A “plasmonic cuvette”: dye chemistry coupled to plasmonic interferometry for glucose sensing

A non-invasive method for the detection of glucose is sought by millions of diabetic patients to improve personal management of blood glucose over a lifetime. In this work, the synergistic advantage of combining plasmonic interferometry with an enzyme-driven dye assay yields an optical sensor capable of detecting glucose in saliva with high sensitivity and selectivity. The sensor, coined a “plasmonic cuvette,” is built around a nano-scale groove-slit-groove (GSG) plasmonic interferometer coupled to an Amplex–red/Glucose–oxidase/Glucose (AR/GOx/Glucose) assay. The proposed device is highly sensitive, with a measured intensity change of 1.7×105%/m (i.e., one order of magnitude more sensitive than without assay) and highly specific for glucose sensing in picoliter volumes, across the physiological range of glucose concentrations found in human saliva (20–240 μm). Real-time glucose monitoring in saliva is achieved by performing a detailed study of the underlying enzyme-driven reactions to determine and tune the effective rate constants in order to reduce the overall assay reaction time to ∼2 min. The results reported suggest that by opportunely choosing the appropriate dye chemistry, a plasmonic cuvette can be turned into a general, real-time sensing scheme for detection of any molecular target, with high sensitivity and selectivity, within extremely low volumes of biological fluid (down to femtoliters). Hereby, we present the results on glucose detection in artificial saliva as a notable and clinically relevant case study.