Optical sensor for in vivo detection of analyte

• US 9,399,076 B2
• Filed: 05/17/2005
• Issued: 07/26/2016
• Est. Priority Date: 05/19/2004
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Yu, Yihua, Kristensen, Jesper S.
• Primary Examiner(s): Berhanu, Etsub
• Assistant Examiner(s): TOTH, KAREN E
• Application Number:
  US11/596,589
• Publication Number:
  US 20090221891A1
• Time in Patent Office: 4,088 Days
• Field of Search: 600/310, 600/312, 600/316, 600/317, 600/322, 600/347, 600/365
• US Class Current: 1/1
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions

Abstract

A sensor for the in vivo detection of glucose comprises:

components of an assay for glucose, a readout of which is a detectable optical signal which can be interrogated transcutaneously by external optical means when the sensor is implanted in vivo; and

a shell of biodegradable material encapsulating the assay components while allowing analyte to contact the assay components, wherein the biodegradable material comprises a co-polymer having hydrophobic and hydrophilic units.

A method of preparing such a sensor preferably comprises coacervation, solvent evaporation and/or extraction, spray drying, spray coating, spray chilling, rotary disk atomisation, fluid bed coating, coextrusion and/or pan coating.

A method of detecting glucose using such a sensor suitably comprises implantation of the sensor into the skin of a mammal, transdermal detection or measurement of glucose using external optical means and degradation of the biodegradable material.

Claims

1. A sensor for the in vivo detection of glucose, comprising:

components of an assay for glucose, a readout of which is a detectable optical signal which can be interrogated transcutaneously by external optical means when the sensor is implanted in vivo; and

a shell of biodegradable material encapsulating the assay components whilst allowing an analyte to contact the assay components, wherein the biodegradable material comprises a co-polymer having hydrophobic units and hydrophilic units, the hydrophilic units each comprising an ester of polyethylene glycol and a diacid.

2. A sensor as claimed in claim 1, wherein the co-polymer is a random co-polymer.

3. A sensor as claimed in claim 1, wherein the co-polymer has a molecular weight cut-off limit of no more than 25000 Da.

4. A sensor as claimed in claim 3, wherein the co-polymer has a molecular weight cut-off limit of no more than 10000 Da.

5. A sensor as claimed in claim 1, wherein the co-polymer has a permeability of at least 5.0×

10<sup>−

10</sup> cm²/s.

6. A sensor as claimed in claim 1, wherein the weight fraction of the hydrophobic units is from 10 to 90% of the co-polymer.

7. A sensor as claimed in claim 1, wherein the hydrophilic units comprise terephthalic acid and/or succinic acid as diacids.

8. A sensor as claimed in claim 7, wherein the hydrophilic units comprise terephthalic acid only as the diacid.

9. A sensor as claimed in claim 7, wherein the ratio of terephthalic acid to succinic acid in the hydrophilic units is between 1:

2 and 2;

1.

10. A sensor as claimed in claim 7, wherein the hydrophilic units comprise terephthalic acid and succinic acid as diacids.

11. A sensor as claimed in claim 1, wherein the molecular weight of each hydrophilic unit is from 400 to 4000 Da.

12. A sensor as claimed in claim 1, wherein the hydrophobic units of the co-polymer comprise an ester of butane-1,4-diol and a diacid.

13. A sensor as claimed in claim 12, wherein the hydrophobic units comprise terephthalic acid and/or succinic acid as diacids.

14. A sensor as claimed in claim 13, wherein the hydrophobic units comprise terephthalic acid only as the diacid.

15. A sensor as claimed in claim 13, wherein the ratio of terephthalic acid to succinic acid is between 1:

2 and 2;

1.

16. A sensor as claimed in claim 1, wherein the assay is a binding assay.

17. A sensor as claimed in claim 16, wherein the binding assay is a competitive binding assay, the components of which include a glucose binding agent and a glucose analogue.

18. A sensor as claimed in claim 17 wherein the glucose analogue is labelled with a first chromophore and the glucose binding agent is labelled with a second chromophore, the emission spectrum of the first chromophore or second chromophore overlapping with the absorption spectrum of the second chromophore or first chromophore respectively.

19. A sensor as claimed in claim 17, wherein the binding agent is an antibody, a Fab fragment, a lectin, a hormone receptor, a drug receptor, an aptamer or a molecularly-imprinted polymer.

20. A sensor as claimed in claim 1, wherein the detectable or measurable optical signal is generated by fluorescence resonance energy transfer, fluorescence polarisation, fluorescence quenching, phosphorescence, luminescence enhancement, luminescence quenching, diffraction or plasmon resonance.

21. A method of preparing a sensor as claimed in claim 1, where the method comprises forming the shell of biodegradable material of claim 1 by forming an open hollow shell of co-polymer, filling the shell with assay components and sealing the shell to make the sensor.

22. A method of detecting glucose using a sensor as claimed in claim 1, comprising implanting the sensor into the skin of a mammal, transdermally detecting or measuring glucose using external optical means and degrading the biodegradable material.

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