Scientific direction Development of key enabling technologies
Transfer of knowledge to industry

PhD : selection by topics

Technological challenges >> Health and environment technologies, medical devices
13 proposition(s).

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Wearable dynamic fluidic chamber dedicated to transcutaneous monitoring of oxygen and carbon dioxide blood concentration

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Systèmes Pour la Personne

SL-DRT-21-0415

rodrigue.rousier@cea.fr

Health and environment technologies, medical devices (.pdf)

The development of wearable medical devices is a fundamental and essential in order to promote ambulatory medicine. So-called "conventional" as opposed to outpatient medicine commonly uses blood gas analysis to assess the efficiency of pulmonary exchanges and diagnose respiratory diseases. In particular, it detects an abnormal change in the oxygen and carbon dioxide concentrations in arterial blood going to the tissues. Since this analysis requires a blood test, it is therefore an invasive method and does not allow monitoring of concentrations in real time. An alternative to taking blood is a transcutaneous gas analysis, i.e. measuring the concentrations of gases that diffuse through the skin. This method is non-invasive and guarantees continuous monitoring of blood gases. The objective of this thesis is to study and develop an instrumented wearable dynamic fluidic chamber. This chamber will measure in real time the concentrations of oxygen and carbon dioxide which diffuse through the skin. The work will consist in modeling the gas exchanges between the skin and the fluidic chamber, then designing and instrumenting the chamber and finally testing it on a gas test bench. This subject requires a highly motivated person with skills in simulation, medical device design and instrumentation.

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Elastic wave sensors for field biological detection

Département Composants Silicium (LETI)

Laboratoire Composants Radiofréquences

01-09-2021

SL-DRT-21-0437

alexandre.reinhardt@cea.fr

Health and environment technologies, medical devices (.pdf)

Monitoring of the sanitary quality of water becomes increasingly a public health issue. In this context, CEA-LETI is developping sensors to detect bacteria in liquid samples. Among the technologies under investigation, electromechanical elastic wave sensors appear as particularly promissing. The aim of this PhD is to evaluate the use of such components, initially developped for radiofrequency signal processing, to biological detection in liquid samples. More precisely, the PhD subject proposed aims in a first stage at analysing the biological structures we want to detect, their possible interactions with a sensors and the associated detection mechanisms which could be exploited. This will allow the design of suitable sensors, by selecting the type of resonator, the vibration mode leading to the highest sensitivity and compatible with operation in liquids, and a scheme for the electronic readout of the sensor output. The candidate will then fabricate prototypes in the CEA-LETI clean rooms and will functionalize them and evaluate their performance in the laboratory. Ultimately, the sensors will be adapted so that they can be integrated in a multi-sensors detection platform developped in parallel by the CEA-LETI teams.

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Development of biofunctionalized photonic circuits for the analysis of volatile organic compounds at very low concentrations for environmental and medical applications

Département d'Optronique (LETI)

Laboratoire des Capteurs Optiques

01-10-2021

SL-DRT-21-0473

loic.laplatine@cea.fr

Health and environment technologies, medical devices (.pdf)

The identification and quantification of volatile organic compounds (VOCs) in the air is a crucial issue in many fields. The analysis of outdoor air makes it possible, for example, to monitor and control pollution linked to industry or motorway traffic. Likewise, the analysis of exhaled air allows the diagnosis of certain pathologies. This requires the ability to measure dozens of different VOCs at very low concentrations (ppb) in complex gas matrices. CEA Grenoble recently developed sensors using integrated silicon photonic circuits chemically functionalized by biomolecules capable of specifically capturing certain VOCs, similar to human olfaction. They are currently used for measuring odors. These biomimetic photonic sensors offer great potential in terms of miniaturization, improvement in sensitivity, multiplexing for the measurement of complex mixtures, and can be manufactured at low cost by methods derived from microelectronics. In particular, they make it possible to consider gas analyzes in situ and in real time. The thesis is positioned at the frontier of electronic noses and analytical systems and will aim at the design and instrumentation of an experimental device to improve the detection limit and identification. The thesis will be highly multidisciplinary and will include the design and characterization of integrated photonic circuits on wafers and chips, the design and characterization of microfluidic circuits, surface chemistry and biofunctionalization, as well as data analysis (classification, modeling, learning, etc?). We will explore certain applications at the end of the thesis, in particular on the analysis of exhaled air and the detection of atmospheric pollutants.

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On-Chip moniToring of Organoids using an oPtoflUidiC systEm

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2021

SL-DRT-21-0534

charlotte.parent@cea.fr

Health and environment technologies, medical devices (.pdf)

The thesis is positioned in the domain of organoids, which enable fundamental tissue mechanisms to be studied in-vitro. The project aims at developing a new microfluidic system with integrated simple, robust and compact optical reading, and allowing for in-situ monitoring of the secretome evolution during the cell culture. The chosen model system is the culture of islets of Langerhans responsible for the endocrine function of the pancreas and playing an important role in diabetes. To reach our objective, we propose to combine two approaches within a microfluidic chip: a chip with photonic-crystal sensors that are compatible with lens-less optical reading (LED + CMOS), and a microfluidics technology integrating the pneumatic actuation of an elastic membrane. The main challenges of the project are related to the sensors sensitivity, the optical chip integration in the microfluidic system and the sampling of aliquots without perturbation of the organoid. The thesis will be in collaboration between two complementary laboratory, CEA-LETI (microfluidics, technology), and INL (photonic biosensors).

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Concentration and capture of pathogens under homogeneous conditions in a microsystem

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2021

SL-DRT-21-0558

jean-maxime.roux@cea.fr

Health and environment technologies, medical devices (.pdf)

The search for pathogens (toxins, viruses, bacteria, fungal spores), whether by immunological or biomolecular tests, is often limited by the preparation of samples. These are often too diluted and require a concentration step to detect quickly a contamination with a low level of pathogens. They can also contain interferents that may falsify the test results by leading to false positives or false negatives. These interferents must be neutralized or eliminated by washing, at the risk of diluting the samples; a concentration step is then necessary again. Innovations are required in the field to develop devices that may contribute to fast field diagnostic for non experts users. The proposed thesis subject is part of a study of uncommon flows within a microfluidic channel to improve the capture and concentration of pathogens, microorganisms and allergens and toxins. The process which will be studied aims on the one hand to circumvent the problems of clogging presented by filters and so-called pillar chips. It also aims to speed up biological analysis tests in a compact and autonomous system.

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Secure information sharing for material and product passports in support of the circular economy

Département Systèmes et Circuits Intégrés Numériques

Laboratoire Intelligence Intégrée Multi-capteurs

01-10-2021

SL-DRT-21-0622

carolynn.bernier@cea.fr

Health and environment technologies, medical devices (.pdf)

The circular economy requires a continual reallocation of materials and components in usage loops including the phases of material extraction, production of components and finished products, reuse, refurbishment, upcyling, repair, maintenance and recycling. In addition, the political context tends towards an enlarged producer responsibility associated to an increased need to guarantee the origins of materials (e.g. conflict-free metals). The digital passport of a material or a product contains information on it constituents and their origins, but also potentially also information necessary for the environmental impact assessment surrounding its fabrication, use and transformation. However a great deal of this data is sensitive and sharing it between different actors poses obvious confidentiality issues. Many solutions for secure data sharing exist (International Data Spaces, blockchain, privacy by design, encryption, data minimization, Fully Homomorphic Encryption) and the purpose of this thesis is first to analyze the specific needs of the digital passport and then to model the coupling of different possible solutions while taking into account the environmental impact of the different solutions. Please send your application to oana.stan@cea.fr and sara.tucci@cea.fr

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Innovative hydrogels for ?minibrain-on-chip ? development to study Alzeimer's disease

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2021

SL-DRT-21-0633

isabelle.texier-nogues@cea.fr

Health and environment technologies, medical devices (.pdf)

Organ-on-chip approaches tackle the limitations of two-dimensional (2D) classic cellular cultures and animal models of neurodegenerative diseases. DRF/JACOB/SEPIA has developed ?mini brains?, i.e. 3D cerebral organoids generated from iPSCs (induced pluripotent stem cells), presently cultivated using Matrigel, a commercial matrix derived from mouse tumor. The objective of the PhD thesis will be to investigate new 3D culture scaffolds, based on hyaluronic acid (HA) hydrogels presenting tunable stiffness and electrical conductivity, developed at DRT/LETI/DTBS. The cell-loaded hydrogels will additionally be formulated as bioinks for advanced printing technologies (extrusion combined with UV/visible photo-crosslinking). The expected outcome of the PhD is an improved ?mini brain? model to study the development of neurodegenerative diseases, which could be applied to therapeutic strategies.

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Multimodal characterization of therapeutic phages

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2021

SL-DRT-21-0634

pierre.marcoux@cea.fr

Health and environment technologies, medical devices (.pdf)

The rapid inexorable spread of antibiotic resistance is one of the critical challenges in health care for the coming decade. Patients increasingly encounter dead-ends, with no effective molecule. The quest for alternatives to antibiotic therapy is a major public health issue and should, according to the WHO, be given priority status. Phage therapy uses viruses known as bacteriophages, or ?phages? for short, that specifically infect and destroy bacteria without impact on human cells. They have been used for decades in some countries in Eastern Europe, but preparations from these countries cannot be imported in France or Western European countries as they fail to meet standard drug agency criteria (ANSM, EMEA). Some new techniques have to be developed and optimized for a better and faster characterization of these therapeutic viruses, during their amplification and purification, as well as during their storage or juste before dispensing medication. The study deals with innovative approaches based on microelectronics and nanotechnologies for rapid in-vitro quantification and characterization of therapeutic phages to facilitate selection of phages and QCs of phage therapeutic products: (i) a lensless imaging technique for fast phage titration based on the monitoring of lysis plaques (from 20-µm- to millimeter-size) over a wide field-of-view (up to at least 864 mm2), suited to continuous detection of phage plaque growth, (ii) a microsystem called SNR (Suspended Nanochannel Resonator) for phage purity assessment without culture/replication requirement based on rapid mass measurement of individual virions.

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Microfluidic bioreactor for in-situ analysis of extracellular vesicles secreted by organoids

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2021

SL-DRT-21-0654

vincent.agache@cea.fr

Health and environment technologies, medical devices (.pdf)

Extracellular vesicles (EVs) are widely recognized as vectors of biological material capable of transferring genetic/molecular content between cells and of contributing to intercellular communication mechanisms leading, for example, to the proliferation of tumors in cancer. However, most of the studies implemented today are conducted on cell populations with intrinsic heterogeneities that introduce bias into the analyzes. In addition, the sources of EVs are generally derived from two-dimensional cell culture poorly representative of the microenvironment of the in vivo extracellular matrix in tissues or organs. Conversely, organoids derived from patients have already been shown to accurately recapitulate many disease traits of patients, including genetic heterogeneity and response to treatment. In this thesis, we propose the development of a system enabling the isolation of one or more organoids in a microfluidic bioreactor, combined with means of collection, concentration, and nanomechanical sensors to allow the in-situ analysis of the secretion rate of EVs and collect their biophysical signature, with the perspective of new therapeutic approaches based on monitoring the kinetics of EV secretion on organoids derived from patients.

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Fast detection of AMR bacteria in water through mid-IR imaging and isotope probing

Département d'Optronique (LETI)

Laboratoire des Capteurs Optiques

01-10-2021

SL-DRT-21-0678

mathieu.dupoy@cea.fr

Health and environment technologies, medical devices (.pdf)

Currently the challenge is to develop automatic and non-invasive measurements to enhance early identification or diagnosis. The optical technologies are the label free methods to detect and identify the chemical composition of the sample. Infrared spectroscopy is a widespread and reliable method to obtain a spectral fingerprint of the sample based on absorption of Mid-IR light. An optical platform has been developed to measure the absorption of light through the sample, combining quantum cascade laser (QCL) and bolometer matrix. The objective of the thesis is to explore the potential of Mid-IR imaging and isotope probing to assess the bacteria antimicrobial resistance. The thesis will aim to create the biological protocol mixing the isotope probe and the constraints of infrared radiation, to carry out the images on several bacteria species, to implement the data processing algorithms in order to evaluate the relevance of this approach.

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Additive manufacturing of biocompatible and bioresorbable microfluidic scaffolds for the development of implantable organ-on-chip (OoC) systems

Département des Technologies des NanoMatériaux (LITEN)

Laboratoire de Formulation des Matériaux

01-10-2021

SL-DRT-21-0728

sebastien.rolere@cea.fr

Health and environment technologies, medical devices (.pdf)

The technical and biological benefits of several additive manufacturing (AM) processes, for the elaboration and production of microfluidic scaffolds used in the development of implantable organ-on-chip, will be investigated during this PhD project. AM technics should lead to the development of new complex 3D microphysiological systems, more representative of the in vivo environment. Furthermore, the PhD student will also focus on the development of new transparent biocompatible and bioresorbable polymer materials compatible with the selected AM technics, for the substitution of currently used polydimethylsiloxane (PDMS). Finally, the model microfluidic chips, based on the components developed in DRF and DRT labs, will be included in biological assessment campaigns.

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Eco-Innovation methodogy

Département des Technologies des NanoMatériaux (LITEN)

Laboratoire Micro-Sources d'Energie

01-10-2021

SL-DRT-21-0729

elise.monnier@cea.fr

Health and environment technologies, medical devices (.pdf)

With Grean Deal and Circular Economy Action plan, European and French strategies need innovation methodologies drastically different from actual practices. Research mindset is expected to change from pure technological breakthrough to final purpose, sustainable impact for the economy, the environment and the society. In other words, form Innovation to Eco-Innovation. This paradigm shift is a new challenge that CEA must take up for competitiveness reasons for industrial partnerships, success to institutional programs and young talents attractively. The objective of this thesis is to define the Eco-Innovation methodology that will suit the best CEA?s research and development activities. She'll need to be easily shared, understandable and practiced by CEA's researchers. This research will be conducted with academic specialists of eco-design, societal aspects and with internal CEA's entities for innovation, eco-design and economy aspects. This thesis falls within a PTC Materiaux project called M.U.E. (for Unified Methology of Eco-Innovation).

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development and characterization of conformable piezoelectric materials for medical application

Département des Technologies des NanoMatériaux (LITEN)

Laboratoire Composants Organiques

01-10-2021

SL-DRT-21-0767

mohammed.benwadih@cea.fr

Health and environment technologies, medical devices (.pdf)

Recent advances in materials, manufacturing, biotechnology, and systems have favored many sensors and actuators based on flexible, biocompatible piezoelectric materials in medical fields.In this internship, the principles, the future opportunities and challenges in the development and characterization of conformable piezoelectric materials for medical use will be examined. An expandable piezoelectric sensor / actuator, made on a stretchable substrate, will be developed with materials (composites / polymers) deposited by printing methods. These developments will make it possible to study the feasibility of using such piezoelectric components in the field of medicine. The PhD student, with the teams in place, will develop a piezoelectric component on a stretchable substrate, via (i) the use of an intrinsically stretchable piezoelectric polymer or via (ii) the implementation of composite materials (inorganic piezoelectric particles in a matrix polymer). The intern will also have electrical characterization work to be carried out on these components. This internship will take place as part of a collaboration between the LGEF laboratory of INSA LYON for piezoelectric characterizations and CEA_Liten for material choice / process development aspects and material characterization.

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