Probe for analyte collection from blood and probe delivery device therefore

Abstract

A probe delivery device for advancing a probe into an indwelling catheter includes an introducer housing, a coupling member, a probe, a probe delivery tube, a probe advancement member configured to move the probe, and a tube advancement member configured to move the probe delivery tube. A distal movement of the tube advancement member collectively moves the probe delivery tube and the probe from a first position within the introducer housing to a second position where a distal end portion of the probe delivery tube and the probe are disposed into or distally past the indwelling catheter. A distal movement of the probe advancement member moves the probe from the second position to a third position, where a distal tip of the probe is moved distally out from the probe delivery tube, such that channels on the probe are exposed to provide for collection of analytes therein.

Description

Attorney Docket No. 09846-2502877 (P-30179.WO01) PROBE FOR ANALYTE COLLECTION FROM BLOOD AND PROBE DELIVERY DEVICE THEREFORE CROSS-REFERENCE TO RELATED APPLICATION

[0001] The present application claims priority to Indian Patent Application No. 202441050507 entitled “Probe for Analyte Collection from Blood and Probe Delivery Device Therefore” filed July 2, 2024, the disclosure of which is hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION Field of the Invention

[0002] The present invention is directed to a probe delivery device for introducing a probe into an indwelling catheter of a vascular access device, with the probe configured to provide for analyte collection from blood. Background of the Invention

[0003] A biopsy is a procedure to remove a piece of tissue or a sample of cells from the body in order to provide for testing of the tissue / cells, with biopsies for cancer detection being a primary example. Tissue biopsies provide an effective sample that can be used for such testing, but are recognized as being invasive. Liquid biopsies, which test a blood sample for analytes or other markers, are less invasive than tissue biopsies, but are currently typically not sensitive enough to provide accurate results – especially when using a single blood draw sample for analysis.

[0004] It is recognized that a biopsy that enriches circulating tumor cells (CTCs) can provide an improved solution over typical liquid biopsies. CTCs are shed from a patient's tumor and circulate throughout their bloodstream. And these tumor derived cells can be analyzed using the same techniques as ctDNA to give the same genomic, epigenomic and transcriptomic information about a patient's tumor. Furthermore, unlike ctDNA, proteomic analysis of CTCs can give information about specific proteins expressed on tumor cells, such as PD-L1. However, a major hurdle to use of CTCs in liquid biopsy testing is the low concentration of CTCs in blood, particularly in non-metastatic patients, which makes a proper analysis impossible following a single blood draw. 6582020.DOCX Page 1 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01)

[0005] Thus, what is required for liquid biopsy testing using CTCs (or other analytes) is a system for collecting large numbers of CTCs from the bloodstream quickly, requiring only a peripheral venous catheter, with the risk of sample contamination being minimized, faster processing being enabled, and the need to repeatedly draw blood being avoided. The system would provide a safer and more reliable alternative to existing tissue- and liquid biopsy procedures, and could be performed as often as necessary within the setup of an in-dwelling IV catheter. SUMMARY OF THE INVENTION

[0006] Provided herein is a probe delivery device for advancing a probe into an indwelling catheter of a vascular access device. The probe delivery device includes an introducer housing having a proximal end portion and a distal end portion, with the housing defining an inner volume. The probe delivery device also includes a coupling member positioned at the distal end portion and coupleable to the vascular access device and a probe movably received within the inner volume and comprising a main body and a distal tip, with the main body comprising a plurality of channels formed therein that trap analytes therein when positioned intravenously within a patient. The probe delivery device further includes a probe delivery tube movably received within the inner volume and defining a tube lumen therein configured to receive the main body, with the distal tip or location near to the distal tip larger than the tube lumen, a probe advancement member movably coupled to the housing and configured to move relative to the housing to move the probe, and a tube advancement member movably coupled to the housing, distal from the probe advancement member, and configured to move relative to the housing to move the probe delivery tube, with a proximal end of the probe delivery tube coupled to the tube advancement member. A distal movement of the tube advancement member relative to the housing collectively moves the probe delivery tube and the probe from a first position, in which the probe delivery tube and probe are disposed within the introducer housing or within the introducer housing and the coupling member, to a second position, in which a distal end portion of the probe delivery tube and the probe are disposed beyond the distal end portion of the introducer housing and into or distally past a distal end of the indwelling catheter. A distal movement of the probe advancement member relative to the housing, subsequent to distal movement of the tube advancement member, moves the probe from the second position to a third position, where the distal tip of the probe is moved further distally from the distal end 6582020.DOCX Page 2 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) portion of the probe delivery tube, such that at least a portion of the plurality of channels are positioned outside of the tube lumen, to provide for collection of analytes within the channels.

[0007] In some embodiments, the probe is formed of a shape memory alloy.

[0008] In some embodiments, the shape memory alloy comprises Nitinol.

[0009] In some embodiments, a majority of the probe is positioned within the tube lumen of the probe delivery tube in a coaxial arrangement, with the distal tip of the probe remaining outside of the tube lumen.

[0010] In some embodiments, the tube advancement member comprises an opening formed therethrough, through which the probe passes to be positioned within and coaxially with the probe delivery tube.

[0011] In some embodiments, the tube advancement member comprises a sealing element positioned in the opening thereof, with the probe extending through the sealing element, and with the sealing element preventing blood and analytes from leaking from the probe delivery tube.

[0012] In some embodiments, with the probe in the third position, a proximal movement of the probe advancement member moves the probe from the third position back to the second position, thereby trapping collected analytes between the channels and the probe delivery tube.

[0013] In some embodiments, each of the probe advancement member and the tube advancement member comprises a first portion comprising an engagement portion movable along a top surface of the housing and a second portion positioned at least partially within the inner volume and joined to the first portion through a slot formed in the top surface of the housing.

[0014] In some embodiments, for the probe advancement member, the second portion is coupled with a proximal end of the probe and, for the tube advancement member, the second portion is coupled with a proximal end of the probe delivery tube.

[0015] In some embodiments, a proximal end of the probe is coupled to the housing at the distal end thereof and the second portion of the probe advancement member comprises a U- shaped channel formed therein through which the probe extends, wherein for the tube advancement member, the second portion is coupled with a proximal end of the probe delivery tube.

[0016] In some embodiments, a distal movement of the probe advancement member relative to the housing by a first distance causes the probe to advance distally by a second distance that is greater than the first distance. 6582020.DOCX Page 3 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01)

[0017] In some embodiments, a shape of the channel determines a length of the second distance, with the second distance being twice the first distance or greater.

[0018] In some embodiments, the probe advancement member comprises an advancement wheel secured to the housing and rotatable in a first direction and a second direction relative thereto, wherein the tube advancement member comprises a first portion comprising an engagement portion movable along a top surface of the housing and a second portion positioned at least partially within the inner volume and joined to the first portion through a slot formed in the top surface of the housing, wherein for the probe advancement member, the advancement wheel is coupled with a proximal end of the probe; and wherein, for the tube advancement member, the second portion is coupled with a proximal end of the probe delivery tube.

[0019] In some embodiments, rotation of the advancement wheel causes subsequent to distal movement of the tube advancement member, moves the probe from the second position to the third position.

[0020] In some embodiments, the probe advancement member and the tube advancement member comprises buttons that are pushable and / or rotatable.

[0021] In some embodiments, the coupling device comprises a lock including: a coupler configured to engage the distal end of the housing; a first arm and a second arm configured to engage with the vascular access device or an adapter provided between the vascular access device and the lock; and a blunt cannula extending from the coupler and disposed between the first arm and the second arm, the blunt cannula configured to engage with the vascular access device or the adapter; wherein a lumen extends through the blunt cannula and the coupler, through which the probe delivery tube and probe may be distally advanced.

[0022] Also provided herein is a method for collecting analytes from blood using a probe delivery device. The method comprises moving the tube advancement member distally along the introducer housing to distally advance the probe delivery tube and the probe from a first position to the second position, moving the probe advancement member distally along the introducer housing to distally advance the probe from the second position to the third position, retaining the probe in the third position for a required amount of time, intravenously within the patient, to collect analytes from the blood, moving the probe advancement member proximally along the introducer housing to proximally retract the probe from the third position back to the second position, thereby trapping the analytes between the probe and the probe delivery tube, and moving the probe advancement member and tube advancement member proximally along the introducer housing to proximally retract the probe and the probe delivery tube back to the first position. 6582020.DOCX Page 4 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01)

[0023] Also provided herein is a probe delivery device for advancing a probe into an indwelling catheter of a vascular access device. The probe delivery device includes an introducer housing having a proximal end and a distal end, with the housing defining an inner volume, a coupling member positioned at the distal end and coupleable to the vascular access device, and a probe movably received within the inner volume, the probe comprising a main body and a distal tip, with the main body comprising a plurality of channels formed therein that trap analytes therein when positioned intravenously within a patient, and with a proximal end of the probe connected to the distal end of the housing. The probe delivery device also includes a probe delivery tube movably received within the inner volume and defining a tube lumen therein configured to receive the main body, with the distal tip or location near to the distal tip larger than the tube lumen, and an advancement member movably coupled to the housing and configured to move relative to the housing to move the probe and the probe delivery tube. A distal movement of the advancement member relative to the housing collectively moves the probe delivery tube and the probe distally, with distal movement of the advancement member by a first distance causing the probe delivery tube to advance distally by the first distance and causing the probe to advance distally by a second distance that is greater than the first distance, such that the probe is advanced further distally than the probe delivery tube.

[0024] In some embodiments, the advancement member includes a first portion comprising an engagement portion movable along a top surface of the housing and a second portion positioned at least partially within the inner volume and joined to the first portion through a slot formed in the top surface of the housing, wherein the second portion of the probe advancement member comprises a U-shaped channel formed therein through which the probe extends and a proximal end of the probe delivery tube is secured to the second portion.

[0025] In some embodiments, the advancement member comprises a sealing element positioned in the U-shaped channel thereof, with the probe extending through the sealing element, and with the sealing element preventing blood and analytes from leaking from the probe delivery tube.

[0026] In some embodiments, the second distance is greater than the first distance, such as twice the first distance or three times the first distance. 6582020.DOCX Page 5 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) BRIEF DESCRIPTION OF THE DRAWINGS

[0027] FIG. 1 is a perspective view of a probe delivery device and vascular access device, with the probe delivery device in a first configuration, according to an embodiment of the disclosure;

[0028] FIG. 2 is a cross-sectional view of the probe delivery device illustrated in FIG. 1;

[0029] FIG. 3 is a perspective view of the probe delivery device and vascular access device of FIG. 1, with the probe delivery device in a second configuration;

[0030] FIG. 4 is a perspective view of the probe delivery device and vascular access device of FIG. 1, with the probe delivery device in a third configuration;

[0031] FIG. 5 is a detailed view of a portion of the probe included in the probe delivery device of FIG. 1;

[0032] FIG. 6 is a cross-sectional view of a probe delivery device, according to another embodiment of the disclosure;

[0033] FIG. 7 is a schematic diagram of the probe delivery device of FIG. 6 according to a first arrangement of the probe and probe delivery tube thereof, showing an example initial position, an example partially advanced position, and an example fully advanced position, according to an embodiment of the disclosure;

[0034] FIG. 8 is a schematic diagram of the probe delivery device of FIG. 6 according to a second arrangement of the probe and probe delivery tube thereof, showing an example initial position, an example partially advanced position, and an example fully advanced position, according to an embodiment of the disclosure;

[0035] FIG. 9 is a schematic diagram of the probe delivery device of FIG. 6 according to a third arrangement of the probe and probe delivery tube thereof, showing an example initial position, an example partially advanced position, and an example fully advanced position, according to an embodiment of the disclosure;

[0036] FIG. 10 is a cross-sectional view of a probe delivery device, according to another embodiment of the disclosure;

[0037] FIG. 11 a cross-sectional view of a probe delivery device, according to another embodiment of the disclosure;

[0038] FIG.12A is a cross-sectional view of a probe delivery device, with the probe delivery device in a first configuration, according to another embodiment of the disclosure;

[0039] FIG.12B is a cross-sectional view of the probe delivery device of FIG.12A, with the probe delivery device in a second configuration; and 6582020.DOCX Page 6 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01)

[0040] FIG.12C is a cross-sectional view of the probe delivery device of FIG.12A, with the probe delivery device in a third configuration. DESCRIPTION OF THE INVENTION

[0041] 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.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] 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.

[0046] The present invention is directed to a probe delivery device for delivering a probe for analyte collection from blood through a peripheral intravenous line or catheter, with the probe draw device operable to advance a probe delivery tube and a probe into the indwelling peripheral intravenous line and subsequently collect analytes from the blood of a patient.

[0047] FIGS. 1-5 illustrate a probe delivery device 10 and components thereof according to an exemplary embodiment of the disclosure. The probe delivery device 10 can be any suitable 6582020.DOCX Page 7 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) shape, size, or configuration and can be coupled to a vascular access device (VAD) 100, for example, via a lock and / or adapter. As described in further detail herein, a user can operate the probe delivery device 10 to advance a probe and associated probe delivery tube through an existing, placed, and / or indwelling catheter 102 of the VAD 100 (i.e., when the probe delivery device 10 is coupled to the VAD). In particular, the probe and probe delivery tube are moveable to provide for advancement of a portion of the probe and probe delivery tube from a retracted position inside the probe delivery device 10 to a partially advanced position outside of the probe delivery device 10, such that a distal end of the probe and probe delivery tube may be routed into the VAD 100. The probe may then be advanced further, such that a tip of the probe may be advanced distally out past the probe delivery tube and out past the distal end of an indwelling IV catheter, to enable intravenous collection of an analyte sample from the blood of a patient.

[0048] As shown in FIGS. 1-5, according to a non-limiting embodiment, the probe delivery device 10 includes at least an introducer housing 12, a coupling member or lock 14, a biopsy probe 16, a probe advancement member 18, a probe delivery tube 20, and a tube advancement member 22.

[0049] The introducer housing 12 of probe delivery device 10 can be an elongate member having a proximal end 24 and a distal end 26 and defining an inner volume 28. In some embodiments, the introducer housing 12 may be formed of a pair of housing portions that are coupled together to define the inner volume 28. The introducer housing 12 may include one or more features or surface finishes on an outer surface thereof that can be arranged to increase the ergonomics of the probe delivery device 10, which in some instances can allow a user to manipulate the probe delivery device 10 with one hand (i.e., single-handed use).

[0050] The coupling member 14 of probe delivery device 10 is provided at the distal end 26 of the introducer housing 12, with the coupling member 14 providing for reversible coupling of the probe delivery device 10 to VAD 100, such as via a needleless access connector 104 as shown in FIG. 1. In some embodiments, the coupling member 14 is configured as a lock that includes a blunted cannula 30 and locking arms 32 for coupling to the needleless access connector 104 of VAD 100, with the blunted cannula 30 and locking arms 32 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 a distal end of biopsy probe 16 and probe delivery tube 20 may pass through the coupling member 14 to VAD 100.

[0051] In some embodiments, a seal 33 may also be provided at the distal end 26 of the housing 12 or in the coupling member 14 to selectively seal and / or fluidically isolate the inner 6582020.DOCX Page 8 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) volume 28 of the housing 12. In use, the seal 33 can be transitioned from a sealed or closed configuration to an open configuration to allow, for example, a portion of the probe delivery tube 20 and a portion of the biopsy probe 16 to pass therethrough. In some embodiments, the seal 33 can contact an outer surface of the probe delivery tube 20 to define a seal therebetween that is operable to limit and / or substantially prevent a back flow of fluid between the outer surface of the probe delivery tube 20 and the seal.

[0052] As shown best in FIG.2, the probe advancement member 18 of probe delivery device 10 includes a first portion 34 and a second portion 36. The first portion 34 is movably disposed along an upper surface of the introducer housing 12 and the second portion 36 is movably disposed within the inner volume 28 of the introducer housing 12. The arrangement of the probe advancement member 18 and the introducer housing 12 is such that a connecting portion (not shown) of the probe advancement member 18 that joins the first and second portions 34, 36 is seated within a slot 28 formed in the upper surface of the introducer housing 12 – the slot 28 generally extending between the proximal and distal ends 24, 26 of the introducer housing 12. Movement of the first portion 34 along the upper surface of the introducer housing 12 results in a corresponding movement of the second portion 36 within the inner volume 28.

[0053] The first portion 34 of the probe advancement member 18 may be configured as a tab having a contact surface engageable by a user and an underside that is in contact with the outer surface of the introducer housing 12. In such embodiments, the upper surface of the introducer housing 12 can include a track 38, for example, a set of ribs, ridges, bumps, grooves, and / or the like along which the underside of the tab advances when the probe advancement member 18 is engaged by a user. In this manner, a user can engage the first portion 34 of the probe advancement member 18 and can move the probe advancement member 18 relative to the introducer housing 12.

[0054] The second portion 36 includes an opening 40 extending therethrough that is configured to grip or retain a portion of the biopsy probe 16. Due to a portion of the biopsy probe 16 being retained within the opening 40 of second portion 36, movement of the probe advancement member 18 relative to introducer housing 12 causes a corresponding movement of the biopsy probe 16 relative to the introducer housing 12. In this manner, the distal end of the biopsy probe 16 can be selectively moved out of or back into the inner volume 28 of the introducer housing 12 as desired, such as advancing the distal end of the biopsy probe 16 out of the introducer housing 12 when the probe delivery device 10 has been coupled to the VAD 100 and collection of an analyte sample is to be performed. 6582020.DOCX Page 9 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01)

[0055] As shown best in FIG. 2, the tube advancement member 22 of probe delivery device 10 is formed similarly to probe advancement member 18 and thus includes a first portion 42 and a second portion 44. The first portion 42 is movably disposed along the upper surface of the introducer housing 12 and the second portion 44 is movably disposed within the inner volume 28 of the introducer housing 12. The arrangement of the tube advancement member 18 and the introducer housing 12 is such that a connecting portion (not shown) of the tube advancement member 18 that joins the first and second portions 42, 44 is seated within the slot 28.

[0056] The first portion 42 of the tube advancement member 22 may be configured as a tab having a contact surface engageable by a user and an underside that is in contact with the outer surface of the introducer housing 12. In such embodiments, the underside of the tab may advance along track 38 of the housing when the tube advancement member 22 is engaged by a user. In this manner, a user can engage the first portion 42 of the tube advancement member 22 and can move the tube advancement member 22 relative to the introducer housing 12.

[0057] The second portion 44 includes an opening 46 extending therethrough that is configured to grip or retain a portion of the probe delivery tube 20. Due to a portion of the probe delivery tube 20 being retained within the opening 46 of second portion 44, movement of the tube advancement member 22 relative to introducer housing 12 causes a corresponding movement of the probe delivery tube 20 relative to the introducer housing 12. In this manner, the distal end of the probe delivery tube 20 can be selectively moved out of or back into the inner volume 28 of the introducer housing 12 as desired, such as advancing the distal end of the probe delivery tube 20 out of the introducer housing 12 when the probe delivery device 10 has been coupled to the VAD 100 and collection of an analyte sample is to be performed.

[0058] The second portion 44 also includes a sealing element 48 positioned within the opening 46 thereof. The sealing element 48 functions to seal off a proximal end 66 of the probe delivery tube 20. The sealing element 48 allows a portion of the biopsy probe 16 to pass therethrough and makes contact with an outer surface thereof to define a seal therebetween that is operable to limit and / or substantially prevent a back flow of fluid between the outer surface of the biopsy probe 16 and the sealing element 48 – i.e., the sealing element 48 prevents blood from leaking out of the proximal end 66 of the probe delivery tube 20.

[0059] Following now is a more detailed description of the biopsy probe 16 and the probe delivery tube 20.

[0060] In some embodiments, the biopsy probe 16 is a solid wire made of a flexible material, such as Nitinol, which is a shape memory alloy and hence has anti-kinking properties, such 6582020.DOCX Page 10 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) that the biopsy probe 16 can guide itself inside the indwelling peripheral catheter 102 (which might have bends where it enters the vein from the skin surface). As best shown in FIG. 5, the biopsy probe 16 comprises an elongate member having a main body 50 and a tip 52. The tip 52 is provided at a distal end 54 of the biopsy probe 16, with the main body 50 extending proximally therefrom. The tip 52 is formed to have a larger diameter than the main body 50. As explained in further detail below, the tip diameter is also larger than a diameter of the probe delivery tube 20, so as to provide for advancement of the biopsy probe 16 together with the probe delivery tube 20 when the tube advancement member 22 is pushed distally along housing 12.

[0061] As best shown in FIG. 5, the main body 50 of probe includes a plurality of channels 56 formed therein. In one embodiment, the channels 56 extend lengthwise along the main body 50 – with the channels 56 formed by a plurality of dividers 58 spaced circumferentially about the main body 50 and extending radially outward therefrom. In other embodiments, the channels 56 may be oriented differently, such as being circumferential channels, angled channels, etc. The channels 56 provide for analyte collection by the biopsy probe 16 when positioned within the vasculature of the patient, with the channels 56 collecting analytes from the blood by impeding the flow of blood. The main body 50 may also include one or more circumferential rings 60 thereon where dividers 58 / channels 56 are absent from the main body 50.

[0062] The probe delivery tube 20 may comprise a flexible tubing that defines therein a tube lumen 62. The probe delivery tube 20 is sized such that the tube lumen 62 has a diameter larger than the main body 50 of biopsy probe 16 (i.e., an inner diameter of lumen 62 is larger than an outer diameter of main body 50 of biopsy probe 16), such that the biopsy probe 16 may be at least partially disposed within the lumen 62 defined by the probe delivery tube 20 – i.e., the probe delivery tube 20 is positioned coaxially about the biopsy probe 16. However, a diameter of the tip 52 of biopsy probe 16 is larger than the diameter of the tube lumen 62, such that tip 52 is prevented from moving into the tube lumen. Thus, in an initial configuration of the probe delivery device 10, the tip 52 of biopsy probe 16 is positioned just past a distal end 64 of probe delivery tube 20 and, upon a distal advancement of probe delivery tube 20 during operation of probe delivery device 10, distal advancement of biopsy probe 16 will also occur – as the probe delivery tube 20 will push the biopsy probe 16 distally due to engagement of tip 52 with the distal end 64 of probe delivery tube 20.

[0063] As best shown in FIG. 2, the probe delivery tube 20 is provided in probe delivery device 10 at a location that is distal from the tube advancement member 22, with a portion of 6582020.DOCX Page 11 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) the main body 50 of biopsy probe 16 arranged coaxially with the probe delivery tube 20. The proximal end 66 of the probe delivery tube 20 is coupled to the second portion 44 of the tube advancement member 22 such that movement of the tube advancement member 22 relative to the housing 12 results in a distal movement of the probe delivery tube 20 (and also the biopsy probe 16).

[0064] In operation of the probe delivery device 10, each of the probe advancement member 18 and the tube advancement member 22 of the probe delivery device 10 can be moved along a length of the housing 12 to selectively advance the probe delivery tube 20 and biopsy probe 16.

[0065] In a first operational step of the probe delivery device 10, the tube advancement member 22 may be advanced distally to move the probe delivery tube 20 and biopsy probe 16 from a first position, in which the probe delivery tube 20 and biopsy probe 16 are disposed within the housing 12 (e.g., the entire probe delivery tube 20 and biopsy probe 16 are disposed within the housing 12 or within the housing 12 and the coupling member 16) to a second position, in which the distal end 64 of the probe delivery tube 20 and the distal end 54 of the biopsy probe 16 are disposed in a position distal to the coupling member 16 and within or distal to the distal end of the indwelling catheter 102.

[0066] In a second operational step of the probe delivery device 10, the probe advancement member 18 may be advanced distally to move the biopsy probe 16 from the second position to a third position, in which the distal end 54 of the biopsy probe 16 is advanced further out past the distal end 64 of the probe delivery tube 20 and past the distal end of the indwelling catheter 102. With the biopsy probe 16 moved to the third position, at least a portion of the channels 56 are positioned outside of the probe delivery tube 20 (i.e., outside of tube lumen 62). With the channels 56 of biopsy probe 16 disposed outside of probe delivery tube 20 and out past the distal end of the indwelling catheter 102, the biopsy probe 16 may collect analytes from blood of the patient while the probe remains positioned intravenously within the patient – with analytes being collected in the channels 56 (as blood flow is impeded by the biopsy probe 16 and channels 56 thereof). Analytes may then be trapped in the channels 56 upon retraction of the biopsy probe 16 back into the probe delivery tube 20 – i.e., analytes are trapped between the channels 16 and the probe delivery tube 20.

[0067] Changing of the probe delivery device 10 between the first configuration, the second configuration, and the third configuration is now described in more detail. The probe delivery device 10 can be in the first configuration prior to use and can be transitioned by a user (e.g., a doctor, physician, nurse, technician, phlebotomist, and / or the like) from the first configuration 6582020.DOCX Page 12 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) to the second configuration to dispose at least the distal end 54 of the biopsy probe 16 and the distal end 64 of the probe delivery tube 20 in a distal position relative to the housing 12 (e.g., into / past the distal tip of indwelling catheter 102 (FIG. 1)).

[0068] As shown in FIGS. 1 and 2, the probe delivery device 10 is in the first configuration when the biopsy probe 16 and probe delivery tube 20 are disposed in a first position within the housing 12. In some embodiments, substantially the entire biopsy probe 16 and probe delivery tube 20 are disposed within the housing 12 when in the first position. In such embodiments, the housing 12 can include a seal 33 or the like (as described above) that can substantially seal the distal end portion 26 of the housing 12 to isolate the biopsy probe 16 and probe delivery tube 20 within the inner volume 28. In other embodiments, the biopsy probe 16 and probe delivery tube 20 are disposed within the housing 12 and the coupling member 14 when in the first position.

[0069] With the probe delivery device 10 in the first configuration, the probe advancement member 18 is disposed toward the proximal end 24 of the housing 12 and the tube advancement member 22 is disposed somewhat centrally on the housing 12. The proximal end 68 of the biopsy probe 16 is coupled to the second portion of the advancement member 18, and the biopsy probe 16 extends through the inner volume 28 of the housing 12 and through the tube lumen 62 of probe delivery tube 20, with the tip 52 adjacent the distal end 64 of the probe delivery tube 20.

[0070] To transition the probe delivery device 10 from the first configuration to the second configuration, the user moves the tube advancement member 22 relative to the housing 12, which in turn, moves the probe delivery tube 20 and the biopsy probe 16 from the first position (e.g., disposed within the housing 12) to the second position. In this manner, the probe delivery tube 20 and biopsy probe 16 are moved through the inner volume 28 of housing 12 and advanced into and through the VAD 100, such that the distal ends 64, 54 of the probe delivery tube 20 and biopsy probe 16 extend into or out past the indwelling catheter 102. As explained previously, the biopsy probe 16 is formed of a kink-resistant material such as a shape memory alloy (e.g., Nitinol), which allows the biopsy probe 16 (and probe delivery tube 20) to advance through the VAD 100 without fear of kinking.

[0071] After movement of the tube advancement member 22 in the distal direction, the probe delivery device 10 is considered to be in a second configuration, as shown in FIG. 3, with the probe delivery tube 20 and biopsy probe 16 in the second tube position – where they are advanced into / through VAD 100, but with the tip 52 of biopsy probe 16 still adjacent the distal end 64 of probe delivery tube 20. 6582020.DOCX Page 13 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01)

[0072] Upon the probe delivery device 10 being actuated to the second configuration, a user may then engage the probe advancement member 18 to move the advancement member 18 relative to the housing 12, thereby transitioning the probe delivery device 10 from the second configuration to a third configuration, as shown in FIG. 4. In transitioning to the third configuration, the biopsy probe 16 is moved distally from the second position toward a third position, where the tip 52 and a portion of main body 50 extend out distally from indwelling catheter 102 and into a vein of the patient. As the biopsy probe 16 is moved distally, the biopsy probe 16 is caused to extend out further distally from the probe delivery tube 20 – with the tip 52 of biopsy probe 16 separating from the distal end 64 of probe delivery tube 20 and a portion of the main body 50 of probe extending out from probe delivery tube 20. With a portion of the main body 50 extending out from probe delivery tube 20, at least a portion of the channels 56 formed in / on the main body 50 are exposed and are positioned within a vein of the patient, such that the biopsy probe 16 may collect analytes from blood of the patient while the probe remains positioned intravenously within the patient. That is, analytes are collected in the channels 56 (as blood flow is impeded by the biopsy probe 16 and channels 56 thereof).

[0073] In collecting analytes with the biopsy probe 16 with the biopsy probe 16 in the third position, it is recognized that it is desirable to expose as large an amount as possible of the channels 56 – i.e., to extend out as much of the main body 50 of biopsy probe 16 from probe delivery tube 20. In some embodiments, in order to maximize the amount of the main body 50 that is exposed, the tube advancement member 22 may be moved back proximally by a small amount, in order to retract the probe delivery tube 20 by a controlled distance. With the probe delivery tube 20 retracted by a small amount, a greater length of the main body 50 – and the channels 56 thereon – are exposed from probe delivery tube 20, thereby further maximizing analyte collection by the biopsy probe 16.

[0074] Upon collection of a sufficient amount of analytes by probe (after indwelling of the probe in the vein in the third position for a sufficient length of time), an operator may trap the collected analytes by retracting the biopsy probe 16 back into the probe delivery tube 20. In order to retract the biopsy probe 16, the operator engages the probe advancement member 18 to move the advancement member 18 proximally relative to the housing 12, thereby transitioning the probe delivery device 10 from the third configuration back to the second configuration. As the biopsy probe 16 is retracted back into the probe delivery tube 20, analytes are trapped within the channels 56 as the main body 50 is slid back into the probe delivery tube 20. 6582020.DOCX Page 14 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01)

[0075] Upon transitioning back to the second configuration, the probe delivery device 10 may then be removed from the indwelling catheter 102 by a further transitioning from the second configuration back to the first configuration. In order to transition back to the first configuration, the tube advancement member 22 and / or probe advancement member 18 may be moved back further proximally relative to housing 12 – with proximal movement of the tube advancement member 22 and / or probe advancement member 18 causing the biopsy probe 16 and probe delivery tube 20 to also be retracted proximally out from the VAD 100 and back into the housing 12.

[0076] After removal of the biopsy probe 16 and probe delivery tube 20 from VAD 100, the probe delivery device 10 may be disconnected from the VAD 100. Upon such disconnection, the probe delivery device 10 may then be connected to a collection tube (e.g., using a needle- free connector (NFC)) – with the collected analyte being deposited into the collection tube for further analysis.

[0077] It is recognized that aspects of the disclosure are not limited to the specific probe delivery device 10 shown and described in FIGS. 1-5, and that probe delivery devices with other suitable constructions may also incorporate aspects of the disclosure. Such devices would allow for similar advancement of biopsy probe 16 and probe delivery tube 20 – with both the biopsy probe 16 and probe delivery tube 20 being advanceable outside a housing of the probe delivery device and into a VAD, and with the biopsy probe 16 being further advanceable out of the probe delivery tube 20 and into a vein of the patient to enable collection of analytes from the blood of the patient.

[0078] Referring now to FIGS. 6-9, a probe delivery device 200 is shown that is configured to deliver a biopsy probe 16 and probe delivery tube 20 into a VAD 100, according to another embodiment of the disclosure. The probe delivery device 200 includes a housing 202, a coupling member or lock 204, a biopsy probe 16, an advancement element 206, and a probe delivery tube 20. The advancement element 206 may extend through a slot 208 in the housing and may be configured to move linearly along the slot 208 between an initial position illustrated and an advanced position distal to the initial position.

[0079] The biopsy probe 16 may include a proximal end 210 and a distal end 212. The proximal end 210 of the biopsy probe 16 may fixed to an inner surface of the housing 202 – e.g., toward the distal end 218 of the housing 202. The biopsy probe 16 may extend through a channel 216 in the advancement element 206, such that it is looped through the advancement element 206. In some embodiments, the channel 216 is a U-shaped channel, but channel 216 may be shaped differently – such as being a double U channel. In response to movement of the 6582020.DOCX Page 15 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) advancement element 206 distally a first distance along the slot 208, the second end 212 of the biopsy probe 16 may be configured to advance a second distance. In some embodiments, such as where channel 216 is a U-shaped channel, the second distance may be twice the first distance. In these embodiments, the advancement element 206 and the biopsy probe 16 may have a 1:2 advancement ratio such that for a particular distance the advancement element 206 is moved along the slot 208, the second end 212 of the biopsy probe 16 is moved twice the particular distance. In other embodiments, the second distance may be greater than twice the first such, such as the second distance being three time the first distance when the channel 216 is shaped as being a double U channel.

[0080] The probe delivery tube 20 may include a distal end 218 and a proximal end 220 - with the proximal end 220 of the probe delivery tube 20 coupled to the advancement element 206. In response to movement of the advancement element 206 distally the first distance along the slot 208, the distal end 218 of the probe delivery tube 20 is configured to advance the first distance. In these embodiments, the advancement element 206 and the probe delivery tube 20 may have a 1:1 advancement ratio such that for a particular distance the advancement element 206 is moved along the slot 208, the distal end 218 of the probe delivery tube 20 is moved a distance equal to the particular distance.

[0081] In some embodiments, the instrument delivery device 10 may include a seal 222 disposed within the advancement element 206 that prevents fluid from leaking out the proximal end of the probe delivery tube 20. In some embodiments, the seal 222 may include an elastomeric septum. In some embodiments, a seal 224 may also be provided at the distal end 218 of the housing 12 to selectively seal and / or fluidically isolate the inner volume 28 of the housing 12. The seal 224 allows a portion of the probe delivery tube 20 and a portion of the biopsy probe 16 to pass therethrough and contacts an outer surface of the probe delivery tube 20 to define a seal therebetween that is operable to limit and / or substantially prevent a back flow of fluid between the outer surface of the probe delivery tube 20 and the seal 224.

[0082] FIGS. 7-9 illustrate operation of the probe delivery device 200 for each of three distinct arrangement variations of the probe delivery device 200 (i.e., arrangements of biopsy probe 16 relative to probe delivery tube 20) – with the figures showing the advancement element 206 in an initial position, a partially advanced position, and a fully advanced position, for each of the configurations.

[0083] Referring first to FIG. 7, in a first configuration, the distal end 218 of the probe delivery tube 20 is generally aligned with the distal end 212 of the biopsy probe 16 when the advancement element 206 is in the initial position. Dtubemay correspond to a distance the probe 6582020.DOCX Page 16 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) delivery tube 20 moves, Dusermay correspond to a distance the advancement element 206 is moved by the user, and Dprobe may correspond to a distance the biopsy probe 16 moves, As illustrated in FIG. 7 in some embodiments, Dtube may be equal to Duser and Dprobe may be twice Duser.

[0084] Referring first to FIG. 8, in a second configuration, the distal end 218 of the biopsy probe 16 is distal to the distal end of the probe delivery tube 20 when the advancement element 206 is in the initial position. Dtubemay correspond to a distance the probe delivery tube 20 moves, Duser may correspond to a distance the advancement element 206 is moved by the user, Dprobe may correspond to a distance the biopsy probe 16 moves, and Dprobe / tube may correspond to a distance the biopsy probe 16 extends distally from probe delivery tube 20 with advancement element 206 in the initial position. As illustrated in FIG.8 in some embodiments, Dtube may be equal to Duser minus Dprobe / tube and Dprobe may be twice Duser.

[0085] Referring first to FIG. 9, in a third configuration, the distal end 218 of the probe delivery tube 20 extends distally out past the distal end 212 of the biopsy probe 16 when the advancement element 206 is in the initial position. Dtube may correspond to a distance the probe delivery tube 20 moves, Duser may correspond to a distance the advancement element 206 is moved by the user, Dprobemay correspond to a distance the biopsy probe 16 moves, Dprobe / tubemay correspond to a distance the probe delivery tube 20 extends distally from the probe with advancement element 206 in the initial position, and D2probe / tube may correspond to a distance the biopsy probe 16 extends distally out from the probe delivery tube 20 with advancement element 206 in the fully advanced position. As illustrated in FIG.9 in some embodiments, Dtubemay be equal to Duser and Dprobe may be twice Duser, while D2probe / tube may be equal to a sum of Dprobe / tube and Duser.

[0086] With operation of the probe delivery device 200 being as described above, the probe delivery tube 20 and biopsy probe 16 may be simultaneously moved in a distal direction via actuation of the advancement element 206 from the initial position toward the fully advanced position. In each of the configurations / embodiments, the distal end of biopsy probe 16 extends out distally past the distal end of probe delivery tube 20 as advancement element 206 is actuated from the partially advanced position to the fully advanced position. Thus, with the advancement element 206 is in the fully advanced position, a portion of the main body 50 of biopsy probe 16 extends out from probe delivery tube 20, such that at least a portion of the channels 56 formed in / on the main body 50 are exposed and are positioned within a vein of the patient. In this position, the biopsy probe 16 may collect analytes from blood of the patient while the probe 6582020.DOCX Page 17 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) remains positioned intravenously within the patient. That is, analytes are collected in the channels 56 (as blood flow is impeded by the biopsy probe 16 and channels 56 thereof).

[0087] Upon collection of a sufficient amount of analytes by probe, an operator may trap the collected analytes by retracting the biopsy probe 16 back into the probe delivery tube 20. In order to retract the biopsy probe 16, the operator moves the advancement element 206 proximally relative to the housing 12, back toward the initial position. As the biopsy probe 16 is retracted back into the probe delivery tube 20, analytes are trapped within the channels 56 as the main body 50 is slid back into the probe delivery tube 20.

[0088] For the probe delivery device 200, it is recognized that the biopsy probe 16 and probe delivery tube 20 may be configured similar or identical to as previously described. That is, biopsy probe 16 includes channels 56 formed therein / thereon to enable collection of analytes, but may or may not include an oversize tip thereon. In the device configurations of FIGS. 7 and 8, biopsy probe 16 may include oversize tip 52 thereon, while in the device configuration of FIG. 9, the biopsy probe 16 would not include the oversize tip 52 thereon (such that biopsy probe 16 may be fully contained within probe delivery tube 20 when in the initial position).

[0089] Referring now to FIG. 10, a probe delivery device 300 is shown that is configured to deliver a biopsy probe 16 and probe delivery tube 20 into a VAD 100, according to another embodiment of the disclosure. The probe delivery device 300 includes at least an introducer housing 302, a coupling member or lock 304, a biopsy probe 16, a probe advancement member 306, a probe delivery tube 20, and a tube advancement member 308.

[0090] The probe delivery device 300 may be considered a hybrid or cross of the probe delivery device 10 and probe delivery device 200. That is, similar to probe delivery device 10, probe delivery device 300 includes a separate probe advancement member 306 and tube advancement member 308 for advancing the biopsy probe 16 and probe delivery tube 20, while similar to probe delivery device 200, the tube advancement member 308 may advance the biopsy probe 16 with an advancement rate that is a multiple of the tube advancement member 308 itself. In some embodiments, the tube advancement member 308 and the biopsy probe 16 may have a 1:2 advancement ratio such that for a particular distance the tube advancement member 308 is moved along the housing 302 (i.e., within a slot 310 thereof) the biopsy probe 16 is moved twice the particular distance.

[0091] According to embodiments, a distal end 312 of the probe delivery tube 20 is generally aligned with a distal end 314 of the biopsy probe 16 when the probe advancement member 306 and tube advancement member 308 are in an initial position. The probe delivery tube 20 and the biopsy probe 16 may be distally moved from this first position to a second position by 6582020.DOCX Page 18 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) moving the tube advancement member 308 distally along housing 302 (with oversized tip 52 causing biopsy probe 16 to move collectively with probe delivery tube 20), and the biopsy probe 16 may then be subsequently moved to a third position by moving the probe advancement member 306 distally along housing 302. This movement of the probe delivery tube 20 and biopsy probe 16 between the first, second, and third positions is similar to as previously described for the probe delivery device 10 of FIGS. 1-5, except that movement of the biopsy probe 16 to the third position via actuation of the probe advancement member 306 occurs at an advancement rate that is a multiple of the tube advancement member 308 itself (e.g., 2:1 rate).

[0092] Referring now to FIG.11, a probe delivery device 400 is shown that is configured to deliver a biopsy probe 16 and probe delivery tube 20 into a VAD 100, according to another embodiment of the disclosure. The probe delivery device 400 includes at least an introducer housing 402, a coupling member or lock 404, a biopsy probe 16, a probe advancement member 406, a probe delivery tube 20, and a tube advancement member 408.

[0093] In the probe delivery device 400, probe advancement member 406 is configured as an advancement wheel that is mounted on housing 402 and may be rotated (clockwise and counterclockwise) to selectively advance and retract the biopsy probe 16. A proximal end 410 of biopsy probe 16 may thus be coupled to the probe advancement member 406 such that rotation thereof causes a corresponding movement of the biopsy probe 16.

[0094] Operation of the probe delivery device 400 may be essentially identical to that of probe delivery device 10. According to embodiments, a distal end 412 of the probe delivery tube 20 is generally aligned with a distal end 414 of the biopsy probe 16 when the probe advancement member 406 and tube advancement member 408 are in an initial position. The probe delivery tube 20 and the biopsy probe 16 may be distally moved from this first position to a second position by moving the tube advancement member 408 distally along housing 402, such as within a slot 418 of housing 402 - with oversized tip 52 causing biopsy probe 16 to move collectively with probe delivery tube 20 - and the biopsy probe 16 may then be subsequently moved to a third position by rotating the probe advancement member 406 relative to the housing 402. This movement of the probe delivery tube 20 and biopsy probe 16 between the first, second, and third positions is similar to as previously described for the probe delivery device 10 of FIGS. 1-5.

[0095] Referring now to FIGS. 12A-12C, a probe delivery device 500 is shown that is configured to deliver a biopsy probe 16 and probe delivery tube 20 into a VAD 100, according to another embodiment of the disclosure. The probe delivery device 500 includes at least a 6582020.DOCX Page 19 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) coupling member or lock 504, a biopsy probe 16, a probe advancement button 506, a probe delivery tube 20, and a tube advancement button 508.

[0096] Operation of the probe delivery device 500 may include pushing and / or rotation of probe advancement button 506 and tube advancement button 508 to advance and retract probe delivery tube 20 and biopsy probe 16. According to embodiments, a distal end 510 of the probe delivery tube 20 is generally aligned with a distal end 512 of the biopsy probe 16 when the probe advancement button 506 and tube advancement button 508 are in an initial position. In one embodiment, the probe delivery tube 20 and the biopsy probe 16 may be distally moved from this first position (FIG. 12A) to a second position (FIG. 12B) by pushing both the tube advancement button 508 and probe advancement button 506 distally, and the biopsy probe 16 may then be subsequently moved to a third position (FIG. 12C) by further distally pushing the probe advancement button 506. In other embodiments, the buttons 506, 508 can be moved independent of each other, or movement of probe advancement button 506 could lead to advancement of probe delivery tube 20 and / or rotation of probe advancement button 506 could lead to exposing of the biopsy probe 16 (i.e., advancement of probe out of probe delivery tube 20.

[0097] 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 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. 6582020.DOCX Page 20 of 27

Claims

Attorney Docket No. 09846-2502877 (P-30179.WO01) THE INVENTION CLAIMED IS 1. A probe delivery device for advancing a probe into an indwelling catheter of a vascular access device, the probe delivery device comprising: an introducer housing having a proximal end and a distal end, with the housing defining an inner volume; a coupling member positioned at the distal end and coupleable to the vascular access device; a probe movably received within the inner volume, the probe comprising a main body and a distal tip, with the main body comprising a plurality of channels formed therein that trap analytes therein when positioned intravenously within a patient; a probe delivery tube movably received within the inner volume and defining a tube lumen therein configured to receive the main body, with the distal tip or location near to the distal tip larger than the tube lumen; a probe advancement member movably coupled to the housing and configured to move relative to the housing to move the probe; and a tube advancement member movably coupled to the housing, distal from the probe advancement member, and configured to move relative to the housing to move the probe delivery tube, with a proximal end of the probe delivery tube coupled to the tube advancement member; wherein a distal movement of the tube advancement member relative to the housing collectively moves the probe delivery tube and the probe from a first position, in which the probe delivery tube and probe are disposed within the introducer housing or within the introducer housing and the coupling member, to a second position, in which a distal end of the probe delivery tube and the probe are disposed beyond the distal end of the introducer housing and into or distally past a distal end of the indwelling catheter; and wherein a distal movement of the probe advancement member relative to the housing, subsequent to distal movement of the tube advancement member, moves the probe from the second position to a third position, where the distal tip of the probe is moved further distally from the distal end of the probe delivery tube, such that at least a portion of the plurality of channels are positioned outside of the tube lumen, to provide for collection of analytes within the channels. 6582020.DOCX Page 21 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) 2. The probe delivery device of claim 1, wherein the probe is formed of a shape memory alloy.

3. The probe delivery device of claim 2, wherein the shape memory alloy comprises Nitinol.

4. The probe delivery device of claim 1, wherein a majority of the probe is positioned within the tube lumen of the probe delivery tube in a coaxial arrangement, with the distal tip of the probe remaining outside of the tube lumen.

5. The probe delivery device of claim 1, wherein the tube advancement member comprises an opening formed therethrough, through which the probe passes to be positioned within and coaxially with the probe delivery tube.

6. The probe delivery device of claim 5, wherein the tube advancement member comprises a sealing element positioned in the opening thereof, with the probe extending through the sealing element, and with the sealing element preventing blood and analytes from leaking from the probe delivery tube.

7. The probe delivery device of claim 1, wherein with the probe in the third position, a proximal movement of the probe advancement member moves the probe from the third position back to the second position, thereby trapping collected analytes between the channels and the probe delivery tube.

8. The probe delivery device of claim 1, wherein each of the probe advancement member and the tube advancement member comprises: a first portion comprising an engagement portion movable along a top surface of the housing; and a second portion positioned at least partially within the inner volume and joined to the first portion through a slot formed in the top surface of the housing.

9. The probe delivery device of claim 8, wherein, for the probe advancement member, the second portion is coupled with a proximal end of the probe; and 6582020.DOCX Page 22 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) wherein, for the tube advancement member, the second portion is coupled with a proximal end of the probe delivery tube.

10. The probe delivery device of claim 8, wherein a proximal end of the probe is coupled to the housing at the distal end thereof, and wherein the second portion of the probe advancement member comprises a channel formed therein through which the probe extends; and wherein, for the tube advancement member, the second portion is coupled with a proximal end of the probe delivery tube.

11. The probe delivery device of claim 10, wherein a distal movement of the probe advancement member relative to the housing by a first distance causes the probe to advance distally by a second distance that is greater than the first distance.

12. The probe delivery device of claim 10, wherein a shape of the channel determines a length of the second distance, with the second distance being twice the first distance or greater.

12. The probe delivery device of claim 1, wherein the probe advancement member comprises an advancement wheel secured to the housing and rotatable in a first direction and a second direction relative thereto; and wherein the tube advancement member comprises: a first portion comprising an engagement portion movable along a top surface of the housing; and a second portion positioned at least partially within the inner volume and joined to the first portion through a slot formed in the top surface of the housing; wherein, for the probe advancement member, the advancement wheel is coupled with a proximal end of the probe; and wherein, for the tube advancement member, the second portion is coupled with a proximal end of the probe delivery tube.

13. The probe delivery device of claim 12, wherein rotation of the advancement wheel causes subsequent to distal movement of the tube advancement member, moves the probe from the second position to the third position. 6582020.DOCX Page 23 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) 14. The probe delivery device of claim 1, wherein the probe advancement member and the tube advancement member comprise buttons that are pushable and / or rotatable.

15. The probe delivery device of claim 1, wherein the coupling device comprises a lock including: a coupler configured to engage the distal end of the housing; a first arm and a second arm configured to engage with the vascular access device or an adapter provided between the vascular access device and the lock; and a blunt cannula extending from the coupler and disposed between the first arm and the second arm, the blunt cannula configured to engage with the vascular access device or the adapter; wherein a lumen extends through the blunt cannula and the coupler, through which the probe delivery tube and probe may be distally advanced.

16. A method for collecting analytes from blood using the probe delivery device of claim 1, the method comprising: moving the tube advancement member distally along the introducer housing to distally advance the probe delivery tube and the probe from a first position to the second position; moving the probe advancement member distally along the introducer housing to distally advance the probe from the second position to the third position; retaining the probe in the third position for a required amount of time, intravenously within the patient, to collect analytes from the blood; moving the probe advancement member proximally along the introducer housing to proximally retract the probe from the third position back to the second position, thereby trapping the analytes between the probe and the probe delivery tube; and moving the probe advancement member and tube advancement member proximally along the introducer housing to proximally retract the probe and the probe delivery tube back to the first position.

17. A probe delivery device for advancing a probe into an indwelling catheter of a vascular access device, the probe delivery device comprising: 6582020.DOCX Page 24 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) an introducer housing having a proximal end and a distal end, with the housing defining an inner volume; a coupling member positioned at the distal end and coupleable to the vascular access device; a probe movably received within the inner volume, the probe comprising a main body and a distal tip, with the main body comprising a plurality of channels formed therein that trap analytes therein when positioned intravenously within a patient, and with a proximal end of the probe connected to the distal end of the housing; a probe delivery tube movably received within the inner volume and defining a tube lumen therein configured to receive the main body, with the distal tip or location nearby the tip larger than the tube lumen; and an advancement member movably coupled to the housing and configured to move relative to the housing to move the probe and the probe delivery tube; and wherein a distal movement of the advancement member relative to the housing collectively moves the probe delivery tube and the probe distally, with distal movement of the advancement member by a first distance causing the probe delivery tube to advance distally by the first distance and causing the probe to advance distally by a second distance that is greater than the first distance, such that the probe is advanced further distally than the probe delivery tube.

18. The probe delivery device of claim 17, wherein the advancement member comprises: a first portion comprising an engagement portion movable along a top surface of the housing; and a second portion positioned at least partially within the inner volume and joined to the first portion through a slot formed in the top surface of the housing; wherein the second portion of the probe advancement member comprises a U- shaped channel formed therein through which the probe extends; and wherein a proximal end of the probe delivery tube is secured to the second portion.

19. The probe delivery device of claim 18, wherein the advancement member comprises a sealing element positioned in the U-shaped channel thereof, with the 6582020.DOCX Page 25 of 27Attorney Docket No. 09846-2502877 (P-30179.WO01) probe extending through the sealing element, and with the sealing element preventing blood and analytes from leaking from the probe delivery tube.

20. The probe delivery device of claim 17, wherein the second distance is greater than the first distance, such as twice the first distance or three times the first distance. 6582020.DOCX Page 26 of 27

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