Small – sized analytes biosensing on resonant nanostructures

Biosensors are analytical devices that monitor a variety of health and disease status parameters including ions, proteins, DNA fragments, small molecules and other markers. They do so by incorporating a biological material (a bioreceptor) intimately associated with a physicochemical transducer. These devices are designed with the objective of detecting a target, specifically and rapidly, even at trace amounts and even in a complex environment. One of the greatest challenges in the field of biosensors is the sensitivity. This is particularly true in the case of sensing of small-sized target analyte (haptens, toxins, odorants), as the response of classical detection techniques is generally below the required detection limit. The detection sensitivity of biosensors in some cases could be increased by improving the quality of the biological material. For the detection and quantitative monitoring of small analytes significant progress has been made in increasing the avidity/affinity of bioreceptors, being either antibodies, aptamers, or specific selectors designed to recognize and bind small-sized targets from solution or from air. A different strategy aims at amplifying the signal measured by the transduction techniques to be used. For optical sensors, recent developments of nanostructuring the sensor surface has opened the way to reproducible and reliable benefit from optical enhancement of spectroscopic transduction techniques. Along these lines, we propose a combined piezoelectric-(vibrational) spectroscopic detection of small-sized analytes with two main objectives: (i) at the fundamental level, we aim at getting a detailed understanding of the molecular interactions occurring upon the molecular recognition and the binding event, while (ii) at the applied level we intend to design highly sensitive biosensors for small-sized analytes. We will use both antibodies and aptamers as biomolecular receptors, as well as synthetic chemical structures, referred to as selectors, and propose a combination of visco-elastic mass detection using a Quartz Crystal Microbalance with dissipation monitoring (QCM-D) with spectroscopic information from surface enhanced IR and Raman spectroscopies (SEIRAS and SERS, respectively) employing a nanopatterned QCM gold electrode. The objective of such combination is to enhance the performance of the biosensor. Firstly, the QCM will provide a fast detection of any interaction between the bioreceptor and the chosen target, paving the way for a detailed investigation of the interaction mechanism at the molecular level. Secondly, SERS and the SEIRAS will provide the identification of the analytes as well as any structural modifications due to the interaction with the bioreceptor, through the spectral signature recorded by these vibrational spectroscopies. Such enhanced spectroscopies exploit the plasmonic properties of the metallic nanostructures that create a highly intense electromagnetic field at the vicinity of the nanostructures. This enhanced electromagnetic field will induce an enhancement of the Raman scattering cross section and of the IR absorption. The enhancement factors in SERS and SEIRAS have been estimated to be close to 10 10 and 106, respectively, and have allowed for the observation and the detection of a very small amounts of molecules, opening even the possibility for single molecule detection. Therefore, the designed biosensor based on these enhanced spectroscopies will be highly sensitive. By combining vibrational and piezoelectric techniques in a single set-up, we will be able to propose a fast, reliable, specific and highly sensitive biosensor.