In Vivo Extraction of Interstitial Fluid Using Hollow Microneedles

• US 20160296149A1
• Filed: 03/23/2016
• Published: 10/13/2016
• Est. Priority Date: 04/08/2015
• Status: Abandoned Application

• Current Assignee: Sandia Corporation (Martin Marietta Corporation)
• Original Assignee: Sandia Corporation (Martin Marietta Corporation), UNM Rainforest Innovations (f/k/a STC.UNM) (The University of New Mexico)
• Inventors: Miller, Philip Rocco, Baca, Justin T., Polsky, Ronen
• Application Number:
  US15/078,870
• Publication Number:
  US 20160296149A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• 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 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/165 Evaluating the state of mind, e.g. depression, anxiety
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles

Abstract

A transdermal and/or intradermal diagnostic device comprising a combined hollow microneedle interstitial fluid (IF) extraction device and a detector can monitor biomarkers in-situ. For example, electrode transducers with optimally arrayed and designed microneedles can be combined with a suitable pumping method to determine biomarker levels in human subjects under intense physical exertion to monitor metabolic stress and fatigue. The device can perform real-time, in-situ measurements of lactate in human subjects. Monitoring of other biomarkers is straightforward.

Claims

1. An interstitial fluid extraction device, comprising:

an array of hollow microneedles adapted to penetrate the skin of a human or animal, wherein the skin comprises at least one biomarker in an interstitial fluid; and

a microfluidic chip adapted to extract the interstitial fluid through the hollow microneedles and collect the at least one biomarker in a sample reservoir in the microfluidic chip.

2. The device of claim 1, wherein the at least one biomarker comprises cortisol, a ketone, TNF-α

, glutamine, glutamate, interleukin-6, testosterone, thyroid hormone, human growth hormone, insulin, glucose, adrenaline, or neuropeptide Y.

3. The device of claim 1, wherein the at least one biomarker comprises lactate.

4. The device of claim 1, wherein a concentration of the at least one biomarker in the interstitial fluid correlates with a concentration of the at least one biomarker in the blood plasma of the human.

5. The device of claim 1, further comprising a spectrophotometer for analyzing the at least one biomarker in the extracted interstitial fluid.

6. The device of claim 1, further comprising an electrode transducer for sensing the at least one biomarker in the extracted interstitial fluid.

7. The device of claim 1, wherein the hollow microneedles have a bore opening on the side of each microneedle.

8. The device of claim 7, wherein the bore opening is on the side to the middle third of each microneedle.

9. The device of claim 1, wherein the hollow microneedles each have an aspect ratio between 2 and 5.

10. The device of claim 1, wherein the hollow microneedles each have a base of between 300 and 500 microns.

11. The device of claim 1, wherein the hollow microneedles further comprise a coating to control hydrophilicity and promote fluid flow through the lumen of the hollow microneedle.

12. The device of claim 1, further comprising a vacuum pump for sucking the biomarker-containing interstitial fluid into the sample reservoir.

13. The device of claim 12, wherein the pump comprises a syringe pump, a capillary force pump, or a microdialysis pump

14. The device of claim 12, wherein the pump comprises a pulsatile vacuum pump.

15. The device of claim 1, wherein the microfluidic chip further comprises an injector for injecting saline solution into the skin through the array of hollow microneedles.

16. A method for extracting interstitial fluid from a human, comprising:

providing an interstitial fluid extraction device, the device comprising;

an array of hollow microneedles adapted to penetrate the skin of a human or animal, wherein the skin comprises at least one biomarker in an interstitial fluid; and

a microfluidic chip adapted to extract the interstitial fluid through the hollow microneedles and collect the at least one biomarker in a sample reservoir in the microfluidic chip; and

extracting the interstitial fluid through the array of hollow microneedles and collecting the at least one biomarker in the sample reservoir in the microfluidic chip.

17. The method of claim 16, wherein the extraction device further comprises a vacuum pump and the step of extracting comprises sucking the interstitial fluid through the hollow microneedles into the sample reservoir.

18. The method of claim 16, further comprising injecting a saline solution into the skin through the hollow microneedles to mix with the interstitial fluid and extracting the mixed saline solution back out through the hollow microneedles into the sample reservoir.

19. The method of claim 16, further comprising filling the sample reservoir with a saline solution and diffusing the at least one biomarker from the interstitial fluid through the hollow microneedles into the saline solution in the sample reservoir.