Device for Biosensing With Indwelling Venous Catheter

• US 20170020422A1
• Filed: 04/08/2015
• Published: 01/26/2017
• Est. Priority Date: 04/08/2014
• Status: Active Application

• Current Assignee: Diagnostic Biochips, Inc.
• Original Assignee: Diagnostic Biochips, Inc.
• Inventors: Bigelow, Emma, Pais, Rohan, Collins, Rob, Jamieson, Brian
• Application Number:
  US15/110,469
• Publication Number:
  US 20170020422A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 5/02042 Determining blood loss or bleeding, e.g. during a surgical procedure
• CPC Class Codes: A61B 5/14525 using microdialysis
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/6848 Needles
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61M 25/0009 Making of catheters or other medical or surgical tubes
• CPC Class Codes: A61M 25/0017 specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
• CPC Class Codes: A61M 25/007 Side holes, e.g. their profiles or arrangements; Provisions to keep side holes unblocked
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

Abstract

The specification and drawings show an embodiment of the present invention in the form of a device comprising one or more biosensors either placed or imbedded in a catheter, needle or combination of the two. The catheter or needle comprises exclusionary slits upstream of the biosensor(s), angled so that fluid flows in through the slits and down past the biosensors. The wires connecting the biosensors to external monitoring and/or analytical apparatus are wired through the catheter or needle material. Also provided herein are methods for detection of small molecules using the device described herein.

Claims

1. A device comprising a catheter or needle comprising a lumen, a proximal opening, a distal opening, a plurality of exclusionary slits, at least one sensor, and wiring connected to the sensor, wherein the wiring is configured to permit an external connection at the proximal end of the device.

2. The device of claim 1, wherein the sensor is mounted to the interior wall of the catheter or needle.

3. The device of claim 1, wherein the sensor is positioned within the lumen.

4. The device of claim 3, wherein the sensor is slidably positioned within the lumen.

5. The device of claim 4, wherein the device is configured to permit the sensor to be positioned outside the lumen following insertion of the catheter or needle into a subject.

6. The device of claim 1, wherein the sensor is an aptasensor, enzyme sensor, or ion-sensitive field-effect transistor sensor.

7. The device of claim 1, wherein the slits are located closer to the proximal opening than the sensor.

8. The device of claim 1, wherein the sensor is located at the distal end of the device.

9. The device of claim 1, wherein the slits are small enough to exclude blood cells and proteins while allowing plasma to pass through.

10. The device of claim 1, wherein the slits are configured to reduce flow of fluid through the lumen past the biosensor.

11. The device of claim 1, wherein the wiring comprises traditional insulated wires, polyimide thin flex, or a combination thereof.

12. The device of claim 1, wherein the catheter or needle further comprises an anticoagulant or an antibiotic.

13. The device of claim 12, wherein the anticoagulant is heparin, warfarin, low molecular weight heparin, or riveroxiban.

14. The device of claim 12, wherein the antibiotic is rifampicin, clindamycin, aminoglycosides, or tetracycline.

15. The device of claim 1, wherein one or more of the slits are covered with a semi-permeable membrane or a microfilter.

16. The device of claim 15, wherein the microfilter excludes particles larger than 5 μ

m.

17. The device of claim 15, wherein the semi-permeable membrane is a microdialysis membrane.

18. The device of claim 1, further comprising a null electrode sensor.

19. The device of claim 18, wherein the null sensor is bare, or has a coating that differs from the biosensor.

20. The device of claim 1, wherein the catheter is gradually tapered to produce a thin layer of laminar flow through the distal opening.

21. The device of claim 1, wherein the size of the needle or catheter is from 14 gauge to 28 gauge.

22. The device of claim 1, wherein the needle comprises an extended tip, which projects from the distal end of the needle past the distal opening, and wherein the biosensor is located on the extended tip.

23. The device of claim 1, wherein the sensor comprises a microwire sensor or microfabricated sensor, functionalized with an aptamer layer.

24. The device of claim 23, wherein the sensor further comprises an intermediate polymer layer.

25. The device of claim 1, wherein the sensor comprises a gold surface, a polymer layer covering the gold surface, and an aptamer layer.

26. The device of claim 1, wherein the catheter comprises more than one lumen

27. The device of claim 1, wherein the sensor comprises at least one conductor.

28. The device of claim 27, wherein the conductor is no more than about 50 μ

m in diameter.

29. The device of claim 27, wherein the conductor is coated in an insulating material, except for an exposed sensing area at the distal end of the conductor.

30. The device of claim 27, further comprising a Wye adapter or Luer lock connector.

31. The device of claim 30, wherein the Wye adapter comprises two legs, the conductor is routed into one of the legs of the Wye adapter, and the other leg of the Wye adapter is connected to reservoir of a buffer solution.

33. The device of claim 30, further comprising a female Luer lock connector which comprises spring-loaded pins which make contact with the pads on the barrel when the device is assembled.

34. The device of claim 1, wherein the sensor is covered.

35. The device of claim 33, wherein the cover is retractable.

36. The device of claim 35, wherein the cover is configured to retract into the catheter upon the application of electrical current.

37. The device of claim 1, wherein the sensor is a thin flex-like sensor configured such in a manner that permits it to be rolled up and inserted into the catheter or needle.

38. The device of claim 37, wherein the sensor comprises one or more gold pads on polyimide.

39. A method comprising inserting a device according to claim 1 into a subject.

40. The method of claim 39, further comprising injecting or infusing intravenous (“

IV”

) fluid into the device in an amount sufficient to act as a fluid barrier to prevent blood cells and proteins from fouling the biosensor surface.

41. The method of claim 40, wherein IV fluid flows over the biosensor at a rate of about 0.25 mL/hour to about 5 mL/hour.

42. The method of claim 40, further comprising the step of adjusting the flow of IV fluid to refresh the sensor.

43. A method of calculating total circulating blood volume in a subject, comprising

inserting a device according to claim 1 into a blood vessel of the subject;

intravenously injecting a marker into the bloodstream of the subject, wherein the marker is a molecule that has no undesired pharmacological effects and is quickly cleared from the blood; and

measuring the instantaneous blood concentration of the marker.

32. The device of claim 32, wherein the Luer lock connector comprises a pad exposed on the barrel of the connector for each conductor, and to which the conductor is routed.