Université PSL

Research Projects

L’IPGG offre des financements postdoctoraux pour des projets où la microfluidique joue un rôle central au sein des équipes de recherche membres de l'IPGG.

Nous mettons un accent particulier sur les projets "à haut risque scientifique", ceux qui sont difficiles à financer par les sources habituelles (ANR, etc.).

Nous donnons la possibilité de nous proposer plusieurs thèses pour un seul projet au sein de différents laboratoires de l’IPGG.

Nous souhaitons soutenir un ou deux projets de plus grande ampleur pour lequel, grâce à une synergie mise en œuvre au sein de l’IPGG, il sera possible de relever des défis d’envergure.



Experimental evolution of bio-molecular networks

Team:
LBC
​Project leader:
Philippe NGHE
Year:
2014

How bio-molecular networks evolve is an outstanding question in biology which, so far, has been lacking appropriate experimental models. Here we propose a highly innovative approach to explore the evolutionary potential of networks, by combining DNA computing, droplet microfluidics and deep-sequencing. In a single experiment, we will create ~106 combinatorial genomes made of DNA molecules carried by hydrogel beads and released in droplets after encapsulation. Network topologies, inputs and outputs, will be encoded as reacting oligonucleotides, quantified by deep-sequencing all at once using a bar-coding technology. The unprecedented scale (104-105 fold improvement) of this approach allows to explore the relation between network structure and function, which should lead to a breakthrough in the field of network evolution. It will also provide new strategies for applying synthetic biology approaches to regulatory systems.


Digital Microfluidics for Growing Uncultured Microorganisms

Team:
LCMD
​Project leader:
BAUDRY
Year:
2014

Uncultivable microorganisms represent typically more than 95% of the microbial population in any environments. Access to a vast number of unstudied microbial populations will lead to a better understanding of our natural environment. It will also open practical perspectives, like for the search of new antibiotics.
This project aims to grow part of these microbial populations using new strategies based on high-throughput digital microfluidics and microorganisms co-culture.


Single-cell Dual-molecules detection of protein-protein interactions : A companion diagnosis for second generation targeted therapy of cancer

Team:
MMBM
​Project leader:
S. Descroix
Year:
2014

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


Investigating droplet velocity for droplet-based microfluidics

Team:
MMN
​Project leader:
Marie-Caroline Jullien
Year:
2014

Droplet-based microfluidics is a growing field often requiring an accurate synchronisation for automated systems. Recently, we showed that confinement plays a crucial role in setting the droplet velocity. We thus propose to perform rational experiments for developing accurate models. First, the role of different experimental parameters (viscosity ratio, interfacial rheology, geometry) will be addressed in order to perform complete models used as a reference to predict droplet velocity. Then, the lubrication film will be analysed considering different experimental parameters and a tool allowing the characterisation of the disjoining pressure will be provided to the community.


Competition between normal and transformed cells in controlled microenvironments

Team:
PBME
​Project leader:
I. Bonnet / P. Silberzan
Year:
2014

Situations where groups of cells develop a collective response to their microenvironment are numerous: formation of biofilm, wound healing, stem cell dynamics …. It has recently been proposed that tumors behave as such a coordinated multi-cellular system. The interactions between transformed cells and their environment (including their neighboring normal cells) appear to play a crucial role in the evolution of the tumors; but the precise contribution of the environment remains poorly understood. In this context, new interdisciplinary approaches need to be developed that combine physical measurements with dynamic control of biological activities.
Our project aims at establishing in vitro assays to study these complex interactions between normal and tumor cells, in relation with their mechanical environment. Our model system is the monolayer culture of cell lines expressing, upon induction, constitutively active mutants of the oncogene ras. Our strategy consists in studying the dynamical evolution of well-defined coexisting populations of transformed and non-transformed cells: we will precisely tune in time and space the oncogene activation as well as its level, in an environment where mechanical properties are controlled. Altogether, we will investigate the crosstalk of mechanical and genetics factors on the tissue cohesion during early tumorigenesis.


Electropray mass spectrometry for droplet‐based microfluidics

Team:
SMBP
​Project leader:
Vinh‐Griffiths‐Malaquin‐Tabeling
Year:
2014

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.


SIMBAD: combining next generation SequencIng and droplet-based Microfluidics for the high throughput statistical analysis of Bio-molecule ADaptability

Team:
​Project leader:
Andrew Griffiths
Year:
2013

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.


Toward ths fabrication of liquid crystalline super-atoms

Team:
MMN
​Project leader:
Teresa Lopez-Leon et Olivier Dauchot
Year:
2013

We plan to develop a new method for producing and assembling large quantities of uniform colloidal particles with a variety of controlled non-isotropic interactions. The method consists in functionalizing, with DNA-ligands, the topological defects that appear in liquid crystal shells in order to fabricate colloids with a valence, capable of mimicking atomic interactions. The fascinating way in which topological defects organize themselves on the sphere offers a powerful tool to induce inter-particle
interactions with novel symmetries. Our intention is to study the self-assembly of these unique objects to produce colloidal architectures with new symmetries, which could eventually be exploited for photonic applications.


Bacterial populations in controlled micro-environments

Team:
PBME
​Project leader:
Axel Buguin
Year:
2013

The collective behavior of chemotactic bacteria (E. coli) in confined geometries can lead to striking phenomena such as accumulations or the propagation of concentration waves. The aim of this project is to perform competition experiments with different strains grown separately up to very high densities in different micro-chambers. We will study the competition between these different strains for a limited resource in nutrients. To that end, we have designed a setup where the chambers, in which the bacteria are, are isolated from the outside world by a porous membrane. The pores are too small to allow the passage of bacteria but large enough so that the nutrients and the waste can freely be exchanged with the facing reservoir. By replacing this reservoir by a microfluidic circuit it is possible to address spatially and dynamically medium containing nutrients or repellents and to follow the behavior of the different populations confronted to a limited resource of nutrients.


Développement d’un microréacteur plasma pour la catalyse de polymérisation

Team:
2PM
​Project leader:
Michael Tatoulian
Year:
2013

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.


36 projects.