阅读说明：本技术 生物流体分离装置 (Biological fluid separation device ) 是由 李鹏 S·温策尔 于 2019-06-06 设计创作，主要内容包括：公开了一种血液分离装置,该血液分离装置将血液收集过程与血浆分离过程分开并分离。血液分离装置包括样本收集模块、激活模块和分离模块。因为在血液分离装置与患者断开连接之后发生血浆分离,所以该装置的性能不再受患者血压和针规的影响,并且极大地减轻了患者的不适。(A blood separation device is disclosed that separates and separates a blood collection process from a plasma separation process. The blood separation device includes a sample collection module, an activation module, and a separation module. Because plasma separation occurs after the blood separation device is disconnected from the patient, the performance of the device is no longer affected by the patient's blood pressure and needle gauge, and the patient's discomfort is greatly reduced.)

1. A blood separation device adapted to receive a blood sample having a first phase and a second phase, the blood separation device comprising:

a sample collection module having a housing defining a collection chamber;

an activation module connected to the sample collection module, the activation module having a first seal and a second seal for sealing the housing, the first seal transitionable by actuation of a portion of the activation module from a closed position in which the collection chamber has a first pressure to an open position in which the collection chamber is in fluid communication with a second pressure greater than the first pressure; and

a separation module in fluid communication with the collection chamber of the sample collection module, the separation module defining a first chamber having a first volume and a second chamber having a second volume, and including a separation member disposed between the first chamber and the second chamber, wherein the first volume and the second volume are different.

2. The blood separation apparatus of claim 1, wherein the activation module comprises a switch, wherein actuation of the switch transitions the first seal to the open position.

3. The blood separation device of claim 2, wherein the switch includes a button defining a vent therethrough and a piercing portion, wherein actuation of the switch moves the piercing portion to break the first seal to transition the first seal to the open position.

4. The blood separation device of claim 3, wherein with the first seal in the open position, the collection chamber of the sample collection module is in fluid communication with the second pressure via a vent of the switch.

5. The blood separation apparatus of claim 2, wherein the second seal comprises a cap having a pierceable self-sealing plug within a portion of the cap.

6. The blood separation device of claim 5 wherein the blood separation device is connectable to a blood collection device via the cap.

7. The blood separation device of claim 6, wherein the activation module defines an inlet channel, and wherein the collection chamber receives the blood sample via the inlet channel with the blood collection device connected to the blood separation device via the cap.

8. The blood separation device of claim 7, wherein the collection chamber includes an inlet end and an outlet end and defines a plurality of sequential flow direction alternating collection channels.

9. The blood separation device of claim 7, wherein the collection chamber includes an inlet end and an outlet end and defines: a first collection channel extending from the inlet end to the outlet end; a second collection channel in communication with a portion of the first collection channel and extending from the outlet end to the inlet end; and a third collection channel in communication with a portion of the second collection channel and extending from the inlet end to the outlet end.

10. The blood separation device of claim 8, wherein the inlet end of the collection channel is in fluid communication with the inlet channel of the activation module.

11. The blood separation device of claim 9, wherein the blood sample travels through the first collection channel in a first direction, the blood sample travels through the second collection channel in a second direction opposite the first direction, and the blood sample travels through the third collection channel in a third direction opposite the second direction.

12. The blood separation device of claim 9, wherein the first collection channel is spaced apart from the second collection channel, and the second collection channel is spaced apart from the third collection channel.

13. The blood separation device of claim 10, wherein the first chamber comprises a first chamber inlet and a first chamber outlet, and the second chamber comprises a second chamber outlet.

14. The blood separation device of claim 13, wherein the first chamber inlet is in fluid communication with the outlet end of the collection channel.

15. The blood separation device of claim 13, wherein a first pressure differential between the second pressure defined by atmospheric pressure and the first pressure defined within the collection chamber draws the blood sample into the first chamber with the first seal in the open position.

16. The blood separation device of claim 15, wherein the first volume and the second volume are different with the first seal in the open position, thereby providing a second pressure differential between the first chamber and the second chamber to drive a second phase of the blood sample through the separation member into the second chamber.

17. The blood separation device of claim 16, wherein the separation member captures the first phase in the first chamber and allows the second phase to pass through the separation member into the second chamber.

18. The blood separation device of claim 16 further comprising a second phase collection container in communication with the second chamber outlet, wherein the second phase collection container receives the second phase.

19. The blood separation device of claim 16 further comprising a blood sample discard chamber in communication with the first chamber outlet, wherein the blood sample discard chamber receives the first phase.

20. The blood separation device of claim 16, wherein the separation member comprises a track etched membrane.

21. The blood separation device of claim 18, wherein the collection chamber receives the blood sample via the inlet channel with the blood collection device connected to the blood separation device via the cap.

22. The blood separation device of claim 21, wherein a first pressure differential between the second pressure defined by atmospheric pressure and the first pressure defined within the collection chamber draws the blood sample into the first chamber when the blood collection device is disconnected from the blood separation device and the switch is actuated to transition the first seal to the open position.

23. The blood separation device of claim 22, wherein the first volume and the second volume are different with the first seal in the open position, thereby providing the second pressure differential between the first chamber and the second chamber to drive the second phase of the blood sample through the separation member into the second chamber.

24. The blood separation device of claim 23, wherein the second phase collection container is removable from the blood separation device with the second phase contained within the second phase collection container.

25. The blood separation device of claim 24, wherein the first phase is a cellular fraction and the second phase is a plasma fraction.

1. Field of the invention

The present disclosure relates generally to devices suitable for use with biological fluids. More particularly, the present disclosure relates to devices suitable for separating components of biological fluids.

2. Background of the invention

Blood collection is a common health care procedure involving the withdrawal of at least one drop of blood from a patient. Blood samples are typically collected from hospitalized, home care and emergency room patients by finger prick, heel prick or venipuncture. Blood samples may also be taken from the patient through venous or arterial lines. Once collected, the blood sample can be analyzed for medically useful information including, for example, chemical composition, blood disease, or coagulation.

Blood tests determine the physiological and biochemical state of a patient, such as disease, mineral content, drug availability, and organ function. Blood tests may be performed in a clinical laboratory or at a point of care in the vicinity of the patient. One example of a point-of-care blood test is a conventional test of a patient's blood glucose level, which involves drawing blood via a finger prick and mechanically collecting the blood into a diagnostic cartridge. The diagnostic cartridge then analyzes the blood sample and provides the clinician with a reading of the patient's blood glucose level. Other means of analyzing blood gas electrolyte levels, lithium levels, and calcium ion levels are also available. Some other point-of-care devices identify markers of Acute Coronary Syndrome (ACS) and deep vein thrombosis/pulmonary embolism (DVT/PE).

The blood sample comprises whole blood or a cellular fraction and a plasma fraction. Plasma separation from whole blood has traditionally been achieved by centrifugation, which typically takes 15 to 20 minutes and involves heavy labor or complex work flows. Recently, other techniques for separating plasma have been used or attempted, such as sedimentation, fibrous or non-fibrous membrane filtration, sidestream separation, microfluidic cross-flow filtration, and other microfluidic hydrodynamic separation techniques. However, many of these techniques have various challenges including poor plasma purity, analyte bias (analyte bias) or the need for specific coatings to prevent analyte bias, high hemolysis, the need for dilution, long separation times, and/or difficulty in recovering plasma. For example, most membrane-based separation techniques suffer from analyte bias and often require specific coating treatments for the target analyte. In addition, conventional detachment techniques that occur when the device is directly attached to the patient through a needle can cause patient discomfort.

Background

Disclosure of Invention

The present disclosure provides a blood separation device that separates and isolates a blood collection process from a plasma separation process. The blood separation device includes a sample collection module, an activation module, and a separation module. Because the plasma separation is performed after the blood separation device is disconnected from the patient, the performance of the device is no longer affected by the patient's blood pressure and needle gauge, and the patient's discomfort is greatly reduced.

The present disclosure provides a blood separation device and a separation method that is fully compatible with venous blood collection workflow without centrifugation and power. Advantageously, the blood separation device of the present disclosure allows for immediate separation of plasma during clinical blood draw, and enables collection of the separated plasma sample in a separate plasma container for downstream diagnostics.

Furthermore, the blood separation device of the present disclosure provides a separation device that requires only a short patient body collection time, as compared to conventional blood collection devices that use vacuum tubes (such as BD, which is commercially available from Becton, Dickinson and Company, inc.)A blood collection tube and a corresponding venous access kit) has no difference. In addition, because the plasma separation is performed after the device is disconnected from the patient, the performance of the device is no longer affected by the patient's blood pressure and needle gauge, and the patient's discomfort is greatly reduced.

Because the blood separation device of the present disclosure separates and separates the blood collection process from the plasma separation process, the volume of plasma generated is no longer limited by the time that the patient's body can allow to collect blood. This enables the blood separation device of the present disclosure to potentially be used in other high volume plasma applications outside of the point of care.

Furthermore, another benefit of separating the separation from the collection process is that separation time, plasma quality and yield are no longer affected by the needle gauge and the patient's blood pressure. If the separation is performed while the device is directly connected to the patient through a needle, a lower needle gauge and higher patient blood pressure will decrease the separation time, decrease the amount of yield and increase hemolysis, while a higher needle gauge and lower patient blood pressure will increase the separation time, increase the yield and decrease hemolysis. By isolating the plasma separation process from the blood collection workflow using the blood separation device of the present disclosure, the blood collection kit and the patient's blood pressure will only affect the blood collection time without changing the separation time, yield and hemolysis level.

According to an embodiment of the present invention, a blood separation device adapted to receive a blood sample having a first phase and a second phase comprises: a sample collection module having a housing defining a collection chamber; an activation module connected to the sample collection module, the activation module having a first seal and a second seal for sealing the housing, the first seal transitionable by actuation of a portion of the activation module from a closed position in which the collection chamber has a first pressure to an open position in which the collection chamber is in fluid communication with a second pressure greater than the first pressure; and a separation module in fluid communication with the collection chamber of the sample collection module, the separation module defining a first chamber having a first volume and a second chamber having a second volume, and including a separation member disposed between the first chamber and the second chamber, wherein the first volume and the second volume are different.

In one configuration, the activation module includes a switch, wherein actuation of the switch transitions the first seal to the open position. In one configuration, the switch includes a button defining a vent therethrough and a piercing portion, wherein actuation of the switch moves the piercing portion to break the first seal, thereby transitioning the first seal to the open position. In yet another configuration, with the first seal in the open position, the collection chamber of the sample collection module is in fluid communication with the second pressure via a vent of the switch. In one configuration, the second seal comprises a cap having a pierceable self-sealing plug within a portion of the cap. In another configuration, the blood separation device can be connected to a blood collection device via the cap. In yet another configuration, the activation module defines an inlet channel, and wherein the collection chamber receives the blood sample via the inlet channel with the blood collection device connected to the blood separation device via the cap. In one configuration, the collection chamber includes an inlet end and an outlet end and defines a plurality of sequential flow direction alternating collection channels. In another configuration, the collection chamber includes an inlet end and an outlet end, and defines: a first collection channel extending from the inlet end to the outlet end; a second collection channel in communication with a portion of the first collection channel and extending from the outlet end to the inlet end; and a third collection channel in communication with a portion of the second collection channel and extending from the inlet end to the outlet end. In yet another configuration, the inlet end of the collection channel is in fluid communication with the inlet channel of the activation module. In one configuration, the blood sample travels through the first collection channel in a first direction, the blood sample travels through the second collection channel in a second direction opposite the first direction, and the blood sample travels through the third collection channel in a third direction opposite the second direction. In another configuration, the first collection channel is spaced apart from the second collection channel, which is spaced apart from the third collection channel. In yet another configuration, the first chamber includes a first chamber inlet and a first chamber outlet, and the second chamber includes a second chamber outlet. In one configuration, the first chamber inlet is in fluid communication with the outlet end of the collection channel. In another configuration, a first pressure differential between the second pressure defined by atmospheric pressure and the first pressure defined within the collection chamber draws the blood sample into the first chamber with the first seal in the open position. In yet another configuration, with the first seal in the open position, the first volume and the second volume are different, thereby providing a second pressure differential between the first chamber and the second chamber to drive a second phase of the blood sample through the separation member into the second chamber. In one configuration, the separation member captures the first phase in the first chamber and allows the second phase to pass through the separation member into the second chamber. In another configuration, the blood separation device includes a second phase collection container in communication with the second chamber outlet, wherein the second phase collection container receives the second phase. In yet another configuration, the blood separation device includes a blood sample discard chamber in communication with the first chamber outlet, wherein the blood sample discard chamber receives the first phase. In one configuration, the separating member comprises a track etch film. In yet another configuration, the collection chamber receives the blood sample via the inlet channel with the blood collection device connected to the blood separation device via the cap. In yet another configuration, with the blood collection device disconnected from the blood separation device, and wherein the first pressure differential between the second pressure defined by atmospheric pressure and the first pressure defined within the collection chamber draws the blood sample into the first chamber upon actuation of the switch to transition the first seal to the open position. In yet another configuration, with the first seal in the open position, the first volume and the second volume are different, thereby providing a second pressure differential between the first chamber and the second chamber to drive a second phase of the blood sample through the separation member into the second chamber. In another configuration, the second phase collection container is removable from the blood separation device with the second phase contained within the second phase collection container. In yet another configuration, the first phase is a cellular fraction and the second phase is a plasma fraction.

Drawings

The above-mentioned and other features and advantages of this disclosure, and the manner of attaining them, will become more apparent and the disclosure itself will be better understood by reference to the following description of embodiments of the disclosure taken in conjunction with the accompanying drawings, wherein:

fig. 1 is a perspective view of a blood separation device according to an embodiment of the present invention.

Fig. 2 is an exploded perspective view of a blood separation device according to an embodiment of the present invention.

Fig. 3 is a perspective view of a first step in using the system of the present disclosure, according to an embodiment of the present invention.

Fig. 4 is a perspective view of a second step of using the system of the present disclosure, according to an embodiment of the present invention.

Fig. 5 is a perspective view of a third step of using the system of the present disclosure, showing the device of the present disclosure separating plasma independent of device orientation, according to an embodiment of the present invention.

Fig. 6 is a perspective view of a fourth step using the system of the present disclosure, according to an embodiment of the present invention.

Fig. 7A is a perspective view of an activation module of a blood separation device in a closed position according to an embodiment of the present invention.

Fig. 7B is a cross-sectional view of the activation module of fig. 7A, in accordance with an embodiment of the present invention.

Fig. 8A is a perspective view of an activation module of a blood separation device in an open position according to an embodiment of the present invention.

Fig. 8B is a cross-sectional view of the activation module of fig. 8A, in accordance with an embodiment of the present invention.

FIG. 9 is a perspective view of a collection chamber of a blood separation device according to an embodiment of the present invention.

FIG. 10 is a perspective view of a collection chamber of a blood separation device according to another embodiment of the present invention.

FIG. 11 is a perspective view of a blood separation device according to an embodiment of the present invention.

Fig. 12 is a perspective view of a portion of a separation module of a blood separation device according to an embodiment of the present invention.

Fig. 13 is a perspective view of a blood separation device according to an embodiment of the present invention.

Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the disclosure, and such exemplifications are not to be construed as limiting the scope of the disclosure in any manner.

Detailed Description

The following description is presented to enable any person skilled in the art to make and use the embodiments, which are intended to be used to practice the invention. Various modifications, equivalents, changes, and substitutions will now occur to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the present invention.

For purposes of the following description, the terms "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," "lateral," "longitudinal," and derivatives thereof shall relate to the invention as oriented in the drawing figures. It is to be understood, however, that the invention may assume alternative variations and step sequences, except where expressly specified to the contrary. It is also to be understood that the specific devices and processes illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered as limiting.

Fig. 1 and 2 illustrate an exemplary embodiment of a blood separation device of the present disclosure. Referring to fig. 1 and 2, a blood separation device 10 of the present disclosure is adapted to receive a biological fluid, such as a blood sample 12 (fig. 3-6) having a first phase 14 and a second phase 16. The first phase 14 of the blood sample 12 is a cellular fraction and the second phase 16 of the blood sample 12 is a plasma fraction.

The blood separation device 10 of the present disclosure separates and separates the blood collection process from the plasma separation process. Because the plasma separation is performed after the blood separation device 10 is disconnected from the patient, the performance of the device is no longer affected by the patient's blood pressure and needle gauge, and the patient's discomfort is greatly reduced.

Because the blood separation device 10 of the present disclosure separates and separates the blood collection process from the plasma separation process, the volume of plasma generated is no longer limited by the allowable time for the patient's body to collect blood. This enables the blood separation device 10 of the present disclosure to potentially be used in other high volume plasma applications outside of the point of care.

The present disclosure provides a blood separation device 10 and a separation method that is fully compatible with venous blood collection workflow without centrifugation and power. Advantageously, the blood separation device 10 of the present disclosure allows for immediate separation of plasma during clinical blood draw with the device 10 off the patient, and enables collection of the separated plasma 16 sample in a separate plasma container (e.g., a second phase or plasma collection container 80) for downstream diagnostics.

Moreover, the blood separation device 10 of the present disclosure provides a separation device that requires only a short patient body collection time, as compared to conventional blood collection devices that use vacuum tubes (such as BD, which is commercially available from Becton, Dickinson and Company, inc.)A blood collection tube and a corresponding venous access kit) has no difference. In addition, because the plasma separation is performed after the device 10 is disconnected from the patient, the performance of the device is no longer affected by the patient's blood pressure and needle gauge, and the patient's discomfort is greatly reduced.

Furthermore, another benefit of separating the plasma separation process from the collection process is that separation time, plasma quality and yield are no longer affected by the needle gauge and the patient's blood pressure. If the plasma separation process occurs while the device is directly connected to the patient through the needle, a lower needle gauge and higher patient blood pressure will decrease the separation time, decrease the amount of yield and increase hemolysis, while a higher needle gauge and lower patient blood pressure will increase the separation time, increase the yield and decrease hemolysis. By isolating the plasma separation process from the blood collection process using the blood separation device 10 of the present disclosure, the blood collection set and the patient's blood pressure will only affect the blood collection time without changing the separation time, yield, and hemolysis level.

Referring to fig. 1-13, in an exemplary embodiment, blood separation device 10 generally includes a sample collection module 20, an activation module 22, and a separation module 24. In one embodiment, after the blood sample 12 is collected, the blood separation device 10 is capable of separating the second phase 16 of the blood sample 12 from the first phase 14 of the blood sample 12, as described in more detail below. Advantageously, the blood separation device 10 separates and separates the blood collection process from the plasma separation process. In one embodiment, a portion that is removable from the blood separation device 10 (e.g., the second phase collection container 80) can transfer the second phase 16 of the blood sample 12 to the point-of-care testing device after plasma separation.

Referring to fig. 1-6 and 9-11, in an exemplary embodiment, the sample collection module 20 includes a housing 30 defining a collection chamber 32. In one embodiment, the collection chamber 32 includes an inlet end or port 34 and an outlet end or port 36 and defines a plurality of sequential flow direction alternating collection channels 38.

The collection chamber 32 utilizes a plurality of interconnected parallel channels 38 to maximize collection and storage space within the constrained diameter of the blood collection set, and also to ensure that capillary forces dominate over gravity during filling. As shown in fig. 9-11, the blood sample 12 fills the interconnecting channel 38 of the sample collection module 20 in a reciprocating motion.

For example, referring to fig. 9, in a first exemplary embodiment, the collection chamber 32 of the sample collection module 20 defines: a first collection channel 40 extending from inlet end 34 to outlet end 36; a second collecting channel 42 communicating with a portion of first collecting channel 40 and extending from outlet end 36 to inlet end 34; and a third collection channel 44 in communication with a portion of second collection channel 42 and extending from inlet end 34 to outlet end 36. Referring to fig. 9, the first collection channel 40 is spaced from the second collection channel 42, which is spaced from the third collection channel 44.

In this manner, referring to the arrows in fig. 9 indicating the flow path 100 of the blood sample 12 through the channel 38 of the collection chamber 32, the blood sample 12 collected into the collection chamber 32 travels in a first direction through the first collection channel 40, the blood sample 12 travels in a second direction opposite the first direction through the second collection channel 42, and the blood sample 12 travels in a third direction opposite the second direction through the third collection channel 44. Referring to fig. 9, collection chamber 32 utilizes a plurality of interconnected parallel channels 38 to maximize collection and storage space within the constrained diameter of the blood collection set, and also to ensure that capillary forces dominate over gravity during filling.

In one embodiment, the inlet into collection chamber 32 is inlet 34 of first collection channel 40, and the outlet from collection chamber 32 is outlet 36 of third collection channel 44. The inlet 34 of the first collection channel 40 is in fluid communication with an inlet channel 66 (fig. 7B and 8B) of the activation module 22, as described in more detail below.

Referring to fig. 10, in a second exemplary embodiment, the collection chamber 32 of the sample collection module 20 defines: a first collection channel 40 extending from inlet end 34 to outlet end 36; a second collecting channel 42 communicating with a portion of first collecting channel 40 and extending from outlet end 36 to inlet end 34; a third collecting channel 44 communicating with a portion of the second collecting channel 42 and extending from the inlet end 34 to the outlet end 36; a fourth collecting channel 46 communicating with a portion of third collecting channel 44 and extending from outlet end 36 to inlet end 34; and a fifth collecting channel 48 communicating with a portion of fourth collecting channel 46 and extending from inlet end 34 to outlet end 36. Referring to fig. 10, the first collection channel 40 is spaced from a second collection channel 42, which is spaced from a third collection channel 44, which is spaced from a fourth collection channel 46, which is spaced from a fifth collection channel 48.

In this manner, the blood sample 12 collected in the collection chamber 32 travels in a first direction through the first collection channel 40, the blood sample 12 travels in a second direction opposite the first direction through the second collection channel 42, the blood sample 12 travels in a third direction opposite the second direction through the third collection channel 44, the blood sample 12 travels in a fourth direction opposite the third direction through the fourth collection channel 46, and the blood sample 12 travels in a fifth direction opposite the fourth direction through the fifth collection channel 48. Referring to fig. 10, collection chamber 32 utilizes a plurality of interconnected parallel channels 38 to maximize collection and storage space within the constrained diameter of the blood collection set, and also to ensure that capillary forces dominate over gravity during filling.

In one embodiment, the inlet into the collection chamber 32 is the inlet 34 of the first collection channel 40, and the outlet from the collection chamber 32 is the outlet 36 of the fifth collection channel 48. The inlet 34 of the first collection channel 40 is in fluid communication with an inlet channel 66 (fig. 7B and 8B) of the activation module 22, as described in more detail below.

In other exemplary embodiments, the collection chambers 32 of the sample collection module 20 may define any odd number of channels 38 based on the particular volume requirements. Importantly, the collection chamber 32 of the sample collection module 20 utilizes a plurality of interconnected parallel channels 38 to maximize collection and storage space within the constrained diameter of the blood collection set, and also to ensure that capillary forces dominate over gravity during filling. As described above, the blood sample 12 fills the interconnecting channel 38 of the sample collection module 20 in a reciprocating motion.

In one exemplary embodiment, as shown in fig. 9 and 10, the plurality of sequential flow direction alternating collection channels 38 are configured in a parallel configuration. In other exemplary embodiments, the collection channel 38 is configured in a spiral or serpentine channel configuration, or other configuration that maximizes collection and storage space within the constrained diameter of the blood collection set and also ensures that capillary forces dominate over gravity during filling.

In an exemplary embodiment, the collection chamber 32 is designed to ensure that the blood 12 continuously fills the channel 38 of the collection chamber 32 without trapping air bubbles regardless of the device orientation and blood flow rate. This is accomplished by controlling the diameter of the passage 38 for the desired application. For example, in the exemplary embodiment, to prevent blood flow disruption (breaking up) and trapping bubbles, the diameter of the channel 38 needs to satisfy both requirements. First, the static pressure difference at the flow front at any orientation must be less than the laplace pressure in order for the meniscus to maintain its shape. Second, the diameter chosen is needed to ensure that the inertial force is less than the surface tension at the highest flow rate.

Referring to fig. 1, 2, and 7A-8B, in an exemplary embodiment, activation module 22 is connected or connectable to sample collection module 20 and includes a housing 49, a first seal 50, and a second seal 52 for sealing blood separation device 10, such as housing 30 of sample collection module 20, housing 49 of activation module 22, and housing 68 of separation module 24. In this manner, the seals 50, 52 of the activation module 22 control the pressure within the blood separation device 10, as described in more detail below. The first seal 50 may be transitioned from a closed position (fig. 7A and 7B), in which the collection chamber 32 has a first pressure P1 (fig. 13), to an open position (fig. 8A and 8B), in which the collection chamber 32 is in fluid communication with a second pressure P2 (fig. 13) that is greater than the first pressure P1, by actuating a portion of the activation module 22.

In an exemplary embodiment, referring to fig. 7A-8B, the activation module 22 includes a switch 54. In such embodiments, actuation of the switch 54 transitions the first seal 50 from the closed position (fig. 7A and 7B) to the open position (fig. 8A and 8B). Referring to fig. 7A-8B, the switch 54 includes a button 56 defining a vent 58 therethrough and a piercing portion 60. In this manner, actuation of the switch (e.g., depressing or pushing the button 56 into the position shown in fig. 8A and 8B) moves the piercing portion 60 to break the first seal 50, thereby transitioning the first seal 50 to the open position.

With the first seal 50 in the open position, the collection chamber 32 of the sample collection module 20 is in fluid communication with the second pressure P2 via the vent 58 of the switch 54. The vent 58 provides a venting mechanism for the blood separation device 10. For example, in one embodiment, the piercing portion 60 breaks the first seal 50 (e.g., an aluminum foil seal) to form a vent to power the plasma separation process.

The second pressure P2, defined by atmospheric pressure, is greater than the first pressure P1 defined within the blood separation device 10 (e.g., the collection chamber 32 of the sample collection module 20). In this manner, the pressure differential between the second pressure P2, defined by atmospheric pressure, and the residual vacuum in the blood separation device 10 (i.e., the first pressure P1 defined within the blood separation device 10) continuously drives the plasma separation process, as described in more detail below. Advantageously, using the activation module 22 of the present disclosure, a user can precisely control when a plasma separation process begins.

In an exemplary embodiment, referring to fig. 7A-8B, the second seal 52 of the activation module 22 includes a cap 62 having a pierceable self-sealing plug 64 within a portion of the cap 62. The cap 62 provides a mechanism that allows the blood separation device 10 to be connectable to a blood collection device 200 (fig. 3), as described in more detail below.

In one exemplary embodiment, the cap 62 of the present disclosure may be formed to be substantially similar to the Closure described in U.S. provisional application 62/666,765 entitled "close for a Biological Fluid Collection Device," filed on 4.5.2018, the entire disclosure of which is expressly incorporated herein by reference.

Referring to fig. 7A-8B, in one embodiment, activation module 22 defines an inlet passage 66. Referring to fig. 3, with the blood collection device 200 connected to the blood separation device 10 via the cap 62, the collection chamber 32 of the sample collection module 20 receives the blood sample 12 via the inlet channel 66. The blood sample 12 flows from the inlet channel 66 of the activation module 22 to the plurality of channels 38 of the collection chamber 32 via the inlet 34.

Referring to fig. 1-6 and 11-13, in an exemplary embodiment, separation module 24 is in fluid communication with collection chamber 32 of sample collection module 20 and includes a housing 68 and defines a first chamber 70 having a first volume V1 (fig. 13) and a second chamber 72 having a second volume V2 (fig. 13), and includes a separation member 74 disposed between first chamber 70 and second chamber 72. The first volume V1 of the first chamber 70 and the second volume V2 of the second chamber 72 are different to create a second pressure differential between the first chamber 70 and the second chamber 72 to drive the second phase 16 of the blood sample 12 through the separation member 74 into the second chamber 72, as described in more detail below. In one embodiment, a portion of the separation module 24 forms a microfluidic chip.

Referring to fig. 11 and 12, in the exemplary embodiment, the separation member 74 captures the first phase 14 in the first chamber 70 and allows the second phase 16 to pass through the separation member 74 into the second chamber 72. In one embodiment, the separating member 74 comprises a track etch film. In certain configurations, the film may be less than 100 microns thick, such as 5 to 25 microns thick. The membrane may have submicron pores or pores, such as 0.2 to 0.8 microns in diameter. This dimension allows continuous filtration of the plasma portion of the blood sample flowing parallel to the membrane surface, thereby preventing clogging of the membrane pores or pores. In other embodiments, the separation member 74 may include any filter and/or any other separation device capable of capturing the first phase 14 in the first chamber 70 and allowing the second phase 16 to pass through the separation member 74 into the second chamber 72.

Referring to fig. 11 and 12, the first chamber 70 includes a first chamber inlet 75 and a first chamber outlet 76, and the second chamber 72 includes a second chamber outlet 78. The first chamber inlet 75 is in fluid communication with the outlet 36 of the collection channel 38. In this manner, upon actuation of a portion of activation module 22, blood sample 12 may flow from collection chamber 32 of sample collection module 20 to first chamber 70 of separation module 24 for plasma separation.

Referring to fig. 1-6, 11 and 13, the separation module 24 of the blood separation device 10 includes a second phase collection container 80 in communication with the second chamber outlet 78. The second phase collection container 80 receives the second phase 16 of the blood sample 12. The second phase collection vessel 80 is capable of collecting and storing the separated second phase 16. Advantageously, referring to fig. 6, with the second phase 16 contained within the second phase collection container 80, the second phase collection container 80 may be removed from the blood separation device 10. In this manner, the second phase 16 of the blood sample 12 may be collected or stored in an auxiliary second phase container (e.g., second phase collection container 80) for further diagnostic testing. For example, after separation, with the second phase collection container 80 removed from the blood separation device 10, the second phase collection container 80 can transfer the second phase 16 of the blood sample 12 to a point-of-care testing device or other testing device. In an exemplary embodiment, the second phase collection container 80 includes structure that allows the second phase collection container 80 to dispense a portion of the plasma 16 when desired. In one embodiment, the second phase collection container 80 is sealed via a cap or septum 81 to protectively seal the plasma portion 16 within the second phase collection container 80.

Referring to fig. 11, in an exemplary embodiment, a portion of the second chamber 72 of the separation module 24 is in fluid communication with the interior of the second phase collection container 80 to allow the plasma portion 16 to flow through the separation member 74 and the second chamber 72 into the interior of the second phase collection container 80 for collection.

Referring to fig. 11-13, separation module 24 of blood separation device 10 also includes a blood sample discard chamber 82 in communication with first chamber outlet 76. After the blood sample 12 flows through the separating member 74 in the first chamber 70, the blood sample disposal chamber 82 receives the remaining first phase 14 of the blood sample 12. In this manner, the remaining first phase 14 of the blood sample 12 may be collected and stored in the blood sample discard chamber 82. In addition, the blood sample disposal chamber 82 ensures that the remaining first phase 14 of the blood sample 12 can be safely stored when the remainder of the blood separation device 10 is disposed of after use.

Referring to fig. 3-6, the use of the blood separation device 10 of the present disclosure will now be described.

Referring to fig. 3, a first step in using the blood separation device 10 of the present disclosure involves collecting a blood sample 12 from a patient, such as a blood collection procedure. For example, first, immediately after the blood separation device 10 is connected to the blood collection device 200 (such as the tube holder 202), a given volume of the blood sample 12 from the patient is pulled under vacuum force into the collection chamber 32 of the blood separation device 10. In one embodiment, such a connection includes a non-patient needle (not shown) that pierces the tube holder 202 of the cap's plug 64 (fig. 7B). The opposite end of the tubing line 204 of the tube holder 202 includes a patient needle of a venous access set in communication with a patient.

Referring to fig. 3, with the tube holder 202 of the blood collection device 200 connected to the blood separation device 10 via the cap 62 (fig. 7B), the collection chamber 32 of the sample collection module 20 receives the blood sample 12 via the inlet channel 66 of the activation module 22 (fig. 7B). The blood separation device 10 of the present disclosure collects and stores a fixed amount of patient blood. In one exemplary embodiment, the blood separation device 10 of the present disclosure collects and stores 3mL of patient blood in less than 30 seconds.

The blood sample 12 flows through the inlet channel 66 of the activation module 22 to the collection chamber 32 of the sample collection module 20. Advantageously, the plurality of sequential flow direction alternating collection channels 38 of collection chamber 32 maximize collection and storage space within the constrained diameter of the blood collection set during blood collection, and also ensure that capillary forces dominate over gravity during filling.

The user may select one of a number of ways, sources, or methods in which the blood separation device 10 is capable of receiving the blood sample 12. For example, referring to fig. 3, the blood separation device 10 of the present disclosure is capable of receiving a blood sample 12 from a conventional blood collection device 200. For example, the blood collection device 200 may include a tube holder 202 and a corresponding venous access kit (such as a BD commercially available from Becton, Dickinson and Company, incA blood collection tube). In other alternative embodiments, the blood is collected in a conventional blood collection tube or any other intermediate blood sample container. The blood sample container is then connected to a separation device that exits the patient to generate plasma.

Once the desired amount of blood sample 12 is collected in the collection chamber 32 and the blood collection process is complete, the blood separation device 10 is disconnected from the blood collection device 200. In this manner, the blood separation device 10 of the present disclosure separates and separates the blood collection process from the plasma separation process. Because plasma separation occurs after the blood separation device 10 is disconnected from the patient, the performance of the device is no longer affected by the patient's blood pressure and needle gauge, and the patient's discomfort is greatly reduced.

Upon disconnecting the blood separation device 10 of the present disclosure from the blood collection device 200 and the patient, the collected blood remains stationary in the channel 38 until plasma separation is initiated. The blood separation device 10 accomplishes this by utilizing the second seal 52 (e.g., the plug 64 of the cap 62). The plug 64 of the cap 62 ensures that after the needle of the blood collection device 200 is withdrawn from the plug 64, the second seal 52 is properly resealed so that there is no pressure differential between the forward and rearward ends of the blood stored within the blood separation device 10.

Referring to fig. 4, after disconnecting the blood separation device 10 from the blood collection device 200, the plasma separation process may begin. Advantageously, the blood separation device 10 of the present disclosure does not require connection to a patient for plasma separation. The plasma separation process is fully controllable and can be started at a convenient and desirable time.

Referring to fig. 4, the plasma separation process begins with the blood separation device 10 leaving the patient by simply actuating a switch 54 (fig. 8A and 8B) on the blood separation device 10 (e.g., pushing a button 56). Actuation of the switch 54 allows the blood separation device 10 to automatically generate plasma 16 from a blood sample 12 stored within the blood separation device 10.

Actuation of the switch 54 transitions the first seal 50 to an open position (fig. 8B) in which the collection chamber 32 is in fluid communication with a second pressure P2 defined by atmospheric pressure that is greater than the first pressure P1 defined within the collection chamber 32. In this manner, a first pressure differential (e.g., a pressure differential between second pressure P2 defined by atmospheric pressure and first pressure P1 defined within collection chamber 32) draws blood sample 12 into first chamber 70 of separation module 24. In other words, a first pressure differential between atmospheric pressure and the residual vacuum in the blood separation device 10 continuously drives the plasma separation within the blood separation device 10. In an exemplary embodiment, the separation module 24 allows for continuous plasma separation by utilizing a cross-flow filtration flow pattern in a microfluidic chip (e.g., separation module 24) as the blood sample 12 flows through the first chamber 70 and through the separation member 74, as shown in fig. 12. In one configuration, the pressure in collection chamber 32 is limited by the maximum allowable pressure differential across the membrane, such that the endpoint pressure within collection chamber 32 after blood collection and prior to filtration should be less than 5.5 psi.

Advantageously, the activation module 22 initiates the plasma separation process after blood collection and with the blood separation device 10 disconnected from the blood collection device 200 and the patient. To begin the plasma separation process after blood collection, the pressure gradient must be reestablished on the stored blood within collection chamber 32. This is accomplished by controlling the pressure within the blood separation device 10 via the activation module 22. Prior to activation, the first and second seals 50, 52 of the activation module 22 seal the housing 30 of the blood separation device 10, and with the first seal 50 in the closed position (fig. 7B), the activation module 22 seals the collection chamber 32 at the first pressure P1. After activation of the activation module 22, the first seal 50 transitions to an open position (fig. 8B) in which the collection chamber 32 is in fluid communication with a second pressure P2 defined by atmospheric pressure that is greater than the first pressure P1 defined within the collection chamber 32.

Importantly, a second pressure differential is used within the blood separation device 10 to drive the plasma 16 through the separation member 74 into the second chamber 72 and is collected in the second phase collection container 80. In the open position (fig. 8B) of first seal 50, first volume V1 of first chamber 70 of separation module 24 and second volume V2 of second chamber 72 of separation module 24 are different, thereby providing a second pressure differential between first chamber 70 and second chamber 72 to drive second phase 16 of blood sample 12 through separation member 74 into second chamber 72 and be collected in second phase collection container 80. In other words, the second pressure differential across the blood flow in the first chamber 70 and the plasma flow path in the second chamber 72 and its dynamic profile during separation provides a power source to further drive the plasma separation process. In an exemplary embodiment, for a given plasma separation chip (e.g., separation module 24), a second pressure differential across the blood flow in the first chamber 70 and the plasma flow path in the second chamber 72 and their dynamic profiles is controlled via setting an appropriate initial vacuum level and balancing the volumetric ratios of the blood sample discard chamber 82 and the second phase collection container 80. In an exemplary embodiment, the volume of the blood sample disposal chamber 82 is designed to ensure that the volume is large enough to have sufficient residual vacuum at the end to drive blood flow without clogging the separation member 74. In an exemplary embodiment, the volume also needs to be small enough so that at the end of the separation, the pressure in the blood sample discard chamber 82 is higher than the pressure in the second phase collection container 80 to prevent the separation member 74 from collapsing. In one configuration, the volume of the blood sample discard chamber 82 is at least twice the volume of the collection chamber 32 and is less than the volume of the second phase collection container 80 multiplied by a factor (1-yield)/yield. The pressure difference across the membrane during filtration always needs to be less than 5.5 psi.

The blood 12 is forced to flow through the first chamber 70 and through the separating member 74 using the first and second pressure differentials within the blood separating device 10. As the blood 12 flows through the separation module 24, the plasma 16 is continuously separated from the first phase 14 of the blood sample 12.

During plasma separation, the separation member 74 allows the second phase or plasma 16 to pass through the separation member 74 into the second chamber 72, which may be collected or stored in an auxiliary plasma container (e.g., second phase collection container 80) for further diagnostic testing. Referring to fig. 11, the arrows including dashed lines indicate the second phase flow path 104 that the plasma 16 takes after passing through the separating member 74. In one embodiment, after plasma separation, the second phase collection container 80 may be removed from the blood separation device 10 with the second phase or plasma 16 contained within the second phase collection container 80. The second phase collection container 80 may then be used to transfer the plasma portion 16 to a point of care testing device or other diagnostic testing system.

During plasma separation, the separation member 74 captures the first phase 14 of the blood sample 12 within the first chamber 70, e.g., the first phase 14 of the blood sample 12 is not allowed to pass through the separation member 74 into the second chamber 72. Referring to fig. 11, the arrows comprising straight lines indicate the flow path 102 taken by the blood sample 12 through the collection chamber 32 and the flow path 102 taken by the first phase 14 of the blood sample 12 after passing through the separation member 74 and reaching the blood sample discard chamber 82. Referring to fig. 11 and 12, the first phase 14 of the blood sample 12 flows into the first chamber 70 through the first chamber inlet 75 and over the surface of the separating member 74, and then exits the first chamber 70 via the first chamber outlet 76 into the blood sample discard chamber 82.

In one exemplary embodiment, the blood separation device 10 of the present disclosure is capable of generating 350 to 600uL of plasma 16 from 3mL of stored blood in less than 7 minutes.

Referring to fig. 5, the blood separation device 10 of the present disclosure allows for plasma separation independent of the orientation of the blood separation device 10. In other words, the blood separation device 10 separates plasma regardless of whether the blood separation device 10 is in an upright orientation (e.g., the blood separation device 10 is housed in a tube rack) or whether the blood separation device 10 is in a planar orientation on a table or tray.

Referring to fig. 6, with the second phase or plasma 16 contained within the second phase collection container 80, the second phase collection container 80 may be removed from the blood separation device 10. The second phase collection container 80 may then be used to transfer the plasma portion 16 to a point of care testing device or other diagnostic testing system. In one embodiment, the second phase collection container 80 is removably connected to the blood separation device 10 via a luer lock septum seal.

In other words, after plasma separation is complete, the plasma 16 within the second phase collection container 80 is removed from the blood separation device 10 for clinical testing. The remainder of the blood separation device 10 may then be discarded.

As described herein, the present disclosure provides a blood separation device that separates and isolates a blood collection process from a plasma separation process. The blood separation device includes a sample collection module, an activation module, and a separation module. Because plasma separation occurs after the blood separation device is disconnected from the patient, the performance of the device is no longer affected by the patient's blood pressure and needle gauge, and the patient's discomfort is greatly reduced.

While this disclosure has been described as having an exemplary design, the present disclosure may be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this disclosure pertains and which fall within the limits of the appended claims.