Sensor For Detection Of Carbohydrate

• US 20080188723A1
• Filed: 12/07/2005
• Published: 08/07/2008
• Est. Priority Date: 12/07/2004
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Yu, Yihua, Gregorius, Klaus, Struve, Casper, Kristensen, Jesper Svennin, Frederiksen, John Myhre
• Granted Patent: US 8,700,113 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: C08B 37/0063 Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose

Abstract

A sensor for the detection or measurement of carbohydrate analyte (such as glucose) in fluid comprises components of a competitive binding assay the readout of which is a detectable or measurable optical signal (such as FRET assay) retained by a material that permits diffusion of analyte but not the assay components, the assay components comprising: an animal lectin; and an analyte analogue capable of competing with analyte for binding to the lectin.

Claims

1. A sensor for the detection or measurement of carbohydrate analyte in fluid, the sensor comprising components of a competitive binding assay the readout of which is a detectable or measurable optical signal retained by a material that permits diffusion of analyte but not the assay components, the assay components comprising:

an animal lectin; and

an analyte analogue capable of competing with analyte for binding to the lectin.

2. A sensor as claimed in claim 1, wherein the analyte is glucose.

3. A sensor as claimed in claim 2, wherein the analyte analogue is capable of competing with glucose at physiological calcium concentrations.

4. A sensor as claimed in claim 1, wherein the lectin is a human or humanized lectin.

5. A sensor as claimed in claim 4, wherein the lectin is derived from the human body or is a recombinant lectin.

6. A sensor as claimed in claim 1, wherein the lectin is in multimeric form.

7. A sensor as claimed in claim 1, wherein the lectin is a collectin selected from mannose binding lectin, a pulmonary surfactant protein, conglutinin or collectin-43.

8. A sensor as claimed in claim 7, wherein the lectin is in multimeric form, and wherein the lectin is mannose binding lectin in trimeric and/or tetrameric form.

9. A sensor as claimed in claim 1, wherein the analyte analogue comprises a plurality of carbohydrate or carbohydrate mimetic moieties.

10. A sensor as claimed in claim 9, wherein the analyte analogue comprises at least one carbohydrate moiety selected from D-fructose, D-leucrose, N-acetyl 15 glucosamine, D-mannose, L-fucose, N-acetyl-mannosamine, D-arabinose, myc-inositol, D-tagatose, erlose, Dglucose, D-palatinose, D-turanose, D-ribose, D-sorbitol.

11. A sensor as claimed in claim 1, wherein the analyte analogue bears one or more energy donor or energy acceptor moieties.

12. A sensor as claimed in claim 9, wherein the analyte analogue is an optionally derivatised polymer of carbohydrate and/or carbohydrate mimetic moieties.

13. A sensor as claimed in claim 12, wherein the analyte analogue is selected from optionally derivatised dextran, mannan, amylose, amylopectin, glycogen, hyaluronate, chondroitin, heparin, dextrin, inulin, xylan, fructan and chitin.

14. A sensor as claimed in claim 13, wherein the analyte analogue is optionally derivatised dextran in which the 3- and/or 4-hydroxyl groups of at least one of the glucose units have been inactivated.

15. A sensor as claimed in claim 14, wherein the analyte analogue is optionally derivatised dextran which has been treated with periodate.

16. A sensor as claimed in claim 13, wherein the dextran is aminated.

17. A sensor as claimed in claim 9, wherein the analyte analogue is a carbohydrate-protein conjugate or a carbohydrate-dendrimer conjugate.

18. A sensor as claimed in claim 17, wherein the analyte analogue is a carbohydrate-albumin conjugate.

19. A sensor as claimed in claim 9, wherein the analyte analogue is a flexible water-soluble non-polysaccharide polymer bearing pendant carbohydrate or carbohydrate mimetic moieties.

20. A sensor as claimed in claim 9, wherein the components of the assay are retained by a shell or matrix material.

21. A sensor as claimed in claim 9, wherein the retaining material is biodegradable.

22. A sensor as claimed in claim 20, wherein the components of the assay are retained by a shell of biodegradable material encapsulating the assay components while allowing glucose to contact the assay components, wherein the biodegradable material comprises a co-polymer having hydrophobic and hydrophilic units.

23. A sensor as claimed in claim 1, wherein said detectable or measurable optical signal is generated by proximity based signal generating/modulating moieties.

24. A sensor as claimed in claim 23, wherein the lectin is labelled with one of an proximity based signal generating/modulating moiety pair and the analyte analogue is labelled with the other of the proximity based signal generating/modulating moiety pair.

25. A method of preparing a sensor as claimed in claim 1, comprising one or more of phase separation, solvent evaporation, extraction, spray drying, spray coating, spray chilling, rotary disk atomisation, fluid bed coating, coextrusion and pan coating.

26. A method of detecting glucose using a sensor as claimed in claim 1, comprising implantation of the sensor into the skin of a mammal, detection or measurement of glucose using external optical means and degradation of the biodegradable material.

27. A method of detecting glucose using a sensor as claimed in claim 1, comprising detection or measurement of glucose using external optical means by illumination of a said sensor present in or below the skin of a mammal.

28. A sensor for the detection or measurement of a carbohydrate analyte in fluid, the sensor comprising components of a competitive binding assay the readout of which is a detectable or measurable optical signal retained by a material that permits diffusion of the analyte but not the assay components, the assay components comprising:

a carbohydrate binding molecule labelled with one of a proximity based signal generating/modulating moiety pair; and

a carbohydrate analogue capable of competing with the 15 analyte for binding to the carbohydrate binding molecule, the carbohydrate analogue being a flexible water-soluble polymer comprising;

polymerized residues of monomer units, the first monomer unit residues bearing pendant carbohydrate or carbohydrate mimetic moieties and pendant moieties which are the other of the proximity based signal generating/modulating moiety pair; and

/or co-polymerised residues of first monomer units and second monomer units, the first monomer unit residues bearing pendant carbohydrate or carbohydrate mimetic moieties and the second monomer unit residues bearing pendant moieties which are the other of the proximity based signal generating/modulating moiety pair.