Microneedle arrays for biosensing and drug delivery

• US 9,743,870 B2
• Filed: 12/10/2015
• Issued: 08/29/2017
• Est. Priority Date: 09/02/2011
• Status: Active Grant

• Current Assignee: National Technology & Engineering Solutions Of Sandia LLC (Honeywell International Inc.), Regents of the University of California (University of California), North Carolina State University (University of North Carolina System)
• Original Assignee: National Technology & Engineering Solutions Of Sandia LLC (Honeywell International Inc.), Regents of the University of California (University of California), North Carolina State University (University of North Carolina System)
• Inventors: Wang, Joseph, Windmiller, Joshua Ray, Narayan, Roger, Miller, Philip, Polsky, Ronen, Edwards, Thayne L.
• Primary Examiner(s): WEARE, MEREDITH H
• Application Number:
  US14/965,755
• Publication Number:
  US 20160095541A1
• Time in Patent Office: 628 Days
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/046 in a matrix array
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• 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 5/1473 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 5/150984 Microneedles or microblades
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/276 Protection against electrode failure
• CPC Class Codes: A61B 5/4845 Toxicology, e.g. by detection of alcohol, drug or toxic products A61B5/4848 takes precedence
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: A61B 5/7282 Event detection, e.g. detecting unique waveforms indicative of a medical condition A61B5/4094, A61B5/4818, A61B5/349, A61B5/0823 take precedence
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 5/158 Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G01N 33/48785 : Electrical and electronic details of measuring devices for physical analysis of liquid biological material not specific to a particular test method, e.g. user interface or power supply

Abstract

Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

Claims

1. A method for in situ measurement of one or more target chemical species present in a physiological fluid, the method comprising:

causing a microneedle sensing device to contact the physiological fluid, wherein the microneedle sensing device includes a substrate and an array of electrically-conducting electrodes, wherein each electrically-conducting electrode is respectively disposed in a hollow interior of a hollow microneedle of a hollow microneedle array formed on the substrate, one electrode per hollow microneedle, wherein each electrically-conducting electrode has a tip located inside the hollow interior of its respective hollow microneedle to form a recess microcavity that surrounds the electrode within the hollow interior, wherein the tip is coated to be functionalized for interacting with one or more target chemical species present in a portion of the physiological fluid that is trapped in its respective recess microcavity;

applying a stimulus signal to an electrically conductive structure disposed on the substrate that is coupled to the array of electrically-conducting electrodes to cause biosensing of the physiological fluid entrapped in each recess microcavity; and

reading a resultant signal arising at an interface between the physiological fluid and the coated tip of the electrically-conducting electrode in each recess microcavity as part of the in situ measurement,

wherein a property of said resultant signal is indicative of a concentration of the one or more target chemical species present in said physiological fluid.

2. The method according to claim 1, comprising:

processing the resultant signal to determine whether the concentration of the one or more target chemical species present in said physiological fluid reflects a healthy or disease state.

3. The method according to claim 2, wherein processing the resultant signal includes comparing the resultant signal to a threshold value.

4. The method according to claim 2, wherein processing the resultant signal includes determining a pattern in the resultant signal.

5. The method according to claim 1, wherein the property of said resultant signal includes magnitude of the resultant signal.

6. The method according to claim 1, wherein the property of said resultant signal includes an impedimetric property.

7. A device for in situ measurement of one or more target chemical species present in a physiological fluid, the device comprising:

a substrate;

a hollow microneedle array of hollow microneedles formed on one side of the substrate, each hollow microneedle including a hollow interior;

an array of electrically-conducting electrodes, wherein each electrically-conducting electrode is respectively disposed in the hollow interior of one of the hollow microneedle, one electrode per hollow microneedle, wherein each electrically-conducting electrode has a tip located inside the hollow interior of its respective hollow microneedle to form a recess microcavity that surrounds the electrode within the hollow interior, wherein the tip is coated to be functionalized for interacting with one or more target chemical species present in a portion of the physiological fluid that is trapped in its respective recess microcavity;

an electrically conductive structure disposed on the substrate, wherein the conductive structure is configured to receive an excitation signal and is electrically connected with each of the electrodes to cause electrochemical sensing of a portion of the physiological fluid that is trapped in each recess microcavity.

8. The device of claim 7, wherein the device is configured to measure a resultant signal at an interface between each electrode and the physiological fluid;

and

wherein a property of said resultant signal is indicative of a concentration of the one or more target chemical species present in said physiological fluid.

9. The device according to claim 8, wherein the property of said resultant signal includes magnitude of the resultant signal.

10. The device according to claim 8, wherein the property of said resultant signal includes an impedimetric property.

11. The device according to claim 7, wherein said array of hollow microneedles include at least one of a conal, columnar, triangular, pyramidal, rectangular, or polygonal geometric shape.

12. The device according to claim 7, wherein each microneedle is made of a polymer.

13. The device according to claim 7, wherein said substrate is planar and comprises one of a polymer, semiconductor, metal, glass, or film.

14. The device according to claim 7, wherein each tip is functionalized by a chemical species-selective layer deposited on a surface of said tip and facilitates quantification of the target species.

15. The device according to claim 14, wherein said chemical species includes one of a metabolite, electrolyte, ion, pathogen, microorganism, hormone, protein, enzyme, vitamin, anti-oxidant, nucleic acid, antibodies, neurotransmitter, acid, or drug.

16. The device according to claim 14, wherein the chemical species-selective layer comprises one of an ion-selective membrane, enzyme-loaded membrane, conducting polymer, diffusion-limiting polymer, electrostatically-bound biocatalyst, covalently-bound biocatalyst, or surface-adsorbed biocatalyst.

17. The device according to claim 7, wherein said physiological fluid includes liquids originating from a living human body and lying beneath biological tissues or membranes.

18. The device according to claim 7, wherein the physiological fluid comprises one of interstitial fluid, intracellular fluid, extracellular fluid, blood, plasma, serum, cerebrospinal fluid, mucus, intraocular, or vitreous humor.

19. The device according to claim 7, wherein the electrically-conducting electrodes comprise a platinum coating.

20. The device according to claim 7, wherein each microneedle extends from the substrate to a distance of between 20 to 1500 micrometers.