Small Analyte Biosensing

The detection of low molecular weight targets, known as haptens, remains a central challenge in the field of biosensors since the response of most techniques is dependent on the size of the target. This is the case, for example, for air pollutants or pharmaceutical pollutants. However, despite the small size of these molecules, sometimes a few hundred grams per mole, there are monoclonal antibodies capable of detecting them with unmatched sensitivity and selectivity. There are also specific aptamers, known as synthetic antibodies, capable of ensuring effective recognition of these targets. In both cases, the nature of the interactions between these bioreceptors and their target is unknown. Beyond the inherent interest in understanding the mechanisms involved in molecular recognition, the identification of sites impacted by interaction opens the way to the custom construction of biomimetic receptors for selective recognition. The idea is therefore to measure the vibrational spectra of haptens when they are recognized by a bioreceptor in order to identify the groups involved. We explore this field using quartz crystal microbalance (QCM) as a transduction technique combined with a vibration spectroscopy that can operate at the solid-liquid interface: Raman spectroscopy. Given the low sensitivity of Raman, experiments will have to be carried out on plasmonic nanostructures, which will have to be generated on the surface of quartz, in order to enhance Raman spectroscopy to measure, operando, SERS spectra of adsorbed species. With the same objective, we also combine QCM to LSPR measurements on these substrates using the Acoulyte instrument designed by Insplorion.