Simultaneous band-pass Raman spectroscopy for robust noninvasive continuous glucose monitoring

Abstract The rising incidence of diabetes underscores an urgent need for accurate, user-friendly, and truly noninvasive continuous glucose monitoring (CGM). Raman spectroscopy is an attractive foundation for noninvasive CGM because it is label-free and offers direct molecular specificity to glucose. Building on our previous success with sequential Band-Pass Raman (BPR), we present a next-generation BPR system that performs simultaneous detection of three selected Raman bands, eliminating bulky dispersive optics and CCD-based spectrometers and rejecting redundant full-spectrum information, while significantly improving measurement speed and robustness. This simplified acquisition geometry is compatible with miniaturization and enables streamlined glucose quantification. The robustness and glucose specificity of the approach were validated in vitro via randomized lactate-interference tests over physiologically relevant concentrations. Preliminary in vivo measurements in a healthy volunteer during a standard 4-hour oral glucose tolerance test (OGTT) reveal promising performance, with the calibrated BPR metric achieving clinically relevant accuracy. Together, these results provide a compelling proof-of-concept for our simultaneous BPR implementation, opening new avenues for simplified and miniaturizable Raman-based CGM solutions.