From weak adsorption to selective detection: functionalized interfaces for SERS glucose sensing

Surface-enhanced Raman scattering (SERS) offers molecularly specific, highly sensitive, and potentially miniaturized analysis for glucose sensing, but glucose remains an intrinsically difficult SERS target on bare noble-metal surfaces. As a neutral, highly hydrated, weakly adsorbing aliphatic polyol, glucose does not readily populate plasmonic hotspots or form a stable, selective, and spectroscopically productive interfacial state. Consequently, the central limitation in SERS glucose sensing is not simply weak Raman scattering, but the mismatch between glucose chemistry and the interfacial requirements of SERS detection. This review examines functionalized interfaces as the main route for overcoming that mismatch. We first discuss the SERS principles most relevant to glucose sensing, including electromagnetic and chemical enhancement, distance dependence, adsorption probability, molecular orientation, and matrix competition. We then analyze boronic-acid-centered interfaces, which currently represent the most developed practical strategy because they combine reversible cis-diol recognition, compact surface attachment, and adaptable readout designs. Alternative recognition routes, including biomolecular and molecularly imprinted interfaces, are also assessed as complementary strategies that offer different forms of selectivity but introduce additional challenges related to distance, stability, transport, or interfacial coupling. Across these interface classes, recent progress shows that analytical performance depends not only on receptor chemistry, but also on hotspot proximity, signal-conversion logic, sample handling, and matrix tolerance. By framing SERS glucose sensing as an interfacial problem, this review identifies the design priorities needed to move from weak adsorption toward selective, reproducible, and analytically credible glucose detection.