TRANSDERMAL ANALYTE MONITORING SYSTEMS AND METHODS FOR ANALYTE DETECTION

• US 20080281178A1
• Filed: 03/06/2008
• Published: 11/13/2008
• Est. Priority Date: 03/07/2007
• Status: Active Grant

• Current Assignee: Echo Therapeutics Incorporated
• Original Assignee: Echo Therapeutics Incorporated
• Inventors: Chuang, Han, Kost, Joseph, Hurley, James P.
• Granted Patent: US 8,812,071 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• 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 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/6833 Adhesive patches

Abstract

Transdermal analyte monitoring systems (TAMS) having increased longevity and improved analyte detection are described herein. Kits for use with the TAMS and methods of using the TAMS and kits are also described. In a preferred embodiment, the TAMS includes a protective, semi-permeable membrane covering the surface of the hydrogel. The protective, semi-permeable membrane contacts with the skin of a user and prevents contamination or fouling of the hydrogel. Optionally, the hydrogel comprises one or more humectants and/or an immobilized enzyme. In another preferred embodiment, the TAMS contains at least one channel or pocket for increasing the amount of oxygen provided to the hydrogel. In one embodiment, a method for improving analyte detection by the TAMS is provided. For example, after the skin porosity is increased by an appropriate pretreatment, a skin preparation wipe is applied to the treated skin area and then the TAMS is applied to the treated area.

Claims

1. A transdermal analyte monitoring system comprising:

a sensor assembly, wherein the sensor assembly comprises a hydrogel and a sensor body containing a plurality of electrodes, wherein the sensor body is in fluid communication with the hydrogel and wherein the hydrogel comprises an enzyme, and

a semi-permeable membrane, wherein the membrane is in fluid communication with the hydrogel and wherein the membrane is located at least at the distal end of the sensor assembly.

2. The transdermal analyte monitoring system of claim 1, wherein semi-permeable membrane comprises a poly(ether sulfone) coated with a tetrafluoroethylene-perfluoro-3,6-dioxa-4-methyl-7-octenesulfonic acid copolymer.

3. The transdermal analyte monitoring system of claim 2, wherein the hydrogel and the semi-permeable membrane form an interpenetrating polymer network.

4. The transdermal analyte monitoring system of claim 1, wherein the hydrogel comprises a polymer selected from the group consisting of polyethylene glycol diacrylate (PEDGA), agarose, polyethylene glycol diacrylate/polyethyleneimine (PEGDA-PEI), polyethylene glycol diacrylate-n-vinyl pyrrolidone (PEGDA-NVP), acrylate-polyethylene glycol —

N-hydroxy succinimide (A-PEG-N), and blends and copolymers thereof.

5. The transdermal analyte monitoring system of claim 1, wherein the enzyme is oxidase enzyme.

6. The transdermal analyte monitoring system of claim 1, wherein the enzyme is covalently immobilized in the hydrogel.

7. The transdermal analyte monitoring system of claim 6, the enzyme is covalently immobilized in the hydrogel using an A-PEG-N.

8. The transdermal analyte monitoring system of claim 5, wherein the system utilizes oxidase enzyme as the sensing chemistry to monitor blood glucose, lactate or other analytes.

9. The transdermal analyte monitoring system of claim 1, wherein the hydrogel comprises a negatively charged humectant.

10. The transdermal analyte monitoring system of claim 9, wherein the negatively charged humectant is sodium pyrrolidone carboxylic acid (NaPCA).

11. The transdermal analyte monitoring system of claim 1, wherein the sensor assembly comprises at least one channel or pocket for providing oxygen to the hydrogel.

12. The transdermal analyte monitoring system of claim 11, wherein the sensor assembly further comprises a target plate or a mounting plate, and wherein the at least one channel or pocket for providing oxygen to the hydrogel is located on the target plate or a mounting plate.

13. The transdermal analyte monitoring system of claim 11, wherein the enzyme is immobilized in the hydrogel via non-covalent immobilization.

14. A method for increasing analyte detection by a transdermal analyte monitoring system comprising:

(a) treating a region of skin of the user to increase permeability;

(b) subsequently wiping the treated region of skin with a substrate comprising at least one reagent selected from the group consisting of water, ethanol, isopropanol and glycerol; and

(c) applying a transdermal analyte monitoring system comprising

a sensor assembly, wherein the sensor assembly comprises a hydrogel and a sensor body containing a plurality of electrodes, wherein the sensor body is in fluid communication with the hydrogel and wherein the hydrogel comprises an enzyme, and

a semi-permeable membrane, wherein the membrane is in fluid communication with the hydrogel and wherein the membrane is located at least at the distal end of the sensor assembly.

15. The method of claim 14, wherein the region of skin is treated in step (a) by a method selected from the group consisting of tape stripping, rubbing, sanding, abrasion, laser ablation, radio frequency (RF) ablation, the application of chemicals, sonophoresis, iontophoresis, electroporation, and the application of permeation enhancing agents.

16. The method of claim 14, wherein the substrate is selected from the group consisting of pads, woven and non-woven fabrics, felt, and gauze.

17. The method of claim 14, wherein the substrate comprises an inorganic or organic solvent.

18. The method of claim 17, wherein the inorganic or organic solvent is selected from the group consisting of water, ethanol, and isopropanol.

19. The method of claim 14, wherein the substrate comprises phosphate buffered saline, lactic acid, soap, or a surfactant.

20. A kit comprising

a transdermal analyte detection system;

and

a substrate comprising phosphate buffered saline, lactic acid, soap, a surfactant, or a solvent,

wherein the transdermal analyte monitoring system comprises

a sensor assembly, wherein the sensor assembly comprises a hydrogel and a sensor body containing a plurality of electrodes, wherein the sensor body is in fluid communication with the hydrogel and wherein the hydrogel comprises an enzyme, and

a semi-permeable membrane, wherein the membrane is in fluid communication with the hydrogel and wherein the membrane is located at least at the distal end of the sensor assembly.

21. A kit comprising

a transdermal analyte detection system;

a substrate,

and a reagent selected from the group consisting of phosphate buffered saline, lactic acid, soap, a surfactant, and a solvent,

wherein the transdermal analyte monitoring system comprises

a sensor assembly, wherein the sensor assembly comprises a hydrogel and a sensor body containing a plurality of electrodes, wherein the sensor body is in fluid communication with the hydrogel and wherein the hydrogel comprises an enzyme, and

a semi-permeable membrane, wherein the membrane is in fluid communication with the hydrogel and wherein the membrane is located at least at the distal end of the sensor assembly.

22. A method for enhancing the sensitivity, stability or accuracy of a transdermal analyte sensor comprising providing an enhanced supply of oxygen to a hydrogel.

23. The method of claim 22, wherein the source of oxygen is air.

24. The method of claim 22, wherein an oxidase enzyme is covalently immobilized in the hydrogel.