阅读说明：本技术 基于贴片的生理传感器 (Patch-based physiological sensor ) 是由 马歇尔·迪隆 马克·迪隆 埃里克·唐 劳伦特·尼克勒·米勒·海沃德 马修·巴尼特 詹姆斯· 于 2020-05-08 设计创作，主要内容包括：本发明涉及一种身体佩戴的贴片传感器,用于同时测量患者的血压(BP)、脉搏血氧饱和度(SpO2)和其他生命体征和血液动力学参数,其特征在于感测部分具有柔性外壳,柔性外壳可完全佩戴在患者胸部上并封入电池、无线发射器以及所有传感器的感测和电子组件。贴片传感器测量心电图(ECG)、阻抗体积描记图(IPG)、光电体积描记图(PPG)和心音图(PCG)波形,并共同处理这些波形以确定生命体征和血液动力学参数。测量PPG波形的传感器还包括加热元件,以增加胸部组织的灌注。(The present invention relates to a body-worn patch sensor for simultaneously measuring Blood Pressure (BP), pulse oximetry (SpO2) and other vital signs and hemodynamic parameters of a patient, characterized by a sensing portion having a flexible housing that can be worn entirely on the patient's chest and encloses a battery, a wireless transmitter, and the sensing and electronics components of all sensors. The patch sensor measures Electrocardiogram (ECG), Impedance Plethysmogram (IPG), photoplethysmogram (PPG), and Phonocardiogram (PCG) waveforms, and collectively processes these waveforms to determine vital signs and hemodynamic parameters. The sensor that measures the PPG waveform also includes a heating element to increase perfusion of the breast tissue.)

1. A sensor for measuring a photoplethysmogram (PPG) waveform, a Phonocardiogram (PCG) waveform, an Impedance Plethysmogram (IPG) waveform, and an Electrocardiogram (ECG) waveform from a chest of a patient, the sensor comprising:

a housing configured to be positioned on the patient's chest;

a reflective optical sensor for measuring the PPG waveform;

a digital microphone to measure the PCG waveform;

a set of electrodes attaching the optical sensor and the digital microphone to the patient's chest while the set of electrodes is connected to an ECG sensor configured to measure the ECG waveform,

wherein the set of electrodes is further attached to an IPG sensor configured to measure the IPG waveform, and

wherein the IPG sensor is configured to inject a current into the patient's chest and is further configured to measure the current to determine the IPG waveform.

2. The sensor of claim 1,

the IPG sensor is configured to inject current at a plurality of frequencies into the patient's chest and is further configured to measure the current at a plurality of frequencies to determine the IPG waveform at a plurality of frequencies.

3. The sensor of claim 1,

the IPG sensor is configured to inject a current at a single frequency into the patient's chest and is further configured to measure the current at the single frequency to determine the IPG waveform at the single frequency.

4. The sensor of claim 1,

the reflective optical sensor further includes a heating element.

5. The sensor of claim 4,

the heating element comprises a resistive heater.

6. The sensor of claim 5,

the resistive heater is a flexible film.

7. The sensor of claim 1,

the housing is of a strong, unitary construction.

8. The sensor of claim 1,

the set of electrodes is a single electrode patch.

9. A sensor for measuring a photoplethysmogram (PPG) waveform, a Phonocardiogram (PCG) waveform, an Impedance Plethysmogram (IPG) waveform, and an Electrocardiogram (ECG) waveform from a chest of a patient, the sensor comprising:

a housing configured to be positioned on the patient's chest;

a reflective optical sensor for measuring the PPG waveform;

a digital microphone to measure the PCG waveform;

a set of electrodes attaching the optical sensor and the digital microphone to the patient's chest, the set of electrodes connected to an ECG sensor configured to measure the ECG waveform,

wherein the set of electrodes is further attached to an IPG sensor configured to measure the IPG waveform, an

Wherein respiratory events are determined using the IPG waveform and the PCG waveform.

10. The sensor of claim 9,

the IPG waveform is one of a time-domain bioimpedance waveform and a time-domain bioimpedance waveform.

11. The sensor of claim 9,

the PCG waveform is a time-domain acoustic waveform.

12. The sensor of claim 9,

the respiratory event is one of a cough and a wheeze.

13. The sensor of claim 9,

the IPG sensor is configured to inject a current into the patient's chest and is further configured to measure the current to determine the IPG waveform.

14. The sensor of claim 13,

the IPG sensor is configured to inject current at a plurality of frequencies into the patient's chest and is further configured to measure the current at a plurality of frequencies to determine the IPG waveform at a plurality of frequencies.

15. The sensor of claim 13,

the IPG sensor is configured to inject a current at a single frequency into the patient's chest and is further configured to measure the current at the single frequency to determine the IPG waveform at the single frequency.

16. The sensor of claim 9,

the reflective optical sensor further includes a heating element.

17. The sensor of claim 16, wherein the heating element comprises a resistive heater.

18. The sensor of claim 17, wherein the resistive heater is a flexible film.

19. The sensor of claim 9, wherein the housing is a solid, monolithic construction.

20. The sensor of claim 9,

the set of electrodes is a single electrode patch.

21. A sensor for measuring a bio-reactance waveform from a patient's chest, the sensor comprising:

a circuit for performing a bio-reactance measurement, the circuit configured for injecting a current into the patient's chest and measuring a time-dependent phase change of the injected current to determine the bio-reactance waveform;

a housing configured to be positioned on the patient's chest and comprising the circuitry; and

a set of electrodes in electrical contact with the circuit and configured for affixing the housing to the patient's chest.

22. A sensor for determining cough motion of a patient, the sensor comprising:

a circuit for performing a time-dependent impedance measurement, the circuit configured for injecting a current into the patient's chest and measuring a time-dependent change in the injected current to determine an impedance waveform;

a housing configured to be positioned on the patient's chest and comprising the circuit board and microprocessor;

a set of electrodes in electrical contact with the circuit and configured for affixing the housing to the patient's chest; and

computer code running on the microprocessor and configured to analyze the impedance waveform to determine the cough motion.

Technical Field

The present invention relates to the use of a system for measuring physiological parameters from patients located, for example, in hospitals, clinics and homes.

Background

Many physiological parameters can be assessed by measuring biometric signals from the patient. Some signals, such as Electrocardiogram (ECG), Impedance Plethysmogram (IPG), photoplethysmogram (PPG), and Phonocardiogram (PCG) waveforms, are measured using sensors (e.g., electrodes, optics, microphones) that are directly connected or attached to the patient's skin. Processing these waveforms results in parameters such as Heart Rate (HR), Heart Rate Variability (HRV), Respiration Rate (RR), pulse oximetry (SpO2), Blood Pressure (BP), Stroke Volume (SV), Cardiac Output (CO), and parameters related to thoracic impedance such as pleural effusion content (fleids). When these parameters are obtained at a single point in time, a number of physiological conditions can be identified from these parameters; other parameters may require long or short term continuous evaluation to identify trends in the parameters. In both cases, it is important to obtain parameters that are consistent and have high repeatability and accuracy.

Some devices that measure ECG waveforms are worn entirely on the patient. These devices typically have simple patch-type systems, including analog and digital electronics connected directly to the underlying electrodes. Typically, these systems measure HR, HRV, RR, and in some cases, posture, motion, and falls. Such devices are typically employed for relatively short periods of time, such as periods in the range of days to weeks. They are typically wireless and typically include, for exampleTransceiver, or the like, to transmit information over short distances to a second device, which typically includes a cellular radio to transmit information to a network-based system.

Bioimpedance medical devices measure SV, CO, and FLUIDS by sensing and processing time-dependent ECG and IPG waveforms. Typically, these devices are connected to the patient by disposable electrodes that are adhered to different locations of the patient's body. Disposable electrodes that measure ECG and IPG waveforms are typically worn on the chest or legs of a patient and include: i) a conductive hydrogel in contact with a patient; ii) Ag/AgCl coated eyelets in contact with the hydrogel; iii) a conductive metal post connecting the eyelet to a wire or cable extending from the device; and iv) an adhesive backing to adhere the electrode to the patient. Medical devices that measure BP, including systolic (SYS), Diastolic (DIA), and Mean (MAP) BP, typically use a cuff-based technique known as oscillography or auscultation, or a pressure-sensitive catheter inserted into the arterial system of a patient. The medical device that measures SpO2 is typically an optical sensor that is clipped to a patient's finger or earlobe, or attached to the patient's forehead by an adhesive assembly.

Disclosure of Invention

The present invention relates to a method and system for improving the monitoring of patients in hospitals, clinics and homes. As described herein, a patch sensor is provided to non-invasively measure vital signs such as HR, HRV, RR, SpO2, TEMP, and BP, as well as complex hemodynamic parameters such as SV, CO, and FLUIDS. The patch sensor is adhered to the chest of the patient and continuously and non-invasively measures the above parameters without the need for a cuff and wires. In this way, the traditional protocols for making such measurements, which typically involve multiple machines and may take several minutes to complete, are simplified. The patch sensor wirelessly transmits information to an external gateway (e.g., tablet, smartphone, or non-mobile, plug-in system) that can be integrated with existing hospital infrastructure and notification systems, such as a hospital Electronic Medical Record (EMR) system. With such a system, a caregiver can be alerted to a change in vital signs and, in response, can quickly intervene to help a patient with a worsening condition. Additionally the patch sensor may monitor the patient from a location outside the hospital.

More specifically, the invention features a chest patch sensor that measures the following parameters of a patient: HR, PR, SpO2, RR, BP, TEMP, FLUIDS, SV, CO and a set of parameters sensitive to blood pressure and systemic vascular resistance, which are called Pulse Arrival Time (PAT) and Vascular Transit Time (VTT).

The patch sensor also comprises a motion detection accelerometer from which parameters related to motion can be determined, such as posture, degree of motion, activity level, respiration induced chest fluctuations, and falls. For example, these parameters may determine the posture or movement of the patient during the hospitalization. When motion is minimized and below a predetermined threshold, the patch sensor may operate additional algorithms to process the motion-related parameters to measure vital signs and hemodynamic parameters, thereby reducing artifacts. Furthermore, the patch sensor estimates parameters related to motion, such as posture, to improve the accuracy of the calculation of vital signs and hemodynamic parameters.

Disposable electrodes on the bottom surface of the patch sensor secure it to the patient's body without the need for cumbersome cables. The electrodes measure ECG and IPG waveforms. The electrodes are easily connected (and disconnected) to the circuit board contained within the sensor by a magnet that is electrically connected to the circuit board to provide a signal conducting electrical coupling. Prior to use, the electrodes need only be held near the circuit board and the magnetic attraction causes the electrode patches to snap into place, thereby ensuring proper positioning of the electrodes on the patient's body.

Using Light Emitting Diodes (LEDs) operating in the red (e.g., 660nm) and infrared (e.g., 900nm) spectral regions, the patch sensor measures SpO2 by gently pressing the capillary bed of the patient's chest. The heating element on the bottom surface of the patch sensor contacts the patient's chest and gently heats the underlying skin, thereby increasing the perfusion of the tissue. By operating with reflective mode optics, the patch sensor measures PPG waveforms having both red and infrared wavelengths. The SpO2 is processed by the alternating and static components of these waveforms, as described in more detail below.

The patch sensor measures all of the above characteristics while featuring a form factor that is comfortable and easy to wear. The patch sensor is lightweight (e.g., about 20 grams) and is powered by a rechargeable battery. During use, the patch sensor rests on the chest of the patient with the disposable electrodes holding it in place, as described in more detail below. The patient's chest is unobtrusive, comfortable, removable from the hands, and able to hold the sensor in a position that is not noticeable to the patient. The chest is also relatively motionless compared to extremities such as hands and fingers, so sensors attached to the chest area minimize motion related artifacts. Accelerometers within the sensor compensate to some extent for such artifacts. And because the patch sensor is small and therefore significantly less obtrusive or obtrusive than other various physiological sensor devices, the emotional discomfort of wearing the medical device for extended periods of time is reduced, thereby promoting compliance of the patient with extended use of the device within the monitoring regimen.

In view of the above, in one aspect, the present invention provides a patch sensor for simultaneously measuring BP and SpO2 of a patient. The patch sensor is characterized by a flexible housing for the sensing portion, which is worn entirely on the patient's chest and encloses the battery, wireless transmitter, and all of the sensing and electronic components of the sensor. The sensors measure ECG, IPG, PPG, and PCG waveforms and collectively process these waveforms to determine BP and SpO 2. The sensor that measures the PPG waveform includes a heating element to increase perfusion of the breast tissue.

On its bottom surface, the flexible housing includes an analog optical system, located near the pair of electrode contacts, the analog optical system characterized by a light source that can generate radiation in both the red and infrared spectral ranges. This radiation alone illuminates a portion of the patient's chest that is located below the flexible enclosure. The photodetector detects reflected radiation in different spectral ranges to generate analog red PPG and infrared PPG waveforms.

A digital processing system disposed within the flexible housing includes a microprocessor and an analog-to-digital converter, and is configured to: 1) digitizing the analog ECG waveform to generate a digital ECG waveform; 2) digitizing the analog impedance waveform to generate a digital impedance waveform; 3) digitizing the analog red light PPG waveform to generate a digital red light PPG waveform; 4) digitizing the analog infrared PPG waveform to generate a digital infrared PPG waveform; and 5) digitizing the analog PCG waveform to generate a digital PCG waveform. Once these waveforms are digitized, numerical algorithms running in embedded computer code called "firmware" process these waveforms to determine the parameters described herein.

In another aspect, the invention provides a patch sensor for measuring a PPG waveform of a patient. The patch sensor includes a housing that is worn entirely on the chest of the patient, and a heating element attached to a bottom surface of the housing to contact and heat the chest area of the patient during use. An optical system is located on the bottom surface of the housing proximate the heating element and includes a light source that generates optical radiation that illuminates the chest area of the patient during a measurement. The sensor is further characterized by a temperature sensor in direct contact with the heating element, and a closed loop temperature controller within the housing and in electrical contact with the heating element and the temperature sensor. During the measurement, the closed loop temperature controller receives a signal from the temperature sensor and in response controls the amount of heat generated by the heating element. A photodetector within the optical system generates a PPG waveform by detecting radiation reflected from the chest region of the patient after being heated by the heating element.

Heating the tissue that produces the PPG waveform generally increases blood flow to the tissue (i.e., perfusion), thereby increasing the amplitude and signal-to-noise ratio of the waveform. This is particularly important for measurements made at the chest, since the chest signal is typically much weaker than the signal measured from more traditional locations, such as the fingers, earlobe and forehead.

In an embodiment, the heating element features a resistive heater, such as a flexible film, a metallic material, or a polymeric material (e.g.,) Possibly including a set of embedded electrical traces that increase in temperature as current passes through the electrical traces. For example, the electrical traces may be arranged in a serpentine pattern to maximize and evenly distribute the heat generated during the measurement. In other embodiments, the closed loop temperature controller includes circuitry to apply an adjustable potential difference to a resistive heater controlled by a microprocessor. Preferably, the microcontroller adjusts the potential difference it applies to the resistive heater so that its temperature is between 40 and 45 ℃.

In an embodiment, the flexible film heating element features an opening that transmits the light radiation generated by the light source such that it illuminates a chest area of a patient located below the housing. In a similar embodiment, the flexible membrane features a similar opening or set of openings that transmit optical radiation reflected from the chest region of the patient such that the optical radiation is received by the photodetector.

In yet other embodiments, the housing further comprises an ECG sensor characterized by a set of electrode leads, each electrode lead configured to receive an electrode, the electrodes connected to the housing and electrically connected to the ECG sensor. For example, in an embodiment, a first electrode lead is connected to one side of the casing and a second electrode lead is connected to the opposite side of the casing. During the measurement, the ECG sensor receives ECG signals from both the first and second electrode leads and responsively processes the ECG signals to determine an ECG waveform.

In another aspect, the invention provides a sensor for measuring PPG and ECG waveforms of a patient, which sensor is also worn entirely on the chest of the patient. The sensor is characterized by an optical sensor, a heating element and a temperature sensor similar to those described above. The sensor also includes a closed loop temperature controller located within the housing and in electrical contact with the heating element, the temperature sensor, and the processing system. The closed-loop temperature controller is configured to: 1) receiving a first signal from a temperature sensor; 2) receiving a second signal corresponding to a second fiducial marker from the processing system; 3) processing the first and second signals together to generate a control parameter; and 4) controlling the amount of heat generated by the heating element based on the control parameter.

In an embodiment, a software system included in the processing system determines a first fiducial marker within the ECG waveform, the first fiducial marker being one of a QRS amplitude, a Q point, an R point, an S point, and a T wave. Similarly, the software system determines a second fiducial marker that is one of an amplitude of a portion of the PPG waveform, a foot of the portion of the PPG waveform, and a maximum amplitude of a mathematical derivative of the PPG waveform.

In an embodiment, the closed loop temperature controller features an adjustable voltage source and is configured to control the amount of heat generated by the heating element, such as the amplitude or frequency of the voltage generated by the voltage source, by adjusting the voltage source.

In another aspect, the invention provides a similar chest-worn sensor that measures PPG waveforms of a patient and measures SpO2 values from these waveforms. The sensor features a heating element, temperature, closed loop temperature controller, and optical system similar to those described above. Here, the optical system generates optical radiation in both the red and infrared spectral regions. The sensor also includes an ECG sensor having at least two electrode leads and an ECG circuit that generates an ECG waveform. During the measurement, a processing system characterized by a software system analyzes the ECG waveform to identify a first fiducial marker, and identifies a first set of fiducial markers within the red PPG waveform, and a second set of fiducial markers within the infrared PPG waveform, based on the first fiducial marker. The processing system then processes the first and second sets of fiducial markers together to generate a SpO2 value.

In an embodiment, for example, a first set of fiducial points identified by the software system are characterized by the amplitude of the red PPG waveform baseline (red (dc)) and the amplitude of the heartbeat-inducing pulses within the red PPG waveform (red (ac)), and a second set of fiducial points identified by the software system are characterized by the amplitude of the infrared PPG waveform baseline (ir (dc)) and the amplitude of the heartbeat-inducing pulses within the infrared PPG waveform (ir (ac)). The software system may be further configured to generate the SpO2 value by analyzing the ratio (R) of the ratios of red (dc), red (ac), ir (dc), and ir (ac) using the following equations or their mathematical equivalents:

wherein k1, k2, k3 and k4 are predetermined constants. Typically, these constants are determined during a clinical study called a "breathing study" using a group of patients. During the study, the oxygen concentration supplied to the patients was gradually reduced in successive "plateau" periods, changing their SpO2 values from normal (approximately 98% to 100%) to low oxygen (approximately 70%). As the oxygen concentration decreases, a reference SpO2 value is typically measured on each platform using a calibrated oximeter or a machine that measures the oxygen content of the inspired blood. These are the "true" SpO2 values. The R value was also determined on each platform by the PPG waveform measured by the patch sensor. The predetermined constants k1, k2, k3, and k4 can then be determined by fitting these data using the equations described above.

In other aspects, the invention provides a chest-worn sensor similar to that described above, further comprising an acoustic sensor for measuring a PCG waveform. Here, the sensor is mated with a single-use component that is temporarily attached to the housing of the sensor and is characterized by a first electrode region positioned to connect to the first electrode contact, a second electrode region positioned to connect to the second electrode contact, and an impedance matching region positioned to attach to the acoustic sensor.

In an embodiment, the impedance matching region comprises a gel or plastic material and has an impedance of about 220 Ω at 100 kHz. The acoustic sensor may be a single microphone or a pair of microphones. Typically, the sensor comprises an ECG sensor, and the signals produced by the ECG sensor are subsequently processed to determine a first fiducial point (e.g., a Q-point, R-point, S-point, or T-wave of a heart beat inducing pulse in the ECG waveform). A processing system within the sensor processes the PCG waveform to determine a second fiducial point, which is the S1 heart sound or the S2 heart sound associated with the heartbeat-inducing pulses in the PCG waveform. The processing system then determines a time difference separating the first fiducial and the second fiducial and uses the time difference to determine the blood pressure of the patient. Typically, calibration measurements made by the cuff-based system are used with the time difference to determine the blood pressure.

In an embodiment, the processor is further used to determine the frequency spectrum of the second fiducial point (using, for example, a fourier transform), which is then used to determine the patient's blood pressure.

In yet another aspect, the present invention provides a chest-worn sensor similar to that described above. Here, the sensor is characterized by an optical system located on a bottom surface of the sensor housing, the optical system including: 1) a light source that generates optical radiation that illuminates a chest region of a patient located below the housing; 2) a circular photodetector array surrounding the light source and detecting optical radiation reflected from the chest region of the patient. As before, the zone is heated with a heating element prior to measurement.

In view of the disclosure herein, and not limiting the scope of the invention in any way, in a first aspect of the disclosure, which may be combined with any other aspect listed herein unless otherwise specified, a sensor for measuring a photoplethysmogram (PPG) waveform, a Phonocardiogram (PCG) waveform, an Impedance Plethysmogram (IPG) waveform, and an Electrocardiogram (ECG) waveform of a chest of a patient includes a housing configured to be positioned on the chest of the patient. The sensor includes a reflective optical sensor to measure PPG waveforms. The sensor includes a digital microphone for measuring the PCG waveform. The sensor includes a set of electrodes that attach an optical sensor and a digital microphone to the chest of the patient, the set of electrodes being connected to an ECG sensor configured to measure ECG waveforms. The set of electrodes is further attached to an IPG sensor configured to measure an IPG waveform. The IPG sensor is configured to inject a current into the patient's chest and is further configured to measure the current to determine an IPG waveform.

In a second aspect of the present disclosure, which may be combined with any of the other aspects listed herein, unless otherwise specified, the IPG sensor is configured to inject a plurality of frequencies of electrical current into the patient's chest and is further configured to measure the plurality of frequencies of electrical current to determine a plurality of frequencies of IPG waveforms.

In a third aspect of the present disclosure, which may be combined with any of the other aspects listed herein, unless otherwise specified, the IPG sensor is configured to inject a single frequency current into the chest of the patient and is further configured to measure the single frequency current to determine a single frequency IPG waveform.

In a fourth aspect of the present disclosure, which may be combined with any of the other aspects listed herein, unless otherwise specified, the reflective optical sensor further comprises a heating element.

In a fifth aspect of the disclosure, the heating element comprises a resistive heater, unless otherwise specified, which may be combined with any other aspect listed herein.

In a sixth aspect of the disclosure, the resistive heater is a flexible film, unless otherwise specified, which may be combined with any other aspect listed herein.

In a seventh aspect of the disclosure, the housing is of a robust, unitary construction, unless otherwise specified, in combination with any other aspect listed herein.

In an eighth aspect of the disclosure, the set of electrodes is a single electrode patch, unless otherwise specified, in combination with any other aspect listed herein.

In a ninth aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, a sensor for measuring a photoplethysmogram (PPG) waveform, a Phonocardiogram (PCG) waveform, an Impedance Plethysmogram (IPG) waveform, and an Electrocardiogram (ECG) waveform of a chest of a patient includes a housing configured to be positioned on the chest of the patient. The sensor includes a reflective optical sensor to measure the PPG waveform. The sensor includes a digital microphone for measuring the PCG waveform. The sensor includes a set of electrodes that attach an optical sensor and a digital microphone to the chest of the patient, the set of electrodes being connected to an ECG sensor configured to measure ECG waveforms. The set of electrodes is further attached to an IPG sensor configured to measure an IPG waveform. The IPG waveform and the PCG waveform are used to determine respiratory events.

In a tenth aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, the IPG waveform is one of a time-domain bioimpedance waveform and a time-domain bioimpedance waveform.

In an eleventh aspect of the present disclosure, the PCG waveform is a time-domain acoustic waveform, all of which may be combined with any other aspect listed herein, unless otherwise specified.

In a twelfth aspect of the disclosure, the respiratory event is one of a cough and a wheeze, all of which may be combined with any other aspect listed herein, unless otherwise specified.

In a thirteenth aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, the IPG sensor is configured to inject a current into the chest of the patient and is further configured to measure the current to determine the IPG waveform.

In a fourteenth aspect of the present disclosure, which may be combined with any of the other aspects listed herein, unless otherwise specified, the IPG sensor is configured to inject currents of multiple frequencies into the chest of the patient and is further configured to measure the currents of the multiple frequencies to determine IPG waveforms of the multiple frequencies.

In a fifteenth aspect of the present disclosure, which may be combined with any of the other aspects listed herein, unless otherwise specified, the IPG sensor is configured to inject a single frequency current into the chest of the patient and is further configured to measure the single frequency current to determine a single frequency IPG waveform.

In a sixteenth aspect of the present disclosure, which may be combined with any of the other aspects listed herein unless otherwise specified, the reflective optical sensor further comprises a heating element.

In a seventeenth aspect of the disclosure, the heating element comprises a resistive heater, all of which may be combined with any other aspect listed herein, unless otherwise specified.

In an eighteenth aspect of the disclosure, the resistive heater is a flexible film, unless otherwise specified, which may be combined with any other aspect listed herein.

In a nineteenth aspect of the present disclosure, the housing is of a robust unitary construction, unless otherwise specified, in combination with any other aspect listed herein.

In a twentieth aspect of the disclosure, the set of electrodes is a single electrode patch, unless otherwise specified, in combination with any other aspect listed herein.

In a twenty-first aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, a sensor for measuring a bio-reactance waveform of a patient's chest includes a circuit for performing a bio-reactance measurement, a housing, and a set of electrodes. The circuit is configured to inject a current into the patient's chest and measure a time-dependent phase change of the injected current to determine a bio-reactance waveform. The housing is configured to be positioned on the chest of a patient and includes circuitry. The set of electrodes is in electrical contact with the circuit and is configured to attach the housing to the chest of the patient.

In a twenty-second aspect of the present disclosure, which may be combined with any other aspect listed herein unless otherwise stated, a sensor for determining a cough motion of a patient includes circuitry for performing a time-dependent impedance measurement, a housing, a set of electrodes, and computer code. The circuit is configured to inject a current into the patient's chest and measure a time-dependent change in the injected current to determine an impedance waveform. The housing is configured to be positioned on the chest of a patient and includes a circuit board and a microprocessor. The set of electrodes is in electrical contact with the circuit and is configured to attach the housing to the chest of the patient. Computer code runs on the microprocessor and is configured to analyze the impedance waveform to determine cough motion.

Additional features and advantages of the disclosed apparatus, system, and method are described in, and will be apparent from, the following detailed description and the figures. The features and advantages described herein are not all-inclusive and, in particular, many additional features and advantages will be apparent to one of ordinary skill in the art in view of the drawings and specification. Moreover, any particular embodiment need not necessarily have all of the advantages listed herein. Moreover, it should be noted that the language used in the specification has been principally selected for readability and instructional purposes, and may not have been selected to delineate the scope of the inventive subject matter.

Drawings

Understanding that the drawings depict only typical embodiments of the invention and are not therefore to be considered to be limiting of its scope, the disclosure will be described and explained with additional specificity and detail through the use of the accompanying drawings. The following figures are listed.

FIG. 1 is a perspective view of a patient wearing a patch sensor according to the present invention;

FIG. 2 is a perspective view of the back surface of the patch sensor shown in FIG. 1;

FIG. 3 is a cross-sectional view of an acoustic sensor for use in a patch sensor;

FIG. 4 is an exploded view of an optical sensor for use in a patch sensor;

FIG. 5 is a view of the bottom surface of the optical sensor shown in FIG. 4;

FIGS. 6A-6C are views of different embodiments of disposable electrodes for attaching a patch sensor to a patient's chest;

FIG. 7 is a view of a patient lying on a patient's bed and wearing a patch sensor according to the present invention, wherein the patch sensor transmits information to a cloud-based system through a gateway;

FIG. 8A is a time-dependent graph of an ECG waveform collected from a patient;

figure 8B is a time-dependent graph of a PPG waveform collected simultaneously and from the same patient as the ECG waveform shown in figure 8A;

FIG. 8C is a time-dependent plot of an IPG waveform collected simultaneously and from the same patient as the ECG waveform shown in FIG. 8A;

FIG. 8D is a time-dependent graph of PCG waveforms collected simultaneously and from the same patient as the ECG waveform shown in FIG. 8A;

FIG. 8E is a motion waveform collected simultaneously and from the same patient as the ECG waveform shown in FIG. 8A;

FIG. 9A is a time-dependent graph of ECG and PCG waveforms generated from a single heartbeat of a patient using a patch sensor, and a circular symbol marking a reference point in these waveforms and indicating a time interval associated with S2;

FIG. 9B is a time-dependent plot of the mathematical derivatives of an ECG waveform and an IPG waveform generated from a single heartbeat of a patient using a patch sensor, and a circular symbol marking a fiducial point in these waveforms and indicating a time interval associated with B;

FIG. 9C is a time-dependent plot of the mathematical derivatives of an ECG waveform and an IPG waveform generated from a single heartbeat of a patient using a patch sensor, and a marker and (dZ/dt)_maxArrow signs of the associated amplitudes;

FIG. 9D is a time-dependent plot of ECG and PPG waveforms generated from a single heartbeat of a patch patient using a patch sensor, and circular symbols marking fiducial points in these waveforms and indicating time intervals associated with PAT;

FIG. 9E is a time-dependent plot of the mathematical derivatives of an ECG waveform and an IPG waveform generated from a single heartbeat of a patient using a patch sensor, and a circular symbol marking a fiducial point in these waveforms and indicating a time interval associated with C;

FIG. 9F is a time-dependent graph of ECG and IPG waveforms generated from a single heartbeat of a patient using a patch sensor, and a marker and Z₀Arrow signs of the associated amplitudes;

figure 10A is a time-dependent graph of a PPG waveform measured with the optical sensor of figure 3B before heat is applied to the lower surface of the patient's skin;

figure 10B is a time-dependent graph of a PPG waveform measured with the optical sensor of figure 3B after heat has been applied to the lower surface of the patient's skin;

FIG. 11A is an alternative embodiment of a patch sensor of the present invention;

FIG. 11B is an image of a patient wearing the patch sensor of FIG. 11A on their chest;

FIG. 12 is a graph of resistance and reactance measured at multiple frequencies using an impedance sensor within a patch sensor of the present invention;

figure 13 is a graph of a PPG waveform measured from a wrist of a patient and an IPG waveform simultaneously measured from a chest of the patient during different respiratory events; and

fig. 14 is a graph of IPG and PCG waveforms measured in the time and frequency domains during cough and wheeze events.

Detailed Description

It is to be understood that the invention is not limited in its application to the details of construction and the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of embodiments in addition to those described and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein, as well as the abstract, are for the purpose of description and should not be regarded as limiting.

As such, those skilled in the art will appreciate that the conception upon which this disclosure is based may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.

Patch sensor

As shown in fig. 1 and 2, a patch sensor 10 according to the present invention measures ECG, PPG, PCG, and IPG waveforms of a patient 12, and calculates vital signs (HR, HRV, SpO2, RR, BP, TEMP) and hemodynamic parameters (fleis, SV, and CO) from these waveforms, as detailed below. The IPG waveform may be a bioimpedance waveform or a bioimpedance waveform, as described in more detail below. Once this information is determined, the patch sensor 10 wirelessly transmits the information to an external gateway, which then forwards the information to a cloud-based system. In this manner, a clinician may continuously and non-invasively monitor a patient 12 that may be located in a hospital or home.

The patch sensor 10 is characterized by two main components: a central sensing/electronics module 30 worn near the center of the patient's chest, and a secondary battery 57 worn near the patient's left shoulder. A flexible, wire-containing cable 34 connects the central sensing/electronics module 30 and the battery 57. The central sensing/electronics module 30 includes an optical sensor 36 and an acoustic sensor 46 on its patient contact surface, and includes four electrode leads 41, 42, 43, 45 that connect to the adhesive electrodes and help secure the patch sensor 10 (particularly the optical sensor 36 and the acoustic sensor 46) to the patient 12, the electrode leads connecting to the adhesive electrodes and helping secure the patch sensor 10 (particularly the optical sensor 36 and the acoustic sensor 46) to the patient 12. Two additional electrode leads 47, 48 connect the secondary battery to the chest of the patient. The central sensing/electronics module 30 has two "halves" 39A, 39B, each of which houses sensing and electronics components, described in more detail below, separated by a first flexible rubber gasket 38. Usually formed byA flexible circuit (not shown) with embedded electrical traces is formed to connect a fiberglass circuit board (also not shown) within the acoustic module 32 to the central sensing/electronics module 30Two halves 39A, 39B. A first adhesive, disposable electrode 49 connects the central sensing/electronics module 30 to the patient's chest. A second disposable electrode 69 connects the secondary battery 57 to the chest of the patient.

Referring more particularly to fig. 2, the patch sensor 10 includes a back surface that contacts the patient's chest during use via a set of single-use adhesive electrodes 49, 69. One half 39B of the central sensing/electronics module 30 includes two electrode leads 41, 42. These electrode leads are coupled to electrode leads 47, 48 connected to the optical sensor 36, attached to the set of single-use electrodes by a magnetic interface. The electrode leads 41, 42, 47, 48 form two "paired" leads, wherein one of each pair of leads 41, 47 injects current to measure the IPG waveform and the other of each pair of leads 42, 48 senses the bioelectric signal, which is then processed by electronics in the central sensing/electronics module 30 to determine the ECG and IPG waveforms. The opposite half 39A of the central sensing/electronics module 30 includes another electrode contact 43, which, like the electrode leads 41, 42, 47, 48, connects to a single-use electrode (also not shown) to help secure the patch sensor 10 to the patient 12.

IPG measurements are taken when the current injection electrodes 41, 47 inject high frequency (e.g., 100kHz), low amperage (e.g., 4mA) current into the patient's chest. The current may be injected at other frequencies, or additionally or alternatively, the current may be injected sequentially at different frequencies. The electrodes 42, 48 sense a voltage that will vary with the resistance encountered by the injected current. This in turn affects both the amplitude and the phase of the injected current. The voltage is passed through a series of circuits characterized by analog filters and differential amplifiers that respectively filter and amplify the signal components associated with the two different waveforms. One of the signal components is indicative of an ECG waveform; the other indicates the IPG waveform. Depending on the circuitry used to measure the IPG waveform, the IPG waveform may indicate a time-dependent change in the amplitude or phase of the injected current. In both cases, the IPG waveform has low frequency (DC) and high frequency (AC) components that are further filtered and processed, as described in more detail below, to determine the different impedance waveforms.

The use of the cable 34 to connect the central sensing/electronics module 30 and the optical sensor 36 means that the electrode leads (41, 42 in the central sensing/electronics module 30; 47, 48 in the optical sensor 36) can be separated by a relatively large distance when the patch sensor 10 is attached to the chest of a patient. For example, the optical sensor 36 may be attached near the left shoulder of the patient, as shown in fig. 1. This separation between the electrode leads 41, 42, 47, 48 generally improves the signal-to-noise ratio of the ECG and IPG waveforms measured by the patch sensor 10, as these waveforms are determined by differences in the bioelectric signals collected by the single-use electrodes, which typically increase with electrode separation. Ultimately, this will improve the accuracy of any physiological parameter detected from these waveforms (such as HR, HRV, RR, BP, SV, CO and fleids).

Referring to fig. 3, the acoustic module 46 features a solid-state acoustic microphone that is a thin piezoelectric disc 109 surrounded by foam substrates 111, 112. Another foam substrate 113 contacts the patient's chest during measurement and couples sound from the patient's heart through the first foam substrate 111 and into the piezoelectric disc 109, which then measures heart sounds from the patient 12. The plastic housing 115 encloses the entire acoustic module 46. It should be appreciated that other related types of microphones may also be used, such as microphones characterized by a bell and underlying pressure sensor.

Heart sounds are typically the "lub" and "dub" sounds heard from the heart with a stethoscope; they indicate when the underlying mitral and tricuspid (S1, or "lub" sound) and aortic and pulmonary (S2, or "dub" sound) valves are closed (no detectable sound is generated when the valves are open). Through signal processing, the heart sounds produce a PCG waveform that is used with other signals to determine BP, as described in more detail below. In other embodiments, two solid-state acoustic microphones 45, 46 are used to provide redundancy and better detection of sound. The acoustic module 32, such as half 39A of the central sensing/electronics module 30, includes electrical contacts 43 that connect to single-use electrodes (also not shown) to help secure the patch sensor 10 to the patient 12.

The optical sensor 36 is characterized by an optical system 60, the optical system 60 comprising an array of photodetectors 62 arranged in a circular pattern surrounding LEDs 61 emitting radiation in the red and infrared spectral regions. During the measurement, red and infrared radiation, which is emitted in sequence from the LED 61, illuminates the underlying tissue of the patient's chest and is reflected and detected by the array of photodetectors 62. The detected radiation is modulated by blood flowing through capillary beds in the underlying tissue. Processing the reflected radiation with electronics in the central sensing/electronics module 30 produces PPG waveforms corresponding to red and infrared radiation, which are used to determine BP and SpO2, as described below.

The patch sensor 10 also typically includes a three-axis digital accelerometer and a temperature sensor (not specifically identified in the figures) to measure three time-dependent motion waveforms (along the x, y, and z axes) and TEMP values, respectively.

Fig. 4 and 5 show the optical sensor 36 in more detail. As described above, sensor 36 is characterized by an optical system 60, optical system 60 having a circular array of photodetectors 62 (six distinct detectors are shown, although the number may be between three and nine photodetectors) surrounding a two-wavelength LED 61 that emits red and infrared radiation. Characterised by having embedded electrical conductors arranged in a serpentine patternThe heating element of the film 65 is attached to the bottom surface of the optical sensor 36. Other patterns of electrical conductors may also be used.The film 65 is characterized by cut-outs which allow the radiation emitted by the LED 61 to pass through and be detected by the photodetector 62 after reflection by the patient's skin. Thin sheetTab portion 67 on film 65 is folded over so that it can be inserted into connector 74 on fiberglass circuit board 80. A fiberglass circuit board 80 supports the photodetector array 62 and the LEDs 61 and provides electrical connections. During use, in the patch sensorSoftware running on 10 controls the power management circuitry on the fiberglass circuit board 80 toThe embedded conductor within the film 65 applies a voltage, thereby causing current to flow through the conductor. The resistance of the embedded conductor causes the film 65 to gradually heat up and warm the underlying tissue. The applied heat increases perfusion (i.e., blood flow) to the tissue, which in turn improves the signal-to-noise ratio of the PPG waveform. This is shown in fig. 10A, fig. 10A showing the PPG waveform measured before heat is applied, and in fig. 10B, fig. 10B showing the PPG waveform in usePPG waveform measured after the film 65 is heated. As is clear from the figure, the heat increases the perfusion under the optical sensor 36. This in turn significantly improves the signal-to-noise ratio of the heartbeat-induced pulses in the PPG waveform. This is important for optical measurements of patch sensors because the signal-to-noise ratio of PPG waveforms measured from the chest is typically 10 to 100 times weaker than similar waveforms measured from typical locations where pulse oximeters are used, such as fingers, earlobes, and forehead. A PPG waveform with improved signal-to-noise ratio will generally improve the accuracy of the BP and SpO2 measurements made by the patch sensor 10. The fiberglass circuit board 80 also includes a temperature sensor 76 integrated with the power management circuitry, allowing the software to operate in a closed loop manner to carefully control and adjust the applied temperature. Here, "closed loop mode" means that the software analyzes the amplitude of the heartbeat-induced pulses of the PPG waveform and adds them if necessaryThe voltage of the membrane 65 to raise its temperature and maximize the heartbeat-induced pulses in the PPG waveform. Typically, the temperature is adjusted between 41 ℃ and 42 ℃, which has been proven not to damage underlying tissues, and is also considered safe by the U.S. Food and Drug Administration (FDA).

The plastic housing 44, which features the top 53 and bottom 70, encloses a fiberglass circuit board 80. The base 70 also supportsA film 65 having a cut-out 86 through the light radiation and comprising a pair of catches 84, 85, the catches 84, 85 being connected to mating components on the top 53. The top portion also includes a pair of "wings" enclosing electrode leads 47, 48, which electrode leads 47, 48 are connected to single-use adhesive electrodes (not shown in the figures) that secure the optical sensor 36 to the patient during use. These electrode leads 47, 48 also measure electrical signals for ECG and IPG measurements. The top 53 also includes a mechanical strain relief 68 that supports the cable 34 that connects the optical sensor 36 to the central sensing/electronics module 30.

The patch sensor 10 typically measures waveforms at a relatively high frequency (e.g., 250Hz, for example). Impedance waveforms can be measured using a number of frequencies, typically from 5 KHz to 1000 KHz. In other embodiments, the bio-reactance waveform is measured using a single or multiple frequencies, which is based on the phase difference between the injected current and the measured current. As described above, both impedance and bio-reactance measurements may be measured at multiple frequencies.

An internal microprocessor running firmware processes the waveforms using computational algorithms to generate vital signs and hemodynamic parameters at a frequency of approximately once per minute. Examples of algorithms are described in the following co-pending and issued patents, the disclosures of which are incorporated herein by reference: "NECK-WORN PHYSIOLOGICAL MONITOR" U.S.S.N.14/975,646, filed 12/18/2015; "NECKLACE-SHAPED PHYSIOLOGICAL MONITOR (NECKLACE-SHAPED PHYSIOLOGICAL MONITOR)" U.S.S.N.14/184,616, filed on 21/8/2014; and "BODY-worm SENSOR FOR charaterizing PATIENTS WITH HEART FAILURE (wearable SENSOR FOR CHARACTERIZING heart FAILURE patients)" u.s.s.n.14/145,253, filed on 3/7/2014.

Referring to fig. 6A-6C, different configurations of disposable electrodes 49A-49I are shown that surround the optical sensor 36 and the acoustic sensor 45 and connect the central sensing/electronics module 30 to the patient's chest.

The patch sensor 10 shown in fig. 1-6 is designed to maximize comfort and reduce "cable clutter" when deployed on a patient, while optimizing its measured ECG, IPG, PPG, and PCG waveforms to determine physiological parameters such as HR, HRV, BP, SpO2, RR, TEMP, FLUIDS, SV, and CO. The first 38 and second 51 flexible rubber gaskets allow the sensor 10 to flex over the chest of the patient, thereby improving comfort. The central sensing/electronics module 30 positions the first pair of electrode leads 41, 42 over the heart where the bioelectric signals are typically strong, while the cable-connected optical sensor 36 positions the second pair of electrode leads 47, 48 near the shoulder where the second pair of electrodes is significantly separated from the first pair of electrodes. As described above, this configuration produces ideal ECG and IPG waveforms. The acoustic module 32 is located directly above the patient's heart and includes a plurality of acoustic sensors 45, 46 to optimize the PCG waveform and the heart sounds indicated therein. And the optical sensor is located near the shoulder, where the underlying capillary bed will typically produce a PPG waveform with a good signal-to-noise ratio, especially when the heating element of the sensor increases perfusion.

The design of this patch sensor also allows it to fit comfortably in both male and female patients. An additional benefit of its chest-worn configuration is the reduction of motion artifacts that distort the waveform and cause erroneous values of vital signs and hemodynamic parameters to be reported. This is due in part to the fact that during daily activities, the chest typically moves less than the hands and fingers, and the subsequent artifact reduction ultimately improves the accuracy of the parameters measured from the patient.

Use case

As shown in FIG. 7, in a preferred embodiment, a patch sensor 10 according to the present invention is designed to monitor a patient 12 during an in-patient stay. Typically, a patient 12 is located in a patient bed 11. As indicated above, in a typical use case, the patch sensor 10 continuously measures numerical and waveform data and then transmits this information wirelessly (as indicated by arrow 77) to the gateway 22, which gateway 22 may be a number of different devices. For example, the gateway 22 may be any device that operates a short-range wireless (e.g., bluetooth) transmitter, such as a mobile phone, tablet, vital signs monitor, central station (e.g., a nurse station in a hospital), hospital bed, "smart" television, single board computer, infusion pump, syringe pump, or simple plug-in unit. The gateway 22 wirelessly forwards (as indicated by arrow 87) information from the patch sensor 10 to the cloud-based software system 200. Typically, this is done by wireless cellular radio or radio based on the 802.11a-g protocol. Such information may be used and processed by a variety of different software systems, such as EMRs, third party software systems, or data analysis engines.

In another embodiment, the sensor collects the data, which is then stored in an internal memory. The data may then be transmitted wirelessly at a later time (e.g., to a cloud-based system, EMR, or central station). In this case, for example, the gateway 22 may include an interiorA transceiver that sequentially and automatically pairs with each sensor attached to the charging station. Once all the data collected during use is uploaded, the gateway pairs with another sensor attached to the charging station and repeats the process. This continues until data from each sensor is downloaded.

In other embodiments, the patch sensor may be used to measure ambulatory patients, patients undergoing dialysis in a hospital, clinic, or home, or patients waiting to visit a doctor in a medical clinic. Here, the patch sensor may transmit the information in real time, or it may be stored in a memory for later transmission.

Determining cuff-less blood pressure

The patch sensor determines BP by collectively processing time-dependent ECG, IPG, PPG, and PCG waveforms, as shown in fig. 6A-6E. Each waveform is typically characterized by a "pulse" caused by the heartbeat being affected in some way by the BP. More specifically, embedded firmware running on the patch sensor processes the pulses in these waveforms using a "beat" algorithm to determine a reference mark corresponding to the characteristics of each pulse; these markers are then algorithmically processed, as described below, to determine BP. In fig. 6A to 6E, reference markers for pulses within ECG, IPG, PPG and PCG waveforms are indicated by an "x" symbol.

The ECG waveform measured by the patch sensor is shown in fig. 8A. The ECG waveform includes a QRS complex caused by the heartbeat, which informally marks the beginning of each cardiac cycle. Fig. 8D shows a PCG waveform, which is measured with an acoustic module and is characterized by S1 and S2 heart sounds. Fig. 8B shows a PPG waveform, which is measured by an optical sensor and indicates the volume change of the underlying capillaries resulting from blood flow caused by the heartbeat. The IPG waveform includes DC (Z)₀) And the AC (dZ (t)) component: z₀Indicating the amount of fluid accumulation in the chest cavity by measuring the electrical impedance of the underlying layer and representing a baseline of the IPG waveform; dz (t), as shown in fig. 8C, tracks blood flow in the thoracic vasculature and represents the pulsatile component of the IPG waveform. The time-dependent derivative of dz (t) -dz (t)/dt comprises a well-defined peak indicative of the maximum blood flow rate in the thoracic vasculature. The motion waveform measured by the accelerometer is shown in fig. 8E.

Each pulse in the ECG waveform (fig. 8A) is characterized by a QRS complex that depicts a single heartbeat. A feature detection algorithm running in firmware on the patch sensor calculates the time interval between the QRS complex and the fiducial marker on each of the other waveforms. For example, the time separating the pulse "foot" from the QRS complex in the PPG waveform (fig. 8B) is referred to as PAT. PAT is associated with BP and systemic vascular resistance. During the measurement, the patch sensor calculates PAT and VTT, which is the time difference between the fiducial markers in waveforms other than ECG, such as the time difference between the S1 or S2 point in the pulse in the PCG waveform (fig. 8D) and the foot of the PPG waveform (fig. 8B). Or the time difference between the pulse peak in the dz (t)/dt waveform and the foot of the PPG waveform (fig. 8B). In general, any set of time-dependent fiducials determined from waveforms other than ECG may be used to determine VTT. PAT, VTT and other time-dependent parameters extracted from pulses in the four physiological waveforms are collectively referred to herein as "INT" values. Additionally, firmware in the patch sensor calculates information about the amplitude of the heartbeat-inducing pulses in some waveforms; these are referred to herein as "AMP" values. For example, the pulse amplitude in the derivative of the AC component of the IPG waveform ((dz (t)/dt) max) indicates volumetric expansion of the thoracic artery and positive blood flow, and is related to SYS and contractile force of the heart.

The general model for calculating SYS and DIA involves extracting a set of INT and AMP values from the four physiological waveforms measured by the patch sensor, and then processing these values using algorithms based on machine learning and artificial intelligence to determine blood pressure. For example, fig. 9A-9F show different INT and AMP values that may be associated with BP. INT values include: time to separate R and S2 from the pulse in the PCG waveform (RS2, shown in fig. 9A); time to separate R and pulse derivative bases from the AC component of the IPG waveform (RB, fig. 9B); time of foot to isolate R and pulse from PPG waveform (PAT, fig. 9D); and the time at which R and the maximum of the pulse derivative are separated from the AC component of the IPG waveform (RC, fig. 9E). AMP values include: the maximum value of the pulse derivative of the AC component from the IPG waveform ((dZ (t)/dt) max, FIG. 9C); and the maximum value (Z) of the DC component of the IPG waveform₀Fig. 9F). Any of these parameters may be used in conjunction with the calibration defined below to determine blood pressure. All these reference values can be used as input for a blood pressure model based on machine learning and artificial intelligence.

The method for determining BP according to the present invention involves first calibrating the BP measurement during a short initial period of time and then using the resulting calibration for subsequent measurements. The calibration process typically lasts about 5 days. Calibration involves taking multiple (e.g., 2 to 4) measurements of a patient using the oscillometric method using a cuff-based BP monitor while collecting INT and AMP values as shown in fig. 9A-9F. Each cuff-based measurement produces separate values for SYS, DIA, and MAP. In an embodiment, one of the cuff-based BP measurements is consistent with a "challenge event" that changes the BP of the patient, such as squeezing the handle, changing posture, or raising their leg. Challenge events typically result in variations in calibration measurements; this helps to improve the ability of the calibration to track BP fluctuations. Typically, the patch sensor and cuff-based BP monitor are in wireless communication with each other; this allows the calibration process to be fully automated, such that information between the two systems can be shared automatically without any user input. The INT and AMP values are processed, such as to generate a "BP calibration" using the method shown in fig. 9 and described in more detail below. This includes initial values for SYS and DIA, which are typically averages of multiple measurements made using a cuff-based BP monitor and a patient-specific model used in conjunction with selected INT and AMP values to determine the patient's blood pressure without sleeves. Calibration period (about 5 days), consistent with routine hospital stay; after this, the patch sensor typically needs to be recalibrated to ensure accurate BP measurement.

Alternative embodiments

The patch sensors described herein may have a form factor different than that shown in fig. 1. For example, fig. 11A shows such an alternative embodiment. As with the preferred embodiment described above, the patch sensor 210 in FIG. 11A is characterized by two main components: a central sensing/electronics module 230 worn near the center of the patient's chest, and an optical sensor 236 worn near the patient's left shoulder. The electrode leads 241, 242 measure bioelectrical signals of the ECG and IPG waveforms and secure the central sensing/electronics module 230 to the patient 12, in a manner similar to that described above. A flexible, wire-containing cable 234 connects the central sensing/electronics module 230 and the optical sensor 236. In this case, the central sensing/electronics module 230 is characterized by a substantially rectangular shape, as opposed to the substantially circular shape shown in FIG. 1. The optical sensor 236 includes two electrode leads 247, 248 that connect to the adhesive electrodes and help secure the patch sensor 210 (and in particular the optical sensor 236) to the patient 12. The distal electrode lead 248 is connected to the optical sensor by a hinged arm 245 that allows it to extend further outward near the patient's shoulder, thereby increasing its distance from the central sensing/electronics module 230. Fig. 11B shows the patch sensor 210 worn on the chest of the patient 12.

The electrode leads 241, 242, 247, 248 form two "pairs" of leads, where one of the leads 241, 247 injects current to measure the IPG waveform while the other lead 242, 248 senses the bioelectric signals, which are then processed by electronics in the central sensing/electronics module 230 to determine the ECG and IPG waveforms. The IPG waveform measured by the patch sensor can be measured at multiple frequencies and defined by the impedance magnitude and phase angle, both of which vary over time and can be measured using injection currents of different frequencies. For example, fig. 12 shows the resistance (representing the impedance magnitude) and the reactance (representing the impedance phase angle) measured at different frequencies. In general, the time-dependent reactance waveforms yield more accurate SV and CO values than the conventional IPG waveforms. At low frequencies, the injected current measured from the IPG cannot penetrate the cells it encounters due to the capacitance of the cell wall, thus sampling primarily the extracellular fluid; for this reason, it may be desirable to perform low frequency measurements to characterize parameters such as extracellular fluid. At high frequencies, the injected current is measured from the IPG across the cell wall, thus sampling both intracellular and extracellular fluids. The patch sensor described herein may include IPG, resistance and/or reactance measurements made at one or more frequencies.

The acoustic module 232 includes one or more solid-state acoustic microphones (not shown in the figures, but similar to that shown in fig. 1) that measure heart sounds from the patient 12. The optical sensor 236 is attached to the central sensing/electronics module 30 by a flexible cable 234 and features an optical system (also not shown, but similar to that shown in fig. 1) that includes an array of photodetectors arranged in a circular pattern around LEDs that emit radiation in the red and infrared spectral regions. During the measurement, red and infrared radiation, which is emitted sequentially from the LEDs, illuminates underlying tissue of the patient's chest and reflects off and is detected by the photodetector array.

In other embodiments, the amplitude of the first or second (or both) heart sounds is used to predict blood pressure. Blood pressure generally rises in a linear fashion with the amplitude of heart sounds. In an embodiment, a general calibration describing such a linear relationship may be used to convert heart sound amplitude to blood pressure values. For example, such calibration may be determined from data collected in clinical trials conducted on a large number of subjects. Here, numerical coefficients describing the relationship between blood pressure and heart sound amplitude are determined from fitting data determined during the experiment. These coefficients and linear algorithms are encoded into the sensor for use during actual measurements. Alternatively, the patient specific calibration may be determined by measuring a reference blood pressure value and a corresponding heart sound amplitude during a calibration measurement prior to the actual measurement. The data from the calibration measurements may then be fitted as described above to determine a patient specific calibration, which is then used to convert the heart sounds to blood pressure values.

In an embodiment, IPG and PCG sensors may be used in the patch to detect respiratory conditions. For example, in a study conducted using a patch, N-11 subjects (9M, 2F) experienced: 1) normal breathing (between initial and all respiratory events); 2) cough (5 times; 2 events); 3) wheezing (5 times; 2 events); and 4) apnea (1 event). Subjects were measured using a patch that was attached to the chest of each subject to collect the following time-dependent waveforms: 1) electrocardiogram (ECG); 2) photoplethysmography (PPG); 3) impedance Plethysmogram (IPG); 4) an accelerometer signal (ACC); and 5) acoustic Phonocardiograms (PCGs). For such analysis, the PCG waveform is processed to determine a "Shannon envelope map (Shannon envelope)" which simplifies the analysis by rendering an envelope that substantially represents the underlying high frequency signal. During the three minute measurement period, each subject experienced the 4 respiratory events listed above (normal breathing occurred for the first 60 seconds; followed by respiratory events, as shown by the dashed line in FIG. 13), while the patch measured a time-dependent waveform. Figure 13 shows sample waveforms collected from a single subject participating in a study. After measurement, each waveform was analyzed by a subject problem specialist and ranked according to its ability to accurately characterize different respiratory events, with a "0" level indicating no ability and a "3" level indicating excellent ability. This is an informal analysis that is then performed in a more rigorous manner (e.g., an analysis that includes a ranking of both true positive/negative and false positive/negative). These results are summarized below:

optimal waveform to characterize normal breathing: IPG

Optimal waveform for characterizing apnea: IPG

The best waveform to characterize a cough: IPG, ACC, PPG, PCG

Optimal waveform to characterize wheezing: IPG, ACC, PPG

The above results indicate that the IPG waveform of the patch is well suited to characterize common respiratory events such as normal breathing, coughing, wheezing and apnea. A novel impedance sensor measures this waveform. The impedance sensor features an impedance measurement circuit that injects a high frequency (100kHz), low amperage (-4 mA) current into the patient's chest. Respiratory events change the airflow within the chest and thus its impedance, allowing the impedance measurement circuit and associated embedded code to easily detect them, as shown in fig. 13.

As a subsequent experiment, as shown in fig. 13, a single subject undergoing the above respiratory events was measured simultaneously using an impedance sensor placed on the chest (for IPG waveforms) and an optical sensor placed on the wrist (for PPG waveforms). This allows direct comparison of the patch measurements with measurements made using a conventional wrist-worn activity/heart rate monitor. The resulting waveforms are shown in fig. 13, where the dotted color lines represent coughing, wheezing and apneas as described above, and the dotted gray lines represent normal breathing.

Both IPG and PPG waveforms clearly show heartbeat-induced pulses. Processing pulses in the IPG waveform results in heart rate, stroke volume and cardiac output, while processing them in the PPG waveform results in heart rate and pulse oximetry. However, as described above, the chest-only measured IPG waveform shows a clear amplitude modulation due to normal breathing, coughing, wheezing and apnea; the PPG waveform measured by the wrist does not have any significant features to indicate these respiratory events. The data indicate that chest-worn IPG sensors are superior to wrist-worn PPG sensors in detecting respiratory events.

Time and frequency domain analysis of the IPG and PCG waveforms collected during coughing and wheezing indicate that the two respiratory events have different "breathing patterns," meaning that the sensor may be able to divide between them using conventional signal processing techniques. For example, fig. 14 shows time and frequency domain plots of IPG and PCG waveforms measured at cough (top left and top right, respectively) and wheeze (bottom left and bottom right), respectively, of a single subject. The PCG waveform appears to be particularly sensitive to different respiratory events. Cough is characterized by the appearance of short, time-dependent "bursts" in the waveform, characterized by relatively high frequency components; in contrast, wheezing is characterized by a more elongated profile consisting of relatively low frequency components. Based on these preliminary results, IPG and PCG waveforms processed using standard signal processing techniques (either alone or in combination with more complex machine learning algorithms) appear to be able to classify different respiratory events.

Both the first heart sound and the second heart sound are typically composed of sets or "packets" of audio. Thus, heart sounds are typically characterized by a number of closely packed oscillations within a data packet, when measured in the time domain. This complicates measuring the heart sound amplitude because there are no well-defined peaks. To better characterize the amplitude, an envelope may be drawn around the heart sounds using signal processing techniques, and then the amplitude of the envelope measured. One well-known technique involves the use of a shannon energy envelope map (e (t)), where each data point in e (t) is calculated as follows:

where N is the window size of E (t). In embodiments, other techniques for determining the heart sound envelope may also be used.

Once the envelope is calculated, its magnitude can be determined using standard techniques, such as taking the time dependent derivative and evaluating the zero crossings. Typically, the amplitude is converted to normalized amplitude by dividing the amplitude by an initial amplitude value measured from an earlier heart sound (e.g., the heart sound measured during calibration) before calculating the blood pressure using the amplitude. The normalized amplitude represents the relative change in amplitude that is used to calculate the blood pressure; this will generally make the measurement more accurate.

In other embodiments, an external device may be used to determine the degree of coupling of the acoustic sensor to the patient. For example, such an external device may be a piezoelectric "buzzer" or similar device that generates acoustic sounds and is incorporated into the patch-based sensor, proximate to the acoustic sensor. Prior to the measurement, the buzzer produces an acoustic sound at a known amplitude and frequency. The acoustic sensor measures sound and then compares its amplitude (or frequency) to other historical measurements to determine the degree of coupling of the acoustic sensor to the patient. For example, a relatively low amplitude indicates poor sensor coupling. Such a scenario may result in an alarm alerting the user that the sensor should be reapplied.

In other alternative embodiments, the present invention may use a variation of the algorithm to find INT and AMP values, and then process these values to determine BP and other physiological parameters. For example, to improve the signal-to-noise ratio of pulses within IPG, PCG, and PPG waveforms, embedded firmware running on the patch sensor may run a signal processing technique known as "beatstacking. For example, by beatstacking, an average pulse (e.g., z (t)) is calculated from a number (e.g., seven) of consecutive pulses from the IPG waveform, which are described by analysis of the corresponding QRS complex in the ECG waveform, and then averaged together. Then, the derivative of Z (t) — dZ (t)/dt, is calculated over seven sample windows. The maximum value of Z (t) is calculated and used as [ dZ (t)/dt]_maxThe boundary points of the locations. This parameter is used as described above. Generally, beatstacking can be used to determine the signal-to-noise ratio for any INT/AMP value described above.

In other embodiments, the BP calibration procedure indicated by the flow chart shown in fig. 9 may be modified. For example, more than two INT/AMP values may be selected for the multi-parameter linear fitting process. And less or more than four cuff-based BP measurements may be used to calculate BP calibration data. In yet other embodiments, a non-linear model (e.g., a model using a polynomial or exponential function) may be used to fit the calibration data.

In yet other embodiments, a sensitive accelerometer may be used instead of an acoustic sensor to measure small-scale jarring movements of the chest driven by the patient's underlying beating heart. Such waveforms are known as cardiograms (SCGs), and may be used in place of, or in addition to, PCG waveforms.

While the invention has been described and illustrated in sufficient detail for those skilled in the art to make and use it, various alternatives, modifications, and improvements should become apparent without departing from the spirit and scope of the invention. The examples provided herein are representative of preferred embodiments, are illustrative, and are not intended to limit the scope of the invention. Modifications thereof and other uses will occur to those skilled in the art. Such modifications are intended to be included within the spirit of the invention and defined by the scope of the appended claims.

It will be apparent to those skilled in the art that various substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention.

All patent applications, patents, publications, and other references mentioned in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains, and are each incorporated herein by reference. The references cited herein are not admitted to be prior art to the claimed invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.

The use of the articles "a," "an," and "the" in the specification and claims is to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising …", "having …", "being …" (e.g., "is a chemical formula"), "including …", and "containing …" are to be construed as open-ended terms (i.e., meaning "including, but not limited to …") unless otherwise noted. In addition, whenever "comprising …" or another open term is used in an embodiment, it is understood that the same embodiment may be claimed in a narrower sense using the intermediate term "consisting essentially of … …" or the closed term "consisting of … …".

The terms "about," "approximately," or "approximately," when used in conjunction with a numerical value, are meant to encompass a collection or range of values. For example, "about X" includes a range of values of X ± 20%, ± 10%, ± 5%, ± 2%, ± 1%, ± 0.5%, ± 0.2% or ± 0.1%, wherein X is a numerical value. In one embodiment, the term "about" refers to a range of values that is 10% more or less than the specified value. In another embodiment, the term "about" refers to a range of values that is 5% more or less than the specified value. In another embodiment, the term "about" refers to a range of values that is 1% more or less than the specified value.

Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. Unless otherwise indicated, ranges used herein include both limits of the range. For example, the terms "between X and Y" and "range from X to Y" include X and Y and integers therebetween. On the other hand, when a series of individual values is referred to in this disclosure, any range including any one of the two individual values as both endpoints is also contemplated in this disclosure. For example, the expression "a dose of about 100mg, 200mg or 400 mg" may also mean "a dose range of 100 to 200 mg", "a dose range of 200 to 400 mg" or "a dose range of 100 to 400 mg".

The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein, any one of the terms "comprising …," "consisting essentially of …," and "consisting of …" can be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.