a dose of a substance administered, a dispensed flow rate of the substance, a volume of a substance administered, an occlusion of the cannula, and a contact of the cannula with the body of the subject.

22. The system of claim 21, wherein the patch includes the second sensor.

23. The system of claim 21, wherein the injector comprises the second sensor.

24. The system of claim 1, wherein the patch further comprises one or more transducers.

25. The system of claim 24, wherein the one or more transducers are configured to produce an output signal, wherein the output signal comprises a vibration signal, an audio signal, an electrical signal, or a visual signal.

26. The system of claim 1, wherein the patch is configured to measure a plurality of health or physiological parameters including the health or physiological parameter.

27. The system of claim 1, wherein the body is skin.

28. The system of claim 1, wherein the patch is configured to receive data from the injector.

29. A method for measuring a health or physiological parameter of a subject, comprising:

(a) providing: (i) a patch including a first housing having a sensor and including an opening; and (ii) a syringe having a second housing comprising a cannula in fluid communication with a fluid flow path, wherein the second housing is coupled to the first housing of the patch, and wherein the syringe comprises a reservoir containing a substance and a fluid flow path in fluid communication with the reservoir;

(b) securing the patch to the body of the subject;

(c) when the patch is secured to the body of the subject, directing the cannula through the opening to (i) direct the substance from the reservoir to the fluid flow path, and (ii) direct the substance from the fluid flow path to the subject through the cannula; and

(d) using the sensor to (i) measure the health or physiological parameter from the subject, and (ii) provide one or more outputs corresponding to the health or physiological parameter from the subject.

30. The method of claim 29, further comprising directing the substance from the fluid flow path through the cannula to the subject using a pump integrated with the cannula.

31. The method of claim 29, wherein the cannula is configured to extend toward or retract away from the body of the subject.

32. The method of claim 29, wherein the opening comprises a pierceable membrane.

33. The method of claim 32, wherein the pierceable membrane is pierced by a cannula to create the opening.

34. The method of claim 29, wherein the reservoir is secured to the syringe.

35. The method of claim 34, wherein the reservoir is removable from the syringe.

36. The method of claim 34, wherein the reservoir is part of the syringe.

37. The method of claim 29, wherein the substance is a drug.

38. The method of claim 37, wherein the medicament is for treating one or more diseases selected from the group consisting of: cardiovascular diseases, musculoskeletal diseases, gastrointestinal diseases, skin diseases, immune diseases, ophthalmic diseases, hematological diseases, neurological diseases, neoplastic diseases, endocrine diseases, metabolic diseases, and respiratory diseases.

39. The method of claim 29, wherein the syringe contains the reservoir, wherein the reservoir is configured to contain a formulation with the substance.

40. The method of claim 29, wherein the first housing is removably coupled to the second housing.

41. The method of claim 29, wherein the patch includes a communication interface for transmitting data corresponding to the health or physiological parameter to an electronic device in communication with the communication interface.

42. The method of claim 41, wherein the communication interface comprises a wireless communication interface.

43. The method of claim 42, wherein the communication interface comprises a WiFi interface.

44. The method of claim 42, wherein the communication interface comprises a near field communication interface.

45. The method of claim 42, wherein the communication interface comprises a Bluetooth interface.

46. The system of claim 42, wherein the wireless communication interface comprises an optical wireless interface.

47. The method of claim 41, wherein the communication interface is a wired communication interface.

48. The method of claim 29, wherein the sensor is selected from the group consisting of: conductivity sensors, impedance sensors, capacitance sensors, charge sensors, humidity sensors, temperature sensors, heart rate sensors, gap pressure sensors, resistance sensors, expansion sensors, acoustic sensors, vibration sensors, blood pressure sensors, color sensors, chemical sensors, and substance tracking sensors.

49. The system of claim 48, further comprising a second sensor, wherein the second sensor is selected from the group consisting of: temperature sensor, humidity sensor, flow rate sensor, button position sensor, vibration sensor, auditory sensor, skin sensor.

50. The system of claim 49, wherein the patch includes the second sensor.

51. The system of claim 49, wherein the injector comprises the second sensor.

52. The system of claim 29, wherein the patch further comprises one or more transducers.

53. The system of claim 52, wherein the one or more transducers are configured to produce an output signal, wherein the output signal comprises a vibration signal, an audio signal, an electrical signal, or a visual signal.

54. The system of claim 29, wherein the patch is configured to measure a plurality of health or physiological parameters including the health or physiological parameter.

55. The system of claim 29, wherein the body is skin.

56. The system of claim 29, wherein the patch is configured to receive data from the injector.

57. A syringe, comprising:

(a) a housing;

(b) a drug reservoir disposed in the housing;

(c) an infusion cannula movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir;

(d) a syringe sensor mounted on or within the housing;

(e) a skin attachment layer attached to the housing, the skin attachment layer comprising an adhesive configured to secure the housing to a user's skin with a first retention force;

(f) a patch removably secured to the housing with a second retention force, the patch comprising: a sensor adhesive layer configured to secure the patch to the skin of the user with a third retention force; a patch sensor; and circuitry configured to receive data from the syringe sensor and the patch sensor and transmit the received data to a remote receiver;

(g) wherein the third retention force is greater than the second retention force.

58. The injector according to claim 57, wherein the second retention force is greater than the first retention force and the patch is removably attached to the skin attachment layer.

59. The injector according to claim 58, wherein the patch is removably attached to the skin attachment layer by perforations.

60. The injector according to claim 57, wherein the patch is removably secured to the housing by a magnet.

61. The injector according to claim 60, wherein a magnet is positioned within or on the housing of the injector and the patch includes a metal portion configured to engage with the magnet.

62. The injector according to claim 57, wherein the skin attachment layer includes an opening and the patch is positioned within the opening when the patch is removably secured to the housing of the injector.

63. The syringe of claim 62, wherein the opening is located in a center of the skin attachment layer, and the injection cannula of the syringe passes through the opening of the skin attachment layer and an aperture of the patch when in the dispensing position.

64. The syringe of claim 63, wherein the patch comprises an extension comprising the aperture through which the injection cannula of the syringe passes when in the dispensing position, the extension configured to compress the skin of a user around an injection site.

65. The injector of claim 63, wherein the patch comprises a printed circuit board, the circuit is positioned on the printed circuit board, and the sensor adhesive layer and the patch sensor are attached to the printed circuit board, the sensor adhesive layer comprising a central window through which the extension passes.

66. The syringe of claim 65, wherein the extension is substantially conical.

67. The injector of claim 57, wherein the patch comprises a printed circuit board, the circuit is positioned on the printed circuit board, and the sensor adhesive layer and the patch sensor are attached to the printed circuit board.

68. The injector of claim 57, wherein the circuitry of the patch comprises a microcontroller, microprocessor, or transmitter.

69. The injector according to claim 68, wherein the sensor of the injector comprises a transmitter and the circuit of the patch further comprises a receiver by which data is received from the injector sensor by wireless transmission.

70. The injector according to claim 69, wherein the microcontroller or microprocessor and the transmitter and receiver are combined into a single component.

71. The syringe of claim 68, further comprising a wire connection between the syringe sensor and the circuitry of the patch, the wire connection configured to break upon or after removal of the syringe from the patient.

72. The injector according to claim 68, wherein the microcontroller or microprocessor and the transmitter are combined into a single component.

73. The injector according to claim 50, wherein the transmitter is a Bluetooth transmitter.

74. The injector according to claim 57, wherein the injector sensor comprises a plurality of sensors.

75. The injector according to claim 57, wherein the patch sensor comprises a plurality of sensors.

76. A method for collecting data from an injector and a patient, comprising the steps of:

(a) attaching a syringe including a syringe sensor and a patch including a patch sensor and circuitry to the patient;

(b) receiving data from the syringe sensor and the patch sensor using the patch circuit;

(c) transmitting the received data to a remote receiver using the patch circuit;

(e) removing the syringe from the patient;

(f) receiving additional data from the injector sensor using the patch circuit after removing the injector from the patient;

(g) transmitting the received additional data to a remote receiver using the patch circuit.

77. The method of claim 76, wherein the syringe and the patch are attached to the patient simultaneously.

78. The method according to claim 76, wherein step (a) includes attaching the patch prior to the injection, and further including the steps of receiving data from the patch sensor using the patch circuit, transmitting the received data to a remote receiver using the patch circuit, prior to attaching the injector to the patient.

79. The method of claim 76, wherein the data collected from the patient includes measurable properties that can be affected by a medicament administered by the injection device and/or injection of the medicament using the injector.

80. The method of claim 76, wherein the data collected from the patient includes measurable attributes capable of affecting or indicating the safety and/or effectiveness of a medicament administered by the syringe and/or use of the syringe.

81. A method for monitoring injection site reactions at an injection site of a patient, comprising:

(a) attaching a syringe comprising a patch to the patient, the patch comprising a patch sensor and circuitry, wherein the patch sensor comprises a skin temperature sensor and a skin tone monitor;

(b) receiving data from the patch sensor using the patch circuit;

(c) transmitting the received data to a remote receiver using the patch circuit, wherein the data includes an indication of a temperature increase or a skin color change, enabling identification of an injection site reaction.

82. A syringe, comprising:

(a) a housing;

(b) a drug reservoir disposed in the housing;

(c) an infusion cannula movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir;

(d) a patch sensor configured to receive and transmit data, the patch sensor removably secured to the housing with a first retention force;

(e) an attachment layer attached to the patch sensor, the attachment layer comprising an adhesive configured to secure the patch sensor to the skin of the user with a second retention force;

(f) wherein the second retention force is greater than the first retention force such that the patch sensor remains attached to the skin of the user when the housing is removed from the patch sensor.

83. The system of claim 82, wherein the data is used to adjust device parameters of the patch or the injector.

84. The system of claim 83, wherein the device parameters comprise one or more device parameters selected from the group consisting of: a dose of the substance administered by the syringe, a flow rate at which the substance is dispensed by the syringe, and a volume of the substance administered by the syringe.

85. A system according to claim 84, wherein the data is used to generate a notification to the subject.

86. The system of claim 85, wherein the notifications include one or more notifications selected from the group consisting of: a vibration indicator, an audible indicator, and a visual indicator.

Background

Vials are one of the preferred reservoir or container closure systems used in the pharmaceutical industry due to their extensive clinical history and records of long-term stability with multiple agents. Drugs, including biologicals, are provided in standard containers, such as vials. In addition, the industry makes significant investments in capital equipment for sterile vial filling. However, the vial requires transfer of the contained medicament from the vial to an injection device (e.g., syringe, auto-injector, infuser, etc.) for delivery to the patient. New container closure systems have been introduced, such as pre-filled syringes and cartridges, which allow the medicament to be delivered directly from the syringe or cartridge to the patient. Injection devices such as auto-injectors and pens have been developed to take advantage of these newer forms of container closures. Due to the uncertainty of long-term drug stability, and the already large number of manufacturing resources, the pharmaceutical industry prefers to incorporate standard container closure systems (such as devices of vials, pre-filled syringes or cartridges) over devices requiring custom-formed drug containers.

However, vials, pre-filled syringes and cartridges are not necessarily the best containers for medicament delivery devices. This is particularly the case with delivery devices that deliver relatively high volumes (2-50cc) or high viscosity (over 15cP and up to about 100cP) of medicament. The vial, pre-filled syringe and cartridge are almost entirely cylindrical bodies made of glass, which imposes design constraints on force and geometry. Typical syringes and autoinjectors are limited in the viscosity of the medicament that can be delivered and the force that can be applied to the glass container closure system. New injection devices have been developed that include insulin delivery pumps using custom container closures, but these systems are very expensive, cannot generate high forces or pressures, and are typically reusable and/or refillable.

In an effort to develop injection devices and methods, on-body injection devices that provide benefits such as more comfort and less pain while providing effective subcutaneous injections have been the subject of continued development.

Disclosure of Invention

There is recognized herein a need for new and/or improved devices, systems, and methods for injecting a drug (e.g., a medicament) from a reservoir (e.g., one or more source vials) into and into a subject. Further, there is recognized herein a need for devices, systems, and methods for monitoring health or physiological parameters before, during, and/or after injection of a drug into a subject. Such devices or systems may be useful, for example, in regulatory procedures and patient monitoring.

The present disclosure provides devices, systems, and methods that may be used for medical fluid delivery and injection, as well as methods for administering a substance (e.g., a drug) to a subject and monitoring one or more physical parameters or attributes of the subject before, during, and/or after administration of the substance.

In one aspect, provided herein is a system for measuring a health or physiological parameter of a subject, comprising: (a) a patch comprising a first housing having a sensor configured to: (i) measuring the health or physiological parameter from the subject when the patch is secured to the body of the subject, and (ii) providing one or more outputs corresponding to the health or physiological parameter from the subject, wherein the first housing comprises an opening; and a syringe having a second housing containing a cannula in fluid communication with a fluid flow path, wherein the second housing is coupled to the first housing such that, when the patch is secured to the body, the cannula is directed through the opening and into contact with the body of the subject, wherein the syringe is configured to (i) direct a substance from a reservoir to the fluid flow path in fluid communication with the reservoir, and (ii) direct the substance from the fluid flow path through the cannula into the subject.

In some embodiments, the system further comprises a pump integrated with the cannula, wherein the pump is configured to direct the substance from the fluid flow path through the cannula into the subject. In some embodiments, the cannula is configured to extend toward or retract away from the body of the subject. In some embodiments, the opening comprises a pierceable membrane. In some embodiments, the pierceable membrane is pierced by the cannula to create the opening. In some embodiments, the reservoir is secured to the syringe. In some embodiments, the reservoir may be removable from the syringe. In some embodiments, the reservoir is part of a syringe. In some embodiments, the substance is a drug. In some embodiments, the medicament is for treating one or more diseases selected from the group consisting of: cardiovascular diseases, musculoskeletal diseases, gastrointestinal diseases, skin diseases, immune diseases, ophthalmic diseases, hematological diseases, neurological diseases, neoplastic diseases, endocrine diseases, metabolic diseases, and respiratory diseases. In some embodiments, the syringe comprises a reservoir, wherein the reservoir is configured to contain a formulation with the substance. In some embodiments, the first housing is removably coupled to the second housing. In some embodiments, the patch includes a communication interface for transmitting data corresponding to the plurality of health or physiological parameters to an electronic device in communication with the communication interface. In some embodiments, the communication interface comprises a wireless communication interface. In some implementations, the communication interface includes a Wi-Fi interface. In some implementations, the communication interface includes a near field communication interface. In some embodiments, the communication interface comprises a bluetooth interface. In some embodiments, the communication interface comprises an optical wireless interface. In some embodiments, the communication interface comprises a direct electrical contact digital or analog interface. In some embodiments, the input transducer/sensor of the plurality of sensors is selected from the group consisting of: conductivity sensors, impedance sensors, capacitance sensors, charge sensors, humidity sensors, temperature sensors, heart rate sensors, gap pressure sensors, resistance sensors, optical sensors, expansion sensors, acoustic sensors, vibration sensors, blood pressure sensors, color sensors, chemical sensors, and substance tracking sensors. In some embodiments, the system further comprises a second sensor, wherein the second sensor is configured to measure one or more device parameters selected from the group consisting of: the dose of substance administered, the dispensed flow rate of the substance, the volume of substance administered, the occlusion of the cannula, and the contact of the cannula with the body of the subject. In some embodiments, the patch or syringe comprises a second sensor. In some embodiments, the patch further comprises one or more transducers. In some embodiments, the one or more transducers are configured to generate an output signal, wherein the output signal comprises a vibration signal, an audio signal, or a visual signal. In some embodiments, the output transducer of the plurality of transducers is selected from the group consisting of: tactile (vibration) transducers, audio transducers, visual transducers, and direct electrical stimulation (e.g., transcutaneous electrical nerve stimulation/TENS).

In another aspect, disclosed herein is a method for measuring a plurality of health or physiological parameters of a subject, the method comprising: (a) providing: (i) a patch comprising a first housing having a plurality of sensors and comprising an opening, and (ii) a syringe having a second housing comprising a cannula in fluid communication with a fluid flow path, wherein the second housing is coupled to the first housing of the patch, and wherein the syringe comprises a reservoir containing a substance and a fluid flow path in fluid communication with the reservoir; (b) securing the patch to the body of the subject; (c) when the patch is secured to the body of the subject, directing the cannula through the opening to (i) direct the substance from the reservoir to the fluid flow path, and (ii) direct the substance from the fluid flow path through the cannula into the subject; and (d) using a plurality of sensors to (i) measure a plurality of health or physiological parameters from the subject, and (ii) provide one or more outputs corresponding to the plurality of health or physiological parameters from the subject.

In some embodiments, the method further comprises using a pump integrated with the cannula to direct the substance from the fluid flow path through the cannula into the subject. In some embodiments, the cannula is configured to extend toward or retract away from the body of the subject. In some embodiments, the opening comprises a pierceable membrane. In some embodiments, the pierceable membrane is pierced by the cannula to create the opening. In some embodiments, the reservoir is secured to the syringe. In some embodiments, the reservoir may be removable from the syringe. In some embodiments, the reservoir is part of a syringe. In some embodiments, the substance is a drug. In some embodiments, the medicament is for treating one or more diseases selected from the group consisting of: cardiovascular diseases, musculoskeletal diseases, gastrointestinal diseases, skin diseases, immune diseases, ophthalmic diseases, hematological diseases, neurological diseases, neoplastic diseases, endocrine diseases, metabolic diseases, and respiratory diseases. In some embodiments, the syringe comprises a reservoir, wherein the reservoir is configured to contain a formulation with the substance. In some embodiments, the first housing is removably coupled to the second housing. In some embodiments, the patch includes a communication interface for transmitting data corresponding to the plurality of health or physiological parameters to an electronic device in communication with the communication interface. In some embodiments, the communication interface is a wireless communication interface. In some implementations, the communication interface is a Wi-Fi interface. In some implementations, the communication interface is a near field communication interface. In some embodiments, the communication interface is a bluetooth interface. In some embodiments, the communication interface is an optical wireless interface. In some embodiments, the input transducer/sensor of the plurality of sensors is selected from the group consisting of: conductivity sensors, impedance sensors, capacitance sensors, charge sensors, humidity sensors, temperature sensors, heart rate sensors, gap pressure sensors, resistance sensors, expansion sensors, acoustic sensors, vibration sensors, blood pressure sensors, color sensors, chemical sensors, and substance tracking sensors. In some embodiments, the output transducer of the plurality of transducers is selected from the group consisting of: tactile (vibration) transducers, audio transducers, visual transducers, and direct electrical stimulation (e.g., transcutaneous electrical nerve stimulation/TENS).

In some embodiments, the second sensor of the plurality of sensors is selected from the group consisting of: temperature sensor, humidity sensor, flow rate sensor, button position sensor, vibration sensor, auditory sensor, skin sensor.

In yet another aspect, provided herein is a syringe comprising: a housing; (b) a drug reservoir disposed in the housing; (c) an infusion cannula movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir; (d) an injector transducer/sensor mounted on or within the housing; (e) a skin attachment layer attached to the housing, the skin attachment layer comprising an adhesive configured to secure the housing to the skin of the user with a first retention force; (f) a patch removably secured to the housing with a second retention force, the patch comprising: a sensor adhesive layer configured to secure the patch to the skin of the user with a third retention force; patch input transducers/sensors; an output transducer; and circuitry configured to receive data from the syringe transducer/sensor and the patch transducer/sensor and transmit the received data to a remote receiver; (g) wherein the third retention force is greater than the second retention force.

In some embodiments, the second retention force is greater than the first retention force and the patch is removably attached to the skin attachment layer. In some embodiments, the patch is removably attached to the skin attachment layer by perforations. In some embodiments, the patch is removably secured to the housing by a magnet. In some embodiments, the magnet is positioned within or on the housing of the injector, and the patch includes a metal portion configured to engage with the magnet. In some embodiments, the skin attachment layer includes an opening, and the patch is positioned within the opening when the patch is removably secured to the housing of the injector. In some embodiments, the opening is located in the center of the skin attachment layer, and the injection cannula of the syringe passes through the opening of the skin attachment layer and the aperture of the patch when in the dispensing position. In some embodiments, the patch includes an extension including an aperture through which an injection cannula of the syringe passes when in the dispensing position, the extension configured to compress the skin of the user around the injection site. In some embodiments, the patch includes a printed circuit board on which the circuitry is positioned and to which the sensor adhesive layer and the patch transducer/sensor are attached, the sensor adhesive layer including a central window through which the extension passes.

In some embodiments, the extension is substantially conical. In some embodiments, the patch includes a printed circuit board on which the circuitry is positioned and to which the sensor adhesive layer and patch sensor are attached. In some embodiments, the circuitry of the patch includes a microcontroller/microprocessor and a transmitter. In some embodiments, the sensor of the syringe comprises a transmitter and the circuitry of the patch further comprises a receiver by which data is received from the syringe transducer/sensor by wireless transmission and by which data is transmitted to the transducer by wireless transmission. In some embodiments, the microcontroller/microprocessor, transmitter, and receiver are combined into a single component. In some embodiments, the injector further comprises a wire connection between the injector transducer/sensor and the patch circuit, the wire connection configured to break when or after the injector is removed from the patient. In some embodiments, the microcontroller/microprocessor and transmitter are combined into a single component. In some embodiments, the transmitter is a bluetooth transmitter. In some embodiments, the injector sensor includes a plurality of input transducers/sensors and an output transducer. In some embodiments, the patch sensor includes a plurality of input transducers/sensors and an output transducer. In some embodiments, the patch sensor includes a plurality of input transducers/sensors and an output transducer.

In yet another aspect, provided herein is a method for collecting data from an injector and a patient, the method comprising (a) attaching an injector comprising an injector sensor and a patch comprising a patch sensor, an output transducer, and circuitry to a patient; (b) receiving data from the syringe sensor and the patch sensor using the patch circuit; (c) transmitting the received data to a remote receiver using a patch circuit; (d) removing the syringe from the patient; (e) receiving additional data from the injector sensor using the patch circuit after removing the injector from the patient; and (f) transmitting the additionally received data to a remote receiver using the patch circuit.

In some embodiments, the syringe and patch are attached to the patient simultaneously. In some embodiments, (a) comprises attaching a patch prior to the injection, and further comprising the step of receiving data from the patch sensor using the patch circuit and transmitting the received data to a remote receiver using the patch circuit prior to attaching the injector to the patient. In some embodiments, the data collected from the patient includes measurable properties that may be affected by the medicament administered by and/or injected using the syringe. In some embodiments, the data collected from the patient includes measurable attributes that may affect or indicate the safety and/or effectiveness of the medicament administered by the syringe and/or the use of the injection.

In yet another aspect, provided herein is a method for monitoring an injection site response at an injection site of a patient, the method comprising the steps of: (a) attaching a syringe comprising a patch to a patient, the patch comprising a patch sensor and circuitry, wherein the patch sensor comprises a skin temperature transducer/sensor and a skin tone monitor; (b) receiving data from a patch sensor using a patch circuit; (c) transmitting the received data to a remote receiver using the patch circuit, wherein the data includes an indication of an increase in temperature or a change in skin color, such that an injection site reaction can be identified.

In another aspect, disclosed herein is a syringe comprising (a) a housing; (b) a drug reservoir disposed in the housing; (c) an infusion cannula movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir; (d) a patch sensor configured to receive and transmit data, the patch sensor removably secured to the housing with a first retention force; (e) an attachment layer attached to the patch sensor, the attachment layer comprising an adhesive configured to secure the patch sensor to the skin of the user with a second retention force; (f) wherein the second retention force is greater than the first retention force such that the patch sensor remains attached to the skin of the user when the housing is removed from the patch sensor.

In some embodiments, the subject's body is skin. In some embodiments, the patch is configured to receive data from the injector. In some embodiments, the data is used to adjust device parameters of the patch or syringe. In some embodiments, the device parameters comprise one or more device parameters selected from the group consisting of: the dose of the substance administered by the syringe, the flow rate at which the substance is dispensed by the syringe, and the volume of the substance administered by the syringe. In some embodiments, the data is used to generate a notification to the subject via the transducer. In some embodiments, the notification comprises one or more notifications selected from the group consisting of: vibration indicators, sound indicators, direct electrical stimulation indicators, and visual indicators.

Several aspects of the present subject matter may be implemented separately or together in the apparatus and systems described and claimed below. These aspects may be employed alone or in combination with other aspects of the subject matter described herein, and the description of these aspects together is not intended to exclude the use of these aspects alone or in separate claims of such aspects or in different combinations as set out in the claims appended hereto.

The present subject matter includes any suitable delivery device and/or syringe in any suitable detailed configuration, but delivery devices and syringes that are particularly useful when used in combination with the apparatus herein are described in U.S. patent No. 9,925,333, the contents of which are incorporated herein by reference.

In one aspect, the syringe includes a housing. A drug reservoir is disposed in the housing and an infusion cannula is movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir. The syringe sensor is mounted on or within the housing. The skin attachment layer is attached to the housing and includes an adhesive configured to secure the housing to the skin of the user with a first retention force. The patch is removably secured to the housing with a second retention force and includes a sensor adhesive layer configured to secure the patch to the skin of the user with a third retention force. The third retention force is greater than the second retention force. The patch also includes a patch sensor and circuitry configured to receive data from the syringe sensor and patch sensor and transmit the received data to a remote receiver.

In another aspect, a method for collecting data from an injector and a patient is provided, the method comprising the steps of: attaching a syringe including a syringe sensor and a patch including a patch sensor and circuitry to a patient; receiving data from the syringe sensor and the patch sensor using the patch circuit; transmitting the received data to a remote receiver using a patch circuit; removing the syringe from the patient; receiving additional data from the injector sensor using the patch circuit after removing the injector from the patient; and transmitting the additionally received data to a remote receiver using the patch circuit.

In yet another aspect, a method for monitoring an injection site response at an injection site of a patient includes the steps of: attaching a syringe comprising a patch to a patient, the patch comprising a patch sensor and circuitry, wherein the patch sensor comprises a skin temperature sensor and a skin tone monitor; receiving data from a patch sensor using a patch circuit; and transmitting the received data to a remote receiver using the patch circuit, wherein the data includes an indication of an increase in temperature or a change in skin color such that an injection site reaction can be identified.

In another aspect, a syringe includes a housing having a drug reservoir disposed therein. The infusion cannula is movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir. A patch sensor configured to receive and transmit data is removably secured to the housing with a first retention force. The skin attachment layer is attached to the patch sensor and is configured to secure the patch sensor to the skin of the user with a second retention force, wherein the second retention force is greater than the first retention force.

Another aspect of the disclosure provides a non-transitory computer-readable medium containing machine-executable code that, when executed by one or more computer processors, performs any of the methods described above or elsewhere herein.

Another aspect of the disclosure provides a system comprising one or more computer processors and computer memory coupled thereto. The computer memory contains machine executable code that, when executed by one or more computer processors, performs any of the methods above or elsewhere herein.

Other aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, wherein only illustrative embodiments of the disclosure are shown and described. As will be realized, the disclosure is capable of other and different embodiments and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

Is incorporated by reference

All publications, patents and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and/or take precedence over any such contradictory material.

Drawings

The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also referred to herein as "figures"), wherein:

figure 1 shows a perspective view of a syringe.

Fig. 2 shows a top view of the filled syringe showing the delivery indicator in a full condition.

Fig. 3 shows a top view of the filled syringe showing the delivery indicator in an empty state.

Fig. 4 shows a perspective view showing the underside of a syringe with an attached tape and a fill port.

Fig. 5 shows a perspective view showing the underside of the syringe with the tape removed and the fill and dispense port exposed.

Figure 6 shows a cross section of a syringe on a delivery device.

Fig. 7 shows a perspective view of an injector attached to a body (e.g., skin) with a safety device installed.

Fig. 8 shows a perspective view of the injector attached to the body (e.g., skin) with the safety device removed and the button up in a pre-fired state.

Fig. 9 shows a perspective view of the injector attached to the body (e.g., skin) with the safety device removed and the button down in the fired state.

Fig. 10 shows a cross-sectional view of the injector attached to the body (e.g., skin) with the button up in a pre-fired state.

Fig. 11 shows a cross-sectional view of the injector attached to the body (e.g., skin) with the button down in a first firing state.

Fig. 12 shows a cross-sectional view of the injector attached to the body (e.g., skin) with the button down in the dispensing state.

Fig. 13 shows a cross-sectional view of the syringe attached to the body (e.g., skin), showing the end of delivery indicator being unactuated.

Fig. 14 shows a cross-sectional view of the syringe attached to the body (e.g., skin), showing the end of delivery indicator triggered.

Fig. 15 shows a cross-sectional view of the injector attached to the body (e.g., skin) with the button locked in the post-fired state.

Fig. 16A shows a perspective view of the syringe removed from the body (e.g., skin) with the bandage remaining on the skin. Fig. 16B shows a perspective view of the syringe removed from the body (e.g., skin) with the bandage containing an opening, remaining on the skin.

Fig. 17 shows a perspective view of the syringe with the top housing removed in the filled state.

Fig. 18 shows a top view of the syringe shown in fig. 17.

Fig. 19 shows a perspective view of the syringe with the top housing removed in an empty state.

Fig. 20 shows a top view of the syringe shown in fig. 19.

Figure 21 shows a perspective view of the injector placed on the body (e.g., skin) with the safety device in place.

Fig. 22 shows a perspective view of the syringe placed on the body (e.g., skin) and the safety device removed.

Fig. 23 shows a perspective view of an injector placed on a body (e.g., skin) and a button depressed to fire an injection.

Fig. 24 shows a perspective view of the injector removed from the body (e.g., skin) after injection with the button in the locked position and the bandage remaining on the body (e.g., skin).

Fig. 25 shows a perspective view of the syringe.

Fig. 26 shows the cross-section of fig. 25, showing the syringe with the button in the first position.

Fig. 27 shows a diagram showing four stages of Cannula penetration through Tissue including a) no contact, b) boundary displacement, c) tip insertion, and d) shaft insertion (doctor university of delver science university of Van Gerwen's "canula-Tissue Interaction by Experiment", 2013, ISBN 978-94-6186-238-9, page 11).

Fig. 28 shows the cross-section of fig. 25, showing the syringe with the button in the second or dispensing position.

Fig. 29 shows the cross-section of fig. 25, showing the adhesive/device and adhesive/body (e.g., skin) interface.

Fig. 30 shows a perspective view of the bottom of the syringe showing the different zones of adhesive.

FIG. 31 shows the cross section of FIG. 25 showing the raised tissue on the device with permanently attached adhesive.

FIG. 32 shows the cross section of FIG. 25 showing raised tissue on a device with a multi-zone attachment adhesive.

Fig. 33 shows a perspective view of an alternative syringe top.

FIG. 34 shows the cross-section of FIG. 33 showing the deflection sensor disengaged and the cannula locked in the dispensing position.

FIG. 35 shows the cross section of FIG. 33 showing the deflection sensor engaged and the cannula and button retracted to a post-firing position.

Fig. 36 shows the cross-section of fig. 25, showing the syringe with the button in the first or pause position.

Fig. 37 shows the cross-section of fig. 25 showing the syringe with the button in the second or dispensing position.

FIG. 38 shows the cross-section of FIG. 25 showing the injector with the cannula retracted and the button in the up or pre-fired position.

Fig. 39 shows the cross-section of fig. 25 showing the syringe with the button in the second or dispensing position.

Fig. 40 shows a perspective view of the syringe.

Fig. 41 shows a cross-sectional perspective view of the syringe with the button in the second or dispensing position.

Fig. 42 shows a perspective view of a syringe with an attached safety cannula.

Fig. 43 shows a cross-sectional perspective view of the syringe with the button in the second or dispensing position.

Fig. 44 shows a perspective view of a syringe including a Radio Frequency (RF) tag and a tag reader or interrogator.

Fig. 45 shows a cross-section similar to fig. 44, but showing the syringe.

Figure 46 illustrates a block/flow diagram showing a system employing the present subject matter to monitor patient compliance.

Fig. 47 shows an ultrasound image showing the subcutaneous depth using a commercial infusion pump with a subcutaneous cannula depth of 9 mm.

Fig. 48 shows an ultrasound image showing the depth of a bolus using a syringe 7 with a cannula depth of 5 mm.

Figure 49 depicts a compliance monitoring system.

Figure 50 also depicts a compliance monitoring system.

Figure 51 illustrates additional aspects of compliance monitoring with a syringe of the type described herein.

Fig. 52 illustrates a top perspective view of an RF chip in an embodiment of an injector of the present disclosure.

Fig. 53 illustrates a bottom perspective view of an RF chip of an embodiment of the present disclosure.

FIG. 54 illustrates a top perspective view of an embodiment of the syringe of the present disclosure with a safety tab installed.

FIG. 55 shows a top perspective view of the syringe with the security tag removed.

Fig. 56 shows a cross-sectional view of the syringe showing the button in a raised, extended or up position.

FIG. 57 shows a cross-sectional view of the syringe showing the button in a lowered, retracted or down position.

Fig. 58 illustrates a flow chart showing the processing performed by the microcontroller/microprocessor in an embodiment of the injector of the present disclosure.

Fig. 59 illustrates a bottom perspective view of a syringe having a removable patch in an embodiment of the present disclosure.

Figure 60 shows an exploded view of the syringe and patch of figure 59.

Fig. 61 shows a top side perspective view of a Printed Circuit Board (PCB) chip of the patch of fig. 60.

Fig. 62 shows a bottom perspective view of the PCB chip of the patch of fig. 60.

Figure 63 shows a schematic view of the syringe and patch of figures 59-63.

Figure 64 shows a schematic view of another example of a syringe coupled to a patch.

Figure 65 shows another view of the patch and syringe shown in figure 64.

Figure 66 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 67 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 68 shows a cross-sectional view of the patch and syringe of figure 67.

Figure 69 shows a schematic view of another example of a syringe coupled to a patch.

Figure 70 shows a cross-sectional view of the patch and syringe of figure 69.

Figure 71 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 72 shows a cross-sectional view of the patch and syringe of figure 71.

Figure 73 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 74 shows a cross-sectional view of the patch and syringe of figure 73.

Figure 75 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 76 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 77 shows a schematic view of another example of a syringe coupled to a patch.

Figure 78 shows a cross-sectional view of the patch and syringe of figure 77.

Fig. 79 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 80 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 81 shows a cross-sectional view of the patch and syringe of figure 80.

Figure 82 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 83 shows a cross-sectional view of the patch and syringe of figure 82.

Figure 84 shows a schematic diagram of another example of a syringe coupled to a patch.

Figure 85 shows a cross-sectional view of the patch and syringe of figure 84.

Figure 86 shows a schematic view of another example of a syringe coupled to a patch.

Figure 87 shows a cross-sectional view of the patch and syringe of figure 86.

Fig. 88 shows a schematic view of another example of a syringe coupled to a patch.

Figure 89 shows a cross-sectional view of the patch and syringe of figure 88.

Fig. 90 shows a schematic view of an example patch having a pierceable membrane configured to couple to a syringe.

Figure 91 shows another view of the patch of figure 90.

Fig. 92 shows a schematic view of another example patch having a pierceable membrane configured to couple to a syringe.

Fig. 93 shows a schematic view of an example patch having a pierceable membrane configured to couple to an autoinjector.

Fig. 94 shows a schematic view of a patch sensor of a syringe and an embodiment of the patch of any of fig. 59-93.

Fig. 95 shows a schematic view of a sensor adhesive layer of a patch in an alternative embodiment of the present disclosure.

Fig. 96 shows a schematic view of a sensor adhesive layer of a patch in an embodiment of the present disclosure.

FIG. 97 schematically illustrates an example workflow for a mobile application.

FIG. 98 schematically illustrates another example workflow of a mobile application.

Fig. 99A to 99C schematically show another example workflow of a mobile application.

Diagram 100 illustrates a computer system programmed or otherwise configured to implement the methods provided herein.

Detailed Description

While various embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed.

Whenever the term "at least," "greater than," or "greater than or equal to" precedes the first value in two or more numerical series, the term "at least," "greater than," or "greater than or equal to" applies to each numerical value in the numerical series. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

Whenever the term "not greater than," "less than," or "less than or equal to" precedes the first value in two or more numerical series, the term "not greater than," "less than," or "less than or equal to" applies to each numerical value in the numerical series. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

The term "subject" as used herein generally refers to a user of a device, system or method of the present disclosure, or an individual who is using a device, system or method of the present disclosure. The subject may be a patient (e.g., a patient being treated or monitored by a physician or health care provider). Alternatively, the subject may not be a patient. The subject may have or is suspected of having a disease or disorder. Alternatively, the subject may not have symptoms for the disease or disorder. The subject can be a vertebrate, a mammal (e.g., a human or an animal), a non-human primate, and the like. The subject can be an animal, such as a rodent (e.g., rat or mouse), canine (e.g., dog), feline (e.g., cat), bovine, or other animal.

The term "drug" as used herein generally refers to a substance used to treat a healthy or physiological state or condition (e.g., medical treatment) of a subject. The drug may be a pharmaceutical or therapeutic agent. The medicament may be a solid, liquid, gas, or a combination thereof. The medicament may be an aerosol, pill, tablet, capsule, lozenge, elixir, emulsion, effervescent powder, solution, suspension, tincture, liquid, gel, dry powder, vapor, droplet, ointment, or a combination or variation thereof. The medicament may be used to treat ailments, ailments or diseases, or may be used as a health supplement (e.g., vitamins, minerals, probiotics, etc.).

The present disclosure provides devices, methods, and systems for delivering a substance (e.g., a drug) to a subject and monitoring the subject prior to, concurrently with, and/or after delivery of the substance. The device of the present disclosure may be a syringe for delivering a medicament. Alternatively, or in addition, the device may be a patch configured to monitor the subject and/or communicate with a syringe. In some examples, the syringe and patch are separate devices (e.g., separable from each other). Alternatively, the syringe and patch may be part of a single device (e.g., not separable from each other).

Syringe with a needle

Referring to fig. 1, the injector 7 may be of any suitable configuration. As previously described, the syringe may advantageously employ one or more features of the syringe described in U.S. patent No. 9,925,333, the contents of which are hereby incorporated by reference.

Referring to fig. 1-3, the syringe 7 has a generally low profile disc-shaped outer housing 74, the outer housing 74 having an upper surface 75 and a lower surface 76, the cannula or needle projecting through the outer housing 74 when actuated by a user. Upper surface 75 has an actuator or button 77 for initiating an injection and a section 80 of housing 74 that allows a subject or medical professional to view expandable member 78 to determine the amount of substance 79 (e.g., injectable fluid or drug in the reservoir of syringe 7). In such cases, the section 80 of the housing may comprise a transparent material, and the user may determine whether an injection has begun or ended. In some cases, expandable member 78 and/or section 80 of housing 74 may be graduated, such as by demarcations 127 or the like, so that a subject or medical professional may more accurately visually determine the amount of substance 79 remaining, such as, for example, about 50% complete or about 75% complete. Further, the expandable member 78 may itself include or interact with features on the outer housing 74 to indicate the amount of material 79 remaining in the reservoir of the syringe. For example, when the syringe 7 is filled with the substance 79, the transparent section 80 may display a color, such as, but not limited to, green. When the syringe 7 is free of the substance 79, the transparent section 80 may display a different color, such as, but not limited to, red. In the middle of the assignment, the transparent section 80 may display a combination of colors.

Referring to fig. 4-6, the lower surface 76 of the syringe 7 includes a filling port 81 and a dispensing port 82. The fill port 81 is an interface that allows the transfer device fill tube 83 to transfer the substance 79 to the syringe 7 (e.g., a reservoir of the syringe). The dispensing port 82 also contains an internal path 84 between the substance 79 expelled from the expandable member 78 and the cannula 85. Fill port 81 and dispense port 82 may be in direct fluid communication through internal path 86, or they may be combined into a single port.

Referring to fig. 4-6, the syringe may include a fill port 81, the fill port 81 including a check valve 87 to prevent the pressurized substance 79 from leaking outside the syringe 7 when the syringe 7 is removed from the delivery device 6 and the fill port 81 is removed from the fill tube 83.

Referring to fig. 4-6, the injector 7 may also have a fill port 81, the fill port 81 being configured to accept insertion of a syringe. The syringe may be configured with a luer fitting or cannula. The configuration of the fill port 81 allows a user to manually fill the syringe. The transfer device 6 may still be used but will no longer be needed in the configuration.

Referring to fig. 4-26, the syringe 7 may also have a dispensing port 82, the dispensing port 82 configured to attach directly to a cannula via an attached tubing or standard cannula port.

Referring to fig. 4-6, the lower surface 76 of the injector 7 carries an adhesive 88 for temporarily securing the injector 7 to the body (e.g., skin) of the subject before the injection is completed. During removal of the syringe 7, the adhesive tape pad 89 may be automatically removed, thereby exposing an adhesive surface 88 on the lower surface 76 of the syringe 7, which adhesive surface 88 may be used to adhere the syringe 7 to the patient's body (e.g., skin). Alternatively, the adhesive tape backing 89 may have a tab 90 which the user pulls on the tab 90 to manually remove before adhering the syringe 7 to the skin. Alternatively, the tab may be attached to the surface of the transfer device 4 such that the adhesive tape backing is automatically removed when the syringe 7 is removed.

Referring to fig. 4-6, the syringe 7 may have an adhesive tape flange 91 that extends beyond the bottom base 76. Said flange 91 of the adhesive tape 88 may act as a strain relief between the syringe 7 and the skin surface, thereby reducing the risk of accidental detachment of the syringe 7 from the skin. In other words, similar to the tapered strain relief on the leads entering the connector, the extended adhesive flange 91 serves to distribute the load on both sides of the connection point between the adhesive tape 88 and the lower surface base 76 of the syringe 7 to reduce any strain rise at the interface of the adhesive tape 88 and the skin.

Referring to fig. 4-6, the injector 7 may be configured to have a tapered underside surface 98 that presses against the adhesive flange 91 to securely attach the adhesive tape 88 to the skin without further user intervention when the user secures the injector 7 to the skin. By taking advantage of the compliance of the human skin when the injector 7 is pressed against the skin, the tapered underside surface 98 of the injector 7 effectively presses the flange 91 of the adhesive tape 88 against the skin, but the upper exposed surface of the portion of the flange 91 is free of exposed adhesive and therefore is not attached to that portion of the tapered underside surface 98. The user does not need to move their finger around the flange 91 to secure the syringe 7 to the skin, which makes it a much simpler method of adhesive tape 88 attachment.

Referring to fig. 4-6, the injector 7 may have an underside surface 76, which underside surface 76 is flexible or compliant, rather than rigid, to allow for improved attachment by conforming the injector 7 to the skin during application.

Referring to fig. 7-9, after the injector 7 is placed against or adhered to the subject's body (e.g., skin) 99, the safety mechanism or locking mechanism may be automatically released and the injector 7 is ready to be fired (injected). In such a case, the syringe 7 is prevented from being actuated (it is locked) until it is placed against the skin. Alternatively, the user may manually remove the safety device 100, such as a safety pin, safety cannula, tab, or collar, to release the syringe ready for firing (injecting or guiding the cannula through the opening into the subject). In some cases, the injector 7 cannot be fired until the safety mechanism 100 is released. The safety mechanism 100 may be passive or active and is triggered manually by a user or automatically by the injector 7.

Referring to fig. 7-9, the syringe 7 may use an actuator or button 77 in combination with a visual indicator 101 to indicate parameters of the syringe 7 after the syringe 7 is removed from the delivery device. For example, when the button 77 is in the up position and the indicator 101 has a color (such as, but not limited to, green), this may indicate that the syringe 7 is ready to begin an injection. In addition, the button 77 may have a sidewall 102 that is a different color than its top 103. When the button 77 is pressed, the user cannot see the sidewall 102 of the button 77; this may indicate that the syringe 7 is in use. When the injection of the medicament is completed, the injector 7 may alert the user. The alert may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof. The button 77 is desirably designed to provide audible, visual, and tactile feedback to the subject or user when the button 77 "pops" into the locked position. The syringe 7 may indicate to the subject that it has completed dispensing and has delivered the full dose to the patient with the button 77 in the up position and the indicator window 101 showing that the syringe reservoir is empty. For example, when the button 77 is in the up position and the indicator 101 displays a different color (such as, but not limited to, red), this may indicate that the injector 7 has completed an injection.

Referring to fig. 10-12, the injector 7 may have an actuator or button 77, which the subject or user presses on the injector 7 to initiate an injection. The button 77 may be configured as an on/off switch (such as a light switch), i.e. having only two states, open and closed. This prevents the user from pushing the button 77 half way without actuating the syringe 7. Once activated, the "light switch" type button 77 will rapidly guide the cannula 85 into the skin 99 independent of user manipulation of the button 77. Alternatively, the button 77 may have a continuous movement, allowing the user to slowly guide the cannula 85 into the skin 99. The button 77 and cannula 85 may be formed by preferably coupling the button 77 directly to the cannula 85 using an adhesive 104.

Referring to fig. 10-12, the syringe 7 may have a cannula 85, which cannula 85 directs the substance from the reservoir into a fluid flow path in fluid communication with the reservoir when the syringe 7 is coupled to the skin and upon actuation, thereby directing the substance from the reservoir into the skin 99. When the button 77 is actuated, the button 77 initially reaches a first position or depth as shown in fig. 11, and retracts slightly (in some cases automatically) to a second position or depth as shown in fig. 12. The first depth shown in fig. 11 is achieved by over travel of the button 77 during actuation. The first depth may be controlled by a feature 105 in the button 77 that is in direct contact with a base 106 of the syringe 7. The final depth of the cannula 85 is suitable for subcutaneous injection. Alternatively, for intradermal injections, the final depth of the cannula 85 may be reduced. Alternatively, for intramuscular injections, the final depth of the cannula 85 may be increased. When the first depth is reached, the cannula 85 is retracted away from the subject's body to a second depth, as shown in fig. 12. The retraction distance of the cannula to the second depth is in the range of 0.1-2 mm. In such cases, the retraction feature serves to prevent the cannula 85 from becoming clogged with tissue during initial insertion. The tissue blockage may require very high pressures to overcome and prevent the syringe 7 from delivering the medicament. Retraction of the cannula 85 from the first position to the second position creates an open area before the cannula tip 107, allowing the pressure to be reduced to initiate flow of medicament from the cannula 85. In some cases, in order to maintain the syringe 7 at a relatively constant pressure, a substance is introduced through the cannula during the injection, said reduced pressure for initiating the outflow of the medicament from the cannula being necessary.

Referring to fig. 10-12, the syringe 7 may include a cannula 85 having a side opening 108. As shown in fig. 12, once the button 77 on the syringe 7 is fully depressed, the cannula 85 will be fully inserted into the skin 99 through the dispensing port 82 and the syringe 7 will begin dispensing the substance. Until button 77 is fully depressed, side hole 108, and therefore the lumen of cannula 85, is not in communication with fluid passage 86 of dispensing port 82. Both the side opening 108 and the cannula tip 107 remain within the septum 109. With the side opening 108 and cannula tip 107 remaining within the septum 109, the entire medication path remains sterile prior to use. When the button 77 is fully depressed and the cannula 85 is in the dispensing position, the side opening 108 in the cannula 85 communicates with the fluid channel 86 of the dispensing port 82 and injection of the substance (e.g., injectable drug or fluid) begins.

Referring to fig. 10-12, septum 109 provides the advantage of sealing cannula tip 107 and side opening 108 from injectate before and after dispensing. Sealing the cannula tip 107 and the side opening 108 of the cannula 85 at the end of the injection has the particular advantage of preventing dripping of the substance (e.g. injectable liquid) from the syringe 7 after dispensing and/or after removal from the skin surface. It also prevents contaminants from entering the hollow cannula before being actuated into the skin. The septum 109 may comprise a pierceable membrane that may be made of any suitable material to allow sealing once the cannula 85 has pierced it. The material composition of the septum 109 or pierceable membrane may comprise silicone. Alternatively, the material composition of the septum 109 or pierceable membrane may also be a mixture of different materials including, but not limited to, bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, PTFE, natural rubber, and silicone. Alternatively, the fluid path 86, which includes the dispensing port 82, may comprise a rigid plastic with an overmold of injected silicone to create the previously described septum.

Referring to fig. 10-12, the septum 109 at the dispensing port 82 may protrude slightly from the lower surface into the skin surface 99 of the syringe 7 to provide pressure on the skin surface 99 of the injection site. After retraction of the cannula, this pressure on the skin surface 99 by the dispensing port 82 may eliminate the flow of substance from the injection site, commonly referred to as blow back.

Referring to fig. 10-12, the syringe 7 may include a set of spring tabs 110, the set of spring tabs 110 interfacing with the button 77 to perform the locking function. The spring tabs 110 are biased to lock into undercuts 111 in the button 77 to maintain the button 77 in the first upward position or pre-firing position, as shown in FIG. 10. The geometry of the undercut 111 and the spring tab 110 help to generate the previously described light switch actuation force. The lamp switch actuation is achieved by translation of the button 77 relative to the spring tab 110 and the geometry of the mating undercut 111 surface.

Referring to fig. 10-12, syringe 7 may include spring tabs 112, the spring tabs 112 interacting with buttons 77 in syringe 7 to perform a locking feature such that when buttons 77 are actuated to a first depth and slightly retracted to a second depth or dispensing position, undercut features 113 in buttons 77 allow spring tabs 112 to hold buttons 77 in the dispensing position until syringe 7 has completed dispensing.

Referring to fig. 13-14, the syringe 7 may include an end of delivery or empty indicator 114 to sense when all of the substance (e.g., drug or injectable fluid) has been expelled from the expandable member 78 and the syringe 7 has completed dispensing. The empty indicator 114 may be configured with a slot or other opening 115 to slide over the expandable member 78 at the exit port when the expandable member 78 is in a deflated state after all material has been expelled. The null indicator may have two states. As shown in fig. 13, the empty indicator may be in a first position or deflected state when expandable member 78 is full of material at the section and is not received within slot or opening 115. When the diameter of expandable member 78 is greater than its minimum value due to residual matter contained therein, the first position will transition to the non-empty state of expandable member 78. As shown in fig. 14, the null indicator 114 may be in a second position or deflected state when the expandable member 78 is partially or fully received within the slot or opening 115. When the diameter is at a minimum, the second position will transition to the empty state of expandable member 78.

Referring to fig. 13-14, the syringe 7 may include an automatic cannula retraction mechanism at the end of dispensing. The mechanism includes a direct coupling between spring tab 112, button undercut feature 113, and empty indicator 114, all of which were previously mentioned. As shown in fig. 14, when expandable member 78 is filled with a substance (e.g., a drug or an injectable fluid) and push button 77 is pressed from the first pre-fired position to the second dispensing position, undercut features 113 in push button 77 allow spring tabs 112 to retain push button 77 in the dispensing position until syringe 7 is completely dispensed. The spring tab 112 may also be directly coupled to the empty indicator 114, with the empty indicator 114 naturally in a first position or deflected state. The action of depressing the button 77 into the second or dispensing position allows the post feature 116 in the button 77 to provide a bias or pretension on the spring tab 112 to guide the empty indicator 114 into its second or deflected state. However, because expandable member 78 is initially filled with a large diameter substance, empty indicator 114 cannot be moved to the second position or deflected state as shown in FIG. 13. After button 77 is depressed, material begins to be expelled from expandable member 78 through the cannula, as previously described. Once expandable member 78 has expelled all of the material and is at the minimum diameter, empty indicator 114 (under pre-tension from spring tab 112) will move to the second position or deflected state, as shown in FIG. 14. Spring tab 112, which is directly coupled to empty indicator 114, also moves with empty indicator 114. This movement releases the spring tab 112 from the undercut feature 113 in the button 77 to allow the button 77 (and cannula) to move upward to a final or post-fired position after dispensing is complete, as shown in fig. 15.

Referring to fig. 15, the locking spring tab 117 may also interact with the button 77 in the injector 7 to perform a locking function such that when the injection is completed, the button 77 is released and the button 77 is pushed upward by the return spring 118 to a final upward or post-fired position. In the final up position or post-firing position (as shown in fig. 15), the button height 77 relative to the top of the injector 7 may be higher than in the pre-firing position (as shown in fig. 10). The ends of the locking spring tabs 117 move outward to the outer diameter surface 119 of the button 77 within the outer housing 74 to lock the button 77 in the upward or post-firing position and prevent the button 77 from being actuated again.

Referring to fig. 15, the injector 7 may include a return spring 118, the return spring 118 interacting with the push button 77 to bias the push button 77 to a first upward position or pre-firing position. When the button is actuated downward to a second depth or dispensing position, the return spring 118 is compressed, resulting in a greater bias or preload. At the end of the dispensing cycle, the button 77 unlocks from the second depth or dispensing position (as shown in fig. 12) to move upward to a final or post-fired position after dispensing is complete, as previously described. It is the bias of the return spring 118 that urges the button 77 up to the final or post-firing position.

Referring to fig. 15-16, upon removal of the syringe 7 from the skin 99, the syringe 7 will preferably be locked to protect non-destructive access to the cannula or reuse of the syringe 7. The syringe 7 may indicate to the user that the full dose has been delivered. The indication may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof.

Referring to fig. 16, when the injector 7 is removed from the skin 35, the bandage 120 may be released from the injector 7 and remain on the skin surface 35. This may be achieved by using an adhesive on the bandage part that attaches the bandage more firmly to the skin than the adhesive that attaches the bandage to the injector 7. Thus, when the housing is lifted from the skin, bandage 120 remains in place over the injection site, as described in U.S. patent No. 7,637,891 and U.S. patent application No. 12/630996, both of which are incorporated herein by reference. As shown in fig. 16B, bandage 120 may include an opening 120B (e.g., a hole or slit in the center of the bandage).

Referring to fig. 36-39, syringe 7 may preferably include a manifold 121, which manifold 121 is assembled to both expandable member 78 and fill port 81 and dispense port 82, and provides direct fluid communication between expandable member 78 and fill port 81 and dispense port 82 of syringe 7. The manifold 121 may be configured with a larger diameter at the end assembled to the expandable member 78 to facilitate filling and draining of all matter out of the expandable member 78 as previously discussed. The manifold 121 may preferably include an internal passageway 122 to allow fluid to flow into and out of the expandable member 78. The manifold 121 may be configured with a filter 123 in the injectable fluid path 122 for filtering the substance to remove particles before and after introducing the substance into the expandable member 78. The filter 123 may be a membrane, depth filter, or other suitable filtration media having a pore size small enough or effective to remove undesirable particles of undissolved material that may include, but are not limited to, the situation where the material is reconstituted by the delivery device. The manifold 121 may also be configured with a filter 123 for removing air. Such air removal filters 123 may include bubble traps, air gaps, or other configurations in the injectable fluid path 122 that remove air from the injectable fluid path 122 before the air is introduced into the expandable member 78. The air removing filter 123 may be configured to have a hydrophobic filter or a combination of a hydrophobic filter and a hydrophilic filter. The hydrophobic filter will allow air to escape from the transfer device but not liquid to pass through. A hydrophilic filter will allow liquid to pass but not particles or air. The air removal filter 123 may also have a check valve to allow for the discharge of trapped air. Alternatively, the air remover and filter 123 may be located at any point in the fluid path from the fill port 81 to the cannula 85. For example, the most downstream point in the fluid path is the distal end 128 of the expandable member 78. Inner mandrel 124 can be connected to distal end 128 of expandable member 78. An air remover or filter 123 may be integrated into the downstream point to allow trapped air to be expelled during filling of the syringe 7. In addition, the mandrel 124 may include slots along its length that communicate with the downstream filter 123 to help vent air during the filling process.

Referring to fig. 36-39, the syringe 7 may include an elastic expandable member 78, such as an elastic balloon or bladder-like container. The material composition of expandable member 78 may preferably be silicone. Alternatively, the material composition of expandable member 78 may also be a mixture of different materials including, but not limited to, bromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybutadiene, EPDM, PTFE, natural rubber, and silicone. In addition, the expandable members 78 may be coated to improve their surface characteristics. The coating may include parylene, silicone, teflon, and fluorine gas treatments. Alternatively, expandable member 78 may be made of a thermoplastic elastomer.

Referring to fig. 36-39, the syringe 7 may include an elastically expandable member 78, the substance being delivered under pressure to the elastically expandable member 78. This causes the expandable member 78 to expand and the elasticity of the expandable member 78 creates a pressure that tends to expel the material. The pressure chamber of the previously described delivery device (or other pump or pressurizing device as may be employed in the delivery device) delivers the substance under pressure to the syringe 7. Introducing a substance under pressure into expandable member 78 causes both its diameter and length to stretch and expand. One example of this is blowing up a long and thin balloon. The volume of the syringe 7 may range from 0.5 to 30 ml. When expanded, the resilient expandable member 78 applies an expulsion pressure in the range of 1 to 200psi to the substance contained in the expandable member 78, rendering the syringe 7 ready for automatic administration of the substance upon activation by a user depressing a button as previously described. Thus, the delivery device as described previously not only operates to deliver a measured amount of substance (and if necessary mix, dilute and filter it) to the syringe 7, but also simultaneously fills or provides motive pressure to the syringe 7 (by expanding the elastically expandable member 78) so that the syringe 7 is ready to automatically dispense the substance under the pressure exerted by the elastically expandable member 78 upon actuation by the user.

The aspect of the transfer device (simultaneous transfer and charging) is particularly advantageous. While the above-identified application shows the syringe 7 in a pre-filled or filled state for injecting the substance 79 when the syringe 7 is actuated, the present disclosure contemplates that the syringe 7 may remain empty and the expandable member 78 in a more relaxed and unfilled state, i.e., in an unfilled or unfilled state, until administration of the substance is desired. Only then, the substances are mixed or processed as needed and introduced into syringe 7, expanding expandable member 78 to a filled (inflated) state. In the present disclosure, the medicament is stored in its original container closure (vial) until the time of use. Because the substance is typically injected within a few seconds to a few hours after transfer from the vial to the syringe 7, the shelf life of the medicament and the compatibility of the medicament with the material in the fluid path within the syringe 7 are not significant issues. The challenges and expense of designing the syringe 7 and selecting materials for extending the shelf life of the pre-filled syringe 7 are significantly reduced.

With reference to fig. 36-39, the present subject matter may use the features of the syringe 7 described in the patent applications incorporated by reference as previously described. However, the expandable member 78 employed in the syringe 7 may also here preferably take the form of an elongate balloon or bladder-like container, for example, arranged in a planar spiral or helical configuration as shown. As previously described, the syringe 7 includes a circular-shaped outer housing 74, the circular-shaped outer housing 74 having a helical slot or recess 125 formed therein. The elongate balloon or bladder-like container 78 rests in a slot 125 with one end for communicating directly or indirectly with the injection cannula 85 through the fluid path 122 and the other end for communicating directly or indirectly with the dispensing indicator 101. The elongate helical configuration allows the balloon or bladder-like container 78 to have sufficient volume for such amount of substance 79 as may be desired while also facilitating the low-profile configuration of the syringe 7. In some cases, by utilizing a relatively long expandable member 78 with a large aspect ratio, very high pressures and volumes can be achieved with minimal required force. Additionally, the volume of expandable member 78 can be varied by varying the fill length without significantly changing the pressure/volume curve of expandable member 78.

Referring to fig. 36-39, one of the other aspects that may be employed in the present subject matter is the use of an insert or plunger or mandrel 124 within the expandable member 78 to pre-stress the expandable member 78 to a slightly expanded position when unfilled, such that when the expandable member 78 expels material, it will contract or collapse to a still stretched or stressed state and continue to exert pressure on any fluid therein, as shown in fig. 38 and 39. This better ensures that all or substantially all of the substance is completely expelled from the syringe 7. The mandrel or shaft 124 may be a fluid-filled expandable member, if desired. This would allow for a variable size mandrel 124. Alternatively, expandable member 78 may have a sufficiently small internal volume (small diameter) when unstressed so that substantially all of the material is expelled without the need for an internal mandrel or shaft 124. In addition, expandable member 78 may be flattened/stretched by "wrapping" it around a surface within a syringe (such as cylindrical wall 134). The pre-stress created in expandable member 78 will serve to eliminate any residual fluid volume remaining therein.

As previously described, there are a number of different ways to cause expandable member 78 to expand and/or contract in an arcuate manner. Referring back to fig. 15, one way is to design the expandable member 78 with a thicker wall cross-section 126 in an area around the circumference of the expandable member 78, which will cause the expandable member 78 to expand in a circular manner. Alternatively, a separate element 126 may be fixed along the length of the expandable member 78 to effectively reinforce that portion of the circumference of the expandable member 78, which will cause the expandable member 78 to expand in an arcuate manner. Referring again to fig. 17, another approach is to use internal features, such as slots or recesses 125 in the housing 74 of the syringe 7, to guide the expandable member 78 around a circular or helical path. These features 125 can interact with the expandable member 78 in a variety of ways, the simplest being that the outer shape of the expandable member is constrained by a slot 125 in the housing 74 of the syringe 7. Friction between the expandable member 78 and the inner surface 125 of the housing 74 may be reduced by lubricating the outer surface of the expandable member 78, or by inserting the expandable member 78 into a low spring rate spring that will limit both the friction and the outer diameter of the expandable member 78 without constraining the length.

Referring to fig. 36-39, elongate expandable member 78 may preferably be configured to expand along an arc having a predetermined tube diameter without the aid of a wall or guide within the syringe. Referring again to fig. 15, viewing the cross-section of the elongated expandable member 78, a thicker wall region 126 may be added in a small portion of the circumference of the expandable member 78 to cause the elongated expandable member 78 to expand in an arc as previously described. The arcuate expandable member 78 increases in length due to the increase in pressure and volume therein; the thicker sections 126 deflect less than the thinner sections.

Referring to fig. 17, arcuate expandable member 78 will expand in an arcuate shape in length, orienting its thick wall thickness region 126 or smaller deflection region into the interior of a circle. Increasing the wall thickness 126 of the expandable member 78 in the circumferential cells 126 will effectively continue to decrease the radius of the arc of the expandable member 78. The increase in wall thickness 126 may be accomplished by molding or extruding it into the arcuate expandable member 78, or by bonding a strip of material to one side 126 of the expandable member, such that the portion of the wall 126 lengthens at a slower rate, causing the expandable member 78 to expand in an arcuate shape as previously discussed.

Referring to fig. 18, the distal end of expandable member 78 may be secured with an element, such as indicator 101, that is constrained to follow a guided path within an inner surface 125 of housing 74. Alternatively, expandable member 78 may be pre-stretched and flattened around a circular diameter (such as wall 134) within syringe 7 such that there is no change in the length of the expandable member. Alternatively, a straight or curved mandrel 124 having a length greater than the unstressed expandable member may be used to stretch the expandable member into a circular shape within the syringe 7 prior to filling. Alternatively, the spindle 124 may be used as a visual indicator to show the status of the syringe 7 and the progress of the injection. The mandrel 124 may be tinted to allow it to be easily seen through the housing.

Referring to fig. 36-39, a substance is injected into expandable member 78 by the delivery device, and expandable member 78 expands to a particular outer diameter controlled by the configuration of inner surface 125 of housing 74. In this manner, the entire length of expandable member 78 may be filled with a known volume of the agent, and the outer diameter at each longitudinal location along expandable member 78 is known. It is desirable to fill and empty the expandable member 78 along its length from one end to the other in a controlled manner to encourage complete emptying of the expandable member 78 and to allow for easy and accurate measurement of the substance in the expandable member. To visually assist in determining how much material is in expandable member 78, graduated markings (similar to a syringe) may be printed on expandable member 78 to indicate the volume remaining in expandable member 78. As previously described and with reference to fig. 21-22, the expandable member 78 and the housing 74 may be transparent to allow the user to see the medicament 74 and the volume remaining in the syringe 7. Alternatively, graduated markings 127 may be printed on housing 74 to indicate the volume remaining in expandable member 78.

Referring to fig. 36-39, in accordance with one aspect of the above-described subject matter, material can be gradually expelled from the distal end 128 toward the proximal end 129 of the elongate expandable member 78. The proximal end 129 of the expandable member is closest to the dispensing cannula 82 or cannula. This allows the user to visually determine or approximate the injection status either alone or with the aid of the graduated markings 127 on the injection housing 74, the window 80 or the expandable member 78. The gradual eviction may be accomplished in a number of ways. For example, the substance exits the expandable member 78 at the manifold 121 at the proximal end exit port section 130, and is preferably located at the proximal end 129 of an elongated expandable member (e.g., balloon or bladder container). The thickness of the wall of expandable member 78 may vary along its length from distal end 128 toward proximal end 129, either uniformly or incrementally. Being constrained by the walls of the helical channel 125 in which the expandable member 78 resides, the expandable member 78 will be inflated to a substantially uniform diameter along its length by the substance. However, the thicker wall at the distal end 128 of the expandable member 78 will exert a greater contraction force on the substance than the thinner wall at the proximal end 129, and thus will first collapse or contract in diameter during substance expulsion. As the wall of the expandable member 78 thins in that direction along its length, the expandable member 78 will then gradually collapse from the distal end 128 toward the proximal end 129. Because the thickness of the expandable member 78 preferably increases substantially uniformly from the proximal end 129 toward the distal or closed end 128, the contractive force of the expandable member 78 wall will increase substantially uniformly along the length of the elongated expandable member 78 from the proximal end 129 toward the distal or closed end 128 when expanded. Thus, as the substance is expelled into the subject, the expandable member 78 will gradually collapse in diameter and also gradually contract in length, as described above, the diameter collapse and length contraction preferably being visible to the user. The distal end 128 of the elongate expandable member may allow for the connection of a movable indicator component 101 in the syringe 7 that the movable indicator component 101 will contract following the length of the elongate expandable member 78. The indicator 101 is preferably visible to the user through the outer housing 74 and indicates the status of the syringe 7 and the progress of the injection. Alternatively, expandable member 78 is configured to have a constant wall thickness and may be pre-stressed in manufacture to bias it to fill from proximal end 129 to distal end 128 and collapse or empty from distal end 128 to proximal end 129 in a progressive manner as previously discussed.

Referring to fig. 36-39, the elongate expandable member 78 of the syringe 7 may be configured with a section 130 of the expandable member 7 adjacent the proximal outlet port end 130, the section 130 filling first and collapsing last during filling and expulsion of substance from the syringe 7. In other words, during filling of the syringe 7 by the delivery device, it is advantageous to have the proximal most outlet port section 130 of the expandable member 79 filled with the injection agent first. Furthermore, during dispensing of the substance from the syringe 7, it is advantageous to contain the last remaining volume of the substance within the most proximal outlet port section 130 of the expandable member 79. The above arrangement has several advantages. The proximal end section 130 of the expandable member 78 may have a thin wall that will cause it to remain inflated at a lower pressure than the remainder of the expandable member 78. This will ensure that sections 130 of expandable member 78 will remain inflated until all material has been expelled from the remaining sections of expandable member 78. As previously discussed, the section 130 may be directly coupled to an empty indicator to provide an indication of full or empty. Furthermore, as previously mentioned, the section 130 may be mechanically coupled to a null indicator to allow automatic withdrawal of the button 77 and cannula 82 when the substance is fully expelled.

Referring to fig. 36-39, alternatively or in addition to varying the wall thickness 126 of the expandable member 78, an elongate internal mandrel or shaft 124 within the expandable member 78 may gradually (linearly or stepwise) decrease in cross-sectional size along the length of the expandable member 78 from a proximal end (outlet port end) 129 toward a distal end (closed end) 128 of the expandable member 78. Furthermore, the manifold 121, which allows for attachment of the expandable member 78 to the syringe 7, may also be configured with a large diameter section 130 at the proximal end 129 of the expandable member 78. The large diameter section 130 of the mandrel 124 or manifold 121 at the proximal end outlet port 129 of the expandable element 78 ensures that the expandable element 78 will fill the substance in that region 129 first. In other words, expandable member 78 is held at a proximal end outlet port 129 by mandrel 120 or large diameter section 130 of manifold 121 at a near fill diameter. As the substance first begins to fill expandable member 78, it first reaches a fill diameter in large diameter section 130, and then gradually fills from proximal end 129 to distal end 128 along the length of expandable member 78 as previously discussed.

Referring to fig. 36-39, as previously discussed, during dispensing of a substance from the expandable member 78, the diameter of the expandable member 78 at its distal end continues to collapse from its distal end 128 to proximal end 129 in a progressive manner (similar to deflating an elongate balloon) until all of the fluid is expelled from the expandable member 78. The large diameter section 130 of the mandrel 124 or manifold 121 provides the same benefits (for filling as previously described) during substance dispensing at the proximal end outlet port 129 of the expandable member 78. The large diameter section 130 ensures that the last remaining substance in expandable member 78 will be contained and dispensed from the region 130. As previously discussed, the section 130 may be directly coupled to an empty indicator to provide an indication of full or empty, as well as automatic withdrawal of the button 77 and cannula 82 upon complete expulsion of the substance.

Referring to fig. 21, the user attaches the injector 7 to their skin 99. At the bottom of the injector 7 there may be an adhesive that allows adhesion to the skin 99 surface and hands-free operation. The adhesive may extend beyond the contour of the syringe to allow the user to securely adhere the tape to the skin. Alternatively, the user may hold the injector 7 against the skin 99 during injection.

Referring to fig. 21 to 23, the user removes the safety device 100 and presses the button 77 on the syringe 7 to start the injection. Once the button 77 on the syringe 7 is fully depressed it locks in place and the cannula will be fully inserted into the patient and the syringe 7 will begin dispensing the injectable medicament. The injector 7 may alert the user that injection of medicament has begun. The alert may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof. The time of injection may range from a few seconds to several hours. The syringe 7 may indicate to the user that it is dispensing the button 77 locked in the downward position and show the indicator window 101 with the syringe 7 not full. The syringe 7 preferably has a transparent section 80, which transparent section 80 allows the user to easily determine the amount of medicament remaining in the syringe 7.

Referring to fig. 24, when the injection of the medicament is completed, the user will be alerted. The alert may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof. The syringe 7 can indicate to the user that it has completed dispensing by a tactile and audible sound of the button 77 moving to the locked position and an indicator window 101 showing the syringe as empty. At the end of dispensing, the cannula will automatically retract to a locked position within the syringe 7.

Referring to fig. 21, when the injector 7 is removed from the skin 99, the bandage 120 may be released from the injector 7 and remain on the skin surface 99. Upon removal from the skin 99, the syringe 7 will preferably be locked to protect non-destructive access to the cannula or reuse of the syringe 7. The syringe 7 may indicate to the user that the full dose has been delivered. The indication may be in the form of a visual indicator, an audible sound, a mechanical movement, or a combination thereof.

In accordance with other aspects of the present subject matter, when performing an infusion with a syringe and cannula intended for subcutaneous infusion, it is desirable to know whether the cannula is properly placed within the skin or improperly placed within the blood vessel. A user performing an Intradermal (ID), Subcutaneous (SC) or Intramuscular (IM) injection typically aspirates the barrel by pulling back on the plunger to create a pressure drop within the barrel to see if any visible blood is entering the barrel from the cannula. If the blood is visualized, this means that the tip of the cannula is in the vessel. Many injectable medicaments for subcutaneous injection are specifically indicated not to be infused into blood vessels. The use of syringes and cannulae to perform blood aspiration is a common technique that can be performed by any well-trained person. In some cases, an auto-injector may be used, and the auto-injector may contain a mechanism for determining whether the auto-injector is properly placed.

Referring to fig. 25-26, the injector 7 may have a cannula 85 with a side opening (e.g., a hole) 108, the side opening 108 operably engaged with a button 77, the button 77 slidable within a septum 109 advanced into the skin 99. The button 77 may have a viewing window 160 on the button top 103 in fluid communication with the proximal end 161 of the cannula 85. The button top 103 may include a cavity 162 for blood 159 to accumulate and be viewed by a user through the button window 160. Cavity 162 may include a central aperture 163 that allows fluid communication with proximal end 161 of cannula 85 via cannula cavity 165. The outer wall 164 of the cavity 162 is formed by the button top 103. Further, a portion of the outer wall 164 may include a hydrophobic filter 166. In this configuration, the proximal end 161 of the cannula 85 is at atmospheric pressure. If the fluid 14 or blood 159 travels up the cavity 165 of the cannula 85, the fluid 14 or blood 159 exits the proximal end 161 of the cannula 85 and fills the cavity 162. Air 167 in chamber 162 is easily displaced through hydrophobic filter 166 until all of air 167 is expelled from chamber 162 and filled with fluid 14 or blood 159. At this point, the flow of fluid 14 or blood 159 ceases because fluid 14 or blood 159 cannot penetrate hydrophobic filter 166 and can be readily seen by the user through window 160 of button top 103, thus providing a method for determining whether cannula 85 of syringe 7 is in blood vessel 158.

Referring to fig. 27, the insertion of the cannula into the tissue can be generally divided into four stages. These include contactless (panel) a, boundary displacement (panel b), tip insertion (panel c) and shaft insertion (panel d). During boundary displacement, the tissue boundary in the contact region deflects under the influence of the load applied by the cannula tip, but the cannula tip does not penetrate the tissue. As the cannula tip begins to penetrate the skin, the boundary of the skin follows the cannula tip up to the point of maximum boundary displacement in the contact area. After the cannula tip penetrates the skin, the shaft is inserted into the tissue. Even after insertion of the tip and shaft, the boundary of the skin surface in the contact area does not return to its original non-contact state, but remains displaced by the distance x. The amount of boundary displacement x is a function of several parameters including, but not limited to, cannula diameter, cannula tip geometry, cannula shaft friction, cannula insertion speed, and physical skin characteristics. The boundary displacement x of the skin in the contact area is characterized by a cannula-based injector, since it affects the extent to which the cannula penetrates the skin and thus reduces the actual cannula penetration depth by the amount of boundary displacement x. If the boundary displacement x can be intentionally induced by stretching or preloading (such as pushing the skin out at the contact site prior to insertion of the cannula tip), there will be no additional boundary displacement of the cannula tip or shaft during insertion and the cannula tip depth can be predictably defined. The advantage of said intentional displacement is that the amount of penetration of the cannula through the tissue is not affected by the change in the boundary displacement x. The actual cannula penetration depth into the skin is not specifically known since some cannula length (depending on the above parameters) is outside the skin due to the naturally occurring boundary displacement x shown in fig. 27, without intentionally causing a boundary displacement at the skin surface before the cannula tip is inserted. On the other hand, if the maximum boundary displacement can be induced at the contact site, the actual cannula penetration depth will not vary with the above parameters (including cannula diameter, cannula tip geometry, cannula shaft friction, cannula insertion speed and physical skin properties).

Referring to fig. 28, the injector 7 may have a skin boundary displacement extension or structure (such as the lower side surface 76) that includes an extension 138 at or around the dispensing port 82 or as part of the dispensing port 82. The extension extends substantially perpendicular to the tissue plane at the cannula insertion point. When the injector 7 is attached to the skin 99, the extension 138 will protrude against the skin 99 surface, resulting in a displacement or compression of the skin 99 in said contact area 139. The compression of the skin helps to reduce or eliminate "tenting" of the tissue surface upon insertion of the cannula. In other words, extension 138 serves to eliminate further tissue defects or tenting, or to cause a more reproducible and lesser amount of skin surface deflection or tenting, by compressing the tissue to "preload" the tissue. During actuation of the button 77 from the pre-fired state to the first position, the cannula 85 is advanced out of the syringe 7 through the dispensing port 82 and/or extension 138 into the skin 99 to begin dispensing medicament. For the reasons described above, when the cannula 85 is advanced outside the syringe 7, the tip of the cannula 107 does not generate further boundary displacements 141 (already intentionally caused by the extensions 138) in the skin 99 at the contact areas 139. Thus, the actual cannula penetration depth 140 into the skin 99 is better characterized and controlled. Furthermore, the extension through which the cannula passes directly compresses the tissue surrounding the cannula, which has several advantages. Compression of the tissue by the extensions 138 in the contact zone 139 during injection increases the local density of the tissue, thus creating a higher pressure zone compared to the surrounding adjacent tissue 99. When the injection enters the skin 99, fluid will migrate from the high pressure region 139 to a low pressure region in the skin 99, which helps prevent the injected fluid or medicament from flowing or migrating into the direct area around the cannula/skin puncture site, and serves to reduce or minimize fluid leakage (reflux) and/or bleeding at the puncture site. The high pressure zone also effectively provides the benefits of a longer infusion cannula. For example, in an ultrasound evaluation comparing the depth of subcutaneous deposition of a 10mL fluid bolus (saline) using a syringe 7 having a 5mm needle depth and an off-the-shelf infusion pump (freem 60, RMS) having a butterfly needle extension assembly (9mm needle depth), the results show that the subcutaneous depth after injection of the 10mL bolus is equal between the syringe 7 having a 5mm needle length and the pump having a 9mm needle length. In all results, the bolus location was characterized by the distance from the skin surface to the top edge of the bolus (Zd). Fig. 47 shows the top edge of a 10mL subcutaneous bolus using a pump with a 9mm cannula length. The distance Zd was measured at 0.44 cm. Fig. 48 shows the top edge of a 10mL subcutaneous bolus using syringe 7 with a 5mm cannula length. The distance Zd was measured at 0.42 cm. Thus, a bolus of similar depth has a cannula depth (5mm) and a tissue displacement structure that is more than 40% shorter than another test cannula (9mm) without a tissue displacement structure.

Another advantage of the extension 138 is to compress the tissue in the contact region 139 after injection is complete. In the post-firing state, the button 77 has sprung up, alerting the user that the injector 7 has been completed. The cannula 85 is fully retracted outside the puncture in the skin 99. The dwell time between the completion of dispensing and removal by the user of the syringe 7 may be a few minutes or more, depending on the circumstances in which the user is at the time of completion. For the same reasons described previously, the compression of tissue by extension 138 in contact zone 139 increases the local density of tissue, thus creating a higher pressure zone than the surrounding adjacent tissue 99. Similar to a nurse who may apply pressure to the injection site with their thumb after injection, the pressure helps to close the puncture and prevent backflow of injected fluid or medicament to the injection site, and serves to reduce or minimize leakage and/or bleeding of fluid from the puncture site.

Referring to fig. 29, there are two interfaces associated with adhering the syringe 7 to the skin 99. The first is the adhesive/device interface 173 and the second is the adhesive/skin interface 174.

Referring to fig. 30, the adhesive 88 may be configured on the syringe 7 with at least two zones. The first zone 175 may comprise a permanent bond between the adhesive 88 and the syringe 7 using mechanical or chemical means, and is preferably positioned within the outer perimeter of the syringe 7. The second zone 176 may be configured to be removable or non-attachable from the syringe 7, and preferably adjacent to zone 1 and on the outside of zone 1 (e.g., radially outward).

Referring to fig. 31, if the adhesive 88 is fully attached to the bottom 76 of the device 7, during the tissue bulge 177 event, the adhesive 88 at the adhesive/skin interface 174 will begin to peel away from the skin 99 because the interface 174 is weaker than the adhesive/device interface 173. This is demonstrated on the convex surface in fig. 31. This may result in the syringe 7 being disengaged from the skin surface 99 and from the patient.

Referring to fig. 30 and 32, the adhesive 88 may be disposed on the syringe 7 having the above-described zones 175, 176, rather than completely permanently attaching the adhesive 88 to the bottom 76 of the syringe 7 as shown in fig. 31. During the tissue up event 177 in the configuration, the adhesive 88 in the second zone 176 will detach from the injector 7 and securely attach to the skin 99 surface at the adhesive/skin interface 174. This will allow the peel edge 178 to transfer from the adhesive skin interface 174 to the adhesive/device interface 173, effectively forming a strain relief at the adhesive/skin interface. The adhesive/device interface 173 may be designed to be more robust and prevent the syringe 7 from separating from the skin surface 99.

When performing self-injections using an auto-injector, it is a beneficial requirement of the device to protect the user from accidental cannula sticks. Typically, the cannula is retracted into the device before and after use, thereby preventing access to the cannula by the user. However, during injection, the cannula may extend outside the device. In some cases, the auto-injector includes a skin displacement sensor to automatically retract the cannula if the device is displaced from the skin during injection.

Referring to fig. 33-35, the skin deflection sensor 179 can be operably engaged with the flexible latch 181 of the button 77 and can slide within the lower housing 180 of the syringe 7. Referring to fig. 34, when the injector 7 is attached to the skin surface 99, the skin displacement sensor 179 is forced into a first or upward position 182 within the injector 7. When button 77 is actuated to the cocked state or second or dispensing position (cannula 85 is exposed), flexible latch 181 is forced into a locked position 187 by skin deflection sensor 179 below latch plate 183. In the downward cocked state or dispensing position, the latch plate 183 retains the button 77 at the latch plate surface 184 on the button 77 until dispensing is complete. At the end of dispensing, the latch plate 183 translates away from the latch plate surface 184 on the button 77, allowing the button 77 and the cannula 85 to retract to a post-firing position where the cannula 85 is contained within the injector 7. Referring to fig. 35, in the event that the injector 7 is disengaged from the skin surface 99 during an injection, the skin disengagement sensor 179 extends to a second or downward position 185 outside of the injector 7. This allows the flexible latch 181 to spring back to the unlocked position and disengage from the latch plate 183. This allows the button 77 and cannula 85 to retract to a post-firing position in which the cannula 85 is contained within the injector 7.

When performing self-injections using a syringe and cannula, the user may need to temporarily stop or pause the injection due to severe pain or irritation at the injection site. This suspension of injection flow into the injection site is accomplished by relieving pressure on the syringe plunger rod, thereby reducing localized pressure and associated pain and irritation by allowing more time for the injection bolus to diffuse into the surrounding tissue, and thereby helping to reduce pain at the injection site. In some cases, the injector includes a mechanism for suspending the injection, for example, automatically or manually.

Referring to fig. 36-37, when the button 77 is actuated, the cannula 85 and the button 77 travel to a first position or depth, as shown in fig. 36. In the first position or depth, the side hole 108 is covered by the septum 109 and, therefore, the lumen 165 of the cannula 85 is not in communication with the fluid channel 86 of the dispensing port 82. The button 77 may be intentionally held in the first position or depth to prevent the injectant 14 from flowing from the fluid channel 86 into the side aperture 108 of the cannula 85 and into the skin 99. As shown in fig. 37, when the button 77 is released, the cannula 85 and button 77 return to a second or dispensing position in which the side aperture 108 is exposed to the fluid channel 86, allowing the injectate 14 to flow from the fluid channel 86 into the side aperture 108 of the cannula 85 and into the skin 99 until the end of the injection. The act of pushing the button 77 to the first position or depth may be performed as many times as desired throughout the injection.

With reference to fig. 38-39, the actuation force 186 of the button 77 is the transitional load applied to the button 77 required to initiate the displacement of the button 77 and cannula 85 from the pre-firing position to the firing state or dispensing position. The force 186 applied to the button 77 is transmitted directly to the injector 7 before the transitional load is met. In particular, the load 186 may be transferred to the adhesive skin interface 174 and/or the adhesive device interface 173 to better secure the injector 7 to the skin surface 99 prior to activating the injector 7.

Referring to fig. 40-41, the arcuate expandable member 78 is positioned and/or preferably will expand in an arcuate shape in length. In the illustrated embodiment, the arcuate shape is formed by providing a less elastic region, such as a thicker or relatively thicker wall thickness region 126, which will result in less deflection of the expandable member in the region and result in the formation of an expanded arcuate shape. The thick wall thickness region 126 can be configured in any shape that allows the expandable member 78 to assume an arcuate shape during expansion. The preferred configuration of the thick wall region 126 is to minimize its thickness or attachment 150 in the circumferential direction on the wall of the expandable member 78 and to maximize the radial thickness or protrusion 151 away from the expandable member 78. This serves to encourage expansion of expandable member 78 in an arcuate shape, but also maximizes the amount of material along the circumference, independent of the thick wall thickness region 126 used for expansion. Additional features, including but not limited to a T-shape, may be configured to the end of the radial protrusion 152 to help urge the expandable member 78 into an arcuate shape.

Referring to fig. 42, a safety device such as a safety pin or safety sleeve 100 may be configured to allow removal from the injector 7 in any direction to release the injector 7 ready for firing (injection).

Referring to fig. 43, the syringe 7 includes a cannula 85 having a side aperture 108, the cannula 85 having the side aperture 108 allowing fluid communication between the fluid passageway 86 and the skin 99 once the button 77 is fully depressed in the syringe 7. This begins dispensing injectate 14. The inner diameter 165 of the cannula 85 is important in controlling the dispensing rate from the syringe 7. Referring to the Hagen-Poiseuille equation for fluid flow in a pipe, the flow rate through a pipe is proportional to the fourth power of the radius of the pipe. Thus, small changes in the inner diameter 165 of the cannula 85 result in large changes in the flow rate through the cannula 85, particularly as the inner diameter 165 becomes smaller. The cannula 85 in the syringe 7 may range from 21G to 34G (short gauge system) in various wall thickness configurations. The range corresponds to an inner diameter 165 range of 0.021 "to 0.003", recognizing that there are manufacturing variations or tolerances for the cannula inner diameter 165 in any given cannula size. This is based on cannula size and can have an inner diameter variation of up to ± 0.00075 ". To limit the range of inner diameters 165 to any given cannula size and to cause variations in flow, the cannula 85 may be modified prior to assembly into the syringe 7. The modification may include crimping, flattening, or rolling the cannula 85 over a portion of its length from the circular shape to the non-circular shape to a new specified effective inner diameter 165. This has the advantage of allowing a specific delivery rate control from the syringe 7.

Radio frequency compliance monitoring

In some cases, the injector includes a mechanism to alert the subject, prescriber, healthcare provider, or another third party participant when non-compliance or non-adherence occurs.

In accordance with other aspects of the present subject matter, when administering an injection with an auto-injector, it is desirable to know when the prescription of the injector is initially filled or refilled, and whether the injector is being used correctly and timely. While many prescription drugs are tracked as patients fill their medication with specialized labels, there are limited options for confirming whether a patient is actually taking a medication. As more and more medicament is present in the injector, the ability to automatically track the prescribed activation is currently limited. Furthermore, there is no ability to automatically track whether the injector is being used correctly.

As described herein, automated tracking of both adherence and compliance may be achieved wirelessly using RF (radio frequency) technology installed within or cooperatively associated with the delivery and/or syringe described herein. Current technology allows the use of Radio Frequency Identification (RFID) to transmit data for the purpose of automatically identifying and tracking tags or microcircuit chips attached to objects. As used herein, RF or RFID or RF tags or chips are used comprehensively and interchangeably and are intended to include wireless electronic tags or chips for transmitting data/information using any suitable wireless communication protocol or technology, such as bluetooth or any other wireless technology (e.g., wireless local area network, wireless PAN, or other wireless technologies described in the Institute of Electrical and Electronics Engineers (IEEE)802 standard).

The RF tag or chip may be active or passive. Although both types use RF energy to communicate between the tag or transponder and the reader, the method of powering the tag is different. Active RFID uses an internal power source (such as a battery) within or associated with the tag to continuously power the tag and its RF communication circuitry, while passive RFID relies on RF energy delivered to the tag from the reader to power the tag. In the present subject matter, the syringe or transfer package may include an RFID tag, may optionally include a power source for the tag, and is read or received by an external reader. In one embodiment, the RF tag or chip is removably associated with the syringe such that the RF tag or chip can be physically removed from the syringe when the syringe is used. This allows subsequent disposal of the syringe without the restrictions or restrictions that may apply if the tag or chip remains as part of the syringe after its use.

Referring to fig. 44-45, the syringe 210 may include an electronic RF tag or chip 211 to monitor the status of the syringe 210. For example, the RF tag 211 may broadcast (if active) or present (if passive, read by the external reader 212) information or status to the external reader 212, such as "the syringe 210 has been prescribed," "the syringe 210 has been removed from its packaging," "the syringe 210 has been actuated," and/or "the syringe 210 has completed its dose," the RF tag reader may also be associated with or communicate (such as by wireless or hardwired connection) with an on-site or off-site data collection facility to allow for recording and editing of information regarding compliance.

Referring to fig. 44-45, the RF tag 211 may be used to monitor whether the syringe 210 has been activated or has started or completed its dosage. The syringe 210 may include an active or passive Radio Frequency (RF) tag or chip 211 in any suitable location. As shown below, when used inside the injector, the RF tag or chip 211 may be attached to the button 213 and slidably communicate with the spring tab 214 during the first and second positions of the button 213. When RF tag 211 is in slidable communication with spring tab 214, RF tag 211 may broadcast (if active) or assume (if passive, read by external reader 212) a first state comprising an unused state. With the syringe 210 activated, the button 213 is depressed to the dispensing position. At the end of the dispense cycle, the button 213 unlocks from the second depth or dispense position (as shown in fig. 45) to move upward to a final or post-fired position. In the post-firing position, RF tag 211 may no longer be in contact with spring tab 214, thus allowing the state (second state) of RF tag 211 to change. In the second state, the RF tag 211 may broadcast (if active) or present (if passive, read by the external reader 212) the second state to include a use state. Alternatively, the RF tag 211 may be deformed or altered in such a way when the syringe is used, such that upon interrogation, the RF tag 211 presents a "used" signature. For example, if an RF tag consists of two coils joined by a conductor, the initial signature of the tag 211 would be a "two-coil" signature. Once the tag 211 is used, two separate coils produce different signatures if the conductor joining the two coils breaks.

For regulatory and/or disposability reasons, it may be desirable to place the RF tag or chip outside the syringe. For example, the RF tag or chip 211 may also be associated with another part of the delivery device or system, such as, for example, a safety sleeve or pull tab 100 (see fig. 42) to activate the tag or chip at one or more selected points in the operation of the delivery device and/or syringe. For example, an active RF tag or chip may be located on the safety sleeve and configured such that removal of the safety sleeve to begin the injection process closes contact between the long-life battery and the tag or chip transmitter.

Referring to fig. 52-55, the RF chip or tag 211 within the injector 210 may have two states, an armed or off state and an active or transmitting state. Referring to fig. 52 and 54, the state can be changed by turning on or off the contact between the battery 262 and the contact 263. This may be accomplished, for example, by configuring the safety release or pull tab 100 to prevent electrical contact between the battery 262 and the contacts 263 by spatial separation when the pull tab 100 is in place on the syringe 210, as shown in fig. 54. As shown in fig. 55, when the tab 100 is removed, the battery 262 and the contact 263 come together to contact each other and make electrical contact. Thus, the RF tag starts to function. Further, different actions associated with delivery and/or use of the syringe may be employed to establish or break contact. For example, when one action is taken, such as when a vial is inserted into the transfer device, a previously inactive RF tag or chip may be activated by closing contact between the battery and the chip or tag transmitter, and the tag or chip deactivated via another action, such as by opening such contact after use of the syringe.

In addition to usage information, the RF tag or chip 211 may also transmit or communicate data associated with a delivery or syringe. For example, the tag or chip may be configured with memory storage capacity to communicate the type of syringe, lot number, amount of fluid administered, drug identification, and other relevant information. FIG. 46 schematically illustrates one type of system that may be employed with the present subject matter. As shown in the figure, the RF tag or chip 250 may be of the active type and, when activated, actively transmits relevant information to a local patient module 252 located within the vicinity of the patient and syringe. For example, the patient module may be a wall-mounted or table-top device located in the patient's home for receiving monitoring information transmitted by an RF tag or chip associated with the injector and/or delivery device. The patient module may also be a cellular phone or the like.

The patient module may include a memory that holds data such as patient identity and related information. The patient module, in turn, communicates with a data manager 254 in a suitable manner (e.g., WIFI, cellular communication, telephone, hard-wired link, or other manner), and the data manager 254 may be any suitable data network or cloud storage device for receiving and/or storing data received from the patient module indicative of injector status and/or usage associated with particular identified patient information. The data manager is accessible to medical personnel responsible for monitoring patient use of the syringe and patient compliance with any prescribed injection regimen. The data manager may also be configured to automatically forward patient compliance information to the appropriate medical personnel, such as a particular physician or clinic 256.

Other aspects of compliance monitoring devices, systems, and methods such as those described herein, as well as the use of syringes, are shown in fig. 49-58. As shown, the system may include a wireless (such as bluetooth) source, such as a battery-powered transmission unit, such as a microchip indicated at 262 in fig. 59. The sending unit may be mounted in any suitable location and may be associated with or attached to a portion of the syringe (and/or delivery device) in the following manner: so that it can be removed from the syringe or transfer device at the time of disposal, allowing most of the syringe or transfer device structure to be recycled, since the electronic circuitry and electronic chip cannot typically be similarly recycled.

In some embodiments, the contactor ring is disposed on the top of the injector housing and prevents the contactor ring from contacting the sensing leads (which are attached to the injector button) when the safety strap is installed. When the safety strap is removed, the contact ring of the housing contacts the sensing lead of the button. The different sequences of injection procedures can then be tracked based on the connection status between the contact ring and the sense lead (i.e., the position of the contact ring relative to the sense lead). Infrared sensors may also be embedded in the syringe to optically track the delivery process, such as by, for example, monitoring the location or amount of injectable fluid in the expandable member of the syringe.

Referring to fig. 52 and 53, an embodiment of the RF tag or chip 211 includes the following components: battery 262, contacts 263, bluetooth module with microcontroller/microprocessor 265, button sensor 267, and antenna 269. The battery 262 provides stored energy to power the system. This may be a coin cell or equivalent battery in the 1.5-3V voltage range with a power output of 5-100 mAh. As previously described, contacts 263 provide an electrical connection between battery 262 and RF tag or chip 211. Contacts 263 are configured to interact with pull tab 100 to allow for no electrical contact until the time of use when the user removes pull tab 100. Bluetooth module 265 has an integrated microcontroller/microprocessor. An example of a suitable bluetooth module is davit 27898ge (Dialog) semiconductor part number DA14580-01 UNA. In an alternative embodiment, the bluetooth module may be separate from the microcontroller/microprocessor.

The button position sensing system in an embodiment of the device is shown in fig. 56 and 57. The sensing system may use an infrared transmitter and receiver sensor combination 267. The RF chip 211 is mounted on the underside surface of the device button 177 with the sensor 267 facing down. The reflective member 112 is fixedly mounted to the bottom of the syringe. When the device button is actuated to move from the up, raised or extended position shown in fig. 56 to the down, lowered or retracted position shown in fig. 57, the sensor 267 detects a decrease in distance from the reflective member 112. Conversely, when the button is released after medicament delivery, such that it moves from the position of fig. 57 to the position of fig. 56, the sensor 267 detects an increase in distance from the reflective member 112. The sensor 267 transmits the button position information to the microcontroller/microprocessor module 265.

In an embodiment of the apparatus, the processing performed by the microcontroller/microprocessor module 265 is presented in fig. 58. As shown at block 302, when the microcontroller/microprocessor is powered on, a start timer is started, such as by removing the safety tab 100 as described above with reference to fig. 54 and 55. Then, as indicated by block 304, the mode or state of the device is set to "cocked" (i.e., ready for dispensing), and bluetooth packets indicating the mode of the device are transmitted to a bluetooth enabled remote reader or receiver (e.g., 212 of fig. 44-45), which may be a smartphone or computer system, for example only. The pattern is displayed to the user on the remote receiver.

The process of block 308a may then be performed to conserve battery life of the device and calculate the timing of the device.

The microcontroller/microprocessor then checks the position of the device button (177 in fig. 56 and 57) using, for example, the IR sensor described above with reference to fig. 56 and 57, as indicated by block 312. If the device button is not pressed in the down position, the process is repeated, as indicated at 314. If the device button has been pressed, the start time for delivery of the injection is recorded as indicated by block 316, and the device mode is set to "dispense" as indicated by block 318. The pattern is transmitted to the remote receiver where it is displayed to the user, as indicated at block 322.

The process of block 308b is then performed to conserve battery life of the device and calculate the timing of the device by intermittently or alternately placing the processor in a low power sleep mode and then waking the processor at one second (or other suitable time) intervals.

The microcontroller/microprocessor then checks the position of the device button as indicated by block 324. If the device button has not returned to the raised or up position, as indicated at 326, the above process from block 322 is repeated. If the device button has been moved to the up position, the end time of the injection delivery is recorded as indicated in block 332, and the device mode is set to "complete" as indicated in block 334. The pattern is transmitted to the remote receiver where it is displayed to the user, as indicated at block 336.

The process of block 308c is then performed to conserve battery life of the device and calculate the timing of the device, after which the "finished" status of the device is again transmitted to the remote receiver (block 336).

Embodiments of the present disclosure may provide a "smart" connected device that enables a patient to self-administer high volume/viscosity medicaments, thereby enabling and facilitating freedom and mobility of the patient. Embodiments may provide a safe, simple, and discreet medicament delivery experience for a user.

Embodiments of the present disclosure may provide a smart device system to provide three pieces of information about the operation of a medicament delivery system: 1) when the device is powered on, 2) when the device starts delivery, and 3) when delivery is complete. In some implementations, the user interaction may include opening a mobile application on their device, as described elsewhere herein, and the smart device will complete the rest without requiring additional action by the subject or user.

Embodiments of the present disclosure may provide advantages such as: small board footprint-the entire electronic package fits within an existing button and is less than 3/8 inches (9.5mm) in diameter. This allows easy removal of the electronic device (button) for disposal and recycling of the electronic device.

Embodiments of the present disclosure may include smart device technology in the transmitting device. For example, the transport may include electronics to track transport usage. The electronics in the delivery device may communicate directly with the electronics in the external receiving device and/or patch/injector. Sensors/sensors within the transfer device electronics may provide information including, but not limited to, environmental conditions, opening of the enclosure or packaging, removal of the transfer device from the outer packaging, orientation of the transfer device (tilt sensing), location of the device (e.g., using global positioning system or GPS), whether the transfer device is on a flat surface, vial insertion, plunger release (venting), and/or removal of the syringe from the transfer device. The electronics in the transfer device may determine whether the correct vial has been inserted based on the electronics in the vial or the reading of the bar code/QRG code. When the outer box or package is opened, it may happen that the electronic device is activated when the transfer device is removed. If the device is not placed on a table or at an angle, additional electronics may be added to vibrate or make a sound. An electronic device in combination with an external receiver may provide voice commands to assist the user in using the device, or instructions if something is wrong.

In certain embodiments of the present disclosure, the injector may utilize bluetooth communication to provide data to the user. Further, embodiments may integrate Bluetooth Low Energy (BLE) into the device. BLE may be designed for low-power, low-cost applications that require lower data throughput rates than traditional bluetooth connections, such as audio streaming or hands-free telephone connections.

Two main connection types are defined in the bluetooth standard: a standard (binding) mode and a broadcast (also referred to as "beacon") mode. In a standard connection or a binding connection, the host (smartphone with installed application) forms a saved connection with the peripheral device (i.e., smart device). In that case, through the pairing process, both the host and the peripheral device share data to form a permanent connection that allows sharing between only one host and one peripheral device. The method has the advantage of a secure connection, allowing the exchange of encrypted information that cannot be decoded without the encryption key.

In broadcast mode (also referred to as "beacon"), the peripheral device sends data periodically, which can be read by any host in the vicinity. In that case, the peripheral device broadcasts only data; data is never received. The mode has several advantages, such as reduced power consumption. In some cases, further power savings may be achieved by a low power "sleep" mode, which only wakes up when new data needs to be broadcast;

furthermore, since the peripheral device may be configured as a transit-only device, enhanced security is provided because the hardware is not "hijacked" or loaded with malware. This reduces or eliminates the risk of unauthorized remote control of the device. The software is loaded onto the device at the factory so that unauthorized changes can be prevented once deployed.

In some cases, installation of an application may be used to protect data privacy, as described elsewhere herein. For example, if the application is not installed correctly, the data may simply consist of a list of unusable binary digits, lacking any text or other readable identifier. Thus, the lack of an encrypted connection does not expose any sensitive user information. The data may also not include patient information (such as name or identification number) that may be associated with a particular individual (thereby complying with HIPAA compliance).

Within embodiments of the present disclosure, an important property of the connected healthcare implementation may be that it does not affect the basic performance functionality of the medicament delivery device. In some embodiments, the feature of the device only reports the status of the device and never changes the function of the medicament delivery device. Some embodiments of the device will complete delivery of the medicament and provide visual feedback to the user regarding the status of the device even in the event of a serious failure of a bluetooth component, such as a battery.

With the bluetooth low energy broadcast mode and through the electronic chip in the device button, some embodiments of the present disclosure can deliver real-time device performance information in a small, low-cost, convenient package.

Syringe with patch

In one aspect, the present disclosure provides a system for measuring a plurality of health or physiological parameters from a subject. The system may include a patch including a first housing having a plurality of sensors configured to (i) measure a plurality of health or physiological parameters from a subject when the patch is secured to the body of the subject, and (ii) provide one or more outputs corresponding to the plurality of health or physiological parameters from the subject. The first housing may include an opening. The system may also include a syringe having a second housing containing a cannula in fluid communication with the fluid flow path. The second housing may be coupled to the first housing such that when the patch is secured to the body, the cannula is directed through the opening and into contact with the body of the subject. The syringe may be configured to (i) direct the substance from the reservoir to a fluid flow path in fluid communication with the reservoir, and (ii) direct the substance from the fluid flow path through the cannula into the subject.

The cannula may be configured to extend toward or retract away from the body of the subject. In some examples, the cannula extends toward the body of the subject to deliver the substance into the body of the subject (e.g., through the skin of the subject). After delivery of the substance, the cannula may be retracted away from the subject's body. The cannula may be connected to the reservoir via a fluid flow path. The cannula may be extended to and/or retracted from the body using a variety of mechanisms (e.g., mechanical, electrical, etc.). The means for cannula extension and retraction may comprise a pump, spring, gear, diaphragm, screw or other means of moving the cannula, or variations or combinations thereof.

The syringe may be detachable from the patch. The patch may include a first housing and the syringe may include a second housing, and the first housing and the second housing may be removably coupled. In one example, one or more fastening mechanisms may be used to mechanically couple the first housing of the patch to the second housing of the syringe. In some cases, the first housing and/or the second housing may contain magnets that allow for removable coupling, as described elsewhere herein. In another example, the first and second housings may be bonded, for example, using an adhesive tape. The adhesive force of the first and second housings may be adjusted based on desired characteristics. For example, it may be desirable to maintain the patch on the body of the subject while the syringe is removed. In such examples, an adhesive layer may be added to the patch, which may facilitate securing the patch to the body of the subject. The body adhering adhesive layer may have a stronger adhesive force between the patch and the subject's body than between the patch and the syringe. In yet another example, the first and second housings may be mechanically coupled, for example, using interlocking geometries of the first and second housings. For example, the first housing may include threads (e.g., threads, internal threads, etc.), and the second housing may include complementary threads that may engage the threads of the first housing. In conjunction with or alternatively, the first housing and/or the second housing may include snap fit joints (e.g., cantilever snap fits, annular snap fits, etc.) that allow the first housing to interlock to the second housing. Alternatively or in combination, the first housing and/or the second housing may contain components that allow for an interference fit, force fit, shrink fit, location fit, or the like. Other examples of fastening mechanisms may include, in non-limiting examples, form-fitting pairs, hooks and loops, latches, threads, screws, staples, clamps, prongs, rings, friction plates, rubber bands, rivets, grommets, pins, ties, snaps, Velcro (Velcro), adhesives (e.g., glue), tapes, vacuums, seals, combinations thereof, or any other type of fastening mechanism. Alternatively, the syringe may be permanently attached to the patch. For example, the first housing may be connected to the second housing, or may be integrally built into the second housing, or vice versa.

In some cases, the patch and syringe may be secured to one another via complementary securing units. For example, the patch and syringe, or the housing of the patch and the housing of the syringe, may complete a form-fitting pair. The patch may include a form-fitting male component and the syringe may include a form-fitting female component, or vice versa. In some cases, the outer diameter of the tab-type fastening unit of the patch may be substantially equal to the inner diameter of the recess-type fastening unit of the syringe, or vice versa, to form an interference fit. Alternatively or additionally, the patch and syringe may contain other types of complementary units or structures that may be fastened together (e.g., hooks and loops, latches, snaps, buttons, nuts and bolts, magnets, etc.). Alternatively or additionally, other fastening mechanisms, such as, but not limited to, nails, clamps, prongs, rings, friction pads, rubber bands, rivets, grommets, pins, ties, snaps, Velcro (Velcro), adhesives (e.g., glue), magnets or magnetic fields, tape, combinations thereof, or any other type of fastening mechanism, may be used to fasten the patch and syringe.

In some cases, the patch and syringe may be secured to one another via an intermediate structure. In some cases, the intermediate structure may be secured to one or both of the patch and the syringe by one or more of any of the securing mechanisms described herein. The intermediate structure may comprise a solid material, a semi-solid material, a liquid material (e.g., a resin configured to cure), or multiple material types. In some cases, the intermediate structure may undergo a phase change (e.g., from liquid to solid for an adhesive). For example, the intermediate structure may contain a fluid adhesive that cures to achieve fastening. In some cases, upon application of a stimulus (e.g., a thermal change, a pH change, a pressure change, an applied force, etc.), the intermediate structure is capable of transitioning from a first phase to a second phase, such as from a liquid to a solid or from a solid to a liquid, to effect the fastening or unfastening (or both). In some cases, the patch and/or syringe may contain intermediate structures. For example, the intermediate structure may be integral with the patch and/or the syringe.

The fastening between the patch and the syringe may be temporary, such as to allow subsequent fastening and unfastening of the patch and syringe without damaging (e.g., plastically deforming, shearing deforming, abrading, compressing, etc.) the patch or syringe. Alternatively, the fastening may be permanent, such as to allow subsequent release of the two patches from the syringe. In some cases, it may be desirable to deform the patch or syringe, and when secured to the syringe or patch, the patch or syringe may be temporarily or permanently deformed (e.g., stretched, compressed, etc.) and/or deformed (e.g., bent, crimped, folded, crimped, etc.) or otherwise manipulated. The opening may comprise a pierceable membrane. The pierceable membrane may be pierced by the cannula to create the opening. The pierceable membrane may be formed from a polymeric material, or the pierceable membrane may be formed from a variety of polymeric materials. The polymeric material may be naturally occurring or may be synthetic. Non-limiting examples of polymeric materials include polyvinyl chloride (PVC), polyethylene, polyurethane. In some cases, the pierceable membrane can further comprise an adhesive layer (e.g., an acrylate, methacrylate, epoxy diacrylate, or other vinyl resin, etc.). In some cases, the pierceable membrane may comprise a self-healing polymer or elastic material such that the opening introduced by the cannula may be closed, for example, after the cannula is retracted. In such cases, the pierceable membrane may comprise an opening (e.g., a hole or a slit) configured to form a seal without a cannula being guided through the opening. In some examples, the pierceable membrane may comprise an opening that is not configured to seal without a cannula being guided through the opening. Alternatively, the opening may not contain a pierceable membrane and the opening may be configured to be in direct line of sight with the body of the subject. The openings can be any suitable shape, for example, slits, triangles, squares, rectangles, diamonds, pentagons, hexagons, heptagons, octagons, polygons, ellipses, circles, and the like. In some cases, the pierceable membrane comprises an absorbent material, such as cotton, rayon, nylon, a polymer blend, or the like. In such cases, the pierceable membrane can serve as a bandage, and bodily fluids (e.g., sweat, blood, etc.) can be collected from the body of the subject. In some cases, the pierceable membrane may comprise an oxygen permeable material that may allow the subject's body or a portion thereof to be exposed to ambient air. In some cases, the pierceable membrane may contain a drug (e.g., an analgesic or a drug for treating pain).

The reservoir may be secured to the syringe. In some cases, the reservoir may be removable from the syringe. For example, the reservoir may contain or be part of a container. The reservoir container may be removably attached to the syringe (e.g., attached to and detached from the housing of the syringe). The housing may receive a fastener to secure the reservoir. Alternatively, the geometry of the syringe may be designed to fit the reservoir or reservoir container. In other cases, the reservoir may be part of the syringe (i.e., non-removable). In one example, a drug reservoir may be disposed in the housing and may be in fluid communication with the infusion cannula. For example, the infusion cannula may be movable within the housing between a pre-dispense position and a dispense position in fluid communication with the reservoir. The reservoir may be configured to contain a formulation having the substance.

The substance may comprise a drug. The drug may be a solution or a mixture. The medicament may be used to treat a range of diseases in the therapeutic field including, but not limited to cardiovascular, musculoskeletal, gastrointestinal, cutaneous, immunological, ophthalmological, hematological, neurological, oncological diseases, endocrine, metabolic and respiratory. The medicament may be for treating discomfort or pain in a subject. For example, the medicament may comprise an analgesic, a non-steroidal anti-inflammatory drug (NSAID) or other pain-reducing, pain-relieving or other pain-managing substance.

The housing of the patch and/or the housing of the syringe may comprise one or more polymers or plastic materials. Non-limiting examples of polymers include polyamides, polycarbonates, polyesters, polyethylenes, polypropylenes, polystyrenes, polyurethanes, polyvinyl chlorides, polyvinylidene chlorides, acrylonitrile butadiene styrene, polymethyl methacrylates, polytetrafluoroethylene, polyimides, polylactic acids, phenolic resins, polyetheretherketones, or derivatives thereof (e.g., high cross-linking, high density, etc.). The housing of the patch and/or the housing of the syringe may comprise a single polymer type (e.g., a homopolymer) or more than one polymer type (e.g., a copolymer), and comprise a random or ordered organization of monomers. For example, the polymer can be a block polymer, alternating copolymer, periodic copolymer, statistical copolymer, stereo block copolymer, gradient copolymer, branched copolymer, graft copolymer, and the like.

The sensor and/or transducer may comprise one or more sensors or transducers that allow one or more health or physiological parameters to be measured or monitored, or that allow device function to be indicated to the subject. Alternatively or in combination, one or more sensors may allow for measurement of patch or syringe parameters. Non-limiting examples of patch or syringe parameters include determining whether the patch is secured (e.g., to the body of the subject), whether the patch or syringe is in communication with the communication interface, whether the cannula is in fluid communication with the reservoir, an occlusion of the cannula, whether the patch and syringe are properly coupled, a flow rate of the substance through the cannula, and the like. The sensors of the plurality of input transducers/sensors may be selected from the group consisting of: conductivity sensors, impedance sensors, capacitance sensors, charge sensors, humidity and/or moisture sensors, temperature sensors, heart rate sensors, gap pressure sensors, resistance sensors, expansion sensors, acoustic sensors, vibration sensors, blood pressure sensors, optical sensors (e.g., color sensors, light sensors, wavelength sensors), chemical sensors, movement and/or activity sensors, and substance tracking sensors. The sensors in the plurality of output transducers may be selected from the group consisting of: a tactile (vibration) transducer, an audio transducer, or a visual transducer. In non-limiting examples, the sensors can be used to detect an environmental condition of the subject using the syringe, a body temperature of the subject, a heart rate, a blood pressure, an interstitial pressure, a tissue density, a skin distension, a bleeding (e.g., internal or external), a delivery of a drug, a dose of a drug delivered and/or delivered to the subject, a perspiration level of the subject, and/or a plurality of analyte measurements (e.g., blood glucose, blood oxygen, etc.) of the subject. One or more measurements may be measured or monitored before, simultaneously with, or after the patch is secured. For example, the patch may be configured to measure one or more health or physiological parameters prior to injection to establish a baseline and/or calibration measurement of the one or more health or physiological parameters. The patch may be secured to the body of the subject separately from the syringe. For example, the patch may be secured to the body of the subject and one or more measurements may be collected. Subsequent attachment of the syringe (e.g., to the patch and/or the body of the user) may then allow the substance to be directed to the subject.

The transducer may comprise any useful component, such as a solenoid, motor, or micro-electromechanical system (MEMS) actuator. In such cases, the housing of the injector or patch may contain conductive contacts that provide both mechanical and electrical contact of the transducer or sensor, for example, in an electronics subsystem housed in the injector.

The patch and/or the injector may include a communication interface that allows for the transmission and/or reception of data corresponding to a plurality of health or physiological parameters of the subject and/or parameters of the patch or injector. The data may be transmitted to an electronic device in communication with the communication interface. As described herein, the communication interface may be a wireless communication interface, a Wi-Fi interface, a near field communication interface, or a bluetooth interface. The electronic device may be a device, such as a mobile device (e.g., a smartphone, a tablet, a laptop, etc.), that may communicate with the communication interface. Alternatively, the communication interface may be a wired communication interface. In some examples, the patch and/or the injector may include a port for communication and/or a power source (e.g., Universal Serial Bus (USB), USB-C type, etc.) for connecting to an electronic device. The patch and/or syringe may include an RFID tag that allows information to be transferred to and optionally recorded by the syringe and/or patch, including but not limited to information about the medicament. This may allow the transmitted data about the injection to include information about the device and the medicament.

In some cases, the patch, injector, and/or electronic device may incorporate methods for data processing, data storage, and/or one or more feedback loops. In one such example, the patch may monitor one or more physiological parameters of the subject after injection to generate data regarding the one or more physiological parameters of the subject. Data may be transmitted to an electronic device (e.g., a mobile device) through a communication interface. In some cases, the mobile device may include methods for processing data and/or storing data (e.g., in a computer-readable memory). Examples of processing include measurement of analyte concentration, identification of analyte, comparison of analyte concentration to a standard, calibration of measurements, summary of collected information, statistical calculations, trend determination, and the like. The processed data may then be used to adjust, for example, in a feedback loop, one or more parameters of the patch or syringe. The processed data may also be sent directly to a third party for further evaluation. For example, measurement of a physiological parameter may measure the concentration of an analyte or substance (e.g., a drug or drug). The data may be transmitted to an electronic device, which may further process the data (e.g., calibrate the concentration, compare to a standard, determine if a change in dosage is required, etc.). Thus, the processed data may be used to alter device parameters, such as the dose of the substance to be administered, the dispensed flow rate of the substance, etc. The data, processed data, or other signals may then be relayed back to the patch or the injector so that subsequent injections by the injector are adjusted (e.g., the next dose is higher or lower). In another example, the measurement of the physiological parameter may measure bleeding of the patient (e.g., colorimetry, measurement of heme iron in blood, etc.). Detection of bleeding or leakage of substance from the site may be used to adjust (e.g., in a feedback loop) the subsequent administration rate or injection. In such examples, the presence of patient bleeding may allow for delaying a subsequent injection, or changing parameters (e.g., injection force, injection speed, etc.) extending toward the cannula of the subject's body. In some cases, no electronics may be required, and the patch may be able to communicate with the syringe directly or through a communication interface. In such cases, the patch and/or syringe may measure a device and/or physiological parameter of the subject, and then use the measurement to adjust the parameter of the syringe or patch. In one non-limiting example, a measurement of a parameter (e.g., a patient's blood glucose) may adjust the subsequent injected dose of the syringe.

In another example, the patch may monitor one or more parameters of the patch and/or the syringe to generate data regarding one or more parameters of the syringe and/or patch. Data may be transmitted to an electronic device (e.g., a mobile device) through a communication interface. In some cases, a mobile device may include a method for processing data. Examples of processing include determining whether the device is properly secured (e.g., whether the patch has an adhesion to the subject's body above or below a threshold), whether the patch is properly connected to a syringe, and the like. The processed data may then be used to adjust one or more parameters of the patch or syringe, for example, in a feedback loop. For example, a measurement of the adhesion of the patch to the body of the subject may be made. The data may be transmitted to an electronic device, which may further process the data (e.g., determine that adhesion is insufficient). Thus, the processed data may be used to change device parameters, e.g., activate a notification to a subject or other user, as described herein. The data, processed data, or other signals may then be relayed back to the patch or syringe so that the parameters of the patch or syringe are adjusted or need to be adjusted before another injection is made (e.g., another dose of substance is administered). In some cases, no electronics may be required, and the patch may be able to communicate with the syringe directly or through a communication interface. In such cases, the patch and/or syringe may measure a parameter of the patch and/or syringe, and then use the measurement to adjust the parameter or a different parameter of the syringe or patch. In one non-limiting example, a measurement of insufficient adhesion to the patch in a feedback loop may prevent subsequent injections by the syringe until the patch is measured to be sufficiently adhered to the subject's body.

The patch and/or syringe may also be or be capable of communicating with a subject or other user. In some cases, the communication with the subject or other user may include a feedback system or loop. Alternatively or in combination, the patch or syringe may be capable of notifying a subject or other user (e.g., physician, nurse, medical practitioner, clinician, etc.) about the device parameter, the health or physiological parameter, or both. For example, the patch or syringe may be capable of producing a sound (e.g., providing direction to a subject or other user), producing a motion (e.g., vibration), or may contain a visual indicator such as a light (e.g., a light emitting diode), a screen or display (e.g., a Liquid Crystal Display (LCD), an organic light emitting diode, a quantum dot display, or variations or derivatives thereof), or other visual indicator. Alternatively or in combination, the patch or syringe may contain a user interface module. In such examples, the subject or other user may be able to interact with the patch and/or the syringe. In one of such examples, the patch or injector may include a screen or display that may generate a string of characters or a sound that may be used to prompt the subject or other user to respond to a command. In another example, the patch or injector may contain a screen or display that may produce a string of characters or a sound that may be used to display an output or result, such as a measurement of a physiological parameter. The subject or other user can then enter a response or command, for example, through a microphone that may be in the housing of the patch and/or syringe, or through a button on the housing of the patch or syringe with which the subject can interact. In some cases, input to the patch or syringe by the subject may result in an adjustment of a parameter of the patch or syringe. In some cases, a subject or other user may be able to input parameters (e.g., pain, discomfort, etc.) that may not be easily measured or obtained from a patch or syringe. These parameters may then be communicated to an external device (e.g., a mobile device), for example, through a communication interface. In some cases, the patch and/or the syringe may contain a feedback system so that input from the subject or other user can adjust parameters of the patch or syringe. For example, the input of pain parameters may result in an adjustment of the flow rate of the substance through the cannula or the frequency of the dose of the substance administered.

The patch and/or syringe may also be configured to communicate with a remote system. In some examples, the patch and/or the syringe may measure one or more physiological parameters of the subject or one or more parameters of the patch and/or the syringe to generate data regarding the one or more physiological parameters of the subject or the one or more parameters of the patch and/or the syringe. The data may be transmitted to a remote server, distributed computing network (e.g., for cloud computing). The processing of the data may then be performed separately from the patch and/or the syringe. In some cases, the processed data may then be transmitted to an electronic device (e.g., a mobile device). In other cases, the processed data may then be transmitted to the patch and/or the injector for adjusting parameters of the patch and/or the injector. Transmitting data to the remote server and/or electronic device may allow the subject to monitor one or more physiological parameters, and/or may additionally or alternatively allow a physician or caregiver to also monitor one or more physiological parameters of the subject.

In another aspect, provided herein is a method for measuring a plurality of health or physiological parameters of a subject. The method may comprise (a) providing: (i) a patch comprising a first housing having a plurality of sensors and comprising an opening; and (ii) a syringe having a second housing containing a cannula in fluid communication with the fluid flow path. The second housing may be coupled to the first housing of the patch and the syringe may contain a reservoir containing a substance and a fluid flow path in fluid communication with the reservoir. The method may further comprise: (b) securing the patch to the body of the subject; (c) when the patch is secured to the body of the subject, directing the cannula through the opening to (i) direct the substance from the reservoir to the fluid flow path, and (ii) direct the substance from the fluid flow path through the cannula into the subject; and (d) using a plurality of sensors to (i) measure a plurality of health or physiological parameters from the subject, and (ii) provide one or more outputs corresponding to the plurality of health or physiological parameters from the subject.

Using embodiments of the present disclosure, a person having any number of physical and/or psychiatric conditions that may be treated with a medicament administered with a syringe (such as the devices described above) may be monitored to ensure that the combination therapy (drug and syringe) is safe and effective. Data collected during monitoring of patient and syringe attributes may be used by patient, caregiver, provider, payer, medicament and device manufacturers to provide feedback to any of the above including confirmation statements/results, and to allow manual and/or automatic intervention by the patient and/or device to improve the safety and effectiveness of the treatment.

In one embodiment shown in fig. 59 and 60, a syringe of the type described above is generally indicated at 402. The device includes a housing that includes a circular base 404. An annular skin attachment layer 406 is secured to the bottom of the syringe with adhesive and features a pull tab 408. The underside of the attachment layer (visible in fig. 59 and 60) is provided with an adhesive that provides a lower retention force than the adhesive that secures the attachment layer 406 to the syringe. Thus, the syringe 404 may be removed from the body (e.g., skin) of the subject by pulling the tab 408 upward away from the skin of the subject.

In addition to the skin attachment layer 406, a patch, generally indicated at 412 in fig. 59, is attached to the bottom of the syringe by a magnetic fastening means, as shown in the exploded view of fig. 60, which will be described in more detail below. As an alternative to magnetic attachment, the patch may be attached to the syringe with an adhesive or by other mechanical means.

Although the patch and skin attachment layer are shown as having a circular profile, alternative shapes may be used.

A generally conical skin boundary displacement extension 414 extends from the bottom of the patch 412 and, as previously described, compresses the skin to help reduce tissue deflection or "tenting" as the cannula is inserted. The extension 414 has a central aperture 416 that aligns with the dispensing port of the syringe.

In an alternative embodiment, the skin boundary displacement extension may be part of, and extend from, the base 404 of the injector itself, as described in the embodiments presented above. In such embodiments, a central hole may be provided at the center of the patch, wherein the hole is smaller than the diameter of the base of the extension. When the injector is positioned such that the skin attachment layer secures the device against the skin, the extension expands the hole in the patch and provides a path for the injector cannula or cannula to enter the skin when the device is activated or "fired" in the manner described above. The cannula may not pass directly through the material and provide an opportunity to plug the cannula or inject foreign bandage material from the cannula into the skin, see fig. 16B. When the syringe is removed from the skin, the expanded central bore of the patch closes to its original smaller size. An absorbent material may optionally be deposited around the central aperture of the patch to absorb any blood or leakage. In this way, the patch acts as a "band aid" after injection.

As shown in fig. 59 and 60, skin attachment layer 406 features a central opening 418, which central opening 418 is sized to receive patch 412. Although the embodiment of fig. 59 and 60 shows the patch 412 separate from the skin attachment layer 406, in alternative embodiments, the patch may be circumferentially attached to the skin attachment layer by a perforation device. As yet another alternative, the patch 412 may be secured to the skin attachment layer via tabs spaced circumferentially around the patch.

As shown in fig. 60, patch 412 includes a sensor 422, a Printed Circuit Board (PCB) chip 424, and a sensor adhesive layer 426. The PCB chip 424 and the sensor adhesive layer 426 are secured to the sensor 422 by adhesive or other fastening mechanisms. As shown in fig. 59, the sensor adhesive layer 426 includes a central window 428 through which the extension 414 protrudes when assembled. The downward facing surface 430 of the sensor adhesive layer 426 is provided with an adhesive for securing the patch to the skin of a user.

The injector 402 and patch 412 are configured such that the patch is applied to the body (e.g., skin, fingers) of a subject (e.g., user) when the injector is attached. In addition, patch 212 remains unchanged after syringe 402 is removed. More specifically, as shown in fig. 60, a plurality of permanent magnets 432 are positioned and secured within the housing of the injector 402. For example only, the magnet may be secured within a corresponding recess 434 formed in the syringe housing by an adhesive, interference fit, or other attachment means, as described elsewhere herein. The top side of the sensor 422 has a metal disk portion 436 (fig. 59 and 60) so that the patch is secured to the bottom of the syringe via magnetic attraction. The adhesive on the surface 430 of the sensor adhesive layer 426 provides a holding force to the user's skin that is greater than the magnetic force holding the patch to the syringe. As an alternative to the disk portion 436 being metal, the disk portion may be provided with a metal portion, as shown in phantom at 437 in fig. 59, which corresponds to and attracts the magnet of the syringe. In alternative embodiments, the metal portion(s) of the patch may have other shapes. A single annular metal portion may also be used.

The use of a magnet to secure the patch to the syringe provides the advantage that there is no residual adhesive exposed on the patch when it is left on the patient. Furthermore, the magnet may be located precisely on the syringe, with the corresponding metal part on the patch, so that when the syringe is removed, we will be able to control the amount and location of the "pulling" force on the patch. Instead of a metal part on the syringe, a magnet may be used. In an alternative embodiment, the magnet may be located on the patch and the corresponding metal portion may be located on the syringe.

In an alternative embodiment, patch 412 may be secured to the bottom of the syringe by an adhesive (such as on the top side of sensor 422) that has less retention than the skin-engaging adhesive on surface 430 of sensor adhesive layer 426.

In another alternative embodiment, the patch 412 may be secured to the bottom of the syringe using a mechanical feature built into the patch, the syringe, or both, with a retention force less than the skin-engaging adhesive on the surface 430 of the sensor adhesive layer 426. In such embodiments, the skin attachment layer 406 of fig. 59 and 60 may be removed so that the syringe is only held to the patient via the attachment between the syringe housing and patch. In such embodiments, both the syringe and patch are secured to the patient only by the sensor adhesive layer. Additional connections between the housing of the syringe and the sensor adhesive layer 426 may also be present (in addition to the syringe being connected to the sensor adhesive layer by a patch, as described elsewhere herein).

As shown in fig. 61 and 62, PCB chip 424 features a circuit that includes a bluetooth module having a microcontroller/microprocessor 444 connected to a battery 442 and an antenna 448. In addition, a bluetooth module 444 is attached to the sensor 422. The battery 442 provides stored energy to power the system. Bluetooth module 444 has an integrated microcontroller/microprocessor. An example of a suitable bluetooth module is davit 27898ge (Dialog) semiconductor part number DA14580-01 UNA. In an alternative embodiment, the bluetooth module may be separate from the microcontroller/microprocessor. In some implementations, direct communication to the cloud can be used, such as, for example, via cellular or other communication technologies.

As shown in fig. 63, the injector 402 is provided with one or more sensors 450a and 450b, which one or more sensors 450a and 450b communicate with the bluetooth module 444 via bluetooth. The sensors 450a and 450b may include a transmitter and may receive power from a battery also positioned within the syringe housing. Alternatively, each sensor may have its own battery. The sensors 450a and 450b may also be passive sensors that do not require battery power. The sensors 450a and 450b may be selected to provide a variety of alternative functions, as described in more detail below.

In an alternative embodiment, communication between the sensors 450a and 450b of the injector and the module 444 of the PCB chip 424 of the patch may be accomplished by alternative wireless communication means known in the art. In other alternative embodiments, the sensors 450a and 450b may communicate with the module 444 of the PCB chip 424 via wire connection(s) that automatically disconnect when the syringe is removed from the patch and the patient.

Of course, the number of sensors 436, 450a and 450b may be different from the number shown in fig. 61 to 63.

Bluetooth module 444 also enables the patch to transmit data collected from sensors 422, 450a and 450b to a remote receiver, such as a personal data device (such as a smartphone), a computer system or a network or cloud. The remote receiver may collect the received data in a database and build the database.

In use, as shown in fig. 59, the initial syringe features an attached patch (via the magnetic means described above). The protective backing sheet is removed from the skin attachment layer 406 such that the adhesive on the surface facing away from the injector is exposed. The backing sheet also removably covers the adhesive on the patch surface 430. The exposed adhesive surfaces of the syringe skin attachment layer 406 and the sensor adhesive layer 426 are then pressed against the user's skin so that the syringe and patch are attached thereto.

In the illustrated embodiment, the patch 412 serves multiple functions. First, it senses the status of the injector and transmits the status of the injector to a remote receiver (such as a personal data device, such as a smartphone, a computer network, or the cloud), i.e. whether the injector has been activated such that an injection is ongoing or an injection has been completed. The second thing is that the patch transmits the status of the patient to a remote receiver via data collected from the sensors. This may be done before, during or after injection and before, during or after attachment and/or removal of the syringe. For example, skin temperature and skin "color" at the injection site may be detected via a simple temperature monitor combined with a light emitting diode/phototransistor circuit included in sensor 422 for communicating tissue temperature and color during and after injection. The feature is useful during clinical studies, can alert workers to Injection Site Reactions (ISRs), and can quantify ISRs based on temperature and tissue color. A third event is that the patch may interact directly with the injector based on data received from the injector and/or data received from the patient and/or data received from itself. The patch may interact with the syringe as a control mechanism, including adjusting the flow rate (faster, slower, or paused), vibrating for user notification and/or pain management, providing an audible sound to provide direction or notification to the user, a visual indicator to indicate a change, reminder, notification, or information to the user, or mechanical interaction to cause a change in the state of the syringe, including but not limited to retracting the button to stop delivery in the event of data from the patient (e.g., pain) or data from the device (e.g., premature removal or detachment).

If useful, a heart rate sensor may also be included in the sensors 422 to obtain the patient EKG signals, and/or a strain gauge sensor may be provided to detect the skin pressure applied by the extensions 414 of FIGS. 59 and 60. Patient mobility, location, and position data may be collected by corresponding sensors (such as accelerometers, GPS sensors, etc.) incorporated in sensors 422. In addition, several electrodes in contact with the skin (included in sensor 422) may detect skin impedance and detect leaks or detachment. Furthermore, the skin contact electrode may detect premature removal of the device, i.e. removal of the device before the device has completed its cycle.

After the injector injection is complete, the injector may be removed from the patient's skin by pulling the tab 408 (fig. 59 and 60) away from the patient's skin. When this is done, the patch is separated from the syringe, allowing only the patch to adhere to the patient. The removable nature of the monitoring patch provides the physician or the like with the ability to continuously monitor the patient between injections.

Alternatively, the patch may be initially detached from the syringe and placed on the patient for monitoring before administration/injection of the one or more medicaments is initiated. This may provide baseline data about the patient prior to administration/injection.

Alternatively, the patch may be applied separately from the syringe and placed on the patient to monitor baseline conditions (e.g., baseline physiological parameters) prior to beginning administration/injection of the one or more medicaments. The syringe may then be coupled to the patch before the injection begins.

Figures 64-65 show exploded views of another embodiment of a patch and syringe. The patch 6401 includes an adhesive layer 6403 and a sensor 6405, which sensor 6405 may comprise a PCB chip. In the described embodiments, as well as other embodiments described below, the patch and/or the syringe may each include one or more sensors, as described in the previous embodiments. The sensor 6405 may be adhered to an adhesive layer 6403, which adhesive layer 6403 may be used to secure the patch 6401 to the subject's body. The syringe 6407 and patch 6401 may be configured such that the patch is applied to the body of the subject when the syringe 6407 is attached. Alternatively, or in addition, the syringe 6407 and patch 6401 may be coupled prior to securing the patch 6401 and syringe 6407 to the subject's body.

The patch 6401 may be coupled to the syringe 6407 using an interlocking bayonet mechanism. For example, the syringe 6407 may contain a protruding element 6409, which may engage with a detent 6411 in the patch 6401. In the first configuration, the detent 6411 may prevent free rotation of the patch 6401 and the protruding element 6409. Upon twisting the patch 6401 or the syringe 6407, the syringe 6407 may move to a second configuration in which the projection 6409 is no longer coupled to the detent 6411, and thus the syringe 6407 may be detached or removed from the patch 6401 (e.g., after the patch is secured to the subject's body and the drug has been delivered).

Figure 66 shows an exploded view of another embodiment of a patch and syringe. Patch 6601 includes an adhesive layer 6603 and a sensor 6605, which sensor 6405 may comprise a PCB chip. The sensor 6605 can be adhered to the adhesive layer 6603, which adhesive layer 6403 can be used to secure the patch 6601 to the body of the subject. The syringe 6607 and patch 6601 can be configured such that the patch is applied to the body of the subject when the syringe 6607 is attached. Alternatively, or in addition, the syringe 6607 and the patch 6601 may be coupled prior to securing the patch 6601 and the syringe 6607 to the body of the subject.

The patch 6601 may be coupled to the syringe 6607 by coupling or mating features 6609 and 6611. Portion 6609 may be coupled to syringe 6607 (e.g., in recess 6613), while portion 6611 may be coupled to patch 6601. The features 6609 and 6611 may be magnets and may be secured to the recess 6613 and patch 6601, respectively, of the syringe 6607 via an adhesive, interference fit, or other attachment means. Adhesive layer 6603 can provide a holding force to the subject's body (e.g., skin) that is greater than the magnetic force holding the patch to the syringe.

Figure 67 shows another embodiment of a patch and syringe. The patch 6701 includes an adhesive layer 6703 and a sensor 6705, which sensor 6405 may comprise a PCB chip. The sensor 6705 can be adhered to an adhesive layer 6703, which adhesive layer 6403 can be used to secure the patch 6701 to the body of the subject. The syringe 6707 and patch 6701 can be configured such that the patch is applied to the body of the subject when the syringe 6707 is attached. Alternatively, or in addition, the syringe 6707 and the patch 6701 may be coupled prior to securing the patch 6701 and the syringe 6707 to the body of the subject.

The patch 6701 may be coupled to a syringe 6707. For example, the sensor 6705 can be configured to couple to the syringe 6707 by being assembled into the recess 6713. The syringe may contain a safety tab or strap. The adhesive layer 6703 can provide a holding force to the subject's body (e.g., skin) that is greater than the magnetic force holding the patch to the syringe.

Figure 68 shows a cross-sectional view of the coupled syringe and patch of figure 67. The syringe may include a latch 6717 connected to a spring (e.g., torsion spring) 6715. In block a, the patch and syringe may be in a first configuration ("ready position") where the device is locked and the patch remains attached to the syringe. The button 6719 is in a starting or ready position and ready for actuation, and when depressed, the button 6719 may be used to direct the cannula toward the subject. In block B, the syringe may be transitioned (e.g., via rotation, removal of the safety tab 6801, or both) into a second configuration ("locked position"). In the second configuration, the torsion spring can be released, translating the latch 6717 to a different position. In such a configuration, the syringe may be removed from the patch and the button 6719 may be in the raised position shown in block B, thereby preventing the cannula from being pressed out of the syringe.

Figure 69 illustrates another embodiment of a patch and syringe. The patch 6901 includes an adhesive layer 6903, a sensor 6905 that may contain a PCB chip, and an attachment module 6911. The attachment module 6911 may contain an adhesive or other fastening mechanism to adhere the patch 6901 to the syringe 6907. The sensor 6905 can be adhered to an adhesive layer 6903, which adhesive layer 6403 can be used to secure the patch 6901 to the body of a subject. The syringe 6907 and patch 6901 can be configured such that the patch is applied to the body of the subject when the syringe 6907 is attached. Alternatively, or in addition, the syringe 6907 and patch 6901 can be coupled prior to securing the patch 6901 and syringe 6907 to the body of the subject. The patch 6901 may additionally comprise an outer layer comprising perforations 6921. For example, the outer layer may comprise a plastic, a polymer (e.g., a heat sensitive polymer such as shrink wrap), or other material. The outer layer may be configured to be removed prior to use of the patch and syringe. When the device is ready for use, the outer layer may be removed via pulling the pull tab 6923, which may remove the outer layer via the perforations 6921, allowing the outer layer to be removed.

Figure 70 shows a cross-sectional view of the coupled syringe and patch of figure 69. The size (e.g., width or diameter) of the patch may be substantially similar to the diameter of the syringe.

Figure 71 shows another embodiment of a patch and syringe. The patch 7101 includes an adhesive layer 7103 and a sensor 7105, which sensor 6405 may comprise a PCB chip. The sensor 7105 may be adhered to an adhesive layer 7103, which adhesive layer 6403 may be used to secure the patch 7101 to the body of the subject. The syringe 7107 and the patch 7101 may be configured such that the patch is applied to the body of the subject when the syringe 7107 is attached. Alternatively, or in addition, the syringe 7107 and the patch 7101 may be coupled prior to securing the patch 7101 and the syringe 7107 to the body of the subject. The patch 7101 may be coupled to a syringe 7107 via a latch 7113. The latch 7113 can be coupled to the syringe 7101 using a press-fit mechanism, and subsequent pushing or application of force to the latch 7113 can cause the patch 7101 to detach from the syringe 7107. Alternatively or in addition, the latch 7113 may comprise a hook that is capable of adhering to the housing of the syringe 7107. The latch may then be actuated by pressing or applying a force on the latch 7113 and pulling the latch away from the housing of the syringe 7107, which allows the patch 7101 to be detached from the syringe 7107.

Figure 72 shows a cross-sectional view of the coupled syringe and patch of figure 71. The latch 7113 comprises a hook that is adhered to the housing of the syringe. By applying force 7115 on the latch, the hook can be released, allowing the patch to be separated or detached from the syringe.

Figure 73 shows another embodiment of a patch and syringe. Patch 7301 includes an adhesive layer 7303 and a sensor 7305, which sensor 6405 may comprise a PCB chip. The sensor 7305 may be adhered to an adhesive layer 7303, which adhesive layer 6403 may be used to secure the patch 7301 to the body of the subject. The syringe 7307 and patch 7301 may be configured such that the patch is applied to the body of the subject when the syringe 7307 is attached. Alternatively, or in addition, the syringe 7307 and patch 7301 may be coupled prior to securing the patch 7301 and syringe 7307 to the body of the subject. Patch 7301 may be coupled to syringe 7307 via flange 7311 and ring 7313. Ring 7313 may comprise rubber or other elastomeric material. Ring 7313 may be coupled to syringe 7307 by being assembled into grooves of flanges 7311 and 7321. The flange 7311 may be complementary to the flange 7321 of the patch 7301.

Figure 74 shows a cross-sectional view of the coupled syringe and patch of figure 73. The flange 7321 of the patch may complementarily mate with the flange 7311 of the syringe. The patch can be detached from the syringe by applying a force 7415 on the flange 7321.

Figure 75 shows another embodiment of a patch and syringe. As shown in block a, patch 7501 includes an adhesive layer 7503 and a sensor 7505, which sensor 7505 may comprise a PCB chip. The sensor 7505 can be adhered to the adhesive layer 7503, which adhesive layer 6403 can be used to secure the patch 7501 to the body of the subject. The syringe 7507 and patch 7501 can be configured such that the patch is applied to the body of the subject when the syringe 7507 is attached. Alternatively, or in addition, syringe 7507 and patch 7501 can be coupled prior to securing patch 7501 and syringe 7507 to the body of the subject, as shown in panel B. The housing of the patch 7501 and the sensor 7505 can partially surround the housing of the syringe 7507. The patch may also include wing features 7513. Features 7513 may allow for better gripping by a subject, or for positioning of the device.

Figure 76 shows another embodiment of a patch and syringe. In block a, the patch 7601 includes an adhesive layer 7603 and a sensor 7605, which sensor 7605 may comprise a PCB chip. The sensor 7605 can be adhered to an adhesive layer 7603, which adhesive layer 6403 can be used to secure the patch 7601 to the body of the subject. The syringe 7607 and patch 7601 can be configured such that the patch is applied to the body of the subject when the syringe 7607 is attached. Alternatively, or in addition, the syringe 7607 and the patch 7601 can be coupled together prior to securing the patch 7601 and the syringe 7607 to the body of the subject, as shown in block B. The patch 7601 may be coupled to the syringe 7601 via a latch 7613, which latch 7613 may be secured to a tab 7611 of the syringe 7611. The latch may be rotatable such that in certain configurations, the latch 7613 does not rest on the tab 7611 such that the patch 7601 is allowed to be separated from the syringe 7607.

Figure 77 shows another embodiment of a patch and syringe. In block a, patch 7701 includes an adhesive layer 7703 and a sensor 7705, which sensor 7605 may comprise a PCB chip. The sensor 7705 can be adhered to an adhesive layer 7703, which adhesive layer 6403 can be used to secure the patch 7701 to the body of the subject. The syringe 7707 and patch 7701 may be configured such that the patch is applied to the body of the subject when the syringe 7707 is attached. Alternatively, or in addition, the syringe 7707 and patch 7701 may be coupled prior to securing the patch 7701 and syringe 7707 to the subject's body, as shown in block B. The patch 7701 may be coupled to the syringe 7707 via an adhesive (e.g., at an interface between the patch 7701 and the syringe 7707). For example, the patch may also include a protruding feature 7713 on the adhesive layer 7703. The protruding feature may allow the patch 7701 to be separated from the syringe 7707 when the subject presses or pulls on the feature 7713.

Figure 78 shows a cross-sectional view of the coupled syringe and patch of figure 77. The protruding feature 7713 may be used to pry the patch from the syringe.

Figure 79 illustrates another embodiment of a patch and syringe. In block a, the patch 7901 includes an adhesive layer 7903 and a sensor 7905, which sensor 7905 may comprise a PCB chip. The sensor 7905 can be adhered to an adhesive layer 7903, which adhesive layer 6403 can be used to secure the patch 7901 to the body of a subject. The syringe 7907 and patch 7901 may be configured such that the patch is applied to the body of the subject when the syringe 7907 is attached. Alternatively, or in addition, the syringe 7907 and patch 7901 may be coupled prior to securing the patch 7901 and syringe 7907 to the subject's body, as shown in block B. Patch 7901 may be coupled to syringe 7907 via a flange 7913 on the patch and a complementary protrusion 7911 on syringe 7907. The flange 7913 may be locked or hooked on the protrusion 7911. In a first configuration the flange 7913 may be locked and in a second configuration the flange 7913 may be released, such as to allow the patch 7901 to be separated from the syringe 7907.

Figure 80 shows another embodiment of a patch and syringe. The patch 8001 includes an adhesive layer 8003 and a sensor 8005, which may be 6405 comprised of a PCB chip. Sensor 8005 can be adhered to adhesive layer 8003, which adhesive layer 6403 can be used to secure patch 8001 to the body of the subject. Syringe 8007 and patch 8001 can be configured such that the patch is applied to the body of the subject when syringe 8007 is attached. Alternatively, or in addition, syringe 8007 and patch 8001 can be coupled prior to securing patch 8001 and syringe 8007 to the body of the subject. The patch 8001 can be coupled to a syringe 8007 via threaded features 8013 on the patch 8001 and complementary threads (not shown) on the syringe 8007. The threaded feature 8013 may be screwed onto a complementary thread of the syringe 8007. Coupling and decoupling of the patch 8001 to the syringe 8007 can occur by twisting the patch 8001 or the syringe 8007.

Figure 81 shows a cross-sectional view of the coupled syringe and patch of figure 80. The threads 8013 of the patch may be complementary to the threads of the syringe. Upon rotating the syringe counterclockwise, the patch may be released from the syringe.

Figure 82 illustrates another embodiment of a patch and syringe. The patch 8201 includes an adhesive layer 8203, a sensor 8205 that may contain a PCB chip, and a deformable surface 8213. The sensor 8205 can be adhered to the adhesive layer 8203, which adhesive layer 6403 can be used to secure the patch 8201 to the body of a subject. The syringe 8207 and patch 8201 can be configured such that the patch is applied to the body of the subject when the syringe 8207 is attached. Alternatively, or in addition, the syringe 8207 and the patch 8201 can be coupled prior to securing the patch 8201 and the syringe 8207 to the body of the subject. The patch 8201 may be coupled to a syringe 8207 via a deformable surface 8213. In a first configuration, the deformable surface 8213 may contain graduated holes 8215 that may be used to secure screws or pins 8217 of the syringe 8207 to the patch 8201. Upon pressing the two ends of the deformable surface 8213 towards each other, the deformable surface may assume a second configuration in which the tapered holes 8215 are large enough that the screws or pins 8217 may be detached from the deformable substrate 8213 of the patch 8201, thereby separating the patch 8201 from the syringe 8207.

Figure 83 shows a cross-sectional view of the coupled syringe and patch of figure 82. In this configuration, the deformable substrate 8213 is locked to the syringe. By pressing the ends of the deformable substrate 8213 together, the graduated holes are moved so that the pins 8217 of the syringe can be lifted from the deformable substrate and patch, so that the patch is separated from the syringe.

Figure 84 illustrates another embodiment of a patch and syringe. The patch 8401 includes an adhesive layer 8403 and a sensor 8405, which sensor 6405 may comprise a PCB chip. The sensor 8405 can be adhered to an adhesive layer 8403, which adhesive layer 6403 can be used to secure the patch 8401 to the body of the subject. The syringe 8407 and patch 8401 may be configured such that the patch is applied to the body of the subject when the syringe 8407 is attached. Alternatively, or in addition, the syringe 8407 and patch 8401 may be coupled prior to securing the patch 8401 and syringe 8407 to the body of the subject. The patch 8401 may be coupled to the syringe 8407 via a ridge 8413 on the patch 8401, which ridge 8413 may be used to secure the patch 8401 to the syringe 8407 via a snap or press fit. The syringe 8407 may additionally contain complementary features that may be secured to the ridge 8413. Separation of patch 8401 from syringe 8407 may occur by twisting patch 8401 or syringe 8407 or by pulling patch 8401 away from syringe 8407.

Figure 85 shows a cross-sectional view of the coupled syringe and patch of figure 84. The ridge 8413 of the patch may be configured to couple to a complementary feature 8513 (e.g., protrusion, ridge, cavity) of the syringe. Detachment of the patch and syringe may occur by applying sufficient force to pry apart the ridge 8413 and the complementary feature 8513.

Figure 86 illustrates another embodiment of a patch and syringe. The patch 8601 includes an adhesive layer 8603 and a sensor 8605, which sensor 6405 may comprise a PCB chip. The sensor 8605 can be adhered to an adhesive layer 8603, which adhesive layer 6403 can be used to secure the patch 8601 to the body of the subject. The syringe 8607 and the patch 8601 can be configured such that the patch is applied to the body of the subject when the syringe 8607 is attached. Alternatively, or in addition, the syringe 8607 and the patch 8601 can be coupled prior to securing the patch 8601 and the syringe 8607 to the body of the subject. The patch 8601 may be coupled to a syringe 8607 by coupling or mating parts 8609 and 8611. Portion 8609 can be coupled to a syringe 8607 (e.g., in a recess 8613), while portion 8611 can be coupled to the patch 8601. Parts 8609 and 8611 may contain magnets and may be secured to the pocket 8613 and patch 8601 of the syringe 8607 via adhesives, interference fit, or other attachment means.

Figure 87 shows a cross-sectional view of the coupled syringe and patch of figure 86. The magnet 8611 of the patch may be configured to couple to the magnet 8609 of the syringe. Separation of the patch and syringe may occur by sufficiently separating the magnet of the patch from the magnet of the syringe.

In some cases, it may be useful to secure both the patch and the syringe to the body of the subject. In such cases, the injector may additionally include features that may be configured to couple the housing of the injector to the body of the subject. For example, the syringe may contain an adhesive layer. The adhesive layer of the syringe may be separate from the mechanism for securing the patch to the body of the subject.

Fig. 88 illustrates another embodiment of a patch and a syringe, wherein both the patch and the syringe are configured to be coupled to a body of a subject. In block a, patch 8801 includes an adhesive layer 8803 and a sensor 8805, which sensor 8805 may contain a PCB chip. The sensor 8805 can be adhered to an adhesive layer 8803, which can be used to secure the patches 8801 to the body of the subject. The patch 8801 may be configured such that the patch 8801 is applied to the body of the subject, the patch 8801 may be secured separately from a syringe 8807, the syringe 8807 may also contain an adhesive layer 8813. Alternatively, or in addition, the syringe 8807 and the patches 8801 may be coupled prior to securing the patches 8801 and 8807 to the body of the subject, as shown in block B. The patch 8801 can be coupled to the syringe 8807 by coupling or mating parts as described elsewhere herein. The adhesive layer 8803 of the patches 8801 can include features 8811, which features 8811 can allow the adhesive layer 8803 of the patches 8801 to separate from the adhesive layer 8813 of the syringe 8807. In such examples, the patch 8801 can be secured to the body of the subject and cannot be removed from the subject until the syringe 8807 is removed. In some cases, the attachment or adhesion force of the patch adhesive layer 8803 to the body (e.g., skin) of the subject may be greater than the attachment or adhesion force of the syringe 8807 to the body (e.g., skin) of the subject. In some cases, the attachment or adhesion force of the patch adhesive layer 8803 to the body of the subject may be greater than the attachment or adhesion force of the patch 8801 attached to the syringe 8807.

Figure 89 shows a cross-sectional view of the coupled syringe and patch of figure 88. Both the patch and the syringe may include an adhesive layer. The adhesive layer 8813 of the syringe may be configured to secure the syringe to the body of the subject.

In some cases, the patch or the opening of the patch may contain a pierceable membrane. The pierceable membrane may comprise an opening (e.g., slit, hole) through which the cannula of the syringe may pass when the cannula is guided from the syringe to the body of the subject. In some cases, the pierceable membrane may be adhered or otherwise secured to the body of the subject. In such cases, the pierceable membrane can comprise an absorbent material, e.g., to absorb bodily fluids (e.g., blood, sweat, etc.) from the subject. It will be appreciated that any of the above embodiments may comprise a patch comprising the sensor (e.g. on a PCB chip) and alternatively or additionally the patch may comprise a pierceable membrane which may comprise the absorbent material.

Fig. 90 illustrates an example patch, or a portion thereof, that includes a pierceable membrane coupled to an adhesive layer of a syringe. In block a, the patch 9001 comprises an adhesive layer 9003. The patch may also contain a sensor (not shown) that may be adhered to the adhesive layer 9003. The adhesive layer 9003 can be used to secure the patch 9001 to the body of a subject. The patch 9001 may be configured such that the patch 9001 is applied to the body of a subject, the patch 8801 may be secured separately from a syringe 9007, the syringe 8807 may also contain an adhesive layer 9013. Alternatively, or in addition, a syringe (not shown) and patch 9001 may be coupled prior to securing patch 9001 and syringe to the body of the subject, as shown in panel B. The patch may also contain an opening 9021, which opening 9021 may contain a pierceable membrane 9023. In some cases, the opening 9021 is a slit, and the material of the pierceable membrane 9023 comprises a self-healing elastomer (i.e., the opening closes after the cannula is retracted away from the subject's body). The adhesive layer 9003 of the patch 9001 may include a feature 9011 (e.g., a tab), which feature 9011 may allow the adhesive layer 9003 of the patch 9001 to separate from the adhesive layer 9013 of the syringe 9007. Fig. 91 shows a bottom-up cross-sectional view of the patch of fig. 90. The patch contains an opening 9021, which opening 9021 is an opening that can pierce the membrane 9023. In some cases, the opening 9021 is a slit, and the material of the pierceable membrane 9023 comprises a self-healing elastomer and/or an absorbent material. The adhesive layer 9003 of the patch may include a feature 9011 (e.g., a tab), which feature 9011 may allow the adhesive layer 9003 of the patch to separate from the adhesive layer of the syringe.

Fig. 92 shows an exploded view of the adhesive layer of the patch and syringe of fig. 90. The patch 9001 comprises a pierceable membrane 9023, which pierceable membrane 9023 may comprise an opening 9021. The pierceable membrane 9023 may be separate from the patch and may remain secured to the subject's body (e.g., as a bandage). In some cases, the opening 9021 is a slit, and the material of the pierceable membrane 9023 comprises a self-healing elastomer as well as an absorbent material. The adhesive layer 9003 of the patch 9001 may include a feature 9011 (e.g., a tab), which feature 9011 may allow the adhesive layer 9003 of the patch to be separated from the adhesive layer 9013 of the syringe.

In some examples, the patch may be configured to couple to an auto-injector. Fig. 93 shows an example patch containing a pierceable membrane coupled to an auto-injector 9307. In block a, the patch 9301 includes an adhesive layer 9303. The patch may also contain a sensor (not shown) that may be adhered to the adhesive layer 9303. The adhesive layer 9303 can be used to secure the patch 9301 to the body of the subject, and in some cases, the adhesive layer 9303 can be secured to the body of the subject. In such cases, the adhesive layer 9303 comprises an absorbent material (e.g., a bandage pad) and will remain on the subject's body after injection. The patch 9301 may be configured such that the patch 9301 is applied to the body of a subject, which patch 9301 may be secured separately from the auto-injector 9307. Alternatively, or in addition, the auto-injector 9307 and the patch 9301 may be coupled prior to securing the patch 9301 to the subject's body, as shown in block B. The patch may also contain an opening 9321, which opening 9321 may be part of the pierceable membrane 9323. In some cases, the opening 9321 is a slit, and the material of the pierceable membrane 9323 comprises a self-healing elastomer (i.e., the opening closes after the cannula is retracted away from the subject's body). The adhesive layer 9303 of the patch 9301 can include features 9311 (e.g., tabs), which features 9311 can allow the adhesive layer 9303 of the patch 9301 to be separated from the auto-injector. In some cases, the patch 9301 may also contain a sensor unit 9305, which sensor unit 9305 may contain a PCB chip.

Embodiments of the present disclosure provide for reporting a combination of injector and patient status during and after an injection. The patch and associated battery and circuitry are initially physically coupled to the syringe. In an alternative embodiment, the patch may be applied and one or more syringes allowed to connect. The patch circuit may communicate one or more parameters of the injector to the receiver prior to fixation to the patient, e.g., via the communication interface. Once the patch/syringe is secured to the patient, the patch communicates the status of both the patient and the syringe. When the syringe is removed, the patch remains directly at the injection site of the patient to transfer the state of the injection site. If sufficient time is available to ensure that no reaction has occurred, the patch may remain there for several hours, or the patch may remain until the next syringe/patch application. That is, after the injection is complete, the patient may remove the syringe and hold the patch on top. The patch may continue to provide data (up to several days) until the next patch change.

In many cases, physicians may be reluctant to have patients self-administer at home due to potential adverse reactions. If the patch is able to monitor any potential complications (ISR, heart rate, respiration, temperature, etc.) and transmit a signal to the physician if there are any abnormalities, this may give the physician confidence that the patient is being returned home for injection. In the outcome-based healthcare model, there is a significant benefit to the system to know that the patient is improving through treatment as evidenced by quantitative data. In the event that the patient's health status changes dramatically (or over the long term), the treating physician has long-term benefits to the patient and overall outcome by the ability to intervene and intervene earlier based on the notification of the continuously accumulating data trend.

This type of "detachable" monitoring patch is also very useful in clinical studies. During the study, various parameters of the patient can be monitored, which can increase compliance and reduce complications, and can even make enrollment easier. For example, if a patient is required to remain in the physician's office for 4 hours after each injection to monitor ISR, they may be able to eliminate the wait by patch monitoring, which may result in improved registration. Moreover, such devices may allow for longitudinal studies that measure patient compliance and provide increased accuracy in data transmission (e.g., via eliminating the need to manually record data).

The patch concept is not limited to the above-described syringes. The patch with and/or without electronics may also be suitable for other syringes. These devices may include an auto-injector. In view of the above, embodiments of the present disclosure may provide, for example, a patch that may include an electronic device or contain only bandage material (e.g., see fig. 90-93). In some examples, the patch may be connected to a syringe, and the securing of the patch and syringe may occur via a force applied to the patch and syringe, thereby eliminating the need for a separate patch application. Alternatively, the patch may be applied directly to the injection site by a syringe, and the cannula entry point may be covered with an expandable/contractible element. As described elsewhere herein, the patch may be magnetically coupled to the syringe. In some examples, the patch may be mechanically coupled to the syringe by a user-desired release mechanism. In some cases, the patch may be smaller than the entire adhesive patch used to adhere the syringe. The patch may include an adhesive pad that is the same size as the patch or smaller than the size of the patch. In some examples, the patch may transmit syringe data prior to application to a patient, transmit syringe and patient data after application to a patient, and/or transmit patient data after removal of the syringe.

Example applications/uses

As shown in fig. 94, the sensors 9401 of the patch may be customized to measure specific device and/or patient attributes or physiological parameters as desired by the patient or physician.

One or more sensors may be used to measure device and/or patient attributes or physiological parameters. Non-limiting examples of sensor types include temperature sensors, interstitial pressure sensors, skin resistance sensors, skin distension sensors, acoustic sensors, vibration sensors, heart rate sensors, blood pressure sensors (BP in fig. 94), color or other optical sensors, moisture sensors, chemical sensors (e.g., sensing, measuring or detecting drug concentration, histamine, oxygen, etc.).

One or more sensors may be used to measure one or more device properties, such as the presence of skin, tracking of substance delivery, and/or occlusion of a device (e.g., a cannula of a syringe).

As shown in fig. 95, the sensor may alternatively be incorporated into a sensor adhesive layer 9501. As previously mentioned, any useful combination of patient perception attributes may provide meaningful conclusions or evidence of outcomes. For example: the site reactions may be detected using temperature measurements, skin resistance and/or impedance measurements, and color measurements, or any combination thereof. In another example of correlating pain with measured site reactions, a temperature measurement, a skin resistance or impedance measurement, a color measurement, a skin expansion measurement, or a gap pressure measurement, or any combination thereof, may be used. In yet another example of contraindicated activity during monitoring therapy, vibration measurements, heart rate measurements, and/or moisture measurements (e.g., to indicate sweat levels) or a combination thereof may be used. In another example, monitoring of wet injections may use moisture measurements. Another example of a subject result may include monitoring for poor bio-absorption by measuring interstitial pressure, tissue density, temperature, skin resistance/impedance, color, and/or skin swelling. In another example of monitoring systemic adverse reactions, moisture (sweat) measurements, EMG/ECG, vibration (e.g., representing agitation), sound increase (e.g., representing stomach or intestinal gas levels), or any combination thereof may be used.

Fig. 96 shows another embodiment of a sensor unit. The sensor units may include, for example, a PCB 9601, hall effect sensors 9602, coin cell batteries 9603, buzzers 9604, tactile vibration sensors 9605, skin presence sensors 9606, humidity and temperature sensors 9607, 3D accelerometers and gyroscopes 9608, reed switches 9609, and a low power core processor 9610. The sensor may comprise more than one layer with different sensors, batteries and other components distributed in each layer or in different layers.

The patch can be used for a variety of functions after injection, after removal of the syringe. In non-limiting examples, the patch may be used to seal injection sites to prevent bleeding, detect any injection site leaks/bleeding using moisture detection, monitor skin temperature and color and pressure to detect ISR, monitor heart rate/EKG, monitor patient position-upright or lying down, and/or monitor skin chemistry/sweat.

In some embodiments, the patch may communicate with the patient to alert him or her of the next injection time, providing an alert if there is an injection site reaction or leak, an increase in temperature, color, heart rate, etc.

Embodiments of the patch may be used during an injection to monitor the status of the syringe/syringes to determine, for example, whether the syringe is filled, the volume or quantity of substance (e.g., medicament or drug) that has been filled into the syringe, whether the syringe is removed from the storage or delivery device base, whether the syringe is placed on the skin, whether the safety band is removed, whether the button is pressed, whether an injection is initiated, the barometer position (including delivery tracking), pressing the button to pause, the button to retract the cannula, the injection is completed (if the syringe is removed from the skin), or any post-injection parameter associated with the patient physiological parameter measurements discussed above.

Additional features/embodiments

In alternative embodiments, the sensor may detect whether another patch is being transported or whether an existing patch is removed. The patch may be transparent to allow the patient to see the injection site, and it will be as unobtrusive as possible so that the patient can wear the patch and continue with daily activities (showering, swimming, etc.).

In other alternative embodiments, sensing elements may be provided that can measure device properties including: presence of skin (cannula retraction or dropout sensing), delivery indicator tracking (including filling and dispensing), occlusion detection, medicament temperature, device status (turn on/off delivery base, turn on/off patient, button status, pause event, etc.), flow rate, internal injector pressure/injection pressure, adhesive adhesion.

Other embodiments may incorporate patient and device sensing elements to allow manual and/or automatic intervention (administration) of the injector. For example, the flow rate of the syringe may be adjusted (e.g., faster, slower, stopped/paused) based on site response sensing information (automatic), pain information from the patient (manual), biological absorbance (automatic), or any combination or variation thereof.

Other embodiments may vibrate (for pain management or notification to the user) the vibrating element in the syringe and/or patch based on site response sensing information, pain information from the patient (manual) or pain sensing information, gap pressure/site dilation information (automatic), or any combination or variation thereof.

In other embodiments, a sound (e.g., for notification and/or communication of information to the user) -a sound element in the syringe and/or patch may be provided and activated based on sensed information from the patient, device sensing elements (occlusion, temperature of the medicament, delivery indication, etc.), or a combination or variation thereof.

In other embodiments, a visual indicator (e.g., indicating a change for notification and/or communicating information to the user) may be provided on the syringe and/or patch-a light emitting diode or equivalent that activates and activates based on sensed information from the patient, the device sensing element, the position of the retraction button-e.g., detecting premature removal/detachment, sensed information from the syringe (skin sensing, etc.), sensed information from the patient (high pressure, temperature, etc.), or a combination or change thereof.

In other embodiments, a lock for injector button pressing (e.g., for safety or to prevent medication misuse) may be provided and activated based on sensed information from the injector (medication temperature, etc.), sensed information from the patient (skin sensing, etc.), sensed information from the mobile application (e.g., time since last injection, user authentication), or a variation or combination thereof.

In other embodiments, subcutaneous/Transcutaneous Electrical Nerve Stimulation (TENS) may be provided (e.g., for pain management or bioabsorption). In such cases, the electrode elements in the cannula and/or patch may be activated based on site response sensing information, pain information from the patient (manual) or pain sensing information, interstitial pressure/site dilation information (automatic), or variations or combinations thereof.

Other embodiments may predict the remaining injection time based on, for example, sensed flow rate and fill volume, sensed device pressure and backpressure, medicament temperature, body temperature, and fill volume.

Still other embodiments may include the following features: the patch senses whether another patch has been applied, is transparent to allow visualization of the underlying tissue, communicates directly with the user/patient, audible signals (e.g., "hey-time of next injection" or "call doctor-you have ISR"), and/or other tactile options, vibrations, electrical stimulation, visual options, light emitting diodes, periodically transmits data to a receiver or directly to the cloud or intermittent data broadcast.

Mobile application

In another aspect, disclosed herein is a system and method for generating a mobile application to monitor one or more health or physiological parameters. Mobile applications may be generated using a variety of methods, such as Application Programming Interfaces (APIs). Mobile applications may contain a number of useful features and may be configured to interact with other mobile applications. In some cases, the mobile application may be configured to display measurements of one or more physiological parameters from the subject or parameters of the patch and/or syringe. The mobile application may incorporate a feedback system that allows for subject or other user input, which may allow for adjustment of the patch and/or syringe (e.g., amount of substance dispensed). The mobile application may also communicate with a remote server, for example, through a communication interface. In some cases, the remote server may be part of or in communication with a separate electronic device (e.g., mobile device, laptop), which may allow a clinician or physician to monitor physiological parameters of the subject. In some cases, the mobile application may allow for input of non-measurable parameters (e.g., pain, discomfort, etc.) from the subject. The mobile application may also contain software for data processing. In non-limiting examples, data processing may include statistical analysis of data, trend plotting and analysis, and graphical representation of data. In some cases, the mobile application can interface or combine with other mobile applications, such as a lifestyle tracking application (e.g., monitoring meals and activities), or other useful mobile applications, e.g., location tracking, accelerometers, calendars (e.g., sending reminders), and so forth.

Fig. 97 schematically shows an example workflow of a mobile application for monitoring one or more health or physiological parameters. The mobile device 9700 may be a laptop computer, a tablet computer, a telephone, or other electronic device (e.g., a portable electronic device). Upon opening or selecting an application on the mobile device 9700, a load screen 9710 may be presented, followed by a menu screen 9720. Menu screen 9720 may provide a plurality of functions 9730. Non-limiting examples of functions 9730 may include starting a new infusion, infusion history, training videos, additional information, and patient profiles. Upon selection of a function 9730 (e.g., infusion history), a second screen 9740 may be presented that is associated with the function. In such examples, a calendar may be presented to the subject. In process 9750, the subject may select a second function on a second screen 9740 that presents a third screen 9760. The third screen may display one or more health or physiological parameters of the subject, device, or substance delivered to the subject (e.g., prescription, time, day of week, group, reminder to patient, alarm, vibration, etc.). In the example third screen 9980, the calendar may contain selectable dates that provide information on one or more health or physiological parameters of the subject at each selected date. In the example fourth screen 9990, the calendar of the mobile application may display additional information, for example, when the subject missed an infusion. In the example fifth screen 9790, the calendar of the mobile application may display additional information, for example, when the subject has received an infusion.

FIG. 98 schematically illustrates an example workflow of a mobile application for monitoring one or more health or physiological parameters, which may be used in conjunction with one or more workflows of the mobile application. When function 9730 is selected (e.g., a new infusion is started, see fig. 97) from menu screen 9720 (see fig. 97), screen 9810 may appear. Mobile applications may allow for the detection of substances or drugs, for example, scanning a barcode or a quick response code (QR code). The mobile application may be integrated with another application on the mobile device, such as a camera, and the camera is displayed on the screen 9820. Screen 9830 shows an example screen of a scanned QR code, which may present information about a substance or device. The mobile application may then verify the compatibility of the medicament and device and/or other parameters of the medicament/device, such as expiration date, dosage, etc. In the event that the medicament or device is not appropriate for the subject (e.g., an expired medicament), a screen 9842 or 9844 may appear which informs the subject that the medicament or device is not appropriate. Where the medicament or device is appropriate for the subject, a screen 9850 may appear, which screen 9850 may provide guidance, instructions, or instructions to the subject. The instructions may be presented in a continuous scrolling format, as illustrated by screen 9852. The mobile application may then be paired with the device. On the example screen 9860, additional directions may be provided to the subject. A security feature may be included in the application, for example, the mobile application may notify the subject if the subject does not perform a security measure (e.g., a security tag). Screen 9870 may display one or more device parameters (e.g., infusion status, injection of cannula into the body of the subject, etc.). An incomplete infusion may present a screen 9872, which screen 9872 may indicate the status of the infusion and may include other indications of device parameters (e.g., "device paused"). After delivery of the substance or medicament is complete, a screen 9880 may be displayed, which screen 9880 may indicate the status of the infusion. In some cases, 9880 may provide the subject with an option to rank infusion experiences. Steps in the process may also include a communication step 9854 (e.g., via bluetooth, Wi-Fi) with a stand-alone device, cloud computing, clinician server, etc.

FIG. 99 illustrates another example workflow of a mobile application for monitoring one or more health or physiological parameters that may be used in conjunction with one or more workflows of the mobile application. When function 9730 (e.g., a training video, see fig. 97) is selected from menu screen 9720 (see fig. 97), screen 9900 may appear. The mobile application may contain a variety of tutorial or training information for the subject. Fig. 99A schematically illustrates a plurality of devices or systems that may be integrated with a mobile application. Upon selection of a device or system (e.g., syringe transport system, handheld system, vial transport system, reconstitution system), a screen 9905, 9910, 9915, or 9920 may appear, which screen 9905, 9910, 9915, or 9920 may contain a video demonstrating a course or method of use of the device or system. Fig. 99B schematically illustrates another example workflow of a mobile application for monitoring one or more health or physiological parameters, which may be used in conjunction with one or more workflows of the mobile application. Upon selection of function 9730 (e.g., additional information, see fig. 97) from menu screen 9720 (see fig. 97), a screen 9925 may appear, which screen 9925 may contain a menu displaying one or more physiological health parameters or one or more device parameters. Additional information (e.g., prescription information, device information, etc.) may be available to the subject. When a function in the menu is selected, a screen 9930 or 9945 may appear, which screen 9930 or 9945 may also contain options to display other information, such as security information (e.g., screen 9935 or 9950) or questions and answers (e.g., screen 9940 or 9955). Fig. 99C schematically illustrates another example workflow of a mobile application for monitoring one or more health or physiological parameters, which may be used in conjunction with one or more workflows of the mobile application. When function 9730 (e.g., patient profile, see fig. 97) is selected from menu screen 9720 (see fig. 97), a screen 9970 may appear, which screen 9970 may contain a menu. The menu may include options for the subject to view and/or enter patient information (e.g., gender, height, weight, activity level). Additional settings, such as alerts, reminders, emails, notifications, etc., may be implemented in the mobile application.

Computer system

The present disclosure provides a computer system programmed to implement the methods of the present disclosure. Fig. 100 illustrates a computer system 10001 that is programmed or otherwise configured to transmit and/or receive data and process data. The computer system 10001 can adjust various aspects of the present disclosure, such as, for example, methods for data analysis, subject monitoring, and measurement of physiological or health parameters and providing an output of the physiological or health parameters. The computer system 10001 can be a user's electronic device or a computer system remotely located from the electronic device. The electronic device may be a mobile electronic device.

The computer system 10001 includes a central processing unit (CPU, also referred to herein as "processor" and "computer processor") 10005, which may be a single or multi-core processor, or multiple processors for parallel processing. Computer system 10001 also includes a memory or storage unit 10010 (e.g., random access memory, read only memory, flash memory), an electronic storage unit 10015 (e.g., hard disk), a communication interface 10020 (e.g., a network adapter) for communicating with one or more other systems, and peripheral devices 10025, such as a cache, other memory, data storage, and/or an electronic display adapter. The memory 10010, the storage unit 10015, the interface 10020, and the peripheral device 10025 communicate with the CPU 10005 through a communication bus (solid line) such as a motherboard. The storage unit 10015 may be a data storage unit (or data repository) for storing data. Computer system 10001 can be operatively coupled to a computer network ("network") 10030 by way of a communication interface 10020. Network 10030 can be the internet, an internet and/or an extranet, or an intranet and/or extranet in communication with the internet. In some cases, network 10030 is a telecommunications and/or data network. Network 10030 may include one or more computer servers, which may implement distributed computing, such as cloud computing. In some cases, with the aid of computer system 10001, network 10030 can implement a peer-to-peer network, which can enable a device coupled to computer system 10001 to behave as a client or a server.

The CPU 10005 can execute a series of machine readable instructions, which can be embodied in a program or software. The instructions may be stored in a memory location, such as memory 10010. Instructions may be directed to CPU 10005, which CPU 10005 may then program or otherwise configure CPU 10005 to implement methods of the present disclosure. Examples of operations performed by the CPU 10005 may include fetch, decode, execute, and write-back.

The CPU 10005 can be part of a circuit, such as an integrated circuit. One or more other components of the system 10001 can be included in the circuit. In some cases, the circuit is an Application Specific Integrated Circuit (ASIC).

The storage unit 10015 may store files (such as drivers, libraries, and saved programs). The storage unit 10015 may store user data, such as user preferences and user programs. In some cases, the computer system 10001 can include one or more additional data storage elements external to the computer system 10001, such as located on a remote server in communication with the computer system 10001 via an intranet or the internet.

Computer system 10001 can communicate with one or more remote computer systems via network 10030. For example, the computer system 10001 can communicate with a remote computer system of a user (e.g., located at a physician's office or a physician's mobile device). Examples of remote computer systems include personal computers (e.g., laptop PCs), tablet or tablet computers (e.g.,iPad、galaxy Tab), telephone, smartphone (e.g., iPhone, Android enabled device,) Or a personal digital assistant. A user may access computer system 10001 via network 10030.

The methods described herein may be implemented by machine (e.g., computer processor) executable code stored on an electronic storage location of computer system 10001, such as, for example, stored on memory 10010 or electronic storage unit 10015. The machine executable or machine readable code may be provided in the form of software. During use, code may be executed by the processor 10005. In some cases, code may be retrieved from storage unit 10015 and stored on memory 10010 for ready access by processor 10005. In some cases, electronic storage unit 10015 may be eliminated, and machine executable instructions stored on memory 10010.

The code may be pre-compiled and configured for use with a machine having a processor adapted to execute the code, or may be compiled during runtime. The code may be supplied in a programming language that may be selected to enable the code to be executed in a pre-compiled or compiled manner.

Aspects of the systems and methods provided herein, such as the computer system 10001, may be implemented in programming. Various aspects of the described technology may be considered as an "article of manufacture" or an "article of manufacture" typically in the form of machine (or processor) executable code and/or associated data that is carried or embodied in a type of machine-readable medium. The machine executable code may be stored on an electronic storage unit, such as a memory (e.g., read only memory, random access memory, flash memory) or a hard disk. "storage" type media may include any or all tangible memory of a computer, processor, etc. or its associated modules, such as various semiconductor memories, tape drives, disk drives, etc., that may provide non-transitory storage for software programming at any time. All or portions of the software may sometimes be communicated over the internet or various other telecommunications networks. For example, such communication may enable loading of software from one computer or processor into another computer or processor, e.g., from a management server or host computer into the computer platform of an application server. Thus, another type of media that can carry software elements includes optical, electrical, and electromagnetic waves, such as those used over physical interfaces between local devices, over networks and various air links, through wired and optical landlines. The physical elements that carry such waves (such as wired or wireless links, optical links, etc.) can also be considered to be media that carry software. As used herein, unless limited to a non-transitory, tangible "storage" medium, terms such as a computer or machine "readable medium" refer to any medium that participates in providing instructions to a processor for execution.

Thus, a machine-readable medium, such as computer executable code, may take many forms, including but not limited to tangible storage media, carrier wave media, or physical transmission media. Non-volatile storage media includes any storage device such as optical or magnetic disks, such as any of the computer(s), etc., such as may be used to implement the databases shown in the figures. Volatile storage media includes dynamic memory, such as the main memory of such computer platforms. Tangible transmission media include coaxial cables, copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media can take the form of electrical or electromagnetic signals, or acoustic or light waves, such as those generated during Radio Frequency (RF) and Infrared (IR) data communications. Thus, common forms of computer-readable media include, for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer can read programming code and/or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

Computer system 10001 can include or be in communication with an electronic display 10035, said electronic display 10035 comprising a User Interface (UI) 10040. Examples of UIs include, but are not limited to, Graphical User Interfaces (GUIs) and web-based user interfaces.

The methods and systems of the present disclosure may be implemented by one or more algorithms. The algorithms may be implemented by software when executed by the central processing unit 10005. The algorithms can, for example, process data, perform statistical analysis, plot, or graphically represent data, and provide feedback to one or more systems (e.g., patches and/or syringes) disclosed herein.

While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. The invention is not intended to be limited to the specific examples provided in the specification. While the invention has been described with reference to the foregoing specification, the description and illustration of the embodiments herein is not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Further, it should be understood that all aspects of the present invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is therefore contemplated that the present invention will also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.