Multilayer encapsulation of cells by a centrifugation device

Cell encapsulation in bio-polymers is a rapidly expanding field in bioproduction, encompassing organoid or spheroid maturation, drug screening, cellular therapies, and bioengineering. This thesis contributes to these applications through the multilayer encapsulation of cells in bio-polymers with a wide viscosity range. The inner layer (core) provides a more favorable environment for the maturation and survival of cells or organoids, while the outer layer ensures mechanical protection (shell) and acts as a filtering barrier against pathogens. Laden with selected biological agents, it allows controlled interaction with the core cells of the capsule.

The objective of this thesis is to develop an innovative ejection nozzle for forming high-frequency multilayer microcapsules using centrifugal force in a laboratory centrifuge. This new thesis builds upon a completed thesis in 2023 that studied, detailed, and developed a predictive model for generating single-layer microcapsules solely through centrifugal force.

The mechanisms of formation and ejection of multilayer capsules are complex, involving the rheological properties of bio-polymers, centrifugal force, surface tension, and interfaces. The design of the ejection nozzle must consider these properties. The first part of this thesis aims to better understand the multilayer formation and ejection mechanisms of microcapsules based on the selected ejection nozzle's geometry. This understanding will enable the prediction and control of formation based on the rheological properties of the bio-polymer(s). The second part involves developing an automated system for aseptic capsule production. Finally, biological validation will confirm the developed technology.

To achieve the study objectives, the candidate must initially conduct an analytical and numerical study, design ejection nozzles, and leverage the laboratory's expertise to manufacture them. Fluidic tests will be performed on models, and the design will be optimized to create and test a microcapsule formation prototype. The candidate should have a background in physics, engineering, and fluid mechanics, with a particular talent for experimental approaches. Prior experience in microfluidics/biology would be advantageous.

Starch-rich microalgae production on wastewater

Microalgae and cyanobacteria have the natural capacity to convert CO2 into a valuable biomass through photosynthesis. These fast-growing microorganisms are capable of producing two main types of storage compounds, lipids and carbohydrates. The main carbohydrate produced by green microalgae is starch, which can reach levels of more than 80% of the microalgae dry weight. It can subsequently be transformed into bioplastic or fermented into bioethanol.
Despite high productivity, starch production costs need to be reduced to make the production of bioplastic or bioethanol economically viable. One of the options is to use effluent as a microalgae culture medium and thus reduce costs for fertilizers.
The objective of this thesis will be to optimize the production of microalgae starch on various effluents. For that, production strategies of starch-rich microalgae will be defined to be compatible with their cultivation on wastewaters.
Candidates with interests in experimental work as well as modelling are welcome to apply. Experience in growing microorganisms and more specifically microalgae will be a valuable asset.

Contribution to the rapid assessment of the potential of photosynthetic microorganisms strains to be cultivated on pilot and industrial scales. Development and qualification of a laboratory device

Photosynthetic microorganisms – microalgae and (cyano)bacteria – represent a biomass of interest for various applications: production of biofuels, bioremediation of liquid and/or gaseous effluents, production of bioplastic, food supplement, human or animal food, cosmetics,… Their ability to capture CO2 also makes them very promising for the circular carbon economy.
To meet the needs of mass markets, it is necessary to select particularly efficient strains of photosynthetic microorganisms among the immense natural diversity (more than 1 million species). The strains thus selected for their better productivity and/or their better capacity to capture CO2 will allow a reduction in production costs favorable to the opening of new applications and new markets.
For practical reasons, strain selection is carried out on a small scale in the laboratory. However, the results obtained are not directly transferable to pilot and industrial scales because the conditions there are very different (strong variations in particular of the weather conditions).
The objective of this PhD project will be to develop short tests reproducing the strong variations in temperature and sunshine encountered in real operating conditions which will make it possible to quickly evaluate in the laboratory the potential of strains of microalgae to be cultivated on pilot and industrial scales.
For this, an experimental tool is being developed on the MicroAlgae and Processes platform at CEA Cadarache. The PhD student will validate this tool and develop the tests on a model microalgae well known to the platform (Chlorella vulgaris NIES 227). The approach will be extended to other strains of microalgae and photosynthetic bacteria, other microorganisms of interest used to carry out the treatment of wastewater and/or the production of molecules of interest (bioplastic, biostimulant, etc.).
The main ambition of this PhD project is to define simple and rapid protocols allowing the selection of industrial strains of microalgae with increased productivity and CO2 capture capacity. It is part of the AlgAdvance project supported by the national research program PEPR B-Best – Biomass, biotechnologies, technologies for green chemistry and renewable energies – developed from 2023 to 2029 as part of the France 2030 investment program.

Development of dense and fluidized granular beds in microfluidic channels for healthcare applications

The major public health problem of sepsis requires breakthrough technologies for ultra-fast diagnosis. Dense, fluidized granular beds are ideal systems for liquid-solid or gas-solid exchange processes. They are widely used in industry thanks to their high surface-to-volume ratio. Over the past decade, microfluidics and lab-on-a-chip have enabled numerous advances, particularly in biological sample preparation. We propose to develop a versatile microfluidic platform that will enable the creation of such dense, fluidized beds. We will first work on the incorporation of membranes into microchannels, drawing on the patented know-how developed in the laboratory. We will then study and characterize the granular beds, and finally test them for the detection of bacteria in biological samples. This work will be carried out in collaboration with our physicists (LEDNA) and biologist (LERI) partners at CEA Saclay.

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