System for point-of-care blood sampling and centrifuge-free plasma or serum separation

Abstract

A system for whole blood sampling and separation includes a blood draw device coupled to a catheter assembly, with the blood draw device including a catheter tube, a housing that movably receives the catheter tube, and an advancement member to move the catheter tube between first and second positions, to enable a distal end of the catheter tube to be disposed within or past a distal tip of an indwelling catheter. A blood separation device is attached to the blood draw device to directly receive a blood sample therefrom and comprises a centrifuge-free mechanism configured to separate a plasma or serum sample from the blood sample. A sample collection container is coupled with the separation device and provides a vacuum pressure that draws the blood sample into the separation device, with the separated plasma or serum sample being drawn into the sample collection container.

Description

Attorney Docket No.09846-2502874 (P-29440.WO01) SYSTEM FOR POINT-OF-CARE BLOOD SAMPLING AND CENTRIFUGE-FREE PLASMA OR SERUM SEPARATION CROSS-REFERENCE TO RELATED APPLICATION

[0001] The present application claims priority to United States Provisional Patent Application No. 63 / 664,250 entitled “System for Point-of-Care Blood Sampling and Centrifuge-Free Plasma or Serum Separation” filed June 26, 2024, the disclosure of which is hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION Field of the Invention

[0002] The present disclosure relates generally to blood draw devices for use with intravenous (IV) catheters and, more specifically, to blood draw devices that are configured to provide centrifuge-free plasma or serum separation from a drawn blood sample on-site. Background of the Invention

[0003] Biomarker testing is a way to look for genes, proteins, and other substances (called biomarkers or tumor markers) that can provide information about certain conditions or diseases, with cancer as a primary example. A common method for performing biomarker testing is via testing of a blood sample, with the blood sample being tested for biomarkers on cells that are circulating in the blood or for pieces of genes, proteins, etc., that are in the blood. It is known that, at least in some cases, whole blood samples are not ideal for biomarker testing, but that biomarker testing is preferably performed on plasma or serum isolated from a blood sample. That is, blood cells may act as interfering elements in analyzing plasma / serum- dissolved biomarker molecules, and that several biomarkers are preferably analyzed in serum or plasma and not in whole blood. In light of the above, it is often desired to separate an acquired blood sample prior to analysis, in order to separate the plasma / serum from the blood cells.

[0004] In performing a biomarker testing, options available include: (1) point-of-care (POC) testing, where the biomarker testing is performed on-site where the blood sample is collected, with testing performed on the whole blood sample, and (2) lab testing, where the blood sample is transferred from the site of blood sample collection to a lab, where the blood sample may be further prepped and tested using specialized testing equipment. 64W5808.DOCX Page 1 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0005] With regard to POC testing, a benefit of such testing is that turn-around time from sample collection to biomarker testing is minimized, which may be desirable for certain tests that require fresh samples for testing (i.e., blood samples tested within 30 minutes of sampling), such as IL-6 testing, labile biomarker testing, and STAT tests. However, it is recognized that the accuracy of POC biomarker testing is lower as compared to laboratory testing, as POC tests may lack specificity and sensitivity compared to laboratory testing.

[0006] With regard to laboratory testing, a benefit of such testing is that the specificity and sensitivity of such testing is the gold standard in biomarker testing. However, it may be difficult to provide suitable plasma / serum samples to the lab within a suitable turn-around time from blood sample collection. First, it may be difficult to perform a separation of the plasma / serum from the remaining blood cells at the lab (such as via centrifugation) and subsequently perform biomarker testing on the plasma / serum all within a required timeframe, as centrifugation is a time-intensive process. Second, the performing of centrifugation itself can lead to numerous pre-analytical errors that affect accuracy of the biomarker testing, with centrifugation errors such as incorrect speed, incorrect or broken blood collection tubes, erroneous temperature, insufficient centrifugation, etc., leading to reduced accuracy of the laboratory testing.

[0007] Based on the above, there is a need to develop a system for blood sample collection and separation, along with subsequent biomarker testing techniques, that can reduce turn- around time between POC sample collection and laboratory biomarker testing of the sample. Such a system would desirably provide for collection of a blood sample of a suitable volume at the POC, and also provide for separation of plasma / serum from the whole blood sample at the POC – with the method of separating the plasma / serum from the whole blood sample being a centrifuge-free method, so as to minimize the length of the separation process and eliminate the potential for centrifugation-related pre-analytical errors. The system and method would provide a separated plasma / serum sample of high quality and with a low turn-around time, allowing for subsequent transfer of the sample to a laboratory testing site for high accuracy biomarker testing. SUMMARY OF THE INVENTION

[0008] Provided herein is a system for blood sampling and testing useable with a catheter assembly comprising an intravenous (IV) catheter and an access port. The system includes a blood draw device coupleable to the near patient access port, with the blood draw device further including a catheter tube, an introducer housing defining an inner volume configured to movably receive the catheter tube and having a proximal end portion and a distal end portion 64W5808.DOCX Page 2 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) coupleable to the catheter assembly, and an advancement member configured to move relative to the introducer housing to move the catheter tube between a first position, in which the catheter tube is disposed within the introducer housing, and a second position, in which a distal end portion of the catheter tube is disposed beyond a distal end portion of the introducer housing, such that at least a first portion of the catheter tube may be disposed within the indwelling IV catheter or past a distal tip thereof. The system further includes a blood separation device attached to the blood draw device proximal to the housing and in fluid communication with the catheter tube, to directly receive a blood sample from the blood draw device when the catheter tube is in the second position, with the blood separation device comprising a centrifuge-free mechanism configured to separate a plasma or serum sample from the blood sample. The system still further includes a sample collection container coupled with the blood separation device and configured to provide a vacuum pressure that draws the blood sample into the blood separation device, with the separated plasma or serum sample being drawn into the sample collection container.

[0009] In some embodiments, the blood draw device includes an extension tube coupled to the advancement member and extending out proximally therefrom and out the proximal end portion of the housing, the extension tube fluidly connecting the catheter tube and the blood separation device, and a coupler connected to a proximal end of the extension tube, and wherein the blood separation device is connected to the extension tube via the coupler.

[0010] In some embodiments, the blood draw device includes a clamp positioned on the extension tube and operable in a closed position and an open position to selectively control a flow of blood through the extension tube, from the catheter tube to the blood separation device.

[0011] In some embodiments, the separation device includes a housing defining an interior housing volume, a distal connector provided on the housing and configured to mate with the coupler to fluidly connect the microfluidic channel to the extension tube, a proximal connector provided on the housing and configured to mate with the sample collection container, a blood collection chamber positioned within the interior housing volume and fluidly connected to the distal connector, the blood collection chamber storing the blood sample received from the blood draw device, and a microfluidic channel positioned within the interior housing volume and extending between the blood collection chamber and the proximal connector, wherein capillary forces act on the blood sample as it is drawn into and through the capillary tubing, to extract plasma or serum from the blood sample, with extracted plasma or serum passing into the sample collection container as the plasma or serum sample. 64W5808.DOCX Page 3 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0012] In some embodiments, the proximal connector of the blood separation device comprises a needle connector including: a needle extending out proximally from the housing; and a sheath positioned over the needle.

[0013] In some embodiments, the sample collection container comprises a vacuumed collection tube, the vacuumed collection tube defining an interior volume and including a tube membrane covering a distal opening thereof.

[0014] In some embodiments, the system further includes a tube holder configured to engage the proximal connector, with the tube holder defining a cavity configured to receive the vacuumed collection tube therein, and wherein with the vacuumed collection tube positioned in the tube holder, the needle pierces the tube membrane to fluidly connect the needle with the vacuumed collection tube.

[0015] In some embodiments, the proximal connector of the blood separation device comprises a female luer connector.

[0016] In some embodiments, the sample collection container comprises a syringe including a syringe barrel defining a chamber for retaining fluid therein and a plunger assembly being axially movable within the syringe barrel from an advanced position to a retracted position, to generate vacuum pressure that facilitates a separation and draw of plasma or serum into the chamber of the syringe barrel, wherein a distal end of the syringe barrel comprises fluid connector component configured as a male luer connection that engages the female luer connector of the blood separation device to fluidly connect the blood separation device and the syringe.

[0017] In some embodiments, one or more of the blood collection chamber and the microfluidic channel is coated with a clot inhibitor or anticoagulant that prevents the blood sample from clotting, to provide for extraction of plasma from the blood sample as it advances into the microfluidic channel.

[0018] In some embodiments, one or more of the blood collection chamber and the microfluidic channel is coated with a clot accelerator that promotes clotting of the blood sample, so as to remove fibrinogen from the blood sample and provide for extraction of serum from the blood sample as it advances into the microfluidic channel.

[0019] In some embodiments, the distal connector comprises a male luer connection and the coupler comprises a female luer connection.

[0020] Also provided is a system for blood sampling and testing useable with a catheter assembly comprising an intravenous (IV) catheter and an access port. The system includes a blood draw device coupleable to the near patient access port, with the blood draw device further 64W5808.DOCX Page 4 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) including a catheter tube, an introducer housing defining an inner volume configured to movably receive the catheter tube and having a proximal end portion and a distal end portion coupleable to the catheter assembly, and an advancement member configured to move relative to the introducer housing to move the catheter tube between a first position, in which the catheter tube is disposed within the introducer housing, and a second position, in which a distal end portion of the catheter tube is disposed beyond a distal end portion of the introducer housing, such that at least a first portion of the catheter tube may be disposed within the indwelling IV catheter or past a distal tip thereof. The system further includes a dual- chambered vacuum tube connectable to the blood draw device proximal to the housing to receive a blood sample therefrom, with the dual-chambered vacuum tube comprising a blood collection tube comprising a tube membrane sealing a distal end thereof, a plasma / serum collection tube positioned proximally from the blood collection tube, a bushing cap configured to secure the blood collection tube with the plasma / serum collection tube, the bushing cap comprising a cap membrane positioned to seal a proximal end of the blood collection tube, and a filter seated within the bushing cap proximal from the cap membrane, the filter configured to filter out blood cells when the blood sample is passed therethrough to provide a separated plasma or serum sample to the plasma / serum collection tube.

[0021] In some embodiments, the blood draw device includes an extension tube coupled to the advancement member and extending out proximally therefrom and out the proximal end portion of the housing and a coupler connected to a proximal end of the extension tube.

[0022] In some embodiments, the system further includes a connector arrangement positioned between the coupler and the dual-chambered vacuum tube, to mechanically and fluidly connect the blood draw device with the dual-chambered vacuum tube, with the connector arrangement comprising a double-ended connector and a needle assembly.

[0023] In some embodiments, the needle assembly comprises a needle engageable with the dual-chambered vacuum tube in each of a first insertion position a second insertion position. With the needle engaged with the dual-chambered vacuum tube in the first insertion position, a tip of the needle pierces through the tube membrane and positioned within a chamber of the blood collection tube, to fluidly connect the blood collection tube with a lumen within the needle. With the needle engaged with the dual-chambered vacuum tube in the second insertion position, the tip of the needle pierces through the cap membrane to form a through-hole in the cap membrane, to fluidly connect a chamber of the plasma / serum collection tube with the chamber of the blood collection tube upon retraction of the needle back out from the through- hole. 64W5808.DOCX Page 5 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0024] In some embodiments, the double-ended connector comprises a distal connector configured to engage the coupler of the blood draw device and a proximal connector configured to engage the needle assembly, with the needle assembly further comprising a needle sleeve that mates with the proximal connector and that secures a distal end of the needle therein and a sheath positioned over a proximal end of the needle, including the tip.

[0025] In some embodiments, the needle comprises a coring needle configured to pierce through the tube membrane without cutting and removing a core therefrom and to cut a core or material out from the cap membrane when pierced therethrough, so as to form the through-hole in the cap membrane.

[0026] In some embodiments, the blood collection tube is coated with a with a clot inhibitor or anticoagulant that prevents the blood sample from clotting, to provide for extraction of plasma from the blood sample as it passes through the filter.

[0027] In some embodiments, the blood collection tube is coated with a clot accelerator that promotes clotting of the blood sample, so as to remove fibrinogen from the blood sample and provide for extraction of serum from the blood sample as it passes through the filter. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] FIG.1 is a perspective view of a system for improved blood sampling and separation, and an accompanying catheter assembly, in accordance with an aspect of the disclosure;

[0029] FIG. 2 is a perspective view of the system of FIG. 1, without the catheter assembly, in accordance with an aspect of the disclosure;

[0030] FIG. 3 is an exploded view of the system of FIG. 2;

[0031] FIG.4 is a side view of the system of FIG.2, showing the blood draw device thereof operated with a catheter tube in a first, retracted position;

[0032] FIG. 5 is a side view of the system of FIG.2, showing the blood draw device thereof operated with the catheter tube in a second, extended position;

[0033] FIG.6 is a detailed view of the blood separation device and vacuumed collection tube of the system of FIG. 2, in accordance with an aspect of the disclosure;

[0034] FIG.7 is a perspective view of a system for improved blood sampling and separation with syringe, in accordance with another aspect of the disclosure;

[0035] FIG. 8 is a detailed view of the blood separation device and syringe of the system of FIG. 7, in accordance with an aspect of the disclosure; 64W5808.DOCX Page 6 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0036] FIG.9 is a perspective view of a system for improved blood sampling and separation, in accordance with another aspect of the disclosure;

[0037] FIG. 10 is an exploded view of the system of FIG. 9;

[0038] FIG.11 is a cross-sectional view of the dual-chambered vacuum tube included in the system of FIG. 9; and

[0039] FIG. 12 is a perspective view of a system for improved blood sampling and separation, in accordance with another aspect of the disclosure. DESCRIPTION OF THE INVENTION

[0040] The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention. Various modifications, equivalents, variations, and alternatives, however, will remain readily apparent 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.

[0041] As used in this specification, the words "proximal" and "distal" refer to the direction closer to and away from, respectively, a user who would place the device into contact with a patient. Thus, for example, the end of a device first touching the body of the patient would be the distal end, while the opposite end of the device (e.g., the end of the device being manipulated by the user) would be the proximal end of the device.

[0042] Spatial or directional terms, such as “left”, “right”, “inner”, “outer”, “above”, “below”, and the like, are not to be considered as limiting as the invention can assume various alternative orientations.

[0043] For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the invention as it is oriented in the drawing figures. However, it is to be understood that the invention may assume various alternative variations, except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary aspects of the invention.

[0044] The terms “first”, “second”, and the like are not intended to refer to any particular order or chronology, but refer to different conditions, properties, or elements.

[0045] As used herein, “at least one of” is synonymous with “one or more of”. For example, the phrase “at least one of A, B, and C” means any one of A, B, or C, or any combination of any two or more of A, B, or C. For example, “at least one of A, B, and C” includes one or 64W5808.DOCX Page 7 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) more of A alone; or one or more of B alone; or one or more of C alone; or one or more of A and one or more of B; or one or more of A and one or more of C; or one or more of B and one or more of C; or one or more of all of A, B, and C.

[0046] The present invention is directed to a system having a blood draw device (alternatively, “line draw device”) to advance a blood draw catheter tube into an indwelling IV catheter and subsequently draw a blood sample from a patient, with the sample being provide to a blood separation device and accompanying collection device attachable to the blood draw device, so as to provide a centrifuge-free plasma / serum separation at the POC.

[0047] Referring to FIG. 1, shown is a non-limiting embodiment of a system 10 for facilitating improved blood sampling and plasma / serum sample separation. System 10 may be useable with a vascular access device (VAD) 11 that includes a catheter assembly 12 having a catheter adapter 14 and associated IV catheter 16. The catheter adapter 14 may include a distal end 18 and a proximal end 20. In some embodiments, the catheter adapter 14 may include an additional adapter port 22 that may be disposed between the distal end 18 and the proximal end 20 or disposed at the proximal end 20. The catheter adapter 14 may include a first lumen 24 extending through the distal end 18 and the proximal end 20, and the first lumen 24 may be sealed at proximal end 20 of catheter adapter 14. The IV catheter 16 may be formed of any suitable material and may be of any useful length, as known to those of skill in the art. IV catheter 16 extends from the distal end 18 of catheter adapter 14 and may be configured as an IV catheter (hereafter “IV catheter 16”) that is placed into the vasculature of the patient, with a distal end or tip 26 of the IV catheter 16 positioned appropriately within a vein 28 to enable a blood draw from the patient.

[0048] In some non-limiting embodiments or aspects, the catheter assembly 12 may include a first fluid conduit 30 extending from the port 22. First fluid conduit 30 may be formed of any suitable material known to those of skill in the art and may have a distal end and a proximal end. The distal end of first fluid conduit 30 is coupled to port 22, while the proximal end of first fluid conduit 30 may be coupled to a connector 36. Connector 36 may be a t-connector (e.g., one side port arranged at a 90 degree angle relative to a longitudinal axis of connector 36), a y-connector (e.g., one side port arranged at a 25, a 60, or a 75 degree angle relative to a longitudinal axis of connector 36), or any other type of connector known in the art. The connector 36 includes a second lumen 38 therethrough, having any number of branches suitable for the type of connector.

[0049] In some non-limiting embodiments or aspects, catheter assembly 12 may include a needleless access connector 46 coupled to a proximal end of connector 36, with the needleless 64W5808.DOCX Page 8 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) access connector 46 providing an access port to the catheter assembly 12. The needleless access connector 46 may be configured as a split-septum connector or self-healing septum connector, as examples. In the illustrated embodiment, the access port provided by needleless access connector 46 is a near-patient access port close to the insertion site of the IV catheter 16, but it is recognized that an access port could be provided at other alternative locations close enough to the insertion site that allow for advancement of a blood draw catheter tube into the indwelling IV catheter 16 and out beyond the distal tip thereof. For example, an access port that provides for advancement of a blood draw catheter tube into the indwelling IV catheter 16 could be located on another connector, such as a proximal connector on an extension set (as described below) of the catheter assembly 12.

[0050] System 10 includes a blood draw device 60 (alternatively, “line draw device”) that may be operated to obtain a blood sample from the patient, with such a blood sample enabling coagulation testing of the blood sample, for example. As shown in FIG.1 and in further detail in FIGS. 2-5, according to a non-limiting embodiment, the blood draw device 60 includes at least an introducer housing 62, a coupling device 64, a catheter tube 66, and an advancement member 68. As will be described in further detail below, the catheter tube 66 is moveable within the introducer housing 62 so as to provide for advancement of a portion of the catheter tube 66 from a first or retracted position inside the introducer housing 62 (FIG. 4) to a second or advanced position outside of the introducer housing 62 (FIG.5), such that a distal end thereof may be routed into the catheter assembly 12. Once a portion of the catheter tube 66 has been routed into the catheter assembly 12 and adjacent to or out past the distal tip 26 of indwelling IV catheter 16, the catheter tube 66 may enable collection of a blood sample.

[0051] According to embodiments, the catheter tube 66 is sized to enable introduction thereof into the fluid path (i.e., into a lumen of IV catheter 16, lumen 24 of catheter adapter 14, and first fluid conduit 30) of catheter assembly 12 and for advancement therethrough. Accordingly, the catheter tube 66 can have an outer diameter (e.g., between a 10-gauge and a 30-gauge) that is smaller than the smallest lumen of the catheter assembly fluid path. The catheter tube 66 can have a length that is sufficient to place a distal end 70 of the catheter tube 66 in a desired position within the fluid path of the system 10. Thus, in one embodiment, the catheter tube 66 may have a length sufficient to provide for advancement of the distal end 70 thereof out from the introducer housing 62 and through the catheter assembly (i.e., through connector 36, fluid conduit 30, catheter adapter 14 and IV catheter 16), and all the way out past the distal tip 26 of IV catheter 16. 64W5808.DOCX Page 9 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0052] In some embodiments, and in order to accommodate positioning of the catheter tube 66 within IV catheter 16 and advancement thereof out past the distal tip 26 of IV catheter 16, the distal end 26 of the IV catheter 16 may include fenestrations formed therein. The fenestrations at the distal end 26 of the IV catheter 16 serve to maintain fluid continuity from the vein and through the IV catheter 16 - i.e., the fenestrations prevent catheter tube 66 from occluding the IV catheter 16 at the distal tip 26 thereof.

[0053] As shown in FIGS.2-5, the introducer housing 62 of blood draw device 60 can be an elongate member having a proximal end 72 and a distal end 74 and defining an inner volume 76. In some embodiments, the introducer housing 62 may be formed of a pair of housing portions that are coupled together to define the inner volume 76. The introducer housing 62 may include one or more features or surface finishes on an outer surface thereof that can be arranged to increase the ergonomics of the blood draw device 60, which in some instances can allow a user to manipulate the blood draw device 60 with one hand (i.e., single-handed use).

[0054] The coupling device 64 of blood draw device 60 is provided at the distal end 74 of the introducer housing 62, with the coupling device 64 providing for reversible coupling of the blood draw device 60 to catheter assembly 12, such as via needleless access connector 46 as shown in FIG.1. In some embodiments, the coupling device 64 is configured as a lock 80 that includes a blunted cannula 82 and locking arms 84 for coupling to the needleless access connector 46 of catheter assembly 12, with the blunted cannula 82 and locking arms 84 forming three points of contact therewith. However, those of skill will appreciate that any connection or coupling, for example a luer, can be used, so long as the distal end 70 of catheter tube 66 may pass through the coupling device 64 to catheter assembly 12.

[0055] The advancement member 68 of blood draw device 60 includes a first portion 86 and a second portion 88. The first portion 86 is movably disposed along an upper surface 90 of the introducer housing 62 and the second portion 88 is movably disposed within the inner volume 76 of the introducer housing 62. The arrangement of the advancement member 68 and the introducer housing 62 is such that a connecting portion (not shown) of the advancement member 68 that joins the first and second portions 86, 88 is seated within a slot 92 formed in the upper surface 90 of the introducer housing 62 – the slot 92 generally extending between the proximal and distal ends 72, 74 of the introducer housing 62. As the first and second portions 86, 88 are joined together, movement of the first portion 86 along the upper surface 90 of the introducer housing 62 results in a corresponding movement of the second portion 88 within the inner volume 76. 64W5808.DOCX Page 10 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0056] As shown in FIGS. 2-5, the first portion 86 of the advancement member 68 may be configured as a tab or tab having a contact surface 94a engageable by a user and an underside 94b that is in contact with the outer surface 90 of the introducer housing 62. In such embodiments, the upper surface 90 of the introducer housing 62 can include a track 96, for example, a set of ribs, ridges, bumps, grooves, and / or the like along which the underside 94b of tab or protrusion advances when the advancement member 68 is engaged by a user. In this manner, a user can engage the first portion 86 of the advancement member 68 and can move the advancement member 68 relative to the introducer housing 62.

[0057] As shown in FIGS. 2-5, the second portion 88 includes an opening 98 extending therethrough that is configured to grip or retain a portion of the catheter tube 66. Due to a portion of the catheter tube 66 being retained within the opening 98 of second portion, 94, movement of the advancement member 68 relative to introducer housing 62 causes a corresponding movement of the catheter tube 66 relative to the introducer housing 62. In this manner, the distal end 70 of the catheter tube 66 can be selectively moved out of or back into the inner volume 76 of the introducer housing 62 as desired, such as advancing the distal end 70 of the catheter tube 66 out of the introducer housing 62 when the blood draw device 60 has been coupled to the catheter assembly 12 and collection of an arterial blood sample is to be performed.

[0058] As further shown in FIGS.2-5, blood draw device 60 includes an extension tube 102 provided at the proximal end 72 of the introducer housing 62. The extension tube 102 has a proximal end portion 104 and a distal end portion 106 and defines a lumen 108. A portion of the extension tube 102 is disposed within and extends through an opening 110 formed in the proximal end 72 of introducer housing 62. As such, the proximal end portion 104 is at least partially disposed outside of the introducer housing 62 and the distal end portion 106 is at least partially disposed within the introducer housing 62, with the distal end portion 106 coupled to the second portion 88 of the advancement member 68. In some embodiments, the extension tube 102 can have a larger diameter than the catheter tube 66, which can function to limit, reduce, and / or substantially prevent hemolysis of a volume of blood as the volume of blood flows through the catheter 66 and the extension tube 102.

[0059] According to embodiments of the disclosure, a clamp 112 is positioned on the extension tube 102 that is operable to selectively enable blood flow along a length of the extension tube 102 from the distal end portion 106 to the proximal end portion 104. That is, the clamp 112 may be actuatable between a closed position in which the clamp 112 stops blood flow through the clamped portion of the extension tube 102 and an open position in which the 64W5808.DOCX Page 11 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) clamp 112 allows blood flow through the clamped portion of the extension tube 102. In some embodiments, the clamp 112 may be configured such that the default position thereof is the closed position.

[0060] According to embodiments of the disclosure, the proximal end portion 104 of the extension tube 102 is coupled to and / or otherwise includes a coupler 114 configured to mate with a blood separation device 116 that is useable with (or is considered part of) the blood draw device 60 to obtain a plasma or serum sample from the whole blood sample. According to some embodiments, the coupler 114 may be configured as a luer connection (i.e., a female luer connection) configured to mate with a corresponding luer connection (i.e., a male luer connection) of the separation device 116, to physically and fluidically couple the extension tube 102 to the separation device 116.

[0061] As shown in more detail in FIGS. 2 and 6, in accordance with one aspect of the disclosure, the separation device 116 connected to blood draw device 60 (via coupler 114) is configured as a microfluidic separation device that separates the plasma or serum sample from the red blood cells of the whole blood sample. The microfluidic separation device 116 includes a housing 118, a distal connector 120 provided on the housing 118, a blood collection chamber 122 positioned within an interior volume 123 of the housing 118 and fluidly connected to the distal connector 120, a microfluidic channel 124 positioned within the interior volume 123 of the housing 118 and having a distal channel end 126 and a proximal channel end 128, with the distal channel end 126 connected to blood collection chamber 122, and a proximal connector 130 provided on the housing 118 and fluidly connected to the proximal channel end 128.

[0062] The distal connector 120 is configured to mechanically and fluidly connect the separation device 116 to the blood draw device 60. In some embodiments, the distal connector 120 comprises a male luer connection (including a rotatable collar and tapered stem) that mates with the coupler 114, which may comprise a female luer connection.

[0063] The proximal connector 130 is configured to mechanically and fluidly connect the separation device 116 to a collection tube or container 132 (of system 10) that collects and stores a volume of serum or plasma that was separated out from the collected blood sample by blood separation device 116. The configuration of the proximal connector 130 may vary based on the configuration of the collection tube or container 132 to be connected thereto, but in the embodiment illustrated in FIGS. 1-6, the proximal connector 130 may comprise a needle connector (with a needle 134 extending out proximally from housing 118 and a sheath 136 provided thereover) that may be mechanically and fluidly connected with a vacuumed 64W5808.DOCX Page 12 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) collection tube 132, such as a Vacutainer® from Becton, Dickinson and Company, as a non- limiting example.

[0064] The microfluidic channel 124 may be formed by a length of capillary tubing 142 that is arranged in a serpentine pattern within the interior housing volume 123. The capillary tubing 142 is connected at the distal channel end 126 thereof to the blood collection chamber 122, with the blood collection chamber 122 in turn connected to distal connector 120, such that the microfluidic channel 124 is placed in fluid communication with the extension tube 102 (through mating of the coupler 114 and distal connector 120). The capillary tubing 142 then proceeds from its distal channel end 126 along a serpentine path to its proximal channel end 128, which is fluidly connected to the proximal connector 130. With the second end of capillary tubing 142 in fluid communication with the proximal connector 130 (i.e., with a lumen 137 within the needle 134 of proximal connector 130), a fluid path is provided through separation device 116.

[0065] As further shown in FIGS. 1-6, in embodiments where proximal connector 130 is a needle connector (with a needle 134 and sheath 136) configured to engage a vacuumed collection tube 132 (e.g., Vacutainer®), a tube holder 138 may be coupled to proximal connector 130 prior to connection of vacuumed collection tube 132. The tube holder 138 may couple with proximal connector 130 and provide a cavity 140 within which the vacuumed collection tube 132 may be received. With the tube holder 138 coupled to proximal connector 130, the needle 134 (and sheath 136) is positioned within the cavity 140 and is positioned to engage the vacuumed collection tube 132 (i.e., pierce a seal or membrane 142 of the tube 132, covering a distal opening of the tube to enclose an interior volume thereof) when the vacuumed collection tube 132 is slid into the cavity 140 of tube holder 138.

[0066] With the needle 134 of proximal connector 130 engaged with vacuumed collection tube 132 and providing a fluid connection thereto, the vacuum within collection tube 132 causes a blood sample (collected by blood draw device 60) to be drawn into the separation device 116 (i.e., into microfluidic channel 124 thereof), with the separation device 116 separating a serum or plasma out from the blood sample, and the serum or plasma being collected by the collection tube 132. That is, plasma or serum may be separated out from the whole blood sample when the blood sample is drawn into / through the capillary tubing 142 - with capillary forces acting on the whole blood sample as it is drawn into / through the capillary tubing 142 to extract the plasma / serum therefrom.

[0067] As indicated above, the separation device 116 is configured to provide for collection of either plasma or serum. As known to those skilled in the art, serum is a component of plasma, 64W5808.DOCX Page 13 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) but serum does not include the fibrinogen (and clotting factors II, V, VIII) found in plasma. According to embodiments of the disclosure, the separation device 116 may be specifically configured to provide for the collection of plasma or of serum in the collection tube or container 132 that may be connected thereto.

[0068] In a first embodiment, the separation device 116 is configured to provide for the collection of plasma in the collection tube or container 132. In such an embodiment, portions of the separation device 116 - including at least the blood collection chamber 122 and the microfluidic channel 124 / capillary tubing 142 (and optionally the distal connector 120) – are coated with a clot inhibitor or anticoagulant (e.g., ethylenediaminetetraacetic acid (EDTA), as a non-limiting example) – generally identified in FIG. 6 as “144”. Coating of the blood collection chamber 122 and the microfluidic channel 124 / capillary tubing 142 with such a clot inhibitor or anticoagulant preventing the whole blood sample from clotting as plasma is extracted therefrom when passing through the separation device 116 – thereby enabling collection of a plasma sample within the collection tube or container 132.

[0069] In a second embodiment, the separation device 116 is configured to provide for the collection of serum in the collection tube or container 132. In such an embodiment, portions of the separation device 116 - including at least the blood collection chamber 122 and the microfluidic channel 124 / capillary tubing 142 (and optionally the distal connector 120) – may be coated with a clot accelerator (e.g., engineered Zeolites, Kaolin, thromboplastin, etc., as non-limiting examples) – generally identified in FIG. 6 as “144”. Coating of the blood collection chamber 122 and the microfluidic channel 124 / capillary tubing 142 with such a clot accelerator allows the whole blood sample to clot faster, thereby removing fibrinogen from the sample as serum is extracted therefrom when passing through the separation device 116 – thereby enabling collection of a serum sample within the collection tube or container 132.

[0070] With the system 10 configured as described above, a method for operating the system 10 to provide for collection of a blood sample and separation of plasma or serum therefrom may be described as follows.

[0071] In a first step of operation of system 10, the blood draw device 60 may be prepared (e.g., removed from packaging) and the microfluidic separation device 116 may be attached thereto (via coupler 114).

[0072] After connection of the microfluidic separation device 116 to the blood draw device 60, a tube holder 138 may be connected to the microfluidic separation device 116 via proximal connector 130 thereof. 64W5808.DOCX Page 14 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0073] Upon connection of the tube holder 138 to microfluidic separation device 116, the blood draw device 60 may be attached to the catheter assembly 12, such as via connection of coupling device 64 of blood draw device 60 to needleless access connector 46 of catheter assembly 12.

[0074] With the blood draw device 60 attached to the catheter assembly 12, the catheter tube 66 may be advanced into / through the indwelling IV catheter 16 of catheter assembly 12, as described in detail above.

[0075] With the catheter tube 66 advanced into / through the indwelling IV catheter 16 of catheter assembly 12, the collection tube or container 132 may be inserted into tube holder 138 such that needle 134 of proximal connector 130 is brought into fluid communication with the tube / container 132. The vacuum within the tube / container 132 causes a blood sample to be drawn into the blood draw device 60, with the blood sample continuing proximally through the blood draw device 60 to the microfluidic separation device 116. When the blood sample is provided to the separation device 116, the blood sample initially collects in the blood collection chamber 122, before being drawn into / through the microfluidic channel 124 / capillary tubing 142. As the blood sample is drawn into / through the microfluidic channel 124 / capillary tubing 142, plasma or serum is extracted / separated from the blood sample and passed into the tube / container 132.

[0076] Upon a full sample of plasma or serum being collected in the tube / container 132, the tube / container 132 may be removed from the tube holder 138 (and with needle 134 withdrawn out from seal / membrane 142), with the sealed tube / container 132 then being sent to a testing device / system at a laboratory or other location for biomarker testing of the plasma / serum sample.

[0077] Referring now to FIGS. 7 and 8, a system 150 for facilitating improved blood sampling and plasma / serum separation is shown in accordance with another aspect of the disclosure. In system 150, the structure of blood draw device 60 is identical to that of system 10 shown in FIGS. 1-6 (and the blood draw device 60 may be connected to vascular access device 12 in the same manner), and thus like members are labeled identically in system 150. However, as provided in detail here below, the separation device 116 of system 150 is modified to provide for connection of a syringe thereto.

[0078] As shown in FIGS.7 and 8, separation device 116 is configured substantially similar to separation device 116, except that a proximal connector 152 thereof is reconfigured to enable connection of a syringe 154 directly thereto. In one embodiment, the proximal connector 152 64W5808.DOCX Page 15 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) may thus be provided as a female luer connection configured to engage a male luer connection of the syringe 154.

[0079] As shown best in FIG.8, syringe 154 may generally include a syringe barrel 156 and a plunger assembly 158 – with the plunger assembly 158 being axially movable within the syringe barrel 156 from an advanced position to a retracted position, to facilitate a blood draw from a patient, for example.

[0080] The syringe barrel 156 is formed of a generally cylindrical outer wall and an end wall that collectively define a chamber 160 for retaining fluid therein. The syringe barrel 156 includes an open proximal end configured to receive the plunger assembly 158 therein and a distal end at which the end wall is positioned. At the distal end, a tip extends distally outward from the end wall and defines a lumen in fluid communication with the chamber 160. A fluid connector component 162 is provided on the tip that is coupleable to the proximal connector 152 of the separation device 116. As indicated above, in some embodiments, fluid connector component 162 is configured as a male luer connection configured to engage the female luer connection of separation device 116.

[0081] The plunger assembly 158 of syringe 154 is formed of an elongate plunger rod 164 and a plunger head or stopper 166. The stopper 166 of plunger assembly 158 is positioned at the distal end of the plunger rod, so as to be movable along with the plunger rod 164 within the chamber 160 of syringe barrel 156. The stopper 166 may be made from a material that is different from the material of the plunger rod 164 and that is capable of forming a tight seal with the syringe barrel 156 as it is moved therethrough. The stopper 166 may further include a pair of spaced-apart annular flanges formed thereon (i.e., O-rings) that form a tight seal with the syringe barrel 156, as known in the art.

[0082] In operation of the syringe 154, the plunger assembly 158 may be retracted proximally from a starting position (with stopper 166 positioned toward the distal end of the syringe barrel 156) to a stop position, with retraction of the plunger assembly 158 creating a vacuum within the syringe barrel 156 that causes plasma or serum to be drawn into the syringe 154 (i.e., into chamber 160).

[0083] As previously described for the embodiment of FIGS. 1-6, the separation device 116 may be specifically configured to provide for the collection of plasma or of serum in the syringe 154 that may be connected thereto. In a first embodiment, the separation device 116 is configured to provide for the collection of plasma in the syringe 154 - with portions of the separation device 116 (i.e., blood collection chamber 122 and microfluidic channel 124 / capillary tubing 142) being coated with a clot inhibitor or anticoagulant 144 to prevent the 64W5808.DOCX Page 16 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) blood sample from clotting as plasma is extracted therefrom when passing through the separation device 116 – thereby enabling collection of a plasma sample within the syringe 154. In a second embodiment, the separation device 116 is configured to provide for the collection of serum in the syringe 154 - with portions of the separation device 116 (i.e., blood collection chamber 122 and microfluidic channel 124 / capillary tubing 142) being coated with a clot accelerator 144 that allows the whole blood sample to clot faster, thereby removing fibrinogen from the sample as serum is extracted therefrom when passing through the separation device 116 and enabling collection of a serum sample within the syringe 154.

[0084] With the system 10 configured as described above, a method for operating the system 150 to provide for collection of a blood sample and separation of plasma or serum therefrom may be described as follows.

[0085] In a first step of operation of system 150, the blood draw device 60 may be prepared (e.g., removed from packaging) and the microfluidic separation device 116 may be attached thereto (via coupler 114).

[0086] After connection of the microfluidic separation device 116 to the blood draw device 60, the syringe 154 may be connected to the microfluidic separation device 116 via proximal connector 152.

[0087] Upon connection of the syringe 154 to microfluidic separation device 116, the blood draw device 60 may be attached to the catheter assembly 12, such as via connection of coupling device 64 of blood draw device 60 to needleless access connector 46 of catheter assembly 12.

[0088] With the blood draw device 60 attached to the catheter assembly 12, the catheter tube 66 may be advanced into / through the indwelling IV catheter 16 of catheter assembly 12, as described in detail above.

[0089] With the catheter tube 66 advanced into / through the indwelling IV catheter 16 of catheter assembly 12, the plunger assembly 158 of syringe 154 may be retracted proximally from a starting position to a stop position. The proximal retraction of the plunger assembly 158 generates a vacuum within the chamber 160 that causes a blood sample to be drawn into the blood draw device 60, with the blood sample continuing proximally through the blood draw device 60 to the microfluidic separation device 116. When the blood sample is provided to the separation device 116, the blood sample initially collects in the blood collection chamber 122, before being drawn into / through the microfluidic channel 124 / capillary tubing 142. As the blood sample is drawn into / through the microfluidic channel 124 / capillary tubing 142, plasma or serum is extracted / separated from the blood sample and passed into the syringe 154. 64W5808.DOCX Page 17 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0090] Upon a full sample of plasma or serum being collected in the syringe 154, the syringe 154 may be disconnected from the proximal connector 152 of separation device 116, with the syringe 154 then being sent to a testing device / system at a laboratory or other location for biomarker testing of the plasma / serum sample.

[0091] While the systems 10 shown and described in FIGS. 1-6 and FIGS. 7 and 8 include a microfluidic separation device 116 that provides for separation of a plasma / serum sample from a whole blood sample provided by the blood draw device 60, it is recognized that a system may be provided that enables separation of a plasma / serum sample from a whole blood sample provided by blood draw device 60 without use of such a microfluidic separation device 116.

[0092] Referring now to FIGS. 9-11, a system 170 for facilitating improved blood sampling and plasma / serum separation is shown in accordance with yet another aspect of the disclosure. Again, in system 170, the structure of blood draw device 60 is identical to that of system 10 shown in FIGS. 1-6 and FIGS. 7 and 8 (and the blood draw device 60 may be connected to vascular access device 12 in the same manner), and thus like members are labeled identically in system 170. However, as provided in detail here below, rather than including a separation device 116, system 170 includes a dual-chambered vacuum tube 172 that may be coupled to the blood draw device 60 (via a connector arrangement 174) to provide for separation of plasma / serum from the collected blood sample.

[0093] According to aspects of the disclosure, the dual-chambered vacuum tube 172 comprises a blood collection tube 176 and a plasma / serum collection tube 178 – with the plasma / serum collection tube 178 positioned proximally from the blood collection tube 176. The blood collection tube 176 may be configured to be open on both ends thereof, with a stopper or thin tube membrane 180 positioned within the distal opening of the blood collection tube 176 to seal the distal end. The plasma / serum collection tube 178 may be open at the distal end thereof and closed at the proximal end.

[0094] The plasma / serum collection tube 178 may be joined to (and separated from) the blood collection tube 176 by a bushing cap 182. The bushing cap 182 may be formed of a rigid plastic material (e.g., polypropylene (PP) or polyethylene (PE), as non-limiting examples) and may generally comprise a coupling portion 184 and a separating cap membrane 186. The coupling portion 184 may be configured to receive each of the plasma / serum collection tube 178 (a distal end thereof) and the blood collection tube 176 (a proximal end thereof), to secure the two tubes together and provide the dual-chambered vacuum tube 172. The cap membrane 186 of the bushing cap 182 seals off the open proximal end of the blood collection tube 176, to 64W5808.DOCX Page 18 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) prevent a flow of fluids from the blood collection tube 176 to the plasma / serum collection tube 178.

[0095] As shown in FIG. 11, the dual-chambered vacuum tube 172 includes a blood filter 188 that is positioned within the bushing cap 182 proximal from the cap membrane 186 – i.e., within a seat 190 of the bushing cap 182. The blood filter 188 is configured to separate out a plasma or serum from the whole blood sample (depending on whether anticoagulant is used) as it passes through the filter 188. In some embodiments, the filter 188 may comprise a microfilter with pore sizes ranging from 5 to 30 μm that are able to isolate plasma / serum from the whole blood sample as blood passes therethrough from the blood collection tube 176 to the plasma / serum collection tube 178, as explained in further detail below.

[0096] According to embodiments of the disclosure, the blood collection tube 176 may include a coating 192 applied to an inner surface thereof that facilitates collection of a plasma or serum sample from the whole blood sample. As previously described for the embodiments of FIGS.1-6 and FIGS.7 and 8, a clot inhibitor or clot accelerator may be utilized to selectively enable collection of a plasma or serum sample. In a first embodiment, the inner surface of the blood collection tube 176 is coated with a clot inhibitor or anticoagulant to prevent the blood sample from clotting in the blood collection tube 176 – thereby enabling collection of a plasma sample within the plasma / serum collection tube 178 upon passing of the blood sample through filter 188. In a second embodiment, the inner surface of the blood collection tube 176 is coated with a clot accelerator that allows the whole blood sample to clot faster in the blood collection tube 176 (and thus remove fibrinogen from the sample) – thereby enabling collection of a serum sample within the plasma / serum collection tube 178 upon passing of the blood sample through filter 188.

[0097] As shown in FIGS. 9 and 10, the dual-chambered vacuum tube 172 may be fluidly and mechanically connected to the blood draw device 60 via connector arrangement 174. The connector arrangement 174 comprises a double-ended connector 194 and a needle assembly 196. The double-ended connector 194 comprises a distal connector 198 and a proximal connector 200 thereon. The distal connector 198 is configured to mechanically and fluidly connect the connector arrangement 174 to the blood draw device 60. In some embodiments, the distal connector 198 comprises a male luer connection (including a rotatable collar and tapered stem) that mates with the coupler 114, which may comprise a female luer connection. The proximal connector 200 is configured to engage and retain the needle assembly 196 therein. In some embodiments, the proximal connector 200 comprises a female luer connection that mates with the needle assembly 196. 64W5808.DOCX Page 19 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0098] The needle assembly 196 comprises a needle 202, a needle sleeve 204, and a sheath 206. The needle sleeve 204 may comprise a connector 208 on a distal end thereof, such as a male luer connection that mates with the female luer connection of proximal connecter 200 (of double-ended connector 194). A channel 210 may extend through a length of the needle sleeve 204, with a distal portion of the needle 202 retained within the channel 210 at the proximal end of the needle sleeve 204 and with a proximal portion of the needle 202 extending out proximally past the sleeve 204. The sheath 206 may be provided over the proximal portion of the needle 202, to protect the needle 202 and prevent accidental needle sticks by a user when handling the needle assembly 196.

[0099] As shown best in FIG.11, the needle 202 may define a lumen 212 therein that extends through a length of the needle 202, to allow a fluid to pass through the needle 202. In some embodiments, the needle 202 may be configured as a coring needle, with a proximal tip 214 of the needle 202 configured to promote or resist coring of the tube membrane 180 and the cap membrane 186 when the needle 202 is pushed therethrough, depending on a construction of the proximal tip 214 of the needle 202 and the materials and thicknesses of the tube membrane 180 and the cap membrane 186. In some embodiments, the proximal tip 214 of the needle 202 may comprise a conical tip with a side-port, that resists coring when the needle 202 is pushed through a softer / elastomeric material, such as the thin rubber tube membrane 180 provided over the distal opening of blood collection tube 176, but promotes coring when the needle 202 is pushed through a more rigid material, such as the PP / PE cap membrane 186 of bushing cap 182.

[0100] According to aspects of the disclosure, the needle 202 may be selectively brought into fluid communication with the blood collection tube 176 and the plasma / serum collection tube 178 depending on a positioning of the needle 202 relative to the dual-chambered vacuum tube 172. In a first insertion position of the needle 202 into the dual-chambered vacuum tube 172, the tip 214 of the needle 202 may be pushed through the tube membrane 180 and positioned within a chamber 216 of the blood collection tube 176, to fluidly connect the blood collection tube 176 with the lumen 212 within the needle 202. In a second insertion position of the needle 202 into the dual-chambered vacuum tube 172, the tip 214 of the needle 202 may be pushed through the cap membrane 186 to form an opening / hole therethrough (i.e., a through- hole 218) that places a chamber 220 of the plasma / serum collection tube 178 in fluid communication with the chamber 216 of the blood collection tube 176. 64W5808.DOCX Page 20 of 31Attorney Docket No.09846-2502874 (P-29440.WO01)

[0101] With the system 170 configured as described above, a method for operating the system 170 to provide for collection of a blood sample and separation of plasma or serum therefrom may be described as follows.

[0102] In a first step of operation of system 170, the blood draw device 60 may be prepared (e.g., removed from packaging) and the double-ended connector 194 may be attached thereto, with the distal connector 198 engaged with coupler 114.

[0103] After connection of the double-ended connector 194 to the blood draw device 60, the needle assembly 196 may be connected to the double-ended connector 194 via the proximal connector 200 thereof.

[0104] Upon connection of the double-ended connector 194 and needle assembly 196 to the blood draw device 60, the blood draw device 60 may be attached to the catheter assembly 12, such as via connection of coupling device 64 of blood draw device 60 to needleless access connector 46 of catheter assembly 12.

[0105] With the blood draw device 60 attached to the catheter assembly 12, the catheter tube 66 may be advanced into / through the indwelling IV catheter 16 of catheter assembly 12, as described in detail above.

[0106] With the catheter tube 66 advanced into / through the indwelling IV catheter 16 of catheter assembly 12, the dual-chambered vacuum tube 172 may then be engaged with the needle assembly 196 – with the dual-chambered vacuum tube 172 being pushed distally onto the needle 202 (with sheath 206) until the needle 202 is at the first insertion position. As the dual-chambered vacuum tube 172 is being pushed distally onto the needle 202, the tip 214 of the needle 202 is forced through the tube membrane 180 (without coring the tube membrane 180) and positioned within a chamber 216 of the blood collection tube 176, to fluidly connect the blood collection tube 176 with a lumen 212 within the needle 202.

[0107] Upon a fluid path being provided between the chamber 216 of the blood collection tube 176 and the needle lumen 212, a vacuum pressure within the chamber 216 causes a blood sample to be drawn into the blood draw device 60, with the blood sample continuing proximally through the blood draw device 60 and into the blood collection tube 176. As previously described, a clot inhibitor or clot accelerator may be coated on the inner surface of the blood collection tube 176 to either prevent clotting of the blood sample collected in the blood collection tube 176 or accelerate clotting of the blood sample collected in the blood collection tube 176 (and thus remove fibrinogen from the sample).

[0108] With a blood sample collected in the blood collection tube 176, the dual-chambered vacuum tube 172 may be pushed further distally onto the needle 202 until the needle 202 is at 64W5808.DOCX Page 21 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) the second insertion position. As the dual-chambered vacuum tube 172 is being pushed further distally onto the needle 202, the tip 214 of the needle 202 is forced through the cap membrane 186 of the bushing cap 182. As the tip 214 of the needle 202 is pushed through the cap membrane 186, the cap membrane 186 is cored by the needle tip 214, such that a permanent through-hole 218 is formed through the cap membrane 186.

[0109] With a through-hole 218 formed through the cap membrane 186 after movement of the needle 202 to the second insertion position, the needle 202 may be retracted back distally and out of engagement with the cap membrane 186. Upon removal of the needle 202 from the cap membrane 186, the chamber 220 of the plasma / serum collection tube 178 is brought into fluid communication with the chamber 216 of the blood collection tube 176 and a vacuum pressure within the plasma / serum collection tube 178 causes the blood sample collected in the blood collection tube 176 to flow through the through-hole 218 in the cap membrane 186 and toward the plasma / serum collection tube 178. As the blood sample flows out from the blood collection tube 176 and toward the plasma / serum collection tube 178, the blood sample is passed through the filter 188 – with the filter 188 functioning to isolate plasma / serum from the blood sample as the blood passes therethrough from the blood collection tube 176 to the plasma / serum collection tube 178. A collection of plasma or serum is thus collected within the plasma / serum collection tube 178.

[0110] Upon a full sample of plasma or serum being collected in the plasma / serum collection tube 178, the dual-chambered vacuum tube 172 may be disconnected from the needle assembly 196, with the dual-chambered vacuum tube 172 then being sent to a testing device / system at a laboratory or other location for biomarker testing of the plasma / serum sample.

[0111] It is recognized that aspects of the disclosure are not limited to the specific blood draw device 60 shown and described in FIGS. 1-11, and that blood draw devices with other suitable constructions may also incorporate aspects of the disclosure. Referring now to FIG. 12, a system 230 is shown that includes a blood draw device 232 according to another embodiment of the disclosure. The blood draw device 232 includes a housing 234 having a proximal end 236 and a distal end 238, and an advancement member 240 slideably received within housing 234 (i.e., within an inner volume 242 of housing 234). In the illustrated embodiment, the advancement member 240 is provided as one or more telescopic cylinders 240a that are provided in a telescoping relationship with housing 234, such that advancement member 240 may be slideably received entirely, or almost entirely, within the inner volume 242 of housing 234. Advancement member 240 also includes a proximal end 244 and a distal 64W5808.DOCX Page 22 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) end 246 and, in non-limiting embodiments, advancement member 240 may have a variable diameter along its length. As one example, the distal end 246 of advancement member 240 may have a larger diameter than other portions of advancement member 240 such that, as advancement member 240 is retracted, one or more features on housing 234 may interact with the enlarged portion of advancement member 240 to prevent pulling advancement member 240 completely out of housing 234. As another example, the distal end 246 of advancement member 240 may have a smaller diameter than other portions of advancement member 240, to keep the advancement member 240 in position at a blood draw forward condition, so that a hand of the operator is freed up to manipulate additional components (e.g., a vacutainer tube).

[0112] Blood draw device 232 further includes a catheter tube 248 having a proximal end 250 and a distal end 252. Catheter tube 248 is received within the inner volume 242 of housing 234 and may be advanced and / or retracted relative to housing 234 by displacement of the advancement member 240 relative to the housing 234. In some embodiments, the catheter tube 248 may be joined to advancement member 240 via a fitting 254 provided at the distal end 246 of advancement member 240, such that displacement of the advancement member 240 relative to the housing 234 causes a corresponding displacement of catheter tube 248. In non-limiting embodiments, catheter tube 248 may be advanced from a first position in which distal end 252 of catheter tube 248 is within housing 234, to a second position in which a distal end 252 of catheter tube 248 is positioned distally of housing 234 (and also positioned distally of IV catheter 16), as previously described regarding blood draw device 60 and operation thereof.

[0113] Blood draw device 232 also includes a coupling device 256 thereon which may be identical to the coupling device shown and described in the blood draw device of FIGS. 1-7. That is, coupling device 256 is configured as a lock 80 that includes a blunted cannula 82 and locking arms 84 for coupling to the needleless access connector 46 of catheter assembly 12, with the blunted cannula 82 and locking arms 84 forming three points of contact therewith. However, it is appreciated that alternative embodiments of blood draw device 232 may include a coupling device 256 of another type to secure blood draw device 232 to catheter assembly 12, including luer connections, clips, blunt plastic cannulae, blunt metal cannulae, hybrid luers (e.g., with a cannula) friction fits, and the like.

[0114] According to aspects of the disclosure, an extension tube 258 may be routed through the telescopic cylinder 240a of advancement member 240, with the extension tube 258 providing a fluid connection between the catheter tube 248 and a coupler 260 provided at the proximal end portion of the extension tube 258. In some embodiments, and as shown in FIG. 10, the coupler 260 may mate with a blood separation device 116 (and accompanying 64W5808.DOCX Page 23 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) vacuumed collection tube 132 or syringe 154) or a dual-chambered vacuum tube 172 (via an intermediate connector arrangement 174), such as shown described in the various embodiments of FIGS. 1-11, to provide a system 230 for blood sampling and centrifuge-free separation of a plasma or serum sample from the acquired blood sample, as described in detail above.

[0115] Still other blood draw devices (i.e., other than blood draw device 60 and blood draw device 232) may be used in connection with the blood separation devices shown and described in FIGS. 1-11, according to additional aspects of the disclosure. One additional non-limiting example is the BD Minidraw™ Capillary Blood Collection System from Becton, Dickinson and Company. The Minidraw device may acquire a whole blood sample from the fingertip of a patient, and a blood separation device and accompanying sample collection container (for plasma / serum collection) may be connected with the Minidraw device to provide for collection of a plasma or serum sample. In one example, a microfluidic separation device 116 and associated syringe 154 (such as shown in FIG.8) may be used in connection with the Minidraw device, to separate a whole blood sample acquired thereby and collect the plasma / serum separated out from the blood sample. This arrangement of the Minidraw device along with the previously described blood separation device and accompanying sample collection container provides for separation and collection of plasma or serum in a home-care setting.

[0116] Beneficially, embodiments of the disclosure thus provide a system for blood sampling and separation. The system enables the acquisition of a blood sample from an indwelling IV catheter, as to eliminate the needle for multiple needle sticks for sample acquisition. The blood sample is provided to an on-site blood separation device as part of a closed sample acquisition and separation system, with the separation device comprising a centrifuge-free device that separates out a plasma or serum sample from the whole blood sample on site. The plasma or serum sample may be collected in a collection container or tube that attaches to the blood separation device or is incorporated therewith, with the collection container or tube containing the plasma / serum sample. The system thus provides a separated plasma / serum sample of high quality and with a low turn-around time, allowing for subsequent transfer of the sample to a laboratory testing site for high accuracy biomarker testing.

[0117] Although the present disclosure has been described in detail for the purpose of illustration based on what is currently considered to be the most practical and preferred embodiments or aspects, it is to be understood that such detail is solely for that purpose and that the present disclosure is not limited to the disclosed embodiments or aspects, but, on the contrary, is intended to cover modifications and equivalent arrangements that are within the spirit and scope of the appended claims. For example, it is to be understood that the present 64W5808.DOCX Page 24 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) disclosure contemplates that, to the extent possible, one or more features of any embodiment may be combined with one or more features of any other embodiment. 64W5808.DOCX Page 25 of 31

Claims

Attorney Docket No.09846-2502874 (P-29440.WO01) THE INVENTION CLAIMED IS 1. A system for blood sampling and separation, useable with a catheter assembly comprising an intravenous (IV) catheter and an access port, the system comprising: a blood draw device coupleable to the access port to be in fluid communication with the IV catheter via the catheter assembly, the blood draw device comprising: a catheter tube; a housing having a proximal end portion and a distal end portion, the distal end portion coupleable to the access port, the housing defining an inner volume configured to movably receive the catheter tube; and an advancement member configured to move relative to the housing to move the catheter tube between a first position, in which the catheter tube is disposed within the housing, and a second position in which a distal end of the catheter tube is disposed beyond the distal end portion of the housing and within the IV catheter or past a distal tip of the IV catheter; a blood separation device attached to the blood draw device proximal to the housing and in fluid communication with the catheter tube, to directly receive a blood sample from the blood draw device when the catheter tube is in the second position, the blood separation device comprising a centrifuge-free mechanism configured to separate a plasma or serum sample from the blood sample; and a sample collection container coupled with the blood separation device and configured to provide a vacuum pressure that draws the blood sample into the blood separation device, with the separated plasma or serum sample being drawn into the sample collection container.

2. The system of claim 1, wherein the blood draw device comprises: an extension tube coupled to the advancement member and extending out proximally therefrom and out the proximal end portion of the housing, the extension tube fluidly connecting the catheter tube and the blood separation device; and a coupler connected to a proximal end of the extension tube, and wherein the blood separation device is connected to the extension tube via the coupler.

3. The system of claim 2, wherein the blood draw device comprises a clamp positioned on the extension tube and operable in a closed position and an open position 64W5808.DOCX Page 26 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) to selectively control a flow of blood through the extension tube, from the catheter tube to the blood separation device.

4. The system of claim 2, wherein the blood separation device comprises: a housing defining an interior housing volume; a distal connector provided on the housing and configured to mate with the coupler to fluidly connect the microfluidic channel to the extension tube; a proximal connector provided on the housing and configured to mate with the sample collection container; a blood collection chamber positioned within the interior housing volume and fluidly connected to the distal connector, the blood collection chamber storing the blood sample received from the blood draw device; and a microfluidic channel positioned within the interior housing volume and extending between the blood collection chamber and the proximal connector; wherein capillary forces act on the blood sample as it is drawn into and through the capillary tubing, to extract plasma or serum from the blood sample, with extracted plasma or serum passing into the sample collection container as the plasma or serum sample.

5. The system of claim 4, wherein the proximal connector of the blood separation device comprises a needle connector including: a needle extending out proximally from the housing; and a sheath positioned over the needle.

6. The system of claim 5, wherein the sample collection container comprises a vacuumed collection tube, the vacuumed collection tube defining an interior volume and including a tube membrane covering a distal opening thereof.

7. The system of claim 5, further comprising a tube holder configured to engage the proximal connector, with the tube holder defining a cavity configured to receive the vacuumed collection tube therein, and wherein with the vacuumed collection tube positioned in the tube holder, the needle pierces the tube membrane to fluidly connect the needle with the vacuumed collection tube. 64W5808.DOCX Page 27 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) 8. The system of claim 4, wherein the proximal connector of the blood separation device comprises a female luer connector.

9. The system of claim 8, wherein the sample collection container comprises a syringe comprising: a syringe barrel defining a chamber for retaining fluid therein; and a plunger assembly being axially movable within the syringe barrel from an advanced position to a retracted position, to generate vacuum pressure that facilitates a separation and draw of plasma or serum into the chamber of the syringe barrel; wherein a distal end of the syringe barrel comprises fluid connector component configured as a male luer connection that engages the female luer connector of the blood separation device to fluidly connect the blood separation device and the syringe.

10. The system of claim 4, wherein one or more of the blood collection chamber and the microfluidic channel is coated with a clot inhibitor or anticoagulant that prevents the blood sample from clotting, to provide for extraction of plasma from the blood sample as it advances into the microfluidic channel.

11. The system of claim 4, wherein one or more of the blood collection chamber and the microfluidic channel is coated with a clot accelerator that promotes clotting of the blood sample, so as to remove fibrinogen from the blood sample and provide for extraction of serum from the blood sample as it advances into the microfluidic channel.

12. The system of claim 4, wherein the distal connector comprises a male luer connection and the coupler comprises a female luer connection.

13. A system for blood sampling and separation, useable with a catheter assembly comprising an intravenous (IV) catheter and an access port, the system comprising: a blood draw device couplable to the access port to be in fluid communication with the IV catheter via the catheter assembly, the blood draw device comprising: a catheter tube; a housing having a proximal end portion and a distal end portion, the distal end portion coupleable to the access port, the housing defining an inner volume configured to movably receive the catheter tube; and 64W5808.DOCX Page 28 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) an advancement member configured to move relative to the housing to move the catheter tube between a first position, in which the catheter tube is disposed within the housing, and a second position in which a distal end of the catheter tube is disposed beyond the distal end portion of the housing and within the IV catheter or past a distal tip of the IV catheter; and a dual-chambered vacuum tube connectable to the blood draw device proximal to the housing to receive a blood sample therefrom, the dual-chambered vacuum tube comprising: a blood collection tube comprising a tube membrane sealing a distal end thereof; a plasma / serum collection tube positioned proximally from the blood collection tube; a bushing cap configured to secure the blood collection tube with the plasma / serum collection tube, the bushing cap comprising a cap membrane positioned to seal a proximal end of the blood collection tube; and a filter seated within the bushing cap proximal from the cap membrane, the filter configured to filter out blood cells when the blood sample is passed therethrough to provide a separated plasma or serum sample to the plasma / serum collection tube.

14. The system of claim 13, wherein the blood draw device comprises: an extension tube coupled to the advancement member and extending out proximally therefrom and out the proximal end portion of the housing; and a coupler connected to a proximal end of the extension tube.

15. The system of claim 14, further comprising a connector arrangement positioned between the coupler and the dual-chambered vacuum tube, to mechanically and fluidly connect the blood draw device with the dual-chambered vacuum tube, with the connector arrangement comprising a double-ended connector and a needle assembly.

16. The system of claim 14, wherein the needle assembly comprises a needle engageable with the dual-chambered vacuum tube in each of a first insertion position a second insertion position, and wherein: with the needle engaged with the dual-chambered vacuum tube in the first insertion position, a tip of the needle pierces through the tube membrane and positioned within 64W5808.DOCX Page 29 of 31Attorney Docket No.09846-2502874 (P-29440.WO01) a chamber of the blood collection tube, to fluidly connect the blood collection tube with a lumen within the needle; and with the needle engaged with the dual-chambered vacuum tube in the second insertion position, the tip of the needle pierces through the cap membrane to form a through- hole in the cap membrane, to fluidly connect a chamber of the plasma / serum collection tube with the chamber of the blood collection tube upon retraction of the needle back out from the through-hole.

17. The system of claim 16, wherein the double-ended connector comprises a distal connector configured to engage the coupler of the blood draw device and a proximal connector configured to engage the needle assembly, with the needle assembly further comprising: a needle sleeve that mates with the proximal connector and that secures a distal end of the needle therein; and a sheath positioned over a proximal end of the needle, including the tip.

18. The system of claim 16, wherein the needle comprises a coring needle configured to: pierce through the tube membrane without cutting and removing a core therefrom; and cut a core or material out from the cap membrane when pierced therethrough, so as to form the through-hole in the cap membrane.

19. The system of claim 13, wherein the blood collection tube is coated with a with a clot inhibitor or anticoagulant that prevents the blood sample from clotting, to provide for extraction of plasma from the blood sample as it passes through the filter.

20. The system of claim 13, wherein the blood collection tube is coated with a clot accelerator that promotes clotting of the blood sample, so as to remove fibrinogen from the blood sample and provide for extraction of serum from the blood sample as it passes through the filter. 64W5808.DOCX Page 30 of 31

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