Phosphorescence Lifetime Imaging for Monitoring an Insertable Hydrogel Multianalyte Sensor

Oxidoreductase enzymes paired with oxygen-sensitive phosphorescent dyes can be immobilized in sensor structures that allow for continuous monitoring following insertion with minimal insult to the tissue. However, oxidoreductase-based sensors are limited by their consumption of oxygen, requiring knowledge and control of local oxygen conditions. Further, oxygen-responsive phosphors also exhibit temperature dependence. In this paper, we present a novel sensor design capable of providing glucose measurements while also reporting local oxygen and temperature variations. The sensor was composed of a miniature hydrogel multicompartment device containing phosphorescent sensing assays for glucose, oxygen, and temperature. The sensor was monitored using phosphorescence lifetime time-gated imaging using a custom system. The sensor response to buffer solutions of varying glucose (0, 100, 200, 400 mg/dL), oxygen (0-210 μM), and temperature (32, 37, 42 C) was collected. The lifetime measured from the sensor compartments was found to correlate closely with the Stern-Volmer relationship for luminescence response to changing oxygen concentration. This demonstrates feasibility of a multianalyte sensor platform, laying the foundation for development of tools for minimally-invasive simultaneous monitoring of multiple biomarkers.Clinical Relevance: Chronic conditions such as diabetes can benefit greatly from continuous monitoring. Oxidoreductase sensing of analytes such as glucose is highly sensitive, highly specific, and well established, but may be affected by local oxygen and temperature variations. In this paper, we present a sensor design that can compensate for environmental fluctuations and improve accuracy, all within a minimally invasive form factor.