Development of an Implantable Optical Glucose Sensor

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9908439CoteDiabetes mellitus is a chronic disease that, if unregulated, can give rise to large fluctuations in blood glucose levels. In order to maintain normal glucose levels, blood glucose must be monitored frequently throughout the day. In this proposal a plan is forwarded to design and develop novel implantable, fluorescent-doped, intradermal polymer transducers that will be combined with an optical probe to quantify blood glucose levels.Currently, only invasive blood glucose monitors are commercially available, which require a finger stick for each reading. In this research, fluorescence-tagged polymer microspheres will be injected 0.15 mm below the epidermis in a manner equivalent to a tattoo. The polymers used in this research will be made from crosslinked hydrogels of poly(ethylene glycol) (PEG) which have been shown by this team and others to be stable, nontoxic, and non-antigenic in vivo. Polymer hydrogel microspheres that exhibit fluorescence intensity proportional to glucose in the surrounding media will be fabricated from photopolymerized PEG containing a concanavalin A (a glucose binding protein abbreviated ConA) fluorophore conjugate and a dextran-fluorophore conjugate. Both ConA and dextran will be tethered to the gel backbone to prevent instability due to leaching. In the absence of glucose, ConA and dextran are non-covalently bound, resulting in the quenching of the dextran fluorophore. In the presence of glucose, dextran is displaced from ConA binding sites (in proportion to the glucose concentration), resulting in an increase in the fluorescence of the dextran fluorophore. After implantation by injection 150 mm below the skin, the glucose specific fluorescent microspheres, when illuminated, will act as a "smart tattoo" and will emit light at an intensity proportional to the glucose concentration in the interstitial fluid surrounding the microspheres. To acquire the emitted light through the skin, an optical sensor will be designed, constructed and optimized based on analysis of light propagation through the turbid medium. The system (consisting of the microspheres and optical sensor) will initially be studied using simply glucose solution in a test cell. The microspheres will then be tested in a complex multi-chemical solution followed by a multi-chemical solution in a test cell wrapped in 0.15 mm of pig epidermis in an effort to optimize the design prior to in vivo experiments. Lastly preliminary in vivo studies in both non-diabetic and diabetic animals will be performed using a hairless rat animal model. Post-processing algorithms using techniques such as wavelength selection and PLS will be developed to improve accuracy and sensitivity of the measurement. Unlike other noninvasive and non-specific optical approaches such as near-infrared spectroscopy reported in the literature, this technique promises to be highly specific to the concentration of glucose because of the chemical sensitivity of microsphere fluorescence to glucose.