Analyte detection system and method for intradermal implantation of biocompatible optode nanosensors

• US 9,974,471 B1
• Filed: 12/23/2014
• Issued: 05/22/2018
• Est. Priority Date: 10/24/2014
• Status: Active Grant

• Current Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Kam, Kimberly, Schwartz, Jerrod Joseph, Demas, Vasiliki, Bajaj, Vikram Singh
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Liu, Chu Chuan (JJ)
• Application Number:
  US14/580,768
• Time in Patent Office: 1,246 Days
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/1451 for 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 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/685 Microneedles

Abstract

A device and system for measuring and/or monitoring an analyte present on the skin is provided. The system includes a skin-mountable device that may be attached to an external skin surface and a reader device. The skin-mountable device includes a substrate, a plurality of micro-needles, and nanosensors. The micro-needles are attached to the substrate such that attachment of the substrate to an external skin surface causes to the micro-needles to penetrate into the epidermis, intradermis, or dermis. The nanosensors include a detectable label and are configured to interact with a target analyte present in the interstitial fluid in the epidermis, intradermis, or dermis. The reader device is configured to detect the analyte in interstitial fluid via interaction with the skin-mountable device.

Claims

1. A device comprising:

a plurality of micro-needles, each having a base end and a tip;

a planar optically transparent substrate directly attached to the base ends of the micro-needles, wherein the substrate can attach to an external skin surface such that the micro-needles penetrate into the skin;

nanoparticles associated with the micro-needles, the nanoparticles having an optically detectable label for interacting with a target analyte present in interstitial fluid; and

water-soluble adhesive material for attaching the base ends of the micro-needles to the substrate.

2. The device of claim 1, wherein the adhesive material is located on the substrate for attaching the substrate to the external skin surface and for attaching the base ends of the micro-needles to the substrate.

3. The device of claim 2, wherein the adhesive is water-soluble such that the substrate can be detached from the base end of the micro-needles and from the external skin surface in the presence of water.

4. The device of claim 1, wherein the micro-needles are arranged in a three dimensional spatially-controlled array.

5. The device of claim 1, wherein the micro-needles are solid, hollow or porous.

6. The device of claim 1, wherein the nanoparticles are bound to a surface of the micro-needles.

7. The device of claim 1, wherein the nanoparticles are encapsulated in the micro-needles.

8. The device of claim 1, wherein the micro-needles comprise hollow or porous spaces comprising the nanoparticles.

9. The device of claim 1, wherein the micro-needles, the nanoparticles, or both are biodegradable.

10. The device of claim 1, wherein the micro-needles are non-dissolvable and are coated with a dissolvable coating of a polymer and the nanoparticles.

11. A system comprising:

(a) a skin-mountable device, comprising;

a plurality of micro-needles, each having a base end and a tip;

a planar optically transparent substrate directly attached to the base ends of the micro-needles, wherein the substrate can attach to an external skin surface such that the micro-needles penetrate into the skin; and

nanoparticles associated with the micro-needles, the nanoparticles having an optically detectable label for interacting with a specific target analyte present in interstitial fluid;

water-soluble adhesive material for attaching the base ends of the micro-needles to the substrate; and

(b) a reader device, wherein the target analyte can be detected by the reader device via interaction with the skin-mountable device.

12. The system of claim 11, wherein the detectable label comprises a fluorophore.

13. The system of claim 12, wherein the target analyte can be detected by the reader device by optically interrogating the nanoparticles in the skin-mountable device.

14. The system of claim 13, wherein the reader device comprises:

a light source; and

a photodetector, wherein light is directed toward the substrate by the light source and wherein light from the substrate is detected by the photodetector.

15. The system of claim 14, wherein an optically-detectable change related to the nanoparticles interacting with the target analyte is detected by the reader device.

16. The system of claim 15, wherein the optically-detectable change comprises a change in at least one of optical absorption, reflectivity, or fluorescence.

17. The system of claim 16, wherein the optically-detectable change is fluorescence.

18. The system of claim 11, wherein the skin-mountable device further comprises an antenna, and wherein the target analyte is detected by the reader device based on data communicated via the antenna.

19. The system of claim 18, wherein the data communicated via the antenna is indicative of one or more measurements obtained by the skin-mountable device.

20. The system of claim 11, wherein the reader device is a wearable device.

21. A method, comprising:

mounting a skin-mountable device to a skin surface, wherein the skin-mountable device comprises (i) a plurality of micro-needles, each having a base end and a tip, (ii) a planar optically transparent substrate directly attached to the base ends of the micro-needles, wherein the substrate can attach to an external skin surface such that the micro-needles penetrate into the skin, (iii) nanoparticles associated with the micro-needles, the nanoparticles having a fluorophore for interacting with a target analyte present in interstitial fluid, and (iv) water-soluble adhesive material for attaching the base ends of the micro-needles to the substrate;

transmitting incident light from a reader device to the skin-mountable device;

receiving, by the reader device, fluorescence light emitted by the nanoparticles interacting with the target analyte in response to the incident light;

detecting the target analyte based on the fluorescence light received by the reader; and

removing the planar optically transparent substrate from the skin surface and from the micro-needles.

22. The method of claim 21, wherein detecting the target analyte based on the fluorescence light received by the reader comprises determining a concentration of the target analyte in the interstitial fluid based on the fluorescence light received by the reader.

23. The method of claim 21, wherein the substrate comprises a polymeric material transparent to the incident light and the fluorescence light.

24. The method of claim 21, wherein the target analyte is Na⁺, K⁺, Ca²⁺, glucose, urea, creatinine, bicarbonate, or chloride.