Abstract

This study presents an in vivo optical hydrogel microneedle platform that measures levels of analytes in interstitial fluid. The platform builds on a previously published technique for molding hydrogel microneedles by developing a composite hydrogel (i.e., PEGDA and polyacrylamide) that is sufficiently stiff to penetrate skin in the hydrated state and whose fluorescence changes dynamically-via a conjugated aptamer-depending on level of analyte. In a demonstration relevant to hypercalcemia, the hydrogel microneedle distinguished varying concentrations of calcium (within a range of 0 to 2 mM, which spans physiologically meaningful variations for hypoparathyroidism) within 10 minutes. In rats, a compact CMOS sensor measuring fluorescence from microneedles distinguished low hypercalcemic (1.7 mM) from high hypercalcemic (2.3 mM) ionized calcium levels as determined from reference blood measurements. Overall, this work demonstrates in vivo feasibility of a concept-which we call mPatch-for an optical hydrogel microneedle to measure small changes in levels of analytes in interstitial fluid, which does not rely on extraction of interstitial fluid out of the dermis.

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