This paper presents a dielectric affinity microsensor that consists of an in situ prepared hydrogel attached to a pair of coplanar electrodes for dielectrically based affinity detection of glucose in subcutaneous tissue in continuous glucose monitoring applications. The hydrogel, incorporating N-3-acrylamidophenylboronic acid that recognizes glucose via affinity binding, is synthetically prepared on the electrodes via in situ gelation. When implanted in subcutaneous tissue, glucose molecules in interstitial fluid diffuse rapidly through the hydrogel and bind to the phenylboronic acid moieties. This induces a change in the hydrogel’s permittivity and hence in the impedance between the electrodes, which can be measured to determine the glucose concentration. The in situ hydrogel preparation allows for a reduced hydrogel thickness (~10 µm) to enable the device to respond rapidly to glucose concentration changes in tissue, as well as covalent electrode attachment of the hydrogel to eliminate the need for semipermeable membranes that would otherwise be required to restrain the sensing material within the device. Meanwhile, the use of coplanar electrodes is amenable to the in situ preparation and facilitates glucose accessibility of the hydrogel, and combined with dielectrically based transduction, also eliminates mechanical moving parts often found in existing affinity glucose microsensors that can be fragile and complicated to fabricate. Testing of the device in phosphate-buffered saline at pH 7.4 and 37 °C has shown that at glucose concentrations ranging from 0 to 500 mg/dL, the hydrogel-based microsensor exhibits a rapid, repeatable, and reversible response. In particular, in the glucose concentration range of 40–100 mg/dL, which is of great clinical interest to monitoring normal and low blood sugar levels, the device response is approximately linear with a resolution of 0.32 mg/dL based on effective capacitance and 0.27 mg/dL based on effective resistance, respectively. Thus, the device holds the potential to enable reliable and accurate continuous monitoring of glucose in subcutaneous tissue.
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We gratefully acknowledge financial support from the National Institutes of Health (Grant Nos. 1DP3DK101085-01 and 2P41EB002033-19A1), the National Science Foundation (Grant No. ECCS-1509760), and the National Natural Science Foundation of China (Grant No. 61428402).
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