Predicting Concentrations of Mixed Sugar Solutions with a Combination of Resonant Plasmon-Enhanced SEIRA and Principal Component Analysis

The detection and quantification of glucose concentrations in human blood or in the ocular fluid gain importance due to the increasing number of diabetes patients. A reliable determination of these low concentrations is hindered by the complex aqueous environments in which various biomolecules are present. In this study, we push the detection limit as well as the discriminative power of plasmonic nanoantenna-based sensors towards the physiological limit. We utilize plasmonic surface-enhanced infrared absorption spectroscopy (SEIRA) to study aqueous solutions of mixtures of up to five different physiologically relevant saccharides, namely the monosaccharides glucose, fructose, and galactose, as well as the disaccharides maltose and lactose. Resonantly tuned plasmonic nanoantennas in a reflection flow cell geometry allow us to enhance the specific vibrational fingerprints of the mono- and disaccharides. The obtained spectra are analyzed via principal component analysis (PCA) using a machine learning algorithm. The high performance of the sensor together with the strength of PCA allows us to detect concentrations of aqueous mono- and disaccharides solutions down to the physiological levels of 1 g/L. Furthermore, we demonstrate the reliable discrimination of the saccharide concentrations, as well as compositions in mixed solutions, which contain all five mono- and disaccharides simultaneously. These results underline the excellent discriminative power of plasmonic SEIRA spectroscopy in combination with the PCA. This unique combination and the insights gained will improve the detection of biomolecules in different complex environments.