Biological Fluid Separator

Abstract

A blood separation device is disclosed that separates and separates the blood separation process from the plasma separation process. The blood separation device includes a sample collection module, a start-up module, and a separation module. Because plasma separation occurs after the blood separation device is disconnected from the patient, the device's performance is not affected by the patient's blood pressure and needle gauge, significantly reducing patient discomfort.

Description

[Technical field]

[0001] Cross-references to related applications This application is filed in accordance with the 8 This application claims priority to U.S. Provisional Application No. 62 / 681,894, entitled "Biological Fluid Separation Apparatus," filed Jun. 7, 2004, the disclosure of which is incorporated herein by reference in its entirety.

[0002] 2. Background of the Invention 1. Field of disclosure The present disclosure relates generally to devices configured for use with biological fluids. More specifically, the present disclosure relates to devices configured to separate components of biological fluids. [Background technology]

[0003] 2. Description of Related Technology Phlebotomy is a common health care procedure that involves drawing at least one drop of blood from a patient. Blood samples are commonly taken from hospitalized, homebound, and emergency room patients by either finger stick, heel stick, or venipuncture. Blood samples can also be drawn from patients by venous or arterial lines. After collection, blood samples can be analyzed to obtain medically useful information, such as chemical composition, hematology, and coagulation.

[0004] Blood tests measure a patient's physiological and biochemical status, such as disease, mineral content, drug effectiveness, and organ function. Blood tests can be performed in a clinical laboratory or at the point of care near the patient. One example of a point-of-care blood test is the routine testing of a patient's blood glucose level, which involves drawing blood with a finger stick 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 devices are also available that analyze blood gases electrolyte levels, lithium levels, and ionized calcium levels. Some other point-of-care devices identify markers for acute coronary syndromes (ACS) and deep vein thrombosis / pulmonary thrombosis (DVT / PE). Summary of the Invention [Problem to be solved by the invention]

[0005] A blood sample includes a whole blood or cellular portion and a plasma portion. Plasma separation from whole blood has traditionally been achieved by centrifugation, which typically takes 15-20 minutes and involves heavy labor or complex workflow. Recently, other techniques have been used or attempted to separate plasma, such as sedimentation, fibrous or non-fibrous membrane filtration, lateral flow separation, microfluidic cross-flow filtration, and other microfluidic hydrodynamic separation techniques. However, many of these techniques have various challenges, such as low plasma purity, analyte bias, the need for specific coatings to prevent analyte bias, high hemolysis, the need for dilution, long separation times, and / or difficulties in recovering plasma. For example, most membrane-based separation techniques suffer from analyte bias issues and often require specific coating treatments for the compounds of interest. Furthermore, traditional separation techniques, which are performed while the device is directly connected to the patient via a needle, cause discomfort to the patient. [Means for solving the problem]

[0006] Summary of the Invention The present disclosure provides a blood separation device that decouples and separates the blood collection process from the plasma separation process, the blood separation device including a sample collection module, a start-up module, and a separation module, where plasma separation occurs after the blood separation device is disconnected from the patient, so that the device performance is not affected by the patient's blood pressure or needle gauge, and patient discomfort is greatly reduced.

[0007] The present disclosure provides a blood separation device and separation process that is fully compatible with venous blood collection workflows without the need for centrifugation and power. Advantageously, the blood separation device of the present disclosure allows for immediate separation of plasma during clinical blood draw and collection of the separated plasma sample in a self-contained plasma container for downstream diagnostics.

[0008] Additionally, the blood separation device of the present disclosure provides a separation device that requires no more than a short patient draw time compared to conventional blood collection devices that use evacuated tubes, such as BD Vacutainer® blood collection tubes, and corresponding venous access sets, available from Becton, Dickinson and Company. Furthermore, because plasma separation occurs after the device is disconnected from the patient, device performance is not affected by the patient's blood pressure or needle gauge, resulting in significantly less discomfort to the patient.

[0009] Because the blood separation device of the present disclosure decouples and separates the blood collection process from the plasma separation process, the amount of plasma produced is no longer limited by the patient's acceptable blood collection time, enabling the potential use of the blood separation device of the present disclosure for other high volume plasma applications beyond the point of care.

[0010] Additionally, another advantage of decoupling the separation from the collection process is that separation time, plasma quality, and yield are not affected by needle gauge and patient blood pressure. If separation is performed when the device is directly connected to the patient via a needle, low needle gauge and high patient blood pressure will decrease separation time, yield, and increase hemolysis. On the other hand, high needle gauge and low patient blood will increase separation time, yield, and decrease hemolysis. By decoupling the plasma separation process from the blood collection workflow using the blood collection device of the present disclosure, the blood collection set and patient blood pressure only affect the blood collection time, and do not change the separation time, yield, and hemolysis level.

[0011] According to an embodiment of the present invention, a blood separation device configured to receive a blood sample having a first phase and a second phase, comprising: a sample collection module having a housing forming a collection chamber; a start-up module connected to the sample collection module, the start-up module having a first seal and a second seal for sealing the housing, the first seal being movable by actuation of a portion of the start-up 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, the second pressure being higher than the first pressure; a separation module in fluid communication with the collection chamber of the sample collection module, the separation module forming a first chamber having a first volume and a second chamber having a second volume, and further including a separation member disposed between the first chamber and the second chamber, where the first volume and the second volume are different;

[0012] In one configuration, the activation module includes a switch, where activation of the switch transitions the first seal to the open position. In another configuration, the switch includes a push button forming a vent therethrough and a piercing portion, where activation 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 through the vent of the switch. In one configuration, the second seal includes a cap with a pierceable self-sealing stopper within a portion of the cap. In another configuration, the blood separation device is connectable to a blood collection device through the cap. In yet another configuration, the activation module defines an inlet passageway, where the collection chamber receives the blood sample through the inlet passageway with the blood collection device connected to the blood separation device through the cap. In one configuration, the collection chamber includes an inlet end and an outlet end, forming a plurality of continuous flow-direction alternating collection passageways. In another configuration, the collection chamber has an inlet end and an outlet end, forming a first collection passageway extending from the inlet end to the outlet end, a second collection passageway in communication with a portion of the first collection passageway and extending from the outlet end to the inlet end, and a third collection passageway in communication with a portion of the second collection passageway and extending from the inlet end to the outlet end. In yet another configuration, the inlet ends of the collection passageways are in fluid communication with the inlet passageway of the activation module. In one configuration, the blood sample moves through the first collection passageway in a first direction, the blood sample moves through the second collection passageway in a second direction opposite the first direction, and the blood sample moves through the third collection passageway in a third direction opposite the second direction. In another configuration, the first collection passageway is spaced apart from the second collection passageway, which is spaced apart from the third collection passageway. In yet another configuration, the first chamber includes a first chamber inlet and a first chamber outlet, and the second chamber has a second chamber outlet.In one configuration, the first chamber inlet is in fluid communication with the outlet end of the collection passage. In another configuration, with the first seal in the open position, a first pressure difference between the second pressure created by atmospheric pressure and the first pressure created in the collection chamber draws the blood sample into the first chamber. In yet another configuration, with the first seal in the open position, the difference between the first and second volumes creates a second pressure difference between the first and second chambers, which drives the second phase of the blood sample through the separation member and 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 and into the second chamber. In another configuration, the blood separation device has a second phase collection container in communication with the second chamber outlet, where the second phase collection container receives the second phase. In yet another configuration, the blood separation device has a blood sample waste chamber in communication with the first chamber outlet, where the blood sample waste chamber receives the first phase. In one configuration, the separation member has a track-etched membrane. In another configuration, with the blood collection device connected to the blood separation device via the cap, the collection chamber receives the blood sample via the inlet passage. In yet another configuration, with the blood collection device disconnected from the blood separation device and upon actuation of the switch to transition the first seal to the open position, the blood sample is drawn into the first chamber by the first pressure differential between the second pressure created by the atmospheric pressure and the first pressure created in the collection chamber. In one configuration, with the first seal in the open position, the difference between the first and second volumes creates the second pressure differential between the first and second chambers, driving the second phase of the blood sample through the separation member and into the second chamber. In another configuration, with the second phase contained within the second phase collection container, the second phase collection container is removable from the blood separation device.In yet another configuration, the first phase is a cellular portion and the second phase is a plasma portion. [Brief description of the drawings]

[0013] The above and other features and advantages of the present disclosure, and the manner in which the same are accomplished, will become more apparent and better understood by referring to the following description taken in conjunction with the accompanying drawings. [Figure 1] FIG. 1 is a perspective view of a blood separation device according to one embodiment of the present invention. [Diagram 2] FIG. 2 is an exploded perspective view of a blood separation device according to one embodiment of the present invention. [Diagram 3] FIG. 3 is a perspective view of a first step in using the system of the present disclosure according to one embodiment of the present invention. [Figure 4] FIG. 4 is a perspective view of a second step using the system of the present disclosure according to one embodiment of the present invention. [Diagram 5] FIG. 5 is a perspective view of a third step of using the system of the present disclosure, illustrating that the device of the present disclosure separates plasma independent of the orientation of the device, according to one embodiment of the present disclosure. [Figure 6] FIG. 6 is a perspective view of a fourth step using the system of the present disclosure according to one embodiment of the present invention. [Figure 7A] FIG. 7A is a perspective view of an activation module of a blood separation device in a closed position according to one embodiment of the present invention. [Figure 7B] FIG. 7B is a cross-sectional view of the start-up module of FIG. 7A according to one embodiment of the present invention. [Figure 8A] FIG. 8A is a perspective view of a start-up module of a blood separation device in an open position according to one embodiment of the present invention. [Figure 8B] FIG. 8B is a cross-sectional view of the start-up module of FIG. 8A according to one embodiment of the present invention. [Figure 9] FIG. 9 is a perspective view of a collection chamber of a blood separation device according to one embodiment of the present invention. [Figure 10]FIG. 10 is a perspective view of a collection chamber of a blood separation device according to another embodiment of the present invention. [Figure 11] FIG. 11 is a perspective view of a blood separation device according to one embodiment of the present invention. [Figure 12] FIG. 12 is a perspective view of a portion of a separation module of a blood separation device according to one embodiment of the present invention. [Figure 13] FIG. 13 is a perspective view of a blood separation device according to one embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications herein illustrate embodiments of the present invention, and such exemplifications are not to be construed as limiting the scope of the present disclosure in any way.

[0015] Detailed Description The following description is provided to enable a person skilled in the art to make and use the described embodiments contemplated for practicing the invention. However, various modifications, equivalents, variations, and alternatives will remain readily apparent to those skilled in the art. All such modifications, variations, equivalents, and alternatives are intended to be within the spirit and scope of the present invention.

[0016] For purposes of the following description, the terms "top", "bottom", "right", "left", "vertical", "horizontal", "upper", "lower", "transverse", "longitudinal", and their derivatives shall refer to the invention in the orientation shown in the drawings. However, it should be understood that the invention may assume alternative variations and sequences of steps unless otherwise noted. It should also be understood that the specific devices and processes illustrated in the accompanying drawings and described in the following specification are merely exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting.

[0017] Figures 1 and 2 illustrate an exemplary embodiment of a blood separation device of the present disclosure. With reference to Figures 1 and 2, a blood separation device 10 of the present disclosure is configured to receive a biological fluid, such as a blood sample 12 (Figures 3-6) having a first phase 14 and a second phase 16. The first phase 14 of the blood sample 12 is a cellular portion and the second phase 16 of the blood sample 12 is a plasma portion.

[0018] The blood separation device 10 of the present disclosure decouples 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 patient discomfort is greatly reduced.

[0019] Because the blood separation device 10 of the present disclosure separates and isolates the blood collection process from the plasma separation process, the amount of plasma produced is no longer limited by the patient's acceptable blood collection time, potentially enabling the blood separation device 10 of the present disclosure to be used for other large volume plasma applications beyond the point of care.

[0020] The present disclosure provides a blood separation device 10 and separation process that is fully compatible with venous blood collection workflows without the need for centrifugation and power. Advantageously, the blood separation device 10 of the present disclosure allows for immediate separation of plasma during clinical blood draws, allowing the device 10 to be used on an outpatient basis and for collection of the separated plasma 16 sample in a self-contained plasma container, such as a second phase or plasma collection container 80, for downstream diagnostics.

[0021] Additionally, the blood separation device 10 of the present disclosure provides a separation device that requires only short patient collection times that are no different from conventional blood collection devices that use evacuated tubes and corresponding venous access sets, such as BD Vacutainer® blood collection tubes available from Becton, Dickinson and Company. Furthermore, because plasma separation occurs after the device 10 is disconnected from the patient, device performance is no longer affected by the patient's blood pressure and needle gauge, and patient discomfort is greatly reduced.

[0022] Furthermore, another advantage of decoupling 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 is performed when the device is directly connected to the patient via a needle, a low needle gauge and high patient blood pressure will decrease separation time, yield, and increase hemolysis. On the other hand, a high needle gauge and low patient blood pressure will increase separation time and yield, and decrease hemolysis. By decoupling 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.

[0023] 1-13, in an exemplary embodiment, a blood separation device 10 generally includes a sample collection module 20, a start-up module 22, and a separation module 24. In one embodiment, after collecting a blood sample 12, the blood separation device 10 can separate a second phase 16 of the blood sample 12 from a first phase 14 of the blood sample 12, as described in more detail below. Advantageously, the blood separation device 10 decouples and separates the blood collection process from the plasma separation process. In one embodiment, after plasma separation, a removable portion of the blood separation device 10, such as a second phase collection container 80, can transfer the second phase 16 of the blood sample 12 to a point-of-care test.

[0024] 1-6 and 9-11, in an exemplary embodiment, the sample collection module 20 includes a housing 30 that defines a collection chamber 32. In one embodiment, the collection chamber 32 includes an inlet end or inlet 34 and an outlet end or outlet 36 and defines a plurality of sequential flow direction alternating collection passages 38.

[0025] The collection chamber 32 utilizes multiple interconnected parallel passages 38 to maximize collection and storage space within the limited diameter of the blood collection set and ensure that capillary forces exceed gravity during filling. The blood sample 12 fills the interconnected passages 38 of the sample collection module 20 in a reciprocating motion, as illustrated in Figures 9-11.

[0026] For example, with reference to Figure 9, in a first exemplary embodiment, the collection chamber 32 of the sample collection module 20 defines a first collection passage 40 extending from the inlet end 34 to the outlet end 36, a second collection passage 42 in communication with a portion of the first collection passage 40 and extending from the outlet end 36 to the inlet end 34, and a third collection passage 44 in communication with a portion of the second collection passage 42 and extending from the inlet end 34 to the outlet end 36. With reference to Figure 9, the first collection passage 40 is spaced from the second collection passage 42, which is spaced from the third collection passage 44.

[0027] 9, which illustrates the flow path 100 of the blood sample 12 through the passages 38 of the collection chamber 32, a blood sample 12 collected in the collection chamber 32 travels through the first collection passage 40 in a first direction, the blood sample 12 travels through the second collection passage 42 in a second direction opposite the first direction, and the blood sample 12 travels through the third collection passage 44 in a third direction opposite the second direction. With reference to FIG. 9, the collection chamber 32 utilizes multiple interconnected parallel passages 38 to maximize collection and storage space within the limited diameter of a blood collection set while ensuring that capillary forces exceed gravity during filling.

[0028] In one embodiment, the inlet to the collection chamber 32 is the inlet 34 of the first collection passage 40, and the outlet from the collection chamber 32 is the outlet 36 of the third collection passage 44. The inlet 34 of the first collection passage 40 is in fluid communication with an inlet passage 66 (FIGS. 7B and 8B) of the start-up module 22, as described in more detail below.

[0029] 10, in a second exemplary embodiment, the collection chamber 32 of the sample collection module 20 defines a first collection passage 40 extending from the inlet end 34 to the outlet end 36, a second collection passage 42 communicating with a portion of the first collection passage 40 and extending from the outlet end 36 to the inlet end 34, a third collection passage 44 communicating with a portion of the second collection passage 42 and extending from the inlet end 34 to the outlet end 36, a fourth collection passage 46 communicating with a portion of the third collection passage 44 and extending from the outlet end 36 to the inlet end 34, and a fifth collection passage 48 communicating with a portion of the fourth collection passage 46 and extending from the inlet end 34 to the outlet end 36. Referring to FIG. 10, the first collection passage 40 is spaced from the second collection passage 42, which is spaced from the third collection passage 44, which is spaced from the fourth collection passage 46, which is spaced from the fifth collection passage 48.

[0030] Thus, blood sample 12 collected within collection chamber 32 travels through first collection passage 40 in a first direction, blood sample 12 travels through second collection passage 42 in a second direction opposite the first direction, blood sample 12 travels through third collection passage 44 in a third direction opposite the second direction, blood sample 12 travels through fourth collection passage 46 in a fourth direction opposite the third direction, and blood sample 12 travels through fifth collection passage 48 in a fifth direction opposite the fourth direction. With reference to Figure 10, collection chamber 32 utilizes multiple interconnected parallel passages 38 to maximize collection and storage space within the limited diameter of a blood collection set while ensuring that capillary forces exceed gravity during filling.

[0031] In one embodiment, the inlet to the collection chamber 32 is the inlet 34 of the first collection passage 40, and the outlet from the collection chamber 32 is the outlet 36 of the fifth collection passage 48. The inlet 34 of the first collection passage 40 is in fluid communication with an inlet passage 66 (FIGS. 7B and 8B) of the start-up module 22, as described in more detail below.

[0032] In one embodiment, the collection chamber 32 of the sample collection module 20 can form any odd number of passages 38 based on the particular volume requirements. Importantly, the collection chamber 32 of the sample collection module 20 utilizes multiple interconnected parallel passages 38 to maximize collection and storage space within the limited diameter of a blood collection set and ensure that capillary forces exceed gravity during filling. Blood sample 12 fills the interconnected passages 38 of the sample collection module 20 in a back and forth motion.

[0033] In one exemplary embodiment, the multiple sequential flow direction alternating collection passages 38 are configured in a parallel configuration as shown in Figures 9 and 10. In other embodiments, the collection passages 38 are configured in a spiral or serpentine passage configuration, or other configuration that maximizes collection and storage space within the limited diameter of the blood collection set and ensures that capillary forces exceed gravity during filling.

[0034] In an exemplary embodiment, the collection chamber 32 is designed to ensure that blood 12 continues to fill the passageway 38 of the collection chamber 32 without trapping air bubbles, regardless of device orientation and blood flow rate. This is accomplished by controlling the diameter of the passageway 38 for the desired application. For example, in an exemplary embodiment, the diameter of the passageway 38 must meet two requirements to prevent blood from collapsing and trapping air bubbles. First, the static pressure difference at the arrow front at any orientation must be less than the Laplace pressure for the meniscus to retain its shape. Second, the selected diameter must ensure that inertial forces are less than surface tension forces at maximum flow rate.

[0035] 1, 2 and 7A-8B, in one embodiment, the activation module 22 is connected or connectable to the sample acquisition module 20 and includes a housing 49, a first seal 50, and a second seal 52 for sealing the blood separation device 10, e.g., the housing 30 of the sample acquisition module 20, the housing 49 of the activation module 22, and the housing 68 of the separation module 24. The seals 50, 52 of the activation module 22 thereby control the pressure within the blood separation device 10, as described in more detail below. The first seal 50 is movable by actuation of a portion of the activation module 22 from a closed position (FIGS. 7A and 7B) in which the collection chamber 32 has a first pressure P1 (FIGS. 13) to an open position (FIGS. 8A and 8B) in which the collection chamber 32 is in fluid communication with a second pressure P2 (FIGS. 13) that is higher than the first pressure P1.

[0036] In one exemplary embodiment, with reference to Figures 7A-8B, the activation module 22 includes a switch 54. In such an embodiment, actuation of the switch 54 transitions the first seal 50 from the closed position (Figures 7A and 7B) to the open position (Figures 8A and 8B). With reference to Figures 7A-8B, the switch 54 includes a push button 56 that defines a vent hole 58 and a piercing portion 60 extending therethrough. Thus, actuation of the switch, for example by pressing the push button 56 to the position shown in Figures 8A and 8B, moves the piercing portion 60 to break the first seal 50, thereby transitioning the first seal 50 to the open position.

[0037] With the first seal 50 in the open position, the collection chamber 32 of the sample collection module 20 is in fluid communication with a 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 breaches the first seal 50, e.g., an aluminum foil seal, to create a vent to power a plasma separation process.

[0038] The second pressure P2 created by atmospheric pressure is greater than the first pressure P1 created within the blood separation device 10, e.g., within the collection chamber 32 of the blood separation device 10. This allows the pressure difference between the second pressure P2 created by atmospheric pressure and the residual vacuum of the blood separation device 10, i.e., the first pressure P1 created within the blood separation device 10, to continuously drive the plasma separation process, as will be explained in more detail below. Advantageously, by using the start-up module 22 of the present disclosure, a user can precisely control when the plasma separation process begins.

[0039] In one exemplary embodiment, the second seal 52 of the activation module 22 includes a cap 62 with a pierceable self-sealing stopper 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.

[0040] In one exemplary embodiment, the cap 62 of the present disclosure may be formed substantially similar to the closure structure described in U.S. Provisional Application No. 62 / 666,765, filed May 4, 2018, entitled "Closure Structure for Biological Fluid Collection Device," the entire disclosure of which is incorporated herein by reference.

[0041] 7A-8B, in one embodiment, the start-up module 22 defines an inlet passage 66. Referring to FIG. 3, when a blood collection device 200 is connected to the blood separation device 10 via the cap 62, the collection chamber 32 of the sample collection module 20 receives a blood sample 12 via the inlet passage 66. The blood sample 12 flows from the inlet passage 66 of the start-up module 22 through the inlet 34 to the multiple passages 38 of the collection chamber 32.

[0042] 1-6 and 11-13, in one exemplary embodiment, the separation module 24 is in fluid communication with the collection chamber 32 of the sample collection module 20, includes a housing 68, 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 the first chamber 70 and the second chamber 72. The first volume V1 of the first chamber 70 and the second volume V2 of the second chamber 72 are distinct, and a second pressure is created 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 and into the second chamber 72, as will be described in more detail below. In one embodiment, a portion of the separation module 24 forms a microfluidic chip.

[0043] 11 and 12, in one 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 and into the second chamber 72. In one embodiment, the separation member 74 is comprised of a track etched membrane. In one configuration, the membrane can be less than 100 microns thick, such as, for example, 5-25 microns thick. The membrane can have submicron pores or holes, such as 0.2-0.8 microns in diameter. This dimensionality allows for continuous filtration of the plasma portion of a blood sample flowing parallel to the membrane surface, thereby preventing clogging of the membrane pores or holes. In other embodiments, the separation member 74 can include any filter and / or other separation device that captures the first phase 14 in the first chamber 70 and allows the second phase 16 to pass through the separation member 74 and into the second chamber 72.

[0044] 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 passage 38 such that activation of a portion of the activation module 22 allows a blood sample 12 to flow from the collection chamber 32 of the sample collection module 20 to the first chamber 70 of the separation module 24 for plasma separation.

[0045] 1-6 and 11-13, 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 container 80 can collect and store the separated second phase 16. Advantageously, with reference to FIG. 6, the second phase collection container 80 is removable from the blood separation device 10 with the second phase 16 housed within the second phase collection container 80. This allows the second phase 16 of the blood sample 12 to be collected or stored in a second second phase container, e.g., the 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 one exemplary embodiment, the second phase collection container 80 includes structure that allows the second phase collection container 80 to dispense, when desired, a portion of the plasma 16. 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.

[0046] Referring to FIG. 11, in one exemplary embodiment, a portion of the second chamber 72 of the separation module 24 is fluidly connected to the interior of the second phase collection container 80, allowing the plasma portion 16 to flow through the separation member 74 and the second chamber 72 and into the second phase collection container 80 for collection.

[0047] 11-13, the separation module 24 of the blood separation device 10 further includes a blood sample waste chamber 82 in communication with the first chamber outlet 76. The blood sample waste chamber 82 receives the remaining first phase 14 of the blood sample 12 after the blood sample 12 flows over the separation member 74 and into the first chamber 70. This allows the remaining first phase 14 of the blood sample 12 to be collected and stored within the blood sample waste chamber 82. The blood sample waste chamber 82 also 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 discarded after use.

[0048] Next, a method of using the blood separation device 10 of the present disclosure will be described with reference to FIGS.

[0049] 3, the first step in using the blood separation device 10 of the present disclosure involves collecting a blood sample 12 from a patient, e.g., a blood draw process. For example, a given amount of blood sample 12 from a patient is first aspirated into the collection chamber 32 of the blood separation device 10 by vacuum force immediately after connection to the blood draw device 200, tube holder 202, etc., of the blood separation device 10. In one embodiment, such connection is made with a non-patient needle (not shown) of the tube holder 202 piercing the stopper 64 of the cap (FIG. 7B). The opposite end of the line 204 of the tube holder 202 is made with a patient needle of venous access set in communication with the patient.

[0050] 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 passage 66 (FIG. 7B) of the start-up module 22. The blood separation device 10 of the present disclosure collects and stores a volume of a patient's blood. In an exemplary embodiment, the blood separation device 10 of the present disclosure collects and stores 3 ml of a patient's blood in less than 30 seconds.

[0051] The blood sample 12 flows through the inlet passage 66 of the activation module 22 into the collection chamber 32 of the sample collection module 20. Advantageously, the multiple sequential flow direction alternating collection passages 38 of the collection chamber 32 maximize collection and storage space within the limited diameter of a blood collection set during blood collection, and allow capillary forces to exceed gravity during filling.

[0052] A user may select one of the methods, sources, or manners by which the blood separation device 10 can accept a patient sample 12. For example, referring to FIG. 3, the blood separation device 10 of the present disclosure may receive 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 set, such as a BD Vacutainer® blood collection tube available from Becton, Dickinson and Company. In other alternative embodiments, blood is collected in a conventional blood collection tube or other intermediate blood sample container. The blood sample container is then connected to the off-patient separation device to produce plasma.

[0053] Once a desired amount of blood sample 12 has been collected in the collection chamber 32 and the blood collection process is completed, 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 decouples 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 patient discomfort is greatly reduced.

[0054] After disconnection of the blood collection device 200 of the blood separation device 10 of the present disclosure from a patient, collected blood remains quiescent in the passageway 38 until plasma separation is accomplished. The blood separation device 10 accomplishes this by utilizing the second seal 52, e.g., the stopper 64 of the cap 62. The stopper 64 of the cap 62 ensures that the second seal 52 reseals properly after the needle of the blood collection device 200 is withdrawn from the stopper 64 such that no pressure differential exists between the front and back ends of stored blood within the blood separation device 10.

[0055] 4, after the blood separation device 10 is disconnected from the blood collection device 200, the plasma separation process can begin. Advantageously, the blood separation device 10 of the present disclosure does not need to be connected to a patient to perform plasma separation. The plasma separation process is fully controllable and can be initiated at any convenient desired time.

[0056] 4, the plasma separation process is initiated off-patient on the blood separation device 10 simply by activating the switch 54 (FIGS. 8A and 8B), e.g., by pressing the push button 56 on the blood separation device 10. Activation of the switch 54 enables the blood separation device 10 to automatically generate plasma 16 from the blood sample 12 stored within the blood separation device 10.

[0057] Activation of the switch 54 transitions the first seal 50 to the open position (FIG. 8B) where the collection chamber 32 is in fluid communication with a second pressure P2 formed by atmospheric pressure and higher than the first pressure P1 formed in the collection chamber 32. This causes the blood sample 12 to be drawn into the first chamber 70 of the separation module 24 by the first pressure difference, i.e., the difference between the second pressure formed by atmospheric pressure and the first pressure formed in the collection chamber 32. In other words, the pressure difference between atmospheric pressure and the residual vacuum in the blood separation device 10 continuously drives the plasma separation in the blood separation device 10. In an embodiment, the separation module 24 utilizes a cross-flow filtration pattern of a microfluidic chip, e.g., the separation module 24 shown in FIG. 12, whereby the blood sample 12 flows through the first chamber 70 and past the separation member 74, thereby enabling the separation module 24 to perform continuous plasma separation. In one configuration, the pressure in the collection chamber 32 is limited by the maximum allowable pressure differential across the membrane such that the endpoint pressure in the collection chamber 32 after blood collection and before filtration is less than 5.5 psi.

[0058] Advantageously, the start-up module 22 initiates the plasma separation process after blood collection, when the blood separation device 10 is disconnected from the blood collection device 200 and the patient. To initiate the plasma separation process after blood collection, it is necessary to re-establish a pressure gradient in the stored blood in the collection chamber 32. This is achieved via the start-up module 22, which controls the pressure in the blood separation device 10. Before activation, the first seal 50 and the second seal 52 of the start-up 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 start-up module 22 seals the collection chamber 32 at a first pressure P1. After activation of the start-up module 22, the first seal 50 moves to the open position (FIG. 8B), where the collection chamber 32 is in fluid communication with a second pressure P2 formed by atmospheric pressure higher than the first pressure P1 formed in the collection chamber 32.

[0059] Importantly, within the blood separation device 10, a second pressure differential is used to drive plasma 16 through the separation member 74 and into the second chamber 72 for collection in the second phase collection container 80. With the first seal 50 in the open position (FIG. 8B), the difference between the first volume V1 of the first chamber 70 of the separation module 24 and the second volume V2 of the second chamber 72 of the separation module 24 allows The second pressure differential is created between the first chamber 70 and the second chamber 72, causing the second phase (plasma) of the blood sample 12 to 16 but The second phase is driven through the separating member 74 into the second chamber 72 and collected in the second phase collection vessel 80. Will be In other words, the second pressure difference across the blood flow in the first chamber 70 and the plasma flow in the second chamber 72 and their dynamic profile during separation provide a power source to further drive the plasma separation process. In one embodiment, the second pressure difference between the blood flow in the first chamber 70 and the plasma flow path in the second chamber and their dynamic profile for a given plasma separation chip, e.g., separation module 24, is achieved by balancing the appropriate initial vacuum level and the volume ratio of the blood sample waste chamber 82 to the second phase collection container 80. In one embodiment, the volume of the blood sample waste chamber 82 is designed such that its volume is large enough to have enough residual vacuum at the end to drive the blood flow without clogging the separation member 74. In an embodiment, the volume also needs to be small enough so that at the end of separation, the pressure in the blood sample waste 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 blood sample waste chamber 82 is designed to have a volume large enough to have enough residual vacuum at the end to drive the blood flow without clogging the separation member 74. sample The volume of the waste chamber 82 is at least twice the volume of the collection chamber 32 and is a factor (1.0) greater than the volume of the second phase collection vessel 80. -yield ) / yield It's multiplied by the law of nature The pressure differential across the membrane may be required to be less than 5.5 psi throughout filtration.

[0060] By utilizing the first and second pressure differentials within the blood separation device 10, blood 12 is forced to flow through the first chamber 70 and past the separation member 74. As blood 12 flows through the separation module 24, plasma 16 is continuously separated from the first phase 14 of the blood sample 12.

[0061] During plasma separation, the separation member 74 allows the second phase or plasma 16 to flow through it and into the second chamber 72 where it can be collected or stored in a second plasma container, e.g., a second phase collection container 80, for further diagnostic testing. With reference to FIG. 11, dashed arrows indicate the second phase flow path 104 that the plasma 16 takes after passing through the separation member 74. In one embodiment, after plasma separation, the second phase collection container 80 can 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 can then be used to transport the plasma portion 16 to a point-of-care device or other diagnostic testing system.

[0062] During plasma separation, the separation member 74 traps the first phase 14 of the blood sample 12 in the first chamber 70, e.g., the first phase 14 of the blood sample 12 cannot flow through the separation member 74 into the second chamber 72. With reference to FIG. 11, straight arrows indicate a flow path 102 for the blood sample 12 through the collection chamber 32 and for the first phase 14 of the blood sample 12 to pass over the separation member 74 into the blood sample waste chamber 82. With reference to FIGS. 11 and 12, the first phase 14 of the blood sample 12 flows through the first chamber inlet 75, over the surface of the separation member 74 into the first chamber 70, and then exits the first chamber 70 via the first chamber outlet 76 into the blood sample waste chamber 82.

[0063] In one embodiment, the blood separation device 10 of the present disclosure can produce 350-600 μl of plasma 16 from 3 ml of stored blood in less than 7 minutes.

[0064] 5, the blood separation device 10 of the present disclosure allows plasma separation to occur 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 position, e.g., stored in a tube rack, or whether the blood separation device 10 is lying flat on a table or tray.

[0065] 6, with the second phase or plasma 16 contained within the second phase collection container 80, the second phase collection container 80 is removable from the blood separation device 10. The second phase collection container 80 can then be used to transfer the plasma portion 16 to a point-of-care device or other diagnostic testing system. In one embodiment, the second phase collection container 80 is removably connectable to the blood separation device 10 via a Luer lock septum seal.

[0066] In other words, after plasma separation is completed, the plasma 16 in the second phase collection container 80 is removed from the blood separation device 10 for use in clinical testing. The remainder of the blood separation device 10 can then be discarded.

[0067] As described herein, the present disclosure provides a blood separation device that decouples and separates the blood collection process from the plasma separation process, the blood separation device having a sample collection module, a start-up module, and a separation module. Since the plasma separation process 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 patient discomfort is greatly reduced.

[0068] While the present disclosure has been described as having specific configurations, the present disclosure can 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 present disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary in the art to which this disclosure pertains and which fall within the scope of the appended claims.

Claims

1. 1. A blood separation device configured 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 forming a collection chamber; a start-up module connected to the sample collection module, the start-up module having a first seal and a second seal for sealing the housing, the first seal being movable by actuation of a portion of the start-up 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, the second pressure being higher than the first pressure; a separation module in fluid communication with the collection chamber of the sample collection module, the separation module including a blood sample waste chamber having a first volume and a second phase collection container having a second volume, and a separation element disposed between the blood sample waste chamber and the second phase collection container, wherein the first volume and the second volume are different.

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

3. 3. The blood separation device of claim 2, wherein the switch includes a push button forming a vent therethrough and a piercing portion, wherein activation of the switch moves the piercing portion to break the first seal, thereby transitioning the first seal to the open position.

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

5. 2. The blood separation device of claim 1, wherein the second seal comprises a cap having a pierceable self-sealing stopper within a portion thereof.

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

7. 7. The blood separation device of claim 6, wherein the activation module defines an inlet passageway, wherein the collection chamber receives the blood sample through the inlet passageway when the blood collection device is connected to the blood separation device via the cap.

8. 2. The blood separation device of claim 1, wherein said collection chamber includes an inlet end and an outlet end forming a plurality of continuous, flow-direction alternating collection passages.

9. 8. The blood separation device of claim 7, wherein the collection chamber has an inlet end and an outlet end defining a first collection passage extending from the inlet end to the outlet end, a second collection passage communicating with a portion of the first collection passage and extending from the outlet end to the inlet end, and a third collection passage communicating with a portion of the second collection passage and extending from the inlet end to the outlet end.

10. The collection chamber includes an inlet end and an outlet end forming a plurality of continuous flow direction alternating collection passages; 8. The blood separation device of claim 7, wherein the inlet ends of the flow-direction alternating collection passages are in fluid communication with the inlet passages of the start-up module.

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

12. 10. The blood separation device of claim 9, wherein the first collection passage is spaced from the second collection passage which is spaced from the third collection passage.

13. 2. The blood separation device of claim 1, wherein the separation element includes a first chamber having a first chamber inlet and a first chamber outlet, a second chamber having a second chamber outlet, and a separation member disposed between the first chamber and the second chamber.

14. 9. The blood separation device of claim 8, wherein the separation module includes a separation element including a first chamber having a first chamber inlet and a first chamber outlet, and a second chamber having a second chamber outlet, the first chamber inlet being in fluid communication with the outlet end of the flow direction alternating collection passage.

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

16. 16. The blood separation device of claim 15, wherein the separation member traps the first phase in the first chamber and allows the second phase to pass through the separation member into the second chamber.

17. 14. The blood separation device of claim 13, wherein the second phase collection vessel is in communication with the second chamber outlet.

18. 14. The blood separation device of claim 13, wherein the blood sample waste chamber is in communication with the first chamber outlet.

19. 14. The blood separation device of claim 13, wherein the separation member comprises a track-etched membrane.

20. the activation module includes a switch, where actuation of the switch transitions the first seal to the open position; the second seal includes a cap having a pierceable self-sealing stopper within a portion thereof; the blood separation device is connectable to a blood collection device via the cap; with the first seal in the open position, a first pressure differential between the second pressure established by atmospheric pressure and the first pressure established in the collection chamber draws the blood sample into the first chamber; 14. The blood separation device of claim 13, wherein 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, the blood sample is drawn into the first chamber by the first pressure differential between the second pressure established by the atmospheric pressure and the first pressure established in the collection chamber.

21. 2. The blood separation device of claim 1, wherein said second phase collection vessel is removable from said blood separation device.

22. 2. The blood separation device of claim 1, wherein said first phase is a cellular portion and said second phase is a plasma portion.

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