A responsive hydrogel-based microneedle system for minimally invasive glucose monitoring

Abstract

Blood glucose (BG) monitoring in patients with diabetes is critical for diabetes management. Minimally invasive BG monitoring is urgently required to increase the patient compliance. Herein, based on a responsive hydrogel system, we developed a smart microneedle patch system for minimally invasive glucose monitoring. The patch consisted of a transparent substrate of photocurable resin and microneedles made of a pH-responsive and glucose-responsive hydrogel. The responsive hydrogel was composed of a photocrosslinkable hydrogel of gelatin methacrylate (GelMA) together with a pH-responsive nanogel (nano(CMC-pHEA)) and glucose oxidase (GOx). The composite hydrogel showed fast response and high sensitivity to glucose levels in physiological range, mainly due to the ionization of CMC-pHEA component and proton balance. The microneedles showed sufficient mechanical strength to penetrate the skin of mice with minimal invasion, and achieved in situ extraction of glucose in interstitial fluid (ISF) and in situ glucose-responsive reaction. We demonstrated the rapid glucose monitoring by microneedle patch system in skin-mimicking gels in vitro and in diabetic mice in vivo. The microneedles quickly and sensitively responded to glucose concentrations, allowed quantitative readouts of glucose levels through the changes of microneedle heights and swelling ratios. Moreover, the readouts in mice in vivo were consistent with BG levels measured by glucometer. This smart microneedle system has potentials to replace blood sampling, and minimize patient discomfort during BG testing, therefore has potentials in minimally invasive, rapid and reliable BG monitoring.