Optical sensor for in vivo detection of analyte
View Patent ↗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.
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 −10 cm 2 /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.