Compositions and methods for analyte detection

• US 6,485,703 B1
• Filed: 07/09/1999
• Issued: 11/26/2002
• Est. Priority Date: 07/31/1998
• Status: Expired due to Term

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.), Texas A&M University System
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.), Texas A&M University System
• Inventors: Pishko, Michael V., Russell, Ryan, Coté, Gerard L., Sirkar, Kaushik, Anderson, Richard Rox
• Primary Examiner(s): Hartley, Michael G.
• Application Number:
  US09/354,914
• Time in Patent Office: 1,236 Days
• Field of Search: 424/9.1, 424/9.6, 424/9.8, 424/422, 424/423, 600/316, 600/317, 600/347, 600/365, 436/14, 524/916, 514/866
• US Class Current: 424/9.1
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0043 Fluorescein, used in vivo
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

Provided are a variety of chemically sensitive, stable (insoluble over a specified period of time), nontoxic, and non-antigenic hydrogel particles which undergo a measurable change in at least one electrochemical or optical property as a function of interaction with one or more substance(s) to be detected. Also provided are methods of using these hydrogel particles to detect one or more selected analytes, and in certain aspects detect one or more analytes in vivo. Further provided are devices used to detect and measure the optical or electrochemical changes.

Claims

1. A method for the detection of an analyte in an animal, wherein the analyte is glucose, comprising the steps of:

(a) implanting by injecting within the epidermis or dermis of the animal a composition comprising a hydrogel and an analyte detection compound, wherein said hydrogel comprises a cross-linked poly(ethylene glycol), poly(ethylene glycol)-co-anhydride, poly(ethylene glycol)-co-lactide, poly(ethylene glycol)-co-glycolide, poly(ethylene glycol)-co-orthoester, poly-isopropylacrylamide, polyHEMA, polyacrylamide, calcium alginate, or a combination thereof; and

wherein said detection compound is selected from the group consisting of the competitive binding pair FITC-Dextran and TRITC-ConA, or FITC-Dextran and TRITC-succinyl-ConA,

(b) measuring the analyte levels.

2. The method of claim 1, wherein said composition is injected in the epidermis of said animal.

3. The method of claim 1, wherein said composition is injected in the dermis of said animal.

4. The method of claim 1, wherein said composition is injected between about 0.05 mm and about 5 mm below the surface of the epidermis of said animal.

5. The method of claim 1, wherein said animal is a human.

6. The method of claim 1, wherein the composition has an average particle size up to about 10 microns in diameter.

7. The method of claim 1, wherein said composition produces an optical change upon contact with glucose.

8. The method of claim 7, wherein said composition produces a fluorescence change upon contact with glucose.

9. The method of claim 8, wherein said composition comprises at least a first fluorophore conjugate.

10. The method of claim 9, further comprising a second fluorophore conjugate, wherein said second fluorophore conjugate can accept photons from said first fluorophore conjugate and quench it.

11. The method of claim 10, said first fluorophore conjugate is FITC-dextran and said second fluorophore conjugate is TRITC-concanavalin A.