| Summary: | The increasing prevalence of diabetes and the severity of long-term complications have
emphasized the need for continuous glucose monitoring. Optically-based methods are
advantageous as they have potential for noninvasive or minimally invasive detection.
Fluorescence-based affinity assays, in particular, can be fast, reagentless, and highly
specific. Poly(ethylene glycol) (PEG) microspheres have been used to encapsulate such
fluorescently labeled molecules in a hydrogel matrix for implantation into the body. The
matrix is designed to retain the sensing molecules while simultaneously allowing
sufficient analyte diffusion. Sensing assays which depend upon a spatial displacement of
molecules, however, experience limited motility and diminished sensor response in a
dense matrix. In order to overcome this, a process of hydrogel microporation has been
developed to create cavities within the PEG that contain the assay components in
solution, providing improved motility for large sensing elements, while limiting leaching
and increasing sensor lifetime. For an implanted sensor to be successful in vivo, it should exhibit long-term stability and
functionality. Even biocompatible materials that have no toxic effect on surrounding
tissues elicit a host response. Over time, a fibrous capsule forms around the implant,
slowing diffusion of the target analyte to the sensor and limiting optical signal
propagation. To prevent this biofouling, a thermoresponsive nanocomposite hydrogel
based on poly(N-isopropylacrylamide) was developed to create a self-cleaning sensor
membrane. These hydrogels exist in a swollen state at temperatures below the volume
phase transition temperature (VPTT) and become increasingly hydrophobic as the
temperature is raised. Upon thermal cycling around the VPTT, these hydrogels exhibit
significant cell release in vitro. However, the VPTT of the original formula was around
33-34 degrees C, resulting in a gel that is in a collapsed state, ultimately limiting glucose
diffusion at body temperature. The hydrogel was modified by introducing a hydrophilic
comonomer, N-vinylpyrrolidone (NVP), to raise the VPTT above body temperature. The
new formulation was optimized with regard to diffusion, mechanical strength, and cell
releasing capabilities under physiological conditions. Overall, this system is a promising
method to translate a glucose-sensitive assay from the cuvette to the clinic for minimally
invasive continuous glucose sensing.
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