A Glucose Biosensor Based on Surface-Enhanced Raman Scattering:  Improved Partition Layer, Temporal Stability, Reversibility, and Resistance to Serum Protein Interference

Abstract

This work updates the recent progress made toward fabricating a real-time, quantitative, and biocompatible glucose sensor based on surface-enhanced Raman scattering (SERS). The sensor design relies on an alkanethiolate tri(ethylene glycol) monolayer that acts as a partition layer, preconcentrating glucose near a SERS-active surface. Chemometric analysis of the captured SERS spectra demonstrates that glucose is quantitatively detected in the physiological concentration range (0−450 mg/dL, 0−25 mM). In fact, 94% of the predicted glucose concentrations fall within regions A and B of the Clarke error grid, making acceptable predictions in a clinically relevant range. The data presented herein also demonstrate that the glucose sensor provides stable SERS spectra for at least 3 days, making the SERS substrate a candidate for implantable sensing. Glucose sensor reversibility and reusability is evaluated as the sensor is alternately exposed to glucose and saline solutions; after each cycle, difference spectra reveal that the partitioning process is largely reversible. Finally, the SERS glucose sensor successfully partitions glucose even when challenged with bovine serum albumin, a serum protein mimic.