Clinical Validation on Healthy Humans of a Portable Non-invasive Continuous Glucose Monitor Based on Transdermal Band-Pass Raman Spectroscopy

BACKGROUND: Accurate and painless glucose monitoring remains a major challenge in diabetes management. To address this need, we developed a compact, portable, and non-invasive continuous glucose monitoring (CGM) device based on transdermal band-pass Raman (BPR) spectroscopy intended for benchtop point-of-care use. METHODS: The BPR-CGM optically probes the molecular vibrations of glucose in the interstitial fluid targeting only three ultra-narrow Raman bands to extract glucose concentration trends while compensating for background variations through intra-spectrum referencing. By refraining from collecting redundant full-spectrum information as in standard Raman spectroscopy, our technology overcomes the need for bulky and expensive components while maintaining high sensitivity, making point-of-care non-invasive CGM a reality. RESULTS: A six-participant clinical study compared the non-invasive BPR-CGM with a standard blood glucometer and two commercial needle-based CGMs during a standard oral glucose tolerance test, inducing dynamic postprandial glucose variations. Glucose trends inferred by the BPR-CGM closely matched reference blood glucose values without algorithmic lag compensation. Across participants, the device achieved a mean absolute relative difference of 11.34 ± 1.96%, statistically indistinguishable from needle-based CGM sensors performance (10.42 ± 2.46% and 12.93 ± 4.69%). All BPR-CGM readings fell within clinically acceptable zones A and B of the Parkes (consensus) error grid. No adverse skin reactions were observed following the trial. CONCLUSIONS: These results demonstrate that the BPR-CGM technology can achieve clinical-grade accuracy comparable to invasive systems, paving the way for wearable, needle-free, and miniaturized glucose monitoring solutions.