Insertable Biomaterial-Based Multianalyte Barcode Sensor toward Continuous Monitoring of Glucose and Oxygen

Chronic diseases, including diabetes, cardiovascular diseases, and microvascular complications, contribute significantly to global morbidity and mortality. Current monitoring tools such as glucometers and continuous glucose monitors only measure one analyte; multiplexing technologies offer a promising approach for monitoring multiple biomarkers, enabling the management of comorbidities and providing more comprehensive disease insights. In this work, we describe a miniaturized optical "barcode" sensor with high biocompatibility for the 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 specifically 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 the 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 the phosphorescence lifetime) over nearly 50 devices. Electron beam sterilization had a negligible effect 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 sensor's multianalyte sensing capabilities without crosstalk between compartments. Additionally, the evaluation of chronic tissue response to sensors inserted in pigs revealed the appropriate biocompatibility of the barcodes as well as excellent material stability over many months. These findings support further development of similar technologies for introducing optical assays for multiple biomarkers that can provide continuous or on-demand feedback to individuals to manage chronic conditions.