Microfluidic biocatalysis

The overall objective of the project is to propose a new mode of biocatalytic production based on continuous flow and combining macro and micro-fluidics. The aim is to develop a biocatalysis process involving fluidic bioreactors capable of ensuring continuous biotransformation, thanks to immobilized enzymes or whole cell catalysts. This process will be optimized to improve the efficiency of enzymatic reactions on the one hand and to obtain important production capacities on the other hand. Two types of enzymes will be studied, nitrilases and ketoreductases.
First, the candidate will be responsible for the search for robust enzymes for the target reactions and screening on the defined substrates. He or she will be responsible for the development of reaction conditions in isolated enzymes and whole cells and the determination of apparent kinetics. Then, he/she will be in charge of setting up the biocatalysis operating conditions and the immobilization of the biocatalyst in versatile continuous reactors.
This subject is carried out between two departments of the CEA (Direction of Fundamental Research/IBFJ/Genoscope in Evry and Direction of Technological Research/Leti in Grenoble).
The candidate will work in pair with a PhD student on the design of the biocatalytic reactor and the scaling up of the biocatalytic process.

Measurement of active cell nematics by lensless microscopy

At CEA-Leti we have validated a video-lens-free microscopy platform by performing thousands of hours of real-time imaging observing varied cell types and culture conditions (e.g.: primary cells, human stem cells, fibroblasts, endothelial cells, epithelial cells, 2D/3D cell culture, etc.). And we have developed different algorithms to study major cell functions, i.e. cell adhesion and spreading, cell division, cell division orientation, and cell death.
The research project of the post-doc is to extend the analysis of the datasets produced by lens-free video microscopy. The post-doc will assist our partner in conducting the experimentations and will develop the necessary algorithms to reconstruct the images of the cell culture in different conditions. In particular, we will challenge the holographic reconstruction algorithms with the possibility to quantify the optical path difference (i.e. the refractive index multiplied by the thickness). Existing algorithms allow to quantify isolated cells. They will be further developed and assessed to quantify the formation of cell stacking in all three dimensions. These algorithms will have no Z-sectioning ability as e.g. confocal microscopy, only the optical path thickness will be measured.
We are looking people who have completed a PhD in image processing and/or deep learning with skills in the field of microscopy applied to biology.

Development of a cell analysis algorithm for phase microscopy imaging

At CEA-Leti we have validated a video-lens-free microscopy platform by performing thousands of hours of real-time imaging observing varied cell types and culture conditions (e.g.: primary cells, human stem cells, fibroblasts, endothelial cells, epithelial cells, 2D/3D cell culture, etc.). And we have developed different algorithms to study major cell functions, i.e. cell adhesion and spreading, cell division, cell division orientation, and cell death.
The research project is to extend the analysis of the datasets produced by lens-free video microscopy. The objective is to study a real-time cell tracking algorithm to follow every single cell and to plot different cell fate events as a function of time. To this aim, researches will be carried on segmentation and tracking algorithms that should outperform today’s state-of-the-art methodology in the field. In particular, the algorithms should yield good performances in terms of biological measures and practical usability. This will allow us to outperform today’s state-of-the-art methodology which are optimized for the intrinsic performances of the cell tracking and cell segmentation algorithms but fails at extracting important biological features (cell cycle duration, cell lineages, etc.). To this aim the recruited person should be able to develop a method that either take prior information into account using learning strategies (single vector machine, deep learning, etc.) or analyze cells in a global spatiotemporal video. We are looking people who have completed a PhD in image processing, with skills in the field of microscopy applied to biology.

Development of a bimodal Brillouin-Raman microscope for biological tissue characterization

The Laboratory of Physics of Cytoskeleton and Morphogenesis (LPCV) at CEA Grenoble has an opening for setting up and characterizing a novel bioimaging modality combining Brillouin and Raman Spectroscopy. This is an interdisciplinary project between LPCV and the Laboratory of Imaging and Acquisition Systems (LISA) of CEA Grenoble. Brillouin microscopy allows non-invasive measurements of the visco-elastic properties of cells and tissue on the micrometer scale, while Raman microscopy gives complementary biochemical information. Such measurements have applications in the study of cytoskeleton organization, and for novel diagnostic tools based on following early mechanical and biochemical tissue alterations.
The postdoctoral scholar will be responsible for developing and coupling a Brillouin spectrometer to the Raman micro-spectrometer of LISA. This includes optical system development, instrument control and numerical data processing. He/She will characterize the instrument on model systems prepared at LPCV, and move forward to first in-cellulo experiments. The successful candidate is expected to coordinate the interaction between LPCV and LISA.

Microfluidic cell encapsulation

The Laboratory of Biology and Microfluidic Architecture is looking for a candidate to establish a new class of microfluidic devices for cell encapsulation using robust, industry-compatible materials. The laboratory is located in the Microtechnologies for Biology and Healthcare Division of LETI, focused on the development of micro and nanotechnologies for applications in the fields of medical imaging, security, in-vitro diagnostic, nanomedicine, medical devices and environment monitoring. LETI is a research institution focused on creating value and innovation through technology transfer to its industrial partners. It specializes in nanotechnologies and their applications, from wireless devices and systems, to biology, healthcare and photonics.

Immunotargeting of based-organic nanoparticles for clinical applications

The project aims to tailor-make based-organic nanocarrier enabling to target antibodies to increase the efficacy of therapy (more particularly mantle cell lymphoma) for clinical applications. Our group has developed a unique delivery system based on lipid nanoparticles for imaging and therapeutic purposes since the last 6 years. Based on this technology, the candidate will:
- optimize the targeting of specific ligands into organic nanoparticles (bioconjugate chemistry)
- optimize the encapsulation of drugs in the immunotargeted nanoparticles
- assess the physico-chemical characterization of all nanoparticles
- evaluate the binding affinity of doped and targeted nanoparticles

Lensfree Cytometry for High-troughput biological analysis

The new lensfree imaging is against the foot of the recent developments in microscopy that focuses today on super-resolution achievements. Instead lensfree imaging offers several advantages: field of view (FOV) can cover several cm2, resolution in the range of 0.5µm to 3µm, mostly compact sizes and ease of use. The technique is based on holography online as invented by Gabor [1]. A biological object is illuminated by a coherent light, micrometric structures of the object diffract and the light interferes with the incident wave. The amplitude of the interference is recorded by a CMOS sensor and the image is reconstructed thanks to inverse-problem approaches. Albeit the method exists since 1970, the recent development of large field, small pixel size digital sensors helped realize the full potential of this method only since 2010.
At CEA-LETI Health Division, a new microscopic platform based on this principle has been developed. Its applicability for performing high-throughput monitoring of major cell functions such as cell-substrate adhesion, cell spreading, cell division, cell division orientation, cell migration, cell differentiation, and cell death have been demonstrated [2,3]. The new project proposed in this PostDoc is dealing with the development of an innovative lensfree cytometry setup aiming at high-throughput analysis of biological samples, e.g. cell counting, cell sorting, etc. The post-doctoral fellow will develop the instrumentation and methods and will conduct the experimentation and analysis of true biological samples.

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