Description du sujet de thèse

This thesis project is part of a highly interdisciplinary project aimed at adapting cutting-edge laser technologies for applications in the field of life electronics and healthcare. For biologists, the complexity of certain organs is a major obstacle to deciphering how they function and better understanding certain pathologies. In this context, the use of simplified in vitro biological models is a promising way of improving our understanding. In the case of electrically active cells (neuronal networks, cardiomyocytes, muscle cells...), these studies require high-resolution recording tools to study and understand their functioning, and the use of multi-site recording devices such as microelectrode arrays (MEAs) are invaluable tools.
Over the last few decades, MEA technology has been constantly improved. Several approaches have been developed, ranging from modification of the electrode surface (carbon nanotubes, Ti3N4, PEDOT), to the development of three-dimensional electrodes (nanowires, "mushrooms") to limit interface impedance and thus improve the sensor's signal-to-noise ratio.
In this context, the emergence of 3D printing techniques, and in particular their recent use in the manufacture of chemical and biological sensors, appears to be a major asset for the further development of MEA technology and for providing new, versatile, low-cost solutions.
Among these technologies, inkjet printing has been widely used and has shown good results, but suffers from several limitations in terms of spatial resolution, deposit reproducibility, nozzle clogging and the impossibility of using high-viscosity bio-inks.
The aim of this thesis will be to take advantage of the laser-assisted deposition technique (LIFT) to manufacture low-cost, highly sensitive multi-electrode arrays (MEAs).
This laser-assisted printing process, which has been developed in our laboratory for over a decade, is an innovative non-contact, nozzle-less technique enabling sub-micrometer resolution. A wide range of viscosities can be used to print a wide range of materials, from metals to polymers, for the creation of electronic devices and even living cells.
Based on this technique, we propose the development of an all-laser manufacturing process to create MEAs with high probe design versatility, very low time consumption and low cost. This manufacturing process will be based on four main steps: (i) LIFT printing of the recording electrodes and conductive lines, (ii) LIFT printing of the passivation layer and (iii) bonding to a printed circuit board by laser metal bonding (LMB).
Initially, the laser printing process will be optimized to enable very high-resolution printing of the various materials making up the chip, then an initial proof-of-concept will be carried out by fabricating a conventional MEA chip using laser printing, which will be tested on cell cultures in vitro. The second stage of this thesis work will involve making the design of the electrodes more complex to improve their recording resolution (3D configurations, surface functionalization, etc.) in an attempt to interface more complex biological models (neuromuscular junctions, organoids, etc.).

Contexte de travail

The Laser Plasma and Photonic Processes Laboratory (LP3-UMR 7341) (www.lp3.fr) is a joint research unit of the CNRS and Aix Marseille University (AMU), headed by Dr Olivier UTEZA. It owns a large number of laser sources and associated equipment. It is a host laboratory for the European Laserlab program (www.laserlab-europe.eu). Its area of expertise is the physics of laser/matter interaction in short and ultra-short regimes (ns to fs) and the development of new laser processes. LP3 has extensive expertise in laser surface structuring for a wide range of applications. It is also one of the world leaders in laser-induced printing, and more specifically in the LIFT technique that will be used during this PhD project. The PhD student will be working with several researchers and teacher-researchers from the laboratory: David GROJO and Adrien Casanova, who will be respectively Director and Co-Director of the thesis, as well as Anne-Patricia Alloncle for LIFT aspects and Ahmed Al-Kattan for functionalization aspects.

Contraintes et risques

The PhD student will be required to handle nanoparticle-based inks and group 1 biological material that is not pathogenic for humans.
During handling, safety rules will be applied (wearing protective gloves and goggles, disposal of waste in specific bins....).