Subcutaneous depth-selective spectral imaging with mμSORS enables noninvasive glucose monitoring.

Noninvasive blood glucose monitoring offers substantial advantages for patients, but current technologies are often not sufficiently accurate for clinical applications or require personalized calibration. Here we report multiple μ-spatially offset Raman spectroscopy, which captures Raman signals at varying skin depths, and show that it accurately detects blood glucose levels in humans. In 35 individuals with or without type 2 diabetes, we first determine the optimal depth for glucose detection to be at or below the capillary-rich dermal-epidermal junction, where we observe a strong correlation between specific Raman bands and venous plasma glucose concentrations. In a second study, comprising 230 participants, we then improve accuracy of our regression model to reach a mean absolute relative difference of 14.6%, without personalized calibration, whereby 99.4% of calculated glucose values fall into clinically acceptable zones of the consensus error grid (zones A and B). These findings highlight the ability and robustness of multiple μ-spatially offset Raman spectroscopy for noninvasive blood glucose measurement in a clinical setting.