Non-invasive in-blood glucose sensing
Non-invasive glucose monitoring (NIGM) is increasingly considered as an alternative to finger pricking for blood glucose assessment and management of diabetes in insulin-dependent patients, due to the pain, risk of infection, and inadequacy of finger pricking for frequent measurements. Nevertheless, current NIGM techniques do not measure glucose in blood, but rely on indirect bulk measurement of glucose in the interstitial fluid, where glucose is less concentrated, diluted in a generally unknown volume, and appears in a delayed fashion relative to blood glucose, impairing NIGM accuracy. We introduce a new biosensor, termed Depth-gated mid-InfraRed Optoacoustic Sensor (DIROS), which offers for the first time non-invasive glucose detection directly in blood, while simultaneously rejecting contributions from the metabolically inactive stratum corneum and other superficial skin layers. This unique ability is achieved by time-gating mid-infrared optoacoustic signals to enable glucose readings from depth-selective localization in the microvasculature of the skin. In measurements of mice in vivo, DIROS revealed marked accuracy improvement over conventional bulk-tissue glucose measurements. We showcase how skin rejection and signal localization are essential for improving the NIGM accuracy, and discuss key results and how DIROS offers a holistic approach to address limitations of current NIGM methods, with high translation potential.