WO2014092910A1

WO2014092910A1 - Vascular access system and method

Info

Publication number: WO2014092910A1
Application number: PCT/US2013/069688
Authority: WO
Inventors: Paul S. VAN WIEREN; Chris J. OKOS
Original assignee: Edwards Lifesciences Corporation
Priority date: 2012-12-12
Filing date: 2013-11-12
Publication date: 2014-06-19

Abstract

The present disclosure provides a system for sampling blood from a patient's vasculature and directing the blood to an analyte sensor. The vascular access system includes an access device comprising a cylindrical body connecting a proximal end and a distal end, the access device having one or more opening formed in at least a portion of the cylindrical body; the access device defining at least one lumen extending from the proximal end to the distal end; where the distal end of the access device and the one or more openings of the access device reside within the patient's vasculature for an extended period of time; where the vascular access system is configured to draw blood through the one or more opening of the access device even when the distal end is occluded; and where the proximal end is connectable in fluid communication with the analyte sensor.

Description

VASCULAR ACCESS SYSTEM AND METHOD

BACKGROUND

[0001] Currently, glucose monitoring systems use a simple, peripheral IV catheter to access patient blood for glucose measurements. Unfortunately, peripheral IV catheters are principally designed for fluid delivery, and thus are not idealized for blood sampling. These catheters display several weaknesses with regards to vascular access, but one major weakness is the fact that they are very susceptible to failed blood draws due to contact with the vessel wall, which results in failed glucose measurement.

SUMMARY

[0002] The present disclosure overcomes the problems of the prior art by providing an analyte sensing system that includes a sensor, a vascular access system, a flow controller and a monitor system. Various embodiments of the vascular access system can include one or more opening formed in the access device adapted to draw blood even when a distal end of the access device is occluded.

[0003] In the various embodiments of the disclosure, a vascular access system for use with a system for sampling blood from a patient's vasculature and directing the blood to an analyte sensor is provided. The vascular access system includes: an access device comprising a cylindrical body connecting a proximal end and a distal end, the access device having one or more opening formed in at least a portion of the cylindrical body; the access device defining at least one lumen extending from the proximal end to the distal end; wherein the distal end of the access device and the one or more openings of the access device reside within the patient's vasculature for an extended period of time; wherein the vascular access system is configured to draw blood through the one or more opening of the access device even when the distal end is occluded; wherein the proximal end is connectable in fluid communication with the analyte sensor.

[0004] In other embodiments of the vascular access system, at least a portion of the access device comprises a heparin coating. In still other embodiments, the vascular access system is configured to flush a fluid through the one or more opening of the access device even when the distal end is occluded. In further embodiments, the one or more openings are positioned a predetermined distance from the distal end of the access device.

[0005] In further embodiments of the disclosure, a sensor system for sensing a parameter in vascular accessed by an access device is provided. The sensor system includes: an analyte sensor coupled to the access device; wherein the access device comprises a cylindrical body connecting a proximal end and a distal end, the access device having one or more opening formed in at least a portion of the cylindrical body; wherein the distal end and the one or more opening of the access device reside within the patient's vasculature for an extended period of time and the proximal end is connectable in fluid communication with the analyte sensor; a flow control system configured to draw blood through the one or more opening of the access device to the analyte sensor or flush the sensor with a calibrant through the one or more opening to evacuate the blood even when the distal end of the access device is occluded; and a monitor connected in communication with the analyte sensor, the monitor configured to receive a blood signal when the sensor is in blood and then to receive a calibration signal when the sensor is in the calibrant and use the calibration signal to determine the parameter from the blood signal.

[0006] In other embodiments of the disclosure, a method for sampling blood from a patient's vasculature and sensing a parameter in the blood is provided. The method includes: providing a sensor system comprising: an analyte sensor coupled to an access device; an access device comprising a cylindrical body connecting a proximal end and a distal end, the access device having one or more opening formed in at least a portion of the cylindrical body; wherein the distal end and the one or more openings of the access device reside within the patient's vasculature for an extended period of time and the proximal end is connectable in fluid communication with the analyte sensor; a flow control system configured to draw blood through the access device to the analyte sensor and flush the sensor with a fluid to evacuate the blood; and a monitor connected in communication with the analyte sensor, the monitor comprising a computer apparatus comprising a memory and a processor; drawing, via the flow control system, blood through at least one of the one or more openings to the analyte sensor and flushing the sensor with a calibrant to evacuate the blood even when the distal end of the access device is occluded; and receiving, at the monitor, a blood signal when the sensor is in the blood and a calibration signal when the sensor is in the calibrant; and determining, via the monitor, the analyte from the blood signal based on the calibration signal.

[0007] In still further embodiments, a method of manufacturing a system for sampling blood from a patient's vasculature is provided. The method includes: providing a fixture having an opening formed therein for receiving an access device comprising a cylindrical body connecting a proximal end a distal end; placing the distal end and at least a portion of the cylindrical body of the access device in the opening of the fixture; providing a sharp device for puncturing the cylindrical body; puncturing, using the sharp device, the cylindrical body adjacent to the distal end to form one or more openings in the access device; wherein the access device is configured such that the distal end of the access device and the one or more openings of the access device reside within a subject's vasculature for an extended period of time; wherein the access device is configured to draw blood through the one or more opening even when the distal end is occluded. In other embodiment of the method, the method includes coating at least a portion of the cylindrical body with heparin.

[0008] These and other features and advantages of the present disclosure will become more readily apparent to those skilled in the art upon consideration of the following detailed description and accompanying drawings, which describe both the preferred and alternative embodiments of the present disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIG. 1 is a perspective view of an analyte sensing system in accordance with various embodiments of the disclosure;

[0010] FIG. 2 is a cross-sectional view of components, including a sampling line assembly, of a flow control system of the analyte sensing system shown in FIG. 1 ;

[0011] FIG. 3 is an enlarged view of an adapter of the components shown in FIG. 2;

[0012] FIG. 4 is a perspective view of the components, including a sampling line assembly, shown in FIG. 2;

[0013] FIG. 5 is a schematic of a rotary pinch valve of a flow control system in accordance with various embodiments of the disclosure; [0014] FIG. 6 is a perspective view of an adapter of the components shown in FIG. 2;

[0015] FIG. 7 is a perspective view of an adapter in accordance with various embodiments of the disclosure;

[0016] FIG. 8 is a perspective view of a catheter in accordance with various embodiments of the disclosure;

[0017] FIG. 9 is a perspective view of a catheter in the vasculature of a subject in accordance with various embodiments of the disclosure;

[0018] FIG. 10A illustrates a catheter for drawing blood samples in accordance with various embodiments of the disclosure;

[0019] FIG. 10B illustrates a catheter for drawing blood samples in accordance with various embodiments of the disclosure;

[0020] FIG. 11 is a perspective view of a catheter for drawing blood samples in the vasculature of a subject in accordance with various embodiments of the disclosure;

[0021] FIG. 12 is a schematic of a system for producing a catheter for drawing blood samples in accordance with various embodiments of the disclosure; and

[0022] FIG. 13 is a graphical depiction of a flow profile of an embodiment of the present disclosure.

DETAILED DESCRIPTION

[0023] The present disclosure now will be described more fully hereinafter with reference to specific embodiments of the disclosure. Indeed, the disclosure can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. As used in the specification, and in the appended claims, the singular forms "a", "an", "the", include plural referents unless the context clearly dictates otherwise. The term "comprising" and variations thereof as used herein is used synonymously with the term "including" and variations thereof and are open, non- limiting terms.

[0024] The term "analyte" as used herein relates to a substance or chemical constituent in a biological sample (e.g., bodily fluids, including, blood, serum, plasma, interstitial fluid, cerebral spinal fluid, lymph fluid, ocular fluid, saliva, oral fluid, urine, excretions, or exudates. Analytes can include naturally occurring substances, artificial substances, metabolites, and/or reaction products. The analyte for measurement by the sensor, devices, and methods is inclusive of glucose. Any other physiological analyte or metabolite can be substituted or combined with the measurement of glucose.

[0025] Embodiments of the present disclosure include an analyte sensing system, e.g., a blood glucose sensing system 10 that includes a monitor 12, a sensor assembly 14, a calibration solution source 16 and a flow control system 18, as shown in Figure 1. Notably, the present disclosure could also be employed with other analyte sensing systems that require drawing of blood or fluid samples from a patient. Blood, as used herein, should be construed broadly to include any body fluid with a tendency to occlude lumens of various body-access devices during sampling. The flow control system 18 includes a flow controller 20, a monitor line 22, a sensor casing 24, an adapter 26, a sampling line assembly 28 and a catheter 30, as shown in Figures 1, 2, 4 and 8. Generally, the flow control system 18 of one embodiment of the present disclosure is configured to mediate flow of small volumes of the calibration solution 16 over the sensor assembly 14 and withdraw small volumes of samples of the blood from the patient for testing by the sensor assembly.

[0026] The flow control system 18 in another embodiment is able to support the flush and draw pressures and volumes, and the high number of sampling cycles over a long multi-day indwell, needed for continuous analyte (glucose) monitoring, while avoiding the formation of thrombi that occur in conventional catheters by providing a small- diameter, smooth and relatively void free surface defining a lumen extending up to the sensor assembly 14. In another embodiment, the sampling line of the sampling line assembly 28 of the flow control system 18 may be employed with a range of existing catheter 30 configurations by having the sampling line sized and configured for insertion into a lumen of an existing catheter. In still other embodiments of the present disclosure, thrombus formation is inhibited by balancing the structure of various components of the flow control system 18 and operation of the flush and draw cycles by the flow controller 20.

[0027] The monitor 12 is connected in communication with the sensor assembly 14 through communication lines or wires 36 and to the flow control system 18 through communication lines or wires 38, as shown in Figure 1. These communication lines 36, 38 could also represent wireless data communication such as cellular, RF, infrared or blue-tooth communication. Regardless, the monitor 12 includes some combination of hardware, software and/or firmware configured to record and display data reported by the sensor assembly 14. For example, the monitor may include processing and electronic storage for tracking and reporting blood glucose levels. In addition, the monitor 12 may be configured for automated control of various operations of other aspects of the sensing system 10. For example, the monitor 12 may be configured to operate the flow control system 18 to flush the sensor assembly 14 with calibration solution from source 16 and/or to draw samples of blood for testing by the sensor assembly. Also, the monitor 12 can be configured to calibrate the sensor assembly 14 based on the flush cycle. In some embodiments, the monitor 12 comprises a computer apparatus that includes a memory and a processor, where a module stored in the memory causes the processor to track, report, and analyze data.

[0028] Referring to Figures 2 and 3, the sensor assembly 14 includes a wire electrode sensor 40 that includes, for example, a glucose-oxidase coated platinum wire covered by a membrane that selectively allows permeation of glucose. The glucose-oxidase responds to the glucose by generating hydrogen peroxide which, in turn, generates an electrical signal in the platinum wire. The platinum wire is connected to a puck-shaped board 42 held in a housing 44 of the sensor assembly 14. The board 42 may include some processing component and/or just communicate the signal up through the communication wires 36 attached thereto for further processing by the monitor 12. The sensor assembly 14 may also include counter and/or reference wire electrodes bundled with the working electrode. Regardless, in the illustrated embodiment, the wire electrode sensor 40 is adapted to extend through and into the sensor casing 24 so as to be within the flow path of the blood sample, as will be described in more detail herein below.

[0029] It should be noted that, although particularly advantageous for sensors 40 directly within the flow path of the blood sample, the particular configuration of the sensor assembly 14 that puts the sensor 40 within the flow of the blood and/or calibrant path may vary and still be within the scope of the present disclosure. For example, the sensor 40 could be a microfluidics sensor that is adjacent to, and routed off of, a portion of the flow control system 18 within the reach of a blood volume draw. Also, the sensor 40 could be an optical or vibrational sensor that senses glucose or other non-glucose blood analytes without contact with the blood sample, such as through a vibrationally or optically transparent adjacent portion of the flow control system.

[0030] The calibrant solution source 16 is supplied, in one embodiment, from a bag 32 mounted on a pole 34. The calibrant solution supply is preferably off-the-shelf and/or not inconvenient to employ in a hospital setting and is also beneficial to the patient and includes attributes that help with function of the sensing system 10. For example, the solution in the bag may be a Plasmalyte or conventional saline with selected amounts of buffers and anti-thrombogenic compounds, such as heparin, that help with flushing the sensor assembly 14 to keep it clear of clots and thrombosis. The solution in the bag 32 may also include various nutrients to keep fluid and nutrition at appropriate levels for the patient. Although the illustrated embodiment employs a fluid bag 32, it should be noted that the calibrant solution source 16 could include several sources, including several sources at one time, and have varying compositions. For example, a pressurized canister or a reservoir may be employed.

[0031] As shown in Figure 1, the monitor line 22 of an embodiment of the flow control system 18 extends from the calibrant solution source 16 through the flow controller 20 and attaches to the rest of the flow control system 18 (sensor casing 24, adapter 26 and sampling line within catheter 30) closer to the sensor assembly 14. Preferably, the monitoring line is an 8 foot length of PVC extension tubing with a .0625 inch internal diameter.

[0032] The flow controller 20 in one embodiment of the present disclosure includes some type of hardware, software, firmware or combination thereof that electromechanically controls one or more valves, or other mechanical flow control devices, to selectively allow or stop flow through the monitor line 22. In the illustrated embodiment of Figure 5, the mechanical aspect of the flow controller 20 includes a rotary pinch valve through which extends the monitor line 22. This rotary pinch valve pinches the fluid line to stop flow and, by sliding along a short length of the fluid line, can advance or retract the calibrant solution or retract the calibrant solution supply in a column extending down to the end of the catheter 30. Different numbers of roller heads may be used, such as two or four heads, the latter aiding with higher draw volumes.

[0033] Notably, the flow controller 20 of the illustrated embodiment employs a combination of the head (primarily, except for the short draw and infusion by pinch point advancement) generated by the elevation of the fluid bag 32 on the pole 34 and the on- off regulation of the flow induced by the head. The flow controller 20, however, could also include a combination with a flow system and associated programmable controller, so as to eliminate the need for the pole 34 that could be combined with the aforementioned calibrant solution source 16. One advantage, however, of the illustrated embodiment is that the gravity feed of the fluid bag 32 on the pole 34 is well-understood and mediated to control the amount of fluid administered to the patient. Regardless, the role of the flow controller 20 can be met flexibly with various combinations of technology and the present disclosure shouldn't necessarily considered limited to any one particular configuration.

[0034] When the flow controller 20 opens its pinch valve, solution from the bag 32 is gravity fed down through the monitor line 22, the sensor casing 24, the adapter 26, the sampling line and (if used) the catheter 30 and into the patient's vasculature. Or, the flow controller 20 could advance the pinch valve in the direction of the catheter 30 and drive the solution to flush the sensor 40 and out through the catheter. If the solution from the bag 32 includes heparin or other anti-thrombogenic agent and/or some anti- thrombogenic mechanical qualities, this flush step clears the catheter and cleans the sensor 40.

[0035] In a draw step, the pinch valve is reversed by the flow controller 14 forming a vacuum and drawing a blood sample up into the catheter from the patient's vasculature. The glucose sensor, during or after this step, can then be activated to sense the glucose concentration in the blood sample. After sufficient time has elapsed to take one or more analyte measurements, the flush cycle is then run, typically in 5 to 10 minute cycles, as described above. This process of flush-and-draw is repeated over the life of the sensing system 10, or at least the life of the glucose sensor. The description above is a more general overview of the flush/draw process. Variations in the specifics of the flush and draw cycles and how they're adapted to work with the present system to avoid thrombosis, minimize flush and draw volumes and work with existing catheter configurations will be described in more detail below.

[0036] In an embodiment of the present disclosure, the flow profile preferably lasts for 5 to 7.5 minutes and delivers less than 500 mL of solution from the bag 32 over a 72- hour period. Also, the flow controller 20 preferably has improvements to ensure accuracy and repeatability of its control of fluid flow through the flow control system 18. For example, the above-described rollers may be accompanied by an encoder coupled with a stepper motor that provides redundant control of the roller head orientation. Also, there may be an air detection sensor distal to the roller head assembly that uses optical or ultrasonic sensing (an ultrasonic pulse) to detect gas or liquid conditions in the tube segment.

[0037] As shown in Figure 2, in one embodiment of the present disclosure, the sensor casing 24 includes a threaded flange 46, a cylindrical body 48 defining an axial lumen 56 and a female connector 50. The sensor casing 24 preferably has a length sufficient to protect the length (approximately 2 cm in a preferred embodiment) of the wire electrode sensor 40, such as about 4 cm. If the sensor casing 24 is too short, the adapter 26 might also supply some protection.

[0038] The threaded flange 46 is molded on the proximal end of the sensor casing 24 and extends around the cylindrical body 48 as a thin annulus with threads defined around its outer surface. The flange 46 is configured to insert into a luer connector at a distal end of the monitor line 22. Defined within the flange 46 is an annular receptacle 58 (an expansion of the axial lumen 56) configured to receive a male portion of the luer connector. Attachment of the threaded portions of the connector and flange 46 should form a fluid tight communication between the lumen of the monitor line 22 and the sensor casing 24.

[0039] The sensor casing 24 also may include an annular seal which is an elastomeric sealing member that is configured to extend between, and is compressed by attachment of, the male end of the luer connector and the threaded flange 46. Such compression seals off the junction between the two components and blocks wicking of blood and flush solution between the two components. [0040] The cylindrical body 48 extends from the threaded flange 46 to the distal end of the sensor casing 24 and ends at the female connector 50. The cylindrical body has an elongate cylindrical shape and supports on its outside surface (and may be integrally constructed with) the housing 44 containing the board 42 through which the wire electrode sensor 40 connects to the communication line 36. The housing 44 has an elliptical or cylindrical shape to fit the "puck" shape of the board 42 and includes a wire mount 54 extending off at about a 30 degree angle with respect to the axis of the sensor casing 24. The wire mount 54 helps to secure the communication lines 36 from detachment from the board 42 and its angle is tailored to having the communication line 36 extend off along and away from the patient and may allow the communication line to be taped to the patient' s arm or bedside against being pulled free.

[0041] The axial lumen 56, as shown in the embodiment of Figures 2-4, has a cylindrical shape with a constant diameter extending down to the distal end of the cylindrical body 48. Optionally, the cylindrical body may also include a sleeve portion that extends around the axial lumen 56 and has smooth and thrombo-resistant properties that are improved with respect to the rest of the sensor casing 24. For example, the sleeve may be a portion of polyurethane or nylon tubing that is press fit into the sensor casing 24 after it is formed.

[0042] The cylindrical body 48 also defines a port 60 through which the wire electrode sensor 40 extends into the axial lumen 56 for exposure to the blood samples drawn therethrough by the flow control system 18. The port 60 is preferably sealed in some manner (such as by an elastomeric valve or being embedded in the material of the cylindrical body 48) against leakage of the calibration fluid and the blood samples and, in addition, is selected to smoothly integrate with the surrounding surface of the cylindrical body 48 that defines the axial lumen 56.

[0043] The axial lumen 56 preferably has a diameter that is selected to provide a smooth transition with the lumen of the monitor line 22 and has sufficient space to fit the diameter of the wire electrode sensor 40. Embodiments of the present disclosure with variations of the diameter of the axial lumen 56 that achieve the objectives of providing for robust analyte sensing and minimized draw/flush volumes and thrombosis will be explored more below. However, for the illustrated embodiment, the diameter of the wire electrode sensor 40 is about 0.008 to .010 inch and the inside diameter of the axial lumen 56 is about .030 inch, which matches up for a smooth transition with a .030 inch lumen diameter of the monitor line 22.

[0044] The female connector 50 at the distal end of the sensor casing 24 has a cylindrical shape with an outer cylindrical wall 64 spaced from an inner cylindrical wall 66 to form an annular female receptacle. The outer cylindrical wall 64 can include threads to enable attachment to a threaded proximal end 68 of the adapter 26. The inner cylindrical wall 66 extends within the proximal end 68 of the adapter 26. The positioning of these two walls brackets the threaded proximal end 68 of the adapter 26 for a firm connection between the two.

[0045] As shown in Figures 6 and 2, the adapter 26 includes the threaded proximal end 68, an annular seal 62, a cylindrical body 72 defining an axial lumen 76 and a threaded distal end 74. The threaded proximal end 68 is formed on the end of the adapter 26 and extends around the cylindrical body 72 to form a male fit with the female connector 50 at the distal end of the sensor casing 24. In particular, the threaded proximal end 68 has a threaded cylinder shape that extends between the outer and inner cylindrical walls 64, 66 of the distal end of the sensor casing 24.

[0046] The cylindrical body 72 extends from the threaded proximal end 68 to the distal end of the adapter 26, ending at the threaded distal end 74. The cylindrical body 72 has an elongate cylindrical shape and in another embodiment may include, as shown in Figure 7, for example, fins 78 projecting outwardly from its surface to act as a stiffener against bending of the adapter 26. The fins 78 flare outwardly in a radial direction as they extend axially toward the threaded distal end 74 of the adapter 26.

[0047] The threaded distal end 74 is fashioned similar to a luer connector with a pair of concentrically positioned, cylindrical outer 80 and inner 82 walls. The cylindrical outer wall 80 has threads extending around its inside surface that is configured to mate with a threaded proximal end 84 of the sampling line. The cylindrical inner wall 82 projects more distal than the outer wall 80 and is configured to extend into the proximal end 84 of the sampling line assembly 28, as shown in Figure 3.

[0048] The axial lumen 76 defined by the cylindrical body 72 of the adapter 26 is configured to accept a free end of the wire electrode sensor 40. The length of the axial lumen 76 is just slightly longer, such as within .05 mm to 2 mm (preferably about 1 mm) the length of the wire electrode sensor 40. In this manner, the axial lumen 76 is configured to accept and allow extension nearly to its end the remaining length of the wire electrode sensor 40. The annular seal 62 is an annular elastomeric tube with a flange that is configured to fit within an expanded proximal end of the axial lumen 76 so as to seal against any leakage between the mating of the sensor casing 24 and the adapter 26.

[0049] Alternatively, the entire length of the axial lumen may be defined by a length of separately manufactured tubing press fit into the remainder of the adapter 26 which is formed as a molded part. This has the advantage of avoiding the difficulties of ensuring tight tolerances of the axial lumen 76 within the molded adapter 26. Ends of the tubing may extend out (e.g., .015 inch) of the surrounding opening within the cylindrical body 72 so as to enable a sealing fit at either of the proximal or distal ends 68, 74 of the adapter 26 when connected to the sensor casing 24 and sampling line assembly 28. Exemplary tubing may be .031 inch ID and .093 inch OD tubing with lumen clearance for .015 inch OD sensor wires, as shown in Figure 3.

[0050] Similar to the axial lumen 56 of the cylindrical body 48 of the sensor casing 24, the axial lumen diameter can vary within ranges depending upon several factors associated with operation of the flow control system 18. However, for the illustrated embodiment, the diameter of the axial lumen 76 is preferably about 0.30 inch which provides .020 inch clearance around the end of the wire electrode sensor 40 extending therethrough.

[0051] Referring again to Figures 2, 3, and 4, the sampling line assembly 28 includes the threaded male proximal end 84, a locking cap 86, an axial lumen (not shown), a sealing member 88, a sampling tube 90 and stress relief member 92. The proximal end 84 has a male shape configured to fit between the walls 80, 82 on the distal end 74 of the adapter 26. It also includes threads that fit the threads of the distal end 74 to secure it thereto in locking engagement. The locking cap 86 at the other, distal end has threads enabling it to fit the male end of a standard luer connector on standard catheters.

[0052] Defined through the proximal end and locking cap 86 is the axial lumen (e.g., the multi-lumen tube 94). The axial lumen is enlarged on the proximal end and necked down through the middle and distal portions to a smaller diameter. The sealing member 88 extends within the axial lumen and is an elastomeric member that has a tightly- toleranced inner diameter configured to fit an outer diameter of the sampling tube 90, so as to secure the sampling tube to the rest of the sampling line assembly 28. The sealing member also acts to seal the connection, through its elastic compressibility, between the adapter 26 and the sampling line assembly 28. The face of the threaded distal end 74 of adapter 26 abuts and compacts the flanged portion of the sealing member 88 when the male proximal end 84 of the sampling line is twisted into the threads of the distal end 74. The flanged shape of the sealing member 88 secures against axial migration. Also, the sealing member 88 helps to secure the sampling tube 90 to the rest of the sampling line assembly 28.

[0053] Also helping to secure the sampling tube 90 is the stress relief member 92, which may be a dab of elastomeric adhesive in a frustoconical shape (as shown in Figure 3) which helps to lock the sampling tube to the sealing member 88 and/or the distal end of the locking cap 86 of the sampling line assembly 28. Or, the stress relief member 92 may be a length of tubing that has a decreasing diameter along its length to help relieve strain on the sampling tube 90.

[0054] The sampling tube 90 in one embodiment is a very small ID tube that has a relatively large OD and is constructed of a material that's mechanically thromboresistant (and may be combined with heparin or other anti-thrombosis agents) due to its internal shape, smoothness and void-free structure. Without being wed to theory, it is believed that the smaller ID is less prone to clotting or other thrombosis since the pressure profile across the cross-section of the blood is more evenly distributed because the red blood cells and other blood components are a larger percentage of the cross section of the lumen defined therethrough. More even pressure distribution helps to ensure that the blood components do not stop against the side of the lumen walls of the sampling tube 90, cutting down on the tendency to clot. In addition, the smaller ID reduces the size of the flush and draw amounts to minimize side effects on the patient. Less blood in the draw means lower flushing volumes with the heparin in the calibration solution.

[0055] The relatively larger OD of the sampling tube 90 is advantageous in that it provides a good buckling stiffness to enable insertion of the sampling tube 90 directly into the patient (preferably in combination with a needle or other introducer) or into the lumen of an existing catheter 30 without bending or kinking. Still, if such a combination is desired, the OD can be constrained to allow the sampling line assembly 28 to be combined with existing catheters or introducers. In one embodiment, for example, the sampling line has an outer diameter of .030 inch configured to fit within a range of standard-sized catheter 30 lumens, such as the three-lumen MULTI-MED central venous catheter or an ADVANCED VENOUS ACCESS (AVA) catheter (Edwards Lifesciences, Irvine, CA). Despite the aforementioned preferred configurations and sizes, a balance may be struck between a range factors, flow rates, adaptability to existing catheters, antithrombotic attributes and the ID/OD, length and other attributes of the sampling tube 9 to create other embodiments of the present disclosure as will be described more below.

[0056] The advantage of inserting the sampling tube 90 into an existing catheter 30 is that a dedicated line for sampling the analyte is no longer needed. In addition, the sampling tube 90 can reduce the cross-sectional area through which blood is drawn to reduce clotting and sample volume. Further, the sampling tube 90 can serve as a sleeve that covers the gaps, transitions and other voids that are present in conventional catheters.

[0057] Conventional catheters 30, for example the catheter shown in Figure 8, frequently include three parts, a multi-lumen tube 94, a back form 96 and lines 98. The multi-lumen tube 94 inserts into the patient and provides lumens that exit at different points of the multi-lumen tube depending upon the function employed with each lumen. For example, one lumen may be a supply lumen 102 for administering drugs that exits at the distal end of the tube 94, another sensing lumen 104 for communicating with a pressure sensor for determining cardiac output that exits at a midpoint from the side of the tube 94 and a third sampling lumen 106 for sampling blood that exits at a proximal point 108 from the side of the tube 94.

[0058] Each of the lumens within the multi-lumen tube communicates with a dedicated channel defined in the back form. These channels diverge within the back form 96 (which typically has a triangular shape as it extends away from the patient) and each of the channels connects up with a dedicated one of the lines 98. Each time a transition between the components 94, 96, 98 occurs, there are discontinuities, gaps, rough surfaces, material variations and other voids that might promote the occurrence of clotting and other thrombosis and/or require less-desirable flow rates for the long-term, high-count sampling needed for the present disclosure.

[0059] In one embodiment of the present disclosure, the sampling line assembly 28 connects, via the locking cap 86, to a luer lock 100 mounted on the proximal end of one of the lines 98 that communicates through the back form 96 with the sampling lumen 106 of the catheter 30. The sampling tube 90 extends through the line 98 and the back form 96 and partially through the sampling lumen 106, stopping about 1 inch short of the proximal exit point 108. Advantageously, the proximal exit point avoids draw of blood samples diluted or otherwise affected by the operations being performed in the other lumens 102, 104. Also, the sampling tube 90 provides a void-free lumen that bypasses the voids formed by the junctions between the components 94, 96, 98, and the varied internal contours of those components, so as to reduce clotting and the volume of blood draws needed to supply the sensor 40. Stopping short of the proximal exit port 108 avoids extension of the sampling tube 90 out of the exit port and making contact with the patient's vasculature.

[0060] As another alternative, the sampling tube 90 may be of sufficient length to extend out of the exit port 108. This embodiment has the advantage of extending the void-free internal diameter of the sampling tube past any irregularities at the end of the sampling lumen 106.

[0061] Although a range of materials may be used to construct the sampling tube 90, polyurethane and nylon 10 have shown experimental success. A factor, however, in selecting the material for the sampling tube 90 is whether the material is transparent or translucent to the point of allowing visibility of blood from the draw cycle, which may impact patient morale. Therefore, opaque materials that mask the presence of blood may be desired, such as a green or opaque color.

[0062] Referring now to Figure 9, an access device 900 positioned in a vessel 910 is illustrated. The vessel 910, in the illustrated embodiment, includes a turn in the fluid pathway of the vessel 910. Examples of the vessel 910 include the vasculature of a subject such as a vein or an artery. Although vasculature of a subject is illustrated in Figure 9, it will be understood that the vessel 910 may include ex-vivo vessels. The access device 900 includes, for example, the catheter 30, the sampling line 90, a tube for flushing fluids and drawing blood, and/or the like. In the illustrated embodiment, the access device 900 includes a cylindrical body with a proximal end and an open distal end. The vessel 910 includes a vessel wall 912, which is fairly elastic. Due to the elasticity of the vessel wall 912, infusing fluids through the opening at the distal end of the access device 900 pushes the wall 912 away from the tip of the access device 900, allowing flow of fluids into the inner space of the vessel 910. However, when blood begins to be drawn into the access device 900, the wall 912 of the vessel 910 is also drawn onto the tip of the access device 900, sealing the tip of the access device 900 and occluding further blood flow. This results in a failed blood drawn and thus a failed analyte measurement.

[0063] In order to correct for this source of failed blood draws, access device 1000 with one or more fluid conduction openings lOlOa-f is provided as shown in Figures 10A, 10B, and 11. As shown in the illustrated embodiments, the one or more fluid conduction opening lOlOa-f are side ports formed in the side walls of the access device 1000. The access device 1000 has a proximal end 1004 and a distal end 1006 with a cylindrical body 1002 positioned between proximal end 1004 and distal end 1006. The distal end 1006 resides in the vasculature of the subject and defines an opening for drawing blood and flushing fluids. The one or more fluid conduction openings lOlOa-f, as illustrated in Figures 10A and 10B, can be formed in any one or more shape, each shape can be of an independent or same size, and/or spatially arranged in a random or patterned configuration in the cylindrical body 1002. The access device 1000 includes, for example, the catheter 30, the sampling line 90, a tube for flushing fluids and drawing blood, and/or the like.

[0064] In the illustrated embodiment of Figure 10A, the openings 1010a are circular and uniformly sized and positioned at equal distances relative to one another. For example, the openings 1010a may be formed such that for one opening, an equally sized and shaped corresponding opening is formed on the opposite side of the cylindrical body 1002. In other embodiments illustrated in Figure 10B, the opening 1010b is circular and does not include a corresponding opening positioned on the opposite side of the cylindrical body 1002, and the opening 1010c is circular and is positioned opposite opening 1010ά, which is square. Other shapes, such as slots or slits can be used. The openings can be formed essentially perpendicular to the longitudinal axis of the access device, or they may be angled in the same or different directions (between 10 and 89 degrees from the longitudinal axis). The one or more fluid conduction openings lOlOa-f formed in the access device 1000 allow a blood draw even though the vessel wall 912 prevents blood flow through the opening at the distal end 1006 (see, Figure 11).

[0065] In some embodiments, the one or more openings lOlOa-f formed in the cylindrical body 1002 are positioned at a predetermined distance from the distal end. For example, the one or more openings lOlOa-f may be positioned adjacent to the distal end such that at least some of the one or more openings lOlOa-f reside in the vasculature of the subject or other vessel when the access device 1000 is in use. In such cases, the portion of the cylindrical body 1002 that resides in any particular vessel can be determined and the openings lOlOa-f can be formed in that portion. Thus, the distance from the distal end may vary based on the size of the targeted vessel.

[0066] In other embodiments, the size, shape, and/or number of the one or more openings lOlOa-f formed in the cylindrical body 1002 are based on the position of the one or more openings lOlOa-f. For example, openings formed closer to the distal end 1006 may be smaller than openings formed further away from the distal end 1006. A subject may move, for example, causing the access device 1000 to also move. Because the portion of the access device 1000 that is farthest away from the distal end may not be entirely within the vessel 910, forming larger openings or having a larger number of openings in such portions may allow the openings lOlOa-f to draw blood even though the entirety of the openings in that portion are not within the vessel 910 and the distal end 1006 is occluded.

[0067] Although the one or more openings lOlOa-f in the access devices 1000 have been described herein in relation to blood draws, it will be understood that the access devices 1000 may also be useful in flushing fluid through the access device 1000. For example, blood clots may form at the distal end 1006 of the access device 1000, within a portion of the lumens of the access devices 1000 near the distal end 1006, or at the one or more opening 1010a- f. The clots may prevent blood from being drawn or fluid from being flushed through the distal end 1006 or at some of the one or more openings 1010a- f. In such cases, the one or more openings lOlOa-f formed in the cylindrical body 1002 of the access device 1000 are configured to allow fluids to be flushed and blood to be drawn. In other embodiments, the access device 1000 is coated with heparin to prevent blood clotting at the one or more openings lOlOa-f. The heparin may be applied to the access device 1000 by spraying, dipping the access device 1000 in a heparin solution, and the like.

[0068] In still further embodiments, an analyte sensor is positioned within the lumen of the access device 1000. In such embodiments, the location of the rearmost opening formed in the cylindrical body 1002 is distal to the location of the sensor in order to ensure effective flushing of the sensor during calibration. In other embodiments where the sensor resides within a sensor housing (such as the sensor housing 24), effective flushing of the sensor is not an issue due to the location of the sensor.

[0069] In Figure 12, a system and environment 1200 for producing the access device 1000 having the one or more openings lOlOa-f is illustrated. A fixture 1202 for forming the one or more openings lOlOa-f in the access device 1000 is provided in Figure 12. The fixture 1202 has an opening formed therein for receiving the access device 1000, and also has an opening for receiving a sharp plunger 1210. In the illustrated embodiment, the access device 1000 is received through a bottom opening in the fixture 1202 and the plunger 1210 is received through a side opening.

[0070] Upon positioning the access device 1000 in the fixture 1202, the sharp plunger 1210 is pushed through the walls of the access device 1000 from the side, creating a puncture hole though both sides of the access device 1000. In other embodiments, the plunger 1210 only punctures one side of the walls of the access device 1000 in any given spot.

[0071] In an exemplary embodiment, the diameter of the opening for receiving the access device is adjustable. For example, the diameter of the opening for receiving the access device in the fixture 1202 may be reduced to firmly hold the access device 1000 in place when the plunger 1220 is pushed through the access device 1000. The diameter of the opening for receiving the access device in the fixture 1202 may also be adjusted to allow movement of the access device 1000 or accommodate varying sizes of access devices. In other embodiments, the opening for receiving the access device in the fixture 1202 is large enough to accommodate the access device 1000, but is not adjustable.

[0072] The system 1200, in some embodiments, is configured to move the access device 1000 up or down in the opening of the fixture 1202, such that the fluid conduction openings lOlOa-f can be formed in the access device 1000 at varying distances from the distal end 1006. Further, the plunger 1210 may be, for example, associated with any number of needles having various configurations for producing a wide array of punctures having different sizes and shapes.

[0073] As shown in Figure 13, an exemplary flow profile of one embodiment of the present disclosure includes a calibration and flush phase of about 276 seconds which includes 3.2 mL/hr for calibration, a flush of 650 mL/hr and trailing rates of 1.9 mL/hr and zero flow for a short time period. In the draw and sample phase, a 3.5 mL/hr draw is used with a zero flow rest period at the end. This is followed by the beginning of the flush phase with a 24 second "clear" flush using a 5mL/hr start and then a ramped-up pre-calibration flush rate of 650 mL/hr.

[0074] In some embodiments, the system 10 may be employed over a 72 hour period and sample blood with 40 to 200 μL volumes in 5 to 10 minute cycles. With a 5 minute target blood glucose cycle and an approximate 90 second time window for draw volume, the maximum draw rate is about 200 mL/hour.

[0075] As will be appreciated by one skilled in the art, aspects of the present disclosure may be embodied as a system, method or computer program product. Accordingly, aspects of the present disclosure may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a "circuit," "module" or "system." Furthermore, aspects of the present disclosure may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied thereon.

[0076] Any combination of one or more computer readable medium(s) may be utilized. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device.

[0077] A computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0078] Program code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.

[0079] Computer program code for carrying out operations for aspects of the present disclosure may be written in any combination of one or more programming languages, including an object oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).

[0080] Aspects of the present disclosure are described below (and above) with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the disclosure. It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.

[0081] These computer program instructions may also be stored in a computer readable medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function/act specified in the flowchart and/or block diagram block or blocks.

[0082] The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.

[0083] The flowchart and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present disclosure. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.

[0084] As is evident from the range of modeled and experimentally verified embodiments described above, the disclosure is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

Claims

THAT WHICH IS CLAIMED:

1. A system for sampling blood from a patient's vasculature and directing the blood to an analyte sensor, the system comprising:

an access device comprising a cylindrical body connecting a proximal end and a distal end, the access device having one or more opening formed in at least a portion of the cylindrical body;

the access device defining at least one lumen extending from the proximal end to the distal end;

wherein the distal end of the access device and the one or more openings of the access device reside within the patient' s vasculature for an extended period of time;

wherein the vascular access system is configured to draw blood through the one or more opening of the access device even when the distal end is occluded;

wherein the proximal end is connectable in fluid communication with the analyte sensor.

2. The system of claim 1, wherein at least a portion of the access device comprises a heparin coating.

3. The system of claim 1, wherein the vascular access system is configured to flush a fluid through the one or more opening of the access device even when the distal end is occluded.

4. The system of claim 1, wherein the one or more openings are positioned a predetermined distance from the distal end of the access device.

5. A sensor system for sensing a parameter in vascular accessed by an access device, the sensor system comprising:

an analyte sensor coupled to the access device; wherein the access device comprises a cylindrical body connecting a proximal end and a distal end, the access device having one or more opening formed in at least a portion of the cylindrical body;

wherein the distal end and the one or more opening of the access device reside within the patient' s vasculature for an extended period of time and the proximal end is connectable in fluid communication with the analyte sensor;

a flow control system configured to draw blood through the one or more opening of the access device to the analyte sensor or flush the sensor with a calibrant through the one or more opening to evacuate the blood even when the distal end of the access device is occluded; and

a monitor connected in communication with the analyte sensor, the monitor configured to receive a blood signal when the sensor is in blood and then to receive a calibration signal when the sensor is in the calibrant and use the calibration signal to determine the parameter from the blood signal.

6. A method for sampling blood from a patient's vasculature and sensing a parameter in the blood, the method comprising:

providing a sensor system comprising:

an analyte sensor coupled to an access device;

wherein the distal end and the one or more openings of the access device reside within the patient's vasculature for an extended period of time and the proximal end is connectable in fluid communication with the analyte sensor;

a flow control system configured to draw blood through the access device to the analyte sensor and flush the sensor with a fluid to evacuate the blood; and

a monitor connected in communication with the analyte sensor, the monitor comprising a computer apparatus comprising a memory and a processor; drawing, via the flow control system, blood through at least one of the one or more openings to the analyte sensor and flushing the sensor with a calibrant to evacuate the blood even when the distal end of the access device is occluded; and

receiving, at the monitor, a blood signal when the sensor is in the blood and a calibration signal when the sensor is in the calibrant; and

determining, via the monitor, the analyte from the blood signal based on the calibration signal.

7. A method of manufacturing a system for sampling blood from a patient's vasculature, the method comprising:

providing a fixture having an opening formed therein for receiving an access device comprising a cylindrical body connecting a proximal end a distal end;

placing the distal end and at least a portion of the cylindrical body of the access device in the opening of the fixture;

providing a sharp device for puncturing the cylindrical body;

puncturing, using the sharp device, the cylindrical body adjacent to the distal end to form one or more openings in the access device;

wherein the access device is configured such that the distal end of the access device and the one or more openings of the access device reside within a subject's vasculature for an extended period of time;

wherein the access device is configured to draw blood through the one or more openings even when the distal end is occluded.

8. The method of claim 7, further comprising:

coating at least a portion of the cylindrical body with an anticoagulant.