Résumé
Because of climate change, certain viruses are re-emerging. This is the case of the Chikungunya virus (CHIKV), an arbovirus transmitted by the bites of CHIKV-infected Aedes aegypti mosquitoes that is beginning to threaten Europe. CHIKV infection has a short incubation time of 3 to 10 days, with most cases asymptomatic. However, other arboviruses can have the same symptoms, hence requiring precise and immediate solutions for virological and serological diagnosis tests. These tests must be accurate, rapid, selective, and cost-efficient to help prevent infections and eventually control a pandemic situation. In this context, the Microelectromechanical Systems (MEMS) industry, especially piezoelectric resonators of all shapes and sizes, is a promising sector that will revolutionize the biological detection market. Ultrahigh-sensitive micromechanical resonators showed the potential of this technology for mass detection. Unfortunately, applying MEMS to the biomedical sector is still limited as it requires challenging biocompatible qualities, making it often unattainable to material scientists and engineers. My thesis project, which is at the interface between MEMS and biology, aims at developing piezoelectric α-quartz/Si resonating MEMS manufactured by cost-efficient soft-chemistry routes to detect the mass response of CHIKV using virus-selective recognition interfaces. This thesis built upon the technology developed in my thesis laboratory (the NanoChemLab team at the IES laboratory), which succeeded in engineering α-quartz MEMS with thicknesses between 500 nm and 15 µm, this is between 10 to 50 times thinner than those obtained by traditional top-down technologies on bulk crystals. Quartz has the advantage of being abundant, non-toxic, and having a high-quality factor. However, the fact that quartz MEMS must be immersed in a liquid medium for biological measurements significantly reduces their mechanical performance compared with vacuum or air. Therefore, during my thesis, I investigated the mechanical characteristics of the α-quartz piezo-MEMS under liquid conditions using optical transduction before exploiting its capabilities as a piezoelectric transducer. To this end, I designed a silicon-based chamber to contain the liquid and perform real-time measurements using a laser vibrometer. Furthermore, the design of the chamber allowed to amplify the displacement amplitude of piezo-MEMS. To selectively monitor the mass response of CHIKV detection, we designed two types of virus recognition interfaces, namely biorecognition layer, on MEMS resonators: 1) a biorecognition layer based on a synthetic system consisting on the covalent bioconjugation of recombinant proteins selectively detecting with the CHIKV envelope E2 proteins, and 2) a biorecognition layer based on a cellular system consisting on human-derived dendritic cells (DCs), which are central regulators of the immune response by detecting pathogens. During my thesis, I could establish the resonance frequency, quality factor (Q), and displacement amplitude of α-quartz piezo-MEMS under different liquid mediums, including phosphate-buffered saline (PBS) buffer or Iscove’s Modified Dulbecco’s Medium (IMDM), an immune cell culture medium. Under these conditions, the quartz MEMS exhibited a mass sensitivity of 23.70 ng/Hz. These results allowed me to monitor the interaction of non-infectious CHIKV-like particles (CHIK-VLPs) with a synthetically engineered biorecognition layer. Consequently, I could determine the experimental masses of CHIKV-VLPs using a piezo bioMEMS. Finally, I investigated how the surface topography of MEMS might modulate the immune response of DCs. I found that specific surface nanotopographies promote the patterning of adhesive actin-enriched structures and immune receptors and regulate ERK-mediated signaling in DCs. Hence potentially modulating pathogen recognition. In conclusion, this thesis sets the stage for the development of a new generation of on-chip piezoelectric quartz bioMEMS for selective virus detection. This new technology, with its potential to be more sensitive, low-cost, non-toxic, integrable, and reusable, opens up exciting possibilities for the future of virus detection.