Continuous Monitoring of Glucose and Oxygen using an Insertable Biomaterial-based Multianalyte Barcode Sensor

Abstract

Chronic diseases including diabetes, cardiovascular diseases, and microvascular complications contribute significantly to global morbidity and mortality. Multiplexing technologies offer a promising approach for the simultaneous detection and management of comorbidities, providing comprehensive disease insights. In this work, we describe a miniaturized optical "barcode" sensor with high biocompatibility for continuous monitoring of glucose and oxygen. This enzymatic sensor relies on oxygen consumption in proportion to local glucose levels and the phosphorescence reporting of tissue oxygen with a lifetime-based probe. The sensor was designed to operate in a tissue environment with low levels of dissolved oxygen. The barcode sensor consists of a poly(ethylene) glycol diacrylate (PEGDA) hydrogel with four discrete compartments separately filled with glucose or oxygen-sensing phosphorescent microparticles. We evaluated the response of the barcode hydrogels to fluctuating glucose levels over the physiological range under low oxygen conditions, demonstrating controlled tuning of dynamic range and sensitivity. Moreover, the barcode sensor exhibited remarkable storage stability over 12 weeks, along with full reversibility and excellent reproducibility ([~]6% variability in phosphorescence lifetime). Electron beam sterilization had a negligible impact on the glucose response of the barcode sensors. Furthermore, our investigation revealed minimal phosphorescence lifetime changes in oxygen compartments while exhibiting increased lifetime in glucose-responsive compartments when subjected to alternating glucose concentrations (0 and 200 mg/dL), showcasing the sensors multianalyte sensing capabilities without crosstalk between compartments. Additionally, evaluation of tissue response to sensors inserted in pigs revealed appropriate biocompatibility of the barcodes.