The IPGG funds scientific projects where nano- and micro-fluidics play a central role in the research teams. During the 1st phase of the IPGG Labex from 2012 to 2017, 6 calls for projects were launched. They allowed 40 doctoral and postdoctoral grants to be awarded.
The 2nd phase of the Labex IPGG was launched in 2020 thanks to the renewal of the Labex in 2019. Since 2020, 17 projects have been funded.
A recent clinical study has demonstrated a statistically significant clinical interest for a new generation targeted therapies, pertuzumab for breast cancer patients presenting an amplification of the HER2 gene. This therapy specifically targets the interaction between HER2 and HER3 proteins. However, so far no clinical biomarker could be found, that could be able to predict responding versus non-responding patients. Quantifying the number of HER2-HER3 dimers seems a natural biomarker, but unfortunately so far no technique able to do that was available. The MMBM group, in collaboration with University of Uppsala, has developed a microfluidic approach able to enumerate protein dimers at the single protein level, in single cells. This method is based on Proximity Ligation Assay (PLA) invented by the Uppsala group. The aim of this project is to apply this new microfluidic method to the quantification of HER2-HER3 first on cell lines, then on samples from breast cancer patients, and correlate the results with the efficiency of the pertuzumab drug. If positive, this will set the first biomarker able to anticipate which patient may benefit from the drug and which may not, and thus select the right treatment
In this proposal 4 groups of IPGG will collaborate to develop a simple and versatile interface to efficiently couple droplet‐based microfluidic and mass spectrometry. The proposed interface will allow the extraction of aqueous droplets from monodisperse stabilized emulsion. The extraction will be obtained through electrocoalescence and hydrophilic treatment of the aqueous stream channel. In order to minimize Taylor‐Aris dispersion the extraction will take place at a minimal distance of the electrospray nozzle. A preconcentration/desalting step using magnetic tweezers will be implemented upstream in order to remove non‐volatile contaminants and to fractionate the sample.
The unique analytical power of MS would allow the screening of microorganisms 1) producing enzymes that degrade natural feedstocks, or 2) producing molecules of industrial or therapeutic interest (e.g. natural products). In addition, the ability to analyse the proteomes (or sub‐fractions of the proteome, such as the secretome) of millions of cells, each at the single cell level would be a transformational tool for life science research and drug discovery.
Darwinian processes, involving iterative rounds of mutation and selection, can be used for the rapid directed evolution of proteins in the laboratory. Directed evolution is a powerful tool to study evolution at a molecular level, to unveil fundamental aspects of protein function, and to optimize enzymes for industrial applications. However the poor current understanding of the relationship between protein sequence and function precludes the rational design of evolution trajectories, and therefore directed protein evolution proceeds often blindly towards a defined goal, resulting in frequent trapping in deadend trajectories or on local optima. Furthermore, cost and time limitations mean that typically only 103 to 105 variants can be screened per round using conventional microtitre-plate based screening systems. We propose to overcome both of these limitations by coupling the evolution of proteins using droplet based microfluidics to next generation sequencing via the barcoding of genes encoding proteins according to their phenotype. This microfluidic approach will allow cost effective, quantitative screening of large repertoires of mutants (≥106) using minimal quantities of reagents (~150 μL) and generate high resolution mapping of protein sequence versus function. This mapping will then allow navigation along well-defined trajectories and to perform much more controlled directed evolution, opening up new enzyme optimization strategies.
L’objectif du projet est de concevoir un microréacteur plasma dédié à la synthèse chimique. La réaction chimique choisie concerne la synthèse de polymères biodégradables qui représente un enjeu important. Le dispositif est novateur puisqu’il propose de déclencher une décharge électrique dans une goutte de liquide qui contient le catalyseur en solution et la molécule à polymériser. Le dispositif permettra d’apporter des éléments essentiels sur les cinétiques de polymérisation catalytiques, et ouvrira également des perspectives importantes qui pourront être utilisées au futur pour des applications environnementales en phase gaz (valorisation du CO2, traitement COV) ou liquides (traitement de polluant en phase aqueuse).
Le projet sera mené par une équipe pluridisciplinaire composée d’experts en Génie des Procédés plasmas (M. Tatoulian/S. Ognier/S. Cavadias/C. Guyon), en microfluidique (P. Tabeling, F. Monti) et en Chimie moléculaire (C. Thomas, E. Brulé). Par ailleurs, une collaboration déjà en place, entre le LGPPTS et le groupe Micro Nano Bio et Microsystèmes de l’Institut d’Electronique Fondamental, garantira un accès privilégié à la Centrale de Technologie Universitaire qui dispose de nombreux équipements impliqués dans la réalisation et la caractérisation de micro et nanosystèmes.
The objective is to develop “chemical microscopy” in microfluidic systems. It is based on the label-free in situ and real time optical monitoring of chemical transformation of a surface and consists of coupling optical imagery detection to electro- or bio-chemical activation of a surface. The principle and methodology have wide application ranges.
Such label-free detection in microfluidic heterogeneous assays will be developed allowing for :
i) the detection of biomolecular recognition owing to the design of new, fast and cheap label-free point-of-care diagnosis platforms and
ii) the detection of single chemical events illustrated in the optical tracking of the individual catalytic reactivity of single nanoparticles.
The adaptive immune response, which allows organisms to develop immunity against a priori unknown pathogens, relies on a multimodal system aimed at detecting, delivering and analyzing information from peripheral tissues to trigger a response specific for the pathogen. Detection is performed by dendritic cells, which patrol peripheral tissues and engulf large amounts of material. This material is then processed and presented at their cell surface. Upon exogeneous or endogeneous triggers called ‘danger signals’, dendritic cells migrate towards lymph vessels and reach draining lymph nodes where they activate T lymphocytes, an essential step for the onset of the specific immune responses. Because it is very difficult to follow single dendritic cells and T lymphocytes through their journey inside the body, the adaptive immune response is often studied at steady state, on large populations of cells extracted at various points from different organs.
A multidisciplinary team of experts in acoustics (M. Tanter, O.Couture), microfluidics (P. Tabeling, F. Monti), and organic chemistry (J. Cossy, S. Arseniyadis), pool their efforts to invent a method for in-vitro (in microfluidic systems) and in-vivo high-speed micro-mixing of reagents. The method consists in dispersing the reactants in submicron droplets, then encapsulated in perfluorocarbon bigger droplets. Then, applying a focused ultrasonic wave vaporizes the perfluorocarbon, and expels, in a few microseconds, the reagents to the external phase where they can mix, under isothermal conditions. We think we can mix reagents on less than 100 microseconds time scales, and win one or two orders of magnitude compared to the fastest methods of micromixture reported in the literature. This is a great breakthrough, establishing a new generation of micro-mixers. There are many applications: in-vivo delivery of drugs and prodrugs, measurement of chemical kinetics, dynamic conformational analysis, etc. In this project, we focus on applications in the field of in-vivo delivery of drugs and prodrugs.
We have recently shown that when a bubble or a drop is submitted to a temperature gradient, it migrates to the coldest region by a mechanical effect, i.e. the deformation of the PDMS causes the element to move to the area where the cavity is the thickest. We have identified some mechanisms involved in this system. We first want to make a general mapping of the response of the bubble/drop depending on different control parameters. We believe that this study may be used for future reference.
The development of original methods dedicated to biomarkers quantitation to improve current medical diagnosis is still challenging. The aim of this project is to develop an integrated platform able to perform multimodal biomarker analysis at ultrasensitive levels. In particular, the system will integrate a high resolution electrophoresis combined with a compartmentalization by biphasic microfluidics. This compartmentalization will allow their further quantitation through a droplet based immunoassay. This project will be validated on the early detection of biomarkers for neurodegenerative diseases, notably Alzheimer.
Developed to promote human health and well being, certain pharmaceuticals are now attracting attention as crucial emerging water contaminants. To deal with this concern, we aim to develop an analytical microsystem that allows selective extraction of targeted pharmaceuticals and their metabolites for the identification and quantification of these contaminants in water samples. The selectivity and sensitivity of this lab-on-chip rest on the implementation of an aptamer-based molecular capture. This will be achieved in a confined zone of the separation channel through an electrochemically induced micro-scale functionalization of its surface. Fluorescent or electrochemical detection systems will be considered as they can be easily integrated in a miniaturized system while offering high selectivity and sensitivity. Eventually, this analytical microsystem will be designed so as to be hyphenated to a miniaturized processing platform either for on-line water purification (ozone oxidation process) or for on-line recovery and recycling of the waste pharmaceuticals.
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