Shedding Light on Glucose: Tip-Enhanced Raman Scattering Achieves Complete Vibrational Fingerprint Coverage (400–3200 cm⁻¹) for Non-Invasive Metabolite Detection

• • TERS captures the complete glucose vibrational fingerprint across 400–3200 cm⁻¹, a spectral window that SERS cannot fully access due to linker molecule interference and incomplete coverage; this eliminates a critical blind spot in label-free glucose quantification, enabling direct correlation of all Raman-active modes with molecular concentration. • • The technique achieves strong near-field confinement and far-field background suppression by integrating a shear-force feedback-controlled scanning probe with a radially polarised vector beam through an optical fibre tip; this configuration boosts near-field enhancement at the tip apex, increasing Raman signal intensity by orders of magnitude relative to conventional Raman spectroscopy, which is essential for detecting glucose at clinically relevant millimolar concentrations. • • Glucose's Raman scattering cross-section is nearly five times smaller than that of benzene, and its poor affinity for bare metal surfaces has historically limited SERS performance; TERS circumvents these material constraints without requiring linker molecules, reducing chemical interference and improving spectral fidelity for in vivo applications. • • The label-free TERS approach enables non-invasive glucose monitoring without finger pricks, addressing a major patient compliance barrier in diabetes management; successful translation could reduce healthcare costs associated with invasive testing and improve continuous monitoring accuracy for millions of diabetes patients worldwide.