Microneedle device for extraction and sensing of bodily fluids

• US 7,344,499 B1
• Filed: 12/02/1999
• Issued: 03/18/2008
• Est. Priority Date: 06/10/1998
• Status: Expired due to Fees

• Current Assignee: Valeritas, LLC
• Original Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Gujral, Inder-Jeet, Prausnitz, Mark R., Allen, Mark G.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/453,109
• Time in Patent Office: 3,029 Days
• Field of Search: 600309-310, 600/316, 600/345, 600347-348, 600/362, 600/369, 600/365, 600573-576, 422/68.1, 604/191, 604/190
• US Class Current: 600/309
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150221 Valves
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150358 Strips for collecting blood, e.g. absorbent optical reagent test strips G01N21/8483; chemical reagent test strips G01N33/4875, G01N33/52
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

Abstract

Microneedle devices are provided for controlled sampling of biological fluids in a minimally-invasive, painless, and convenient manner. The microneedle devices permit in vivo sensing or withdrawal of biological fluids from the body, particularly from or through the skin or other tissue barriers, with minimal or no damage, pain, or irritation to the tissue. The microneedle device includes one or more microneedles, preferably in a three-dimensional array, a substrate to which the microneedles are connected, and at least one collection chamber and/or sensor in communication with the microneedles. Preferred embodiments further include a means for inducing biological fluid to be drawn through the microneedles and into the collection chamber for analysis. In a preferred embodiment, this induction is accomplished by use of a pressure gradient, which can be created for example by selectively increasing the interior volume of the collection chamber, which includes an elastic or movable portion engaged to a rigid base. Preferred biological fluids for withdrawal and/or sensing include blood, lymph, interstitial fluid, and intracellular fluid. Examples of analytes in the biological fluid to be measured include glucose, cholesterol, bilirubin, creatine, metabolic enzymes, hemoglobin, heparin, clotting factors, uric acid, carcinoembryonic antigen or other tumor antigens, reproductive hormones, oxygen, pH, alcohol, tobacco metabolites, and illegal drugs.

Claims

1. A device for collecting a sample of a biological fluid comprising:

one or more hollow or porous microneedles, each having a base end and a tip;

a substrate to which the base end is attached or integrated; and

at least one collection chamber suitable for collecting said sample of said biological fluid, said collection chamber selectably in fluid communication with the base end, and wherein said collection chamber comprises a one-way valve and an upper portion which is formed of a deformable material.

23. The device of any one of claims 1-22, wherein the one or more microneedles each has a length between about 500 μ

m and 1 mm and a width between about 1 μ

m and 500 μ

m.

25. A method for collecting a sample of a biological fluid or analyte therein, comprising the steps:

providing the device of any one of claims 1-24;

inserting said one or more microneedles of the device into a biological barrier comprising biological fluid; and

triggering the transport of a quantity of the biological fluid or analyte therein through said one or more microneedles and into the collection chamber.

26. The method of claim 25, wherein triggering the transport is effected by capillary action, diffusion, mechanical pumps, electroosmosis, electrophoresis, convection, or combinations thereof.

27. The method of claim 25, wherein triggering the transport is effected by a pressure gradient in which the pressure within the microneedles and/or collection chamber is less than the pressure of the biological fluid adjacent the tip of the microneedle.

28. The method of claim 25 wherein the analyte to be collected or sensed is selected from the group consisting of glucose, cholesterol, bilirubin, creatine, metabolic enzymes, hemoglobin, heparin, clotting factors, uric acid, tumor antigens, reproductive hormones, oxygen, pH, alcohol, tobacco metabolites, and illegal drugs.

29. The method of claim 25, wherein the analyte is glucose, and wherein the biological barrier is human skin.

2. A device for collecting a sample of a biological fluid comprising:

one or more hollow or porous microneedles, each having a base end and a tip;

a substrate to which the base end is attached or integrated; and

at least one collection chamber suitable for collecting said sample of said biological fluid, wherein said collection chamber is selectably in fluid communication with the base end, and comprises a plurality of compartments.

3. The device of claim 2, further comprising a means for inducing transport of a biological fluid or component thereof into the collection chamber.

4. The device of claim 3 wherein the pressure within the collection chamber can selectively be reduced.

5. The device of claim 4 wherein the pressure reduction is induced by expanding the internal volume of the collection chamber.

6. The device of claim 5 wherein the collection chamber is a standard or Luer-lock syringe.

7. The device of claim 3 wherein the collection chamber comprises an upper portion which is formed of a material which is deformable.

8. The device of claim 7 wherein the collection chamber comprises a one-way valve.

9. The device of claim 4 wherein the means for inducing transport comprises a plunger movably secured to the substrate, wherein the plunger can deform the collection chamber.

10. The device of claim 2, comprising a three dimensional array of microneedles.

11. The device of claim 2, further comprising an adhesive material for securing the device to a biological barrier surface during fluid withdrawal or sensing.

12. The device of claim 2, further comprising a means for controlling flow through the microneedle.

13. The device of claim 12 wherein the means for controlling flow is a fracturable or removable barrier which is interposed between the collection chamber and base of the microneedle.

14. The device of claim 2, further comprising a sensor in communication with the collection chamber.

15. The device of claim 2, wherein the collection chamber is adapted to receive and use glucose strips.

16. The device of claim 2, wherein the microneedle is hollow and comprises at least one opening in the side of the microneedle.

17. The device of claim 2, wherein the microneedle has a hollow bore containing a material to modulate the flow of biological fluid through the microneedles into the collection chamber.

18. The device of claim 2, wherein the microneedle is hollow.

19. The device of claim 2, wherein the microneedle is perpendicular to a surface of the substrate.

20. The device of claim 2, wherein the microneedle has a diameter between about 40 and 120 μ

m.

21. A device for collecting a sample of a biological fluid comprising:

one or more hollow or porous microneedles, each having a base end and a tip;

a substrate to which the base end is attached or integrated;

at least one collection chamber suitable for collecting said sample of said biological fluid, said collection chamber selectably in fluid communication with the base end; and

a fracturable or removable barrier for controlling flow through the microneedle, said barrier interposed between the collection chamber and base of the microneedle.

22. A device for collecting a sample of a biological fluid comprising:

one or more hollow or porous microneedles, each having a base end and a tip;

a substrate to which the base end is attached or integrated; and

at least one collection chamber suitable for collecting said sample of said biological fluid, said collection chamber selectably in fluid communication with the base end,

wherein the one or more microneedles has a hollow bore containing a material to modulate the flow of biological fluid through the microneedles into the collection chamber.

24. A device for collecting a sample of a biological fluid comprising:

one or more hollow or porous microneedles, each having a base end and a tip, a length between 500 μ

m and 1 mm and a width between about 1 μ

m and 500 μ

m, and comprising a metal;

a substrate to which the base end is attached or integrated; and

at least one collection chamber suitable for collecting said sample of said biological fluid, said collection chamber selectably in fluid communication with the base end.

30. The device of claim 24, wherein the microneedle consists essentially of a metal.

31. A device for sensing an analyte in a biological fluid comprising:

one or more microneedles, each having a base end and a tip, a length between about 500 μ

m and 1 mm and a width between about 1 μ

m and 500 μ

m, and comprising a metal;

a substrate to which the base of the microneedle is attached or integrated; and

at least one sensor which is selectably in fluid communication with the microneedle.

43. A method for sensing an analyte in a biological fluid, comprising the steps:

providing the device of claim 31, 32, or 40;

inserting said one or more microneedles into a biological barrier comprising said biological fluid which contains said analyte; and

contacting the sensor with the biological fluid, thereby sensing the analyte.

44. The method of claim 43 wherein the device further comprises:

at least one collection chamber which is selectably in fluid connection with the base end of the microneedle, and

a means for inducing transport of the biological fluid or the analyte therein into the collection chamber,

wherein, after the microneedles are inserted, the means for inducing is triggered to draw the biological fluid or the analyte therein through the microneedles and into the collection chamber.

45. The method of claim 44 wherein the means for inducing utilizes a pressure gradient in which the pressure within the microneedles and for collection chamber is less than the pressure of the biological fluid adjacent the tip of the microneedle.

46. The method of claim 45 wherein the pressure gradient is created by increasing the volume within the collection chamber.

47. The method of claim 43 wherein the analyte to be collected or sensed is selected from the group consisting of glucose, cholesterol, bilirubin, creatine, metabolic enzymes, hemoglobin, heparin, clotting factors, uric acid, tumor antigens, reproductive hormones, oxygen, pH, alcohol, tobacco metabolites, and illegal drugs.

48. The method of claim 43, wherein the analyte is glucose, and wherein the biological barrier is human skin.

32. A device for sensing an analyte in a biological fluid comprising:

one or more microneedles, each having a base end and a tip;

a substrate to which the base of the microneedle is attached or integrated; and

at least one sensor which is selectably in fluid communication with the microneedle,

wherein the one or more microneedles has a hollow bore containing a material to modulate the flow of biological fluid through the microneedles into a collection chamber.

33. The device of claim 32, wherein the sensor comprises:

a chemical or biochemical agent that react with the analyte, and

electrochemical or optical transducers which measure the reaction of the agent and the analyte.

34. The device of claim 33 wherein the agent is an enzyme selected from the croup consisting of glucose oxidase, glucose dehydrogenase, and combinations thereof.

35. The device of claim 32, further comprising an electronics package in communication with the sensor.

36. The device of claim 32, wherein the microneedle comprises a metal.

37. The device of claim 36, wherein the microneedle consists essentially of a metal.

38. The device of claim 32, wherein the microneedle is hollow.

39. The device of claim 32, wherein the microneedle is perpendicular to a surface of the substrate.

40. A device for sensing an analyte in a biological fluid comprising:

one or more microneedles, each having a base end and a tip; and

a substrate to which the base of the microneedle is attached or integrated, wherein at least one of the microneedles is or comprises a sensor, and wherein the one or more microneedles has a hollow bore containing a material to modulate the flow of biological fluid through the microneedles into a collection chamber.

41. The device of claim 40, wherein the sensor comprises:

a chemical or biochemical agent that reacts with the analyte, and

electrochemical or optical transducers which measure the reaction of the agent and the analyte.

42. The device of claim 40, further comprising an electronics package in communication with the sensor.