Sensor for Detection of Carbohydrate

• US 20090131773A1
• Filed: 12/07/2005
• Published: 05/21/2009
• Est. Priority Date: 12/07/2004
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Precisense A/S (Medtronic Plc)
• Inventors: Yu, Yihua, Kristensen, Jesper Svenning, Gregorius, Klaus, Struve, Casper
• Granted Patent: US 8,478,375 B2
• Time in Patent Office: Days
• US Class Current: 600/317
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A sensor for sensing analyte concentration comprises at least two different variants of an appropriate competitive binding assay, the sensor being capable of sensing accurately a required range of analyte concentrations by means of the variants of the assay each being capable of sensing accurately a part only of the required range of analyte concentrations and the variants of the assay being chosen to sense overlapping or adjoining ranges of concentration covering the whole of the required range.

Claims

1. A sensor for sensing analyte concentration, comprising at least two different variants of an appropriate competitive binding assay, the sensor being capable of sensing accurately a required range of analyte concentrations by means of the variants of the assay each being capable of sensing accurately a part only of the required range of analyte concentrations and the variants of the assay being chosen to sense overlapping or adjoining ranges of concentration covering the whole of the required range.

2. A sensor according to claim 1, wherein the analyte is carbohydrate.

3. A sensor according to claim 2, wherein the analyte is glucose.

4. A sensor according to claim 1, wherein the sensor produces a measurable optical response correlating to the analyte concentration.

5. A sensor according to claim 1, wherein the competitive binding assays each comprise:

an analyte binding agent; and

an analyte analogue comprising at least one analyte analogue moiety;

wherein the analyte binding agent binds the at least one analyte analogue moiety of the analyte analogue to form a complex from which the analyte analogue is displaceable by said analyte, and wherein the different assays are distinguished by the number or nature of the analyte analogue moieties comprised by the analyte analogue.

6. A sensor according to claim 5, wherein the analyte binding agent is labelled with one of a 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, and wherein there is a detectable difference in signal when the analyte analogue and analyte binding agent form the complex and when the analyte analogue is displaced by the analyte from the complex.

7. A sensor according to claim 5, wherein the analyte binding agent is a lectin.

8. A sensor according to claim 7, wherein the analyte binding agent is mannose binding lectin (MBL).

9. A sensor according to claim 5, wherein the at least one analyte analogue moiety is a carbohydrate or carbohydrate mimetic moiety.

10. A sensor according to claim 9, wherein the at least one analyte analogue moiety is a monosaccharide or oligosaccharide moiety.

11. A sensor according to claim 5, wherein the analyte analogue comprises a macromolecule.

12. A sensor according to claim 11, wherein the macromolecule is a protein, dendrimer, polysaccharide or synthetic polymer.

13. A sensor according to claim 12, wherein the macromolecule is a serum albumin.

14. A sensor according to claim 12, wherein the polysaccharide is derivatised to reduce the number of incorporated analyte analogue moieties.

15. A sensor according to claim 5, wherein in each competitive binding assay variant the analyte binding agent is MBL, the macromolecule is HSA and the analyte analogue moieties are mannose, and wherein each variant of the competitive binding assay contains an HSA-mannose conjugate comprising a different number of mannose moieties.

16. A sensor according to claim 5, wherein the analyte is glucose, and in each variant of the competitive binding assay the analyte binding agent is MBL and the macromolecule and analyte analogue moieties together form a derivatised dextran, and wherein each variant of the competitive binding assay contains a dextran derivatised such that the number of analyte analogue moieties incorporated into the dextran is different.

17. A sensor according to claim 16, wherein the sensor comprises two variants of a competitive binding assay, one variant being capable of sensing glucose concentrations in the range 0-10 mM, and the other variant being capable of sensing glucose concentrations in the range 0-25 mM.

18. A sensor according to claim 17, further comprising a third variant of a competitive binding assay, capable of sensing glucose concentrations in the range 15-40 mM.

19. A sensor according to claim 1, wherein the different variants of the assay are contained in separate compartments within the sensor.

20. A sensor according to claim 1, wherein the sensor comprises at least two kinds of particles, each kind of particle containing a different variant of the competitive binding assay.

21. A sensor according to claim 19, wherein the material from which the particles or compartments are made is biodegradable.

22. A sensor according to claim 19, wherein the particles or compartments retain the components of the assay within a shell or matrix material.

23. A sensor according to claim 19, wherein the particles or compartments are permeable to the analyte and allow the analyte to freely diffuse into and out of the sensor and to contact the assay components, but are impermeable to the components of the variants of the competitive binding assay.

24. A method of using the sensor according to claim 1 in a living body, wherein:

the sensor is implanted beneath the surface of the skin of the subject such that it is bathed in interstitial fluid;

time is allowed for the analyte concentration in the interstitial fluid and in the sensor to equalise;

light energy is supplied to the sensor;

an analyte concentration dependent fluorescence property of the assay is measured;

the said measurement is converted into a readout of analyte concentration.

25. A method of using the sensor according to claim 1 in a living body, wherein:

time is allowed for the analyte concentration to equalise in a sensor implanted beneath the surface of the skin of the subject and the interstitial fluid;

light energy is supplied to the sensor;

an analyte concentration dependent fluorescence property of the assay is measured;

the said measurement is converted into a readout of analyte concentration.