Description du sujet de thèse

Research on the size of living cells is a rapidly growing field in biophysics. In recent years many approaches have emerged to quantify the mass of individual cells in suspension or adherent [1]. These approaches are usually based on microfabricated resonators (MEMS) or optical methods. Among these methods, piezoelectric mechanical sensors have unique advantages: i) direct measurement of crystal deformation by electrical methods and ii) no interference with biomolecules, compared to optical systems. In this regard, α-quartz is the best piezoelectric sensing material with a considerable quality factor (Q > 106), exceptional temperature stability, and shallow phase noise. However, to date, α-quartz applied to microelectronics is exclusively synthesized by hydrothermal methods, which produce large crystals, making it impossible to reduce their size below a thickness of 10 µm. Moreover, for most applications, these crystals must be bonded to Si substrates. These characteristics represent a critical obstacle for microelectronics.
Therefore, the current challenge for designing ultrasensitive biosensors requires improving the electromechanical response under liquid conditions and respecting the thickness criteria. This goal could be achieved using high-quality α-quartz piezoelectric resonators [2]. In the last few years, our team has successfully integrated high-quality piezoelectric α-quartz thin films on silicon [3,4] and SOI substrates by chemical solution deposition (CSD) [5,6]. These advances have led to the first quartz-based epitaxial sensor for micro and nanoelectromechanical devices (MEMS/NEMS) with a mass detection sensitivity of 100 ng/Hz [7,8]. These results mean ultrasensitive quartz devices can measure tiny masses (<10 pg) or forces via resonant frequency variation. Furthermore, we have recently shown that these devices are biocompatible and thus suitable for cell culture conditions [7].
The objective of the thesis project is to go beyond the state of the art by performing the first mass measurements with a new generation of microelectromechanical systems (MEMS) on chip based on α-quartz technology. Using this technological approach, the project aims to provide a better understanding of biological processes like endocytosis, which are known to regulate the cell mass response under physiological conditions.
References
[1] T. A. Zangle, M. A. Teitell, Nat Methods 2014, 11, 1221.
[2] C. J. Brinker, P. G. Clem, Science 2013, 340, 818.
[3] A. Carretero-Genevrier, M. Gich, L. Picas, et al., Science 2013, 340, 827.
[4] Process for Preparing an Epitaxial Alpha-Quartz Layer on a Solid Support, Material Obtained and Uses Thereof C Boissiere, A Carretero-Genevrier, M Gich, D Grosso, C Sanchez US Patent US10053795B2, n.d.
[5] Q. Zhang, et al., ACS Applied Materials & Interfaces 2020, 12, 4732.
[6] T. Sansen, et al., ACS Appl. Mater. Interfaces 2020, 12, 29000.
[7] C. Jolly, et al., Advanced Materials Technologies 2021, 6, 2000831.
[8] C. Jolly, et al., JoVE 2020, e61766.

The objective of this project is to monitor the mass response of single cells with sub-picogram resolution across several timescales and determine the role of endocytic mechanisms in cell mass regulation in physiology. To this end, the aim of the project is to develop the first on-chip quartz piezo bioMEMS capable of measuring tiny masses through a variation in the resonant frequency without damping phenomena.

Contexte de travail

The PhD project is highly interdisciplinary, at the interface of nanotechnologies, material sciences cell biology and biophysics. For this reason, it will be performed in co-supervision between two teams located in Montpellier, the laboratory of A. Carretero-Genevrier (at IES CNRS UMR 5214; https://nanochemlab.com), with expertise in nanotechnologies and materials sciences, and L. Picas (IRIM CNRS UMR 9004; https://www.irim.cnrs.fr/index.php/recherche/equipes/biologie-quantitative-du-trafic-membranaire-et-pathogenesis), with expertise in cell biology and biophysics.
The first part of the project will be performed at IES (CNRS UMR 5214) and will focus on the fabrication and characterization of piezoelectric bio-MEMS resonators. The piezoelectric MEMS will be made of (100)α-quartz/(100)Silicon membranes with a thickness of 5 µm and different resonance frequencies depending on their size.
The second part will be realized between IES (CNRS UMR 5214) and IRIM (CNRS UMR 9004). This part will include the development of a microfluidic chip to maintain single cells in culture conditions on the bio-MEMS device and to perform proof of concept measurements to see the mass of individual adherent cells.

Contraintes et risques

This position is located in a sector covered by the protection of scientific and technical potential (PPST) and therefore requires, in accordance with the regulations, that your arrival be authorized by the competent authority of the Ministry of Higher Education and Research (MESR)