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

PhD : selection by topics

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

Point-of-Care medical device development for high sensitivity multiplexed detection of blood biomarkers for health care management of cardiac patients

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Biologie et Architecture Microfluidiques

01-09-2020

SL-DRT-20-0451

myriam.cubizolles@cea.fr

Health and environment technologies, medical devices (.pdf)

Health systems must adapt to new societal and economic constraints that constitute an important challenge to address for the health of tomorrow. In this context, the development of Point-of-Care (POC) devices to carry out in vitro analyses provide valuable assistance to the decision-making of the practitioner for the diagnosis and/or prognosis of the disease. In this context, we propose a PhD subject to explore a new strategy to quantify blood biomarkers (proteins, peptides). This strategy is an alternative to the ELISA gold standard method, based on immuno-detection coupled to enzymatic amplification. We propose an innovative approach to develop a medical device for the high sensitivity detection of various significant blood biomarkers for cardiac diseases. The employed strategy is based on the use of original reagents (aptamers) allowing an isothermal multiplex biomolecular amplification, fast and highly sensitive, coupled with protocol integration and automation inside dedicated microfluidic cartridges. The developed biomedical device will be tested on clinical samples.

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Development of cellulose-based materials for the conception of biomedical devices by stereolithograpy

Département des Technologies des NanoMatériaux (LITEN)

Laboratoire de Formulation des Matériaux

01-11-2020

SL-DRT-20-0628

sebastien.rolere@cea.fr

Health and environment technologies, medical devices (.pdf)

The development of innovative medical devices mainly relies on the use of high performance multifunctional materials. These materials should display high biocompatibility and controlled degradability, and advantageously specific biological properties, such as muco-adhesion, antimicrobial features, or bioaffinity. Such advanced materials are keys for biomedical research activities. Additive manufacturing technologies are particularly well-suited for the technical specifications of biomedical devices. Notably, StereoLithography Apparatus (SLA) allows the processing of complex geometries from UV-light curing of liquid materials. SLA is currently under consideration to develop biomedical devices from cellulose materials. Cellulose is a biocompatible bio-based polymer, extracted from renewable resources. Cellulose chemical structure possesses many hydroxyl functional groups for potential chemical modification and further biomolecules attachment. The aim of the present project is the design and fabrication, using SLA, of biomedical devices able to present various bio-specific properties, from chemically-modified cellulose materials.

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Integrated Bioelectrodes and Biopolymer-Microneedle Devices for Transdermal Electrochemical Sensing

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2020

SL-DRT-20-0673

isabelle.texier-nogues@cea.fr

Health and environment technologies, medical devices (.pdf)

Electrochemical sensors have attracted considerable interest owing to their tremendous promise for portable and rapid monitoring of personal health. Current devices are limited to single analyte detection (mostly glucose) in biofluids over short times using invasive sample collection. In this PhD, we propose to combine electro-enzymatic sensor technology with less-invasive, painless microneedle (MN)-based sampling for rapid detection of different biomarkers (e.g. glucose and nitrate) in interstitial fluid. The goal is to establish a sensitive and convenient platform for analyte detection for better metabolic profiling of diabetes and cardiovascular disease. This PhD project will explore the use of hydrogel-forming microneedles (e.g. saccharide-based) coupled with single/dual bioelectrode systems for signal transduction. The mechanical, structural and sensor properties will be characterised and optimised. Toxicity and in-vivo assays will be performed on rodents with first device prototypes. The PhD. Work will be carried out at DTBS CEA Grenoble in collaboration with Dr. Gross from Dpt. Of Molecular Chemistry (UGA). The applicant should hold a Master degree in Chemistry, with focus on polymer chemistry, biomaterials, or electrochemistry.

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Fast Transcranial Acoustic Simulations and adaptive imaging for Personalized Dosimetry in Ultrasound Brain Therapy

Département Imagerie Simulation pour le Contrôle (LIST)

Laboratoire Simulation et Modélisation en Acoustique

01-10-2020

SL-DRT-20-0700

sylvain.chatillon@cea.fr

Health and environment technologies, medical devices (.pdf)

The treatment of brain diseases remains very difficult, mainly because of the poor access of pharmacological agents to the brain due to the presence of the blood-brain barrier (BBB). Focusing low intensity ultrasound waves in the brain, combined with circulating microbubbles (ultrasound contrast agents), significantly increases the release of the drug into brain tissue, with an established therapeutic effect in many animal models. This permeabilization of the BBB is non-invasive, local and reversible provided that the intensity of the beam is well controlled through the skull because the implosion of microbubbles could lead to microhemorrhages. The structure and the complex geometry of the skull bone lead to a strong attenuation as well as specific phase shifts of the ultrasonic wave front during its crossing. The features of the focal task are severely impaired and the use of personalized simulation is unavoidable to ensure reproducible, controlled and safe therapy. These aberrations can be corrected by using a phased array ultrasonic probe of large aperture associated with delay laws calculated notably from ultrasonic wave propagation models, using a description of the morphology of the skull obtained by MRI or computed tomography (CT). In addition, the relative instability of the microbubbles makes it necessary to monitor their cavitation activity in order to be able to intervene in real time in the event of an acoustic signature announcing a risk of definitive lesion of the tissues (ultra-harmonic and broadband cavitation). Thus, in the previous NeuroSpin work, the use of a feedback loop based on passive cavitation detectors makes it possible to guarantee the safety of the macaque protocol. To go beyond the simple detection of these signals, it would be desirable to be able to map this activity through the skull using passive imaging with correction of aberration on reception. The objective of this hesis is to adapt and optimize the numerical simulation and imaging tools developed by CEA-LIST for Non Destructuve Testing (NDT) applications in order to: (i) predict and correct the pressure field obtained during a Transcranial Focused Ultrasound Therapy and (ii) significantly improve the quality of passive acoustic cavitation mapping during the procedure. This thesis, carried out in collaboration between the S. Chatillon team at the DRT / LIST and that of B. Larrat at the DRF / JOLIOT / NeuroSpin, will comprise the following three stages: - Validation of the propagation model on samples of human skulls. - Optimization of the trajectory to reach a target point to be treated (inverse problem). - Transcranial imaging of microbubble cavitation activity during the procedure

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Colorimetric detection of organophosphorus based pesticides: From organic synthesis to colorimetric paper detector

Département des Technologies des NanoMatériaux (LITEN)

Laboratoire Synthèse et Intégration des Nanomatériaux

01-09-2020

SL-DRT-20-0714

sebastien.penlou@cea.fr

Health and environment technologies, medical devices (.pdf)

This PhD thesis deals with the design and synthesis of chromogenic dyes and the processing method needed for the development of chromogenic detector of organophosphorus pesticides. A chromogenic dye is a molecule that changes color when it is in the presence of a target molecule. At the CEA Grenoble, the LSIN laboratory has developed an expertise around the colorimetric detection, via the screening of a chemical library of commercial chromogenic dyes. We identified commercial reactive structures. The aim of this thesis is to synthesize more reactive structural analogues with controlled color change. It is proposed to validate the actual color changes on organophosphorus pesticides. Finally, the study of the reactivity of chromogenic dyes versus organophosphorus pesticides (NMR, FTIR, UV-vis-NIR, mass spectrometry, ...) should allow us to better understand their reactivity and propose a reaction mechanism explaining the color changes observed. A prototype of a low-cost organophosphorus pesticide colorimetric detector will be developed at the end of the thesis.

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Antimicrobial functionalization of nanostructures by initiated Chemical Vapor Deposition

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2020

SL-DRT-20-0814

guillaume.nonglaton@cea.fr

Health and environment technologies, medical devices (.pdf)

The production of antimicrobial and antibiofouling surfaces without antibiotics or nanoparticles is still a challenge despite the needs of a growing number of applications, particularly in the hospital field and more specifically for implanted medical devices. The number of patients infected each year with nosocomial diseases is still too high and infections related to implanted medical devices remain an unresolved problem. The limit of current solutions is their very short lifetime and their rapid fouling by biofilm generation. The scientific community increasingly studied bio-inspired coatings made of polymers with antimicrobial, antibiofouling or switchable functions. However, these coatings are still difficult to achieve by green chemistry on structured surfaces using conventional methods. Initiated Chemical Vapor Deposition (iCVD) is a unique technique for producing polymeric surface coatings on micro structured surfaces while retaining the chemical functions of polymers. The aim of this thesis is to study the feasibility of iCVD deposition of bioinspired polymers with a double switchable function antimicrobial and antibiofouling on nanostructures. The candidate will have a profile of material chemist or polymer chemist with a strong affinity for microbiology and health applications with a MSc in material chemistry or polymer chemistry.

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biophysical analysis of exosomes for diagnosis, and precision medicine

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Chimie, Capteurs et Biomatériaux

01-10-2020

SL-DRT-20-0819

vincent.agache@cea.fr

Health and environment technologies, medical devices (.pdf)

Cancer is the second leading cause of mortality in Europe, accounting for ~1.3M deaths in 2015. In this thesis we propose a new scenario for cancer liquid biopsy, based on the biophysical fingerprints of exosomes. Recent studies have shown exosomes to mediate signals for hypoxia driven epithelial-mesenchymal transition and metastasis, suggesting they could be powerful cancer biomarkers directly accessible in bodily fluids. There is increasing evidence of the specific biophysical link between exosomes and the parent cell. This thesis aims at developing and implementing new nanomechanical and microfluidics methods to investigate the biophysical signatures of exosomes from different cell lines, including healthy controls and cancer cells, in a perspective of early-cancer diagnosis, and precision medicine.

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Brillouin microspectroscopy for 3D cell microculture

Département Microtechnologies pour la Biologie et la Santé (LETI)

Laboratoire Systèmes d'Imagerie pour le Vivant

01-10-2019

SL-DRT-20-0835

jean-charles.baritaux@cea.fr

Health and environment technologies, medical devices (.pdf)

3D cell cultures are in-vitro models that are increasingly used for fundamental research, as well as for novel clinical and therapeutic applications. There is evidence that the biomechanical properties of these cellular structures are intricately linked with physiological parameters such as viability, fonctionality and response to treatment for instance. Brillouin Light Scattering Microscopy (µBLS) is an emerging technique in bioimaging for measuring the viscoelastic properties at the micrometer scale. It relies on the analysis of the light inelastically scattered by the phonons propagating in the medium, in the Brillouin scattering process. The goal of this PhD thesis is to develop an innovative µBLS system for the monitoring of 3D microcultures, and go towards the proof of concept that the mechanical properties measured in BLS may be used to infer the physiological parameters of interest. The PhD student will work on a custom state of the art µBLS instrument built in the Laboratory for bioimaging systems (LSIV), at CEA Leti in Grenoble, France, and will experiment with several types of 3D cultures, to demonstrate the capabilities of this new approach. Candidates with a strong background in optics, biophysics, experimental physics, or electrical engineering, and who are keen of biomedical application of technology are encouraged to apply.

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Bio sensir using near field propagation of millimeter waves

Département Architectures Conception et Logiciels Embarqués (LIST-LETI)

Laboratoire Architectures Intégrées Radiofréquences

01-10-2020

SL-DRT-20-0933

frederic.hameau@cea.fr

Health and environment technologies, medical devices (.pdf)

In the context of new bio-medical applications, we propose to use solutions from the radio-frequency domain, namely using millimeter wave systems, which had to radiate with nearfield antenna. Depending on the antenna neighborhood, the behavior of the radiated wave changes with its frequency and amplitude. This PhD aims to detecte physiological parameters using this signature of the environnement at different wavelength, signal amplitude and even signal shape (chirp). This physiological parameter could be the sweat, the hartbeat, melanoma, but not only. Target frequency could be from 20GHz to 120GHz which are easy for CMOS integration. From an existing study, the PhD student will have to developpe an accurate solution, which could be based on the antenna impedance variation due to the environement (Power Amplifier output impedance modification tracking) or the analysis of the reflected signal thought a polar receiver (radar mode).

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