Quartz BioNEMS for arbovirus detection

"Arthropod-borne viruses (Arboviruses), such as Chikungunya, Dengue, Zika, and West Nile viruses, are a rising global health threat, with over 3.9 billion people at risk, especially in tropical and subtropical regions. Recent cases in Europe, including France, emphasize the growing risk of local transmission and highlight the urgent need for better surveillance and diagnostics. Today, the gold standards for detecting infections are RT-PCR or ELISA, but these methods require sophisticated equipment and skilled operators, making them virtually impossible to deploy in the field and reach regions with limited resources. In this context, Point-of-care (PoC) testing devices offer a strategy to provide rapid, sensitive, and field-deployable diagnostic solutions with minimal user training. Yet, most existing commercial PoC solutions are based on low-sensitivity approaches. Hence, the integration of piezoelectric materials such as α-quartz in MEMS/NEMS (piezo-MEMS/NEMS) for PoC diagnostics offers significant advantages in terms of sensitivity, miniaturization, energy efficiency, and versatility. Yet, a major challenge in the sector lies in combining high-performance and ultra-sensitive MEMS/NEMS devices with a selective and multiplexed recognition layer capable of detecting a biomarker of interest, such as different arboviruses. The objective of the ArboSENSOR project is to achieve this technological milestone by developing the first α-quartz piezoelectric BioNEMS resonators operating at a super-high frequency, capable of selectively detecting human health-threatening arboviruses in complex samples with high sensitivity, thereby surpassing ELISA and approaching the sensitivity of PCR tests. The specific objectives of the project are: 1) the fabrication and scale-up of the BioNEMS device for pan-arbovirus detection; 2) perform an experimental demonstration of the device in vitro and 3) an experimental demonstration of the device in complex samples. To achieve the above objectives, the ArboSENSOR project capitalizes on a unique, multidisciplinary consortium, bringing together experts in microelectronics, nanotechnology, molecular and cellular virology, entomology, animal models, clinical virology, immunology, and protein engineering. To this end, we have developed a 36-months scientific project organized into three work packages: from the conception of the quartz resonator and its functionalization with an innovative recognition layer based on the SpyTag/SpyCatcher complex coupled with novel customized antibodies and integration into a microfluidic chip, to its experimental demonstration to detect the above arboviruses in vitro and different samples from mouse and infected patients. The results of the ArboSENSOR project should deliver a disruptive technology by combining the high performance of α-quartz piezoelectric NEMS in terms of sensitivity and miniaturization with the enhanced specificity of detection offered by an innovative antibody-based recognition layer. These features, combined with the use of low-cost and scalable lithographic techniques for device manufacturing, should position the consortium to create a compact, precise, rapid, sensitive, and cost-effective device for arbovirus detection. By the end of the project, we expect an experimental demonstration of the BioNEMS to reach at least TRL 3 and establish a technological transfer with a local start-up in the microelectronics sector. The potential impact of this project is significant, as it could revolutionize the field of arbovirus detection, leading to more effective and rapid diagnostic methods while offering a versatile technology that can be tailored in the event of an emerging threat."