Apparatus and methods for transdermal sensing of analytes in interstitial fluid and associated data transmission systems

• US 10,321,858 B2
• Filed: 08/14/2015
• Issued: 06/18/2019
• Est. Priority Date: 08/18/2014
• Status: Active Grant

• Current Assignee: Proteadx, Inc.
• Original Assignee: Proteadx, Inc.
• Inventors: Maiz-Aguinaga, Jose Antonio, Olsson, Lennart
• Primary Examiner(s): Colilla, Daniel J
• Application Number:
  US14/827,186
• Publication Number:
  US 20160058342A1
• Time in Patent Office: 1,404 Days
• CPC Class Codes: A61B 2505/07 Home care
• CPC Class Codes: A61B 5/0004 characterised by the type of physiological signal transmitted
• 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 5/14539 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 5/4845 Toxicology, e.g. by detection of alcohol, drug or toxic products A61B5/4848 takes precedence
• CPC Class Codes: A61B 5/685 Microneedles

Abstract

Provided are transdermal microneedle-based devices for sensing the presence and concentration of analytes such as electrolytes, biomarkers, drugs, and proteins in interstitial fluid. Also provided are methods and systems to transmit the data obtained by wired or wireless connection to a receiver and to relay the data to the user or a clinician.

Claims

1. An apparatus for testing interstitial fluid in a subject comprising a disposable integrated micro-sensing unit and a reusable applicator,

wherein the micro-sensing unit comprises a plurality of hollow transdermal microneedles, a microfluidics chamber, one or more sensors capable of detecting the presence or concentration of one or more analytes, a reference electrode, a pH sensor, a temperature sensor, electronic circuitry to control the testing, a casing, a spacer, a vent, and electrical contacts;

and wherein the micro-sensing unit is configured to transmit data that result from the testing to a receiver.

2. The apparatus of claim 1 wherein the microneedles, microfluidics chamber, analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in a monolithic block of silicon.

3. The apparatus of claim 1 wherein the microneedles are formed in a first block of silicon and the analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in one or more additional block(s) of silicon.

4. The apparatus of claim 1 wherein the microneedles are formed in a material other than silicon.

5. The apparatus of claim 1 further comprising a substrate, wherein the substrate and microneedles are formed in a material other than silicon;

the analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in one or more additional material(s) and placed over the substrate; and

the first and additional materials may be the same or different.

6. The apparatus of claim 5, wherein the analyte sensors, reference electrode, pH and temperature sensors, and electronic control circuitry are formed in material(s) other than silicon.

7. The apparatus of claim 1 wherein the microfluidics chamber is a cavity formed by the spacer, a cavity in the casing, or a cavity in a block of material comprising the microneedles.

8. The apparatus of claim 1 wherein the sensor(s) are conductivimetric, voltammetric, or amperometric.

9. The apparatus of claim 1 wherein the interior width of the hollow portion of the microneedles is less than 1 mm, the dimensions of the microfludics chamber are from 10 μ

m to 2 mm, the lateral dimensions of the micro-sensing unit are from 0.5 mm to 10 mm, and the thickness of the micro-sensing unit is from 0.5 mm to 5 mm.

10. The apparatus of claim 1 wherein the applicator is a pen-like or patch-like device.

11. The apparatus of claim 1 wherein the applicator comprises a battery and electronic circuitry to power the micro-sensing unit.

12. The apparatus of claim 11 wherein the applicator further comprises electronic circuitry to receive data that result from the testing and transmit the data wirelessly or by wire to a smart device or computer.

13. The apparatus of claim 12 wherein the applicator comprises a mechanical, magnetic, or electromagnetic grab-and-hold mechanism and a switch to be actuated by the user.

14. The apparatus of claim 13 wherein actuating the switch initiates the testing event when the device is ready, and wherein the execution of the testing event and transmission of the data are under full automatic control of the control circuitry without further intervention by the user.

15. The apparatus of claim 1 wherein the receiver is a computer, smart phone, smart watch, tablet computing device, or wearable computing device.

16. A method for detecting the presence or concentration of an analyte in a subject, comprising

using the apparatus of claim 1 to apply the micro-sensing unit to the subject such that the microneedles contact interstitial fluid in the subject;

initiating a testing event and allowing sufficient time for the interstitial fluid to reach the sensor(s);

collecting data from the sensor(s) and transmitting the data to a receiver.

17. The method of claim 16 wherein the receiver is a computer, smart phone, smart watch, tablet computing device, or wearable computing device.

18. The method of claim 17 wherein the receiver comprises a software application capable of initiating, controlling, or directing the testing event.

19. The method of claim 17 wherein the receiver communicates the results of the testing to the user.

20. The method of claim 17 wherein the receiver further transmits the data to a server.