Band-Pass Raman Spectroscopy Unlocks Compact Point-of-Care Noninvasive Continuous Glucose Monitoring.

Noninvasive blood glucose monitoring with precision comparable to standard invasive or minimally invasive methods has been a long-sought goal, especially as diabetes rates soar, with 592 million cases worldwide expected by 2035. Various optical and spectroscopic technologies have challenged noninvasive continuous glucose monitoring (CGM), but most methods fail to detect physiological levels or lack miniaturization for practical use. Based on our previous success in direct observation of glucose signals from in vivo skin, we developed a band-pass Raman spectroscopy method that enables noninvasive, physiological-level CGM in a compact device. Using off-axis 830 nm near-infrared illumination and intraspectrum reference, we eliminate most elastically scattered photons, revealing the glucose Raman signal through an amplified photodetector, while compensating for background variations. Our approach, validated on both tissue phantoms and in vivo human skin, overcomes bulky spectrometers and makes portable Raman-based CGM devices a reality.