Macromolecules and Microsystems in Biology and Medicine

Our interdisciplinary group is dedicated to the application of physics and chemistry to biology and medicine, with a strong translational component. It has two main lines of research.

Capture et analyse de cellules tumorales circulantes. Encadré du haut : représentation de la technologie que nous avons développée pour capturer et étudier les cellules tumorales. Un réseau de colonnes formées de particules magnétiques portant des anticorps
Capture and analysis of circulating tumor cells. Left panel: sketch of the technology. Arrays of columns containing magnetic particles with antibodies directed against the cells of interest are self-assembled under a magnetic field in a microfluidic channel. The sample (e.g. blood from a patient) is flown in the channel. The cells bearing the relevant surface antigens are captured, whereas negative cells (blue) are not captured. The captured cells can be stained with different biomarkers, observed and studied with high accuracy (right panel) or released for extended genotyping.

The first deals with bioanalytical tools and methods based on microfluidics, also called “laboratories on chip”. The group developed several innovative technologies, based on its expertise in complex fluids and soft matter: magnetic and convective self-assembly, flow control, non-conventional microfabrication strategies and surface treatments, high content droplet microfluidics.

This is applied to several biomedical projects in collaboration with clinicians :

  • Capture and molecular typing of tumour cells from patients, for the evaluation of metastatic relapse and treatment orientation. The group has notably coordinated the European Project CAMiNEMS on this topic
  • Early diagnosis of Alzheimer disease by microfluidic methods, within the European consortium NADINE: the finality of this project is to diagnose the early steps of the disease development, to apply as soon as possible (and before irreversible brain damage) neuroprotective methods.
  • Portable microfluidic devices for fast and low-cost analysis of pathogens. This is notably developed within the European project LOVE-FOOD, in collaboration with Pasteur Institute and other international laboratories, for the search of pathogens in food.
  • Original systems for the oriented culture of neurones. This project, developed within the ANR “Neuroscreen” and EraNet “Microdeg”, aims at organizing in microfabricated environment arrays of neurons with deterministic connection architectures, and be able to address them specifically by chemical (microfluidic), electrical (microelectrodes) and optical (optogenetics) means. Applications concern both the understanding of biochemcial communication between neurons (involved e.g. in neurodegenerative diseases) and information processing at the single neuron level.
Figure 2: Unique tracking in vivo molecules of myosin V nominal capitals fluorescent nanocrystals ( quantum dots in English ) . In A : each nanocrystal is visible in the form of UN individualized red Point and tubulin Marquee is green.
  • Study of the correlation between mechanical, biochemical and genetic effects in the development of tumours, in order to better understand the competition and interaction between a growing tumour and its environment and find new therapies.
  • The group recently received an ERC-advanced grant, for the project “CellO” “From cells to organs on chips”. The aim of this project is to develop microfluidic platforms for the deterministic organization of functional multicellular assemblies, and use them as model in vitro systems for cell biology and screening applications. This will help to study cell-cell interactions and tissue development (including abnormal tissues as cancer), reduce the need for tests in animals, and increase the power of in vitro drug screening.
  • The group is also involved in fundamental studies of DNA-protein interactions, at the single molecule and single cell level. It has, in particular, developed new single molecule manipulation tools called torque-sensitive magnetic tweezers. Current focus is on:

– The mechanisms of homologous recombination at the single molecule level
– The study of single molecule transport and trafficking in vivo.

Key publications

Year of publication 2014

Morgan Delarue, Fabien Montel, Danijela Vignjevic, Jacques Prost, Jean-François Joanny, Giovanni Cappello (2014 Apr 2)

Compressive stress inhibits proliferation in tumor spheroids through a volume limitation.

Biophysical journal : 1821-8 : DOI : 10.1016/j.bpj.2014.08.031

Year of publication 2012

Anaïs Ali-Cherif, Stefano Begolo, Stéphanie Descroix, Jean-Louis Viovy, Laurent Malaquin (2012 May 18)

Programmable magnetic tweezers and droplet microfluidic device for high-throughput nanoliter multi-step assays.

Angewandte Chemie (International ed. in English) : 10765-9 : DOI : 10.1002/anie.201203862

Year of publication 2011

Jean-Michel Peyrin, Bérangère Deleglise, Laure Saias, Maéva Vignes, Paul Gougis, Sebastien Magnifico, Sandrine Betuing, Mathéa Pietri, Jocelyne Caboche, Peter Vanhoutte, Jean-Louis Viovy, Bernard Brugg (2011 Sep 15)

Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers.

Lab on a chip : 3663-73 : DOI : 10.1039/c1lc20014c
Fabien Montel, Morgan Delarue, Jens Elgeti, Laurent Malaquin, Markus Basan, Thomas Risler, Bernard Cabane, Danijela Vignjevic, Jacques Prost, Giovanni Cappello, Jean-François Joanny (2011 Mar 3)

Stress clamp experiments on multicellular tumor spheroids.

Physical review letters : 188102

Year of publication 2010

Antoine-Emmanuel Saliba, Laure Saias, Eleni Psychari, Nicolas Minc, Damien Simon, François-Clément Bidard, Claire Mathiot, Jean-Yves Pierga, Vincent Fraisier, Jean Salamero, Véronique Saada, Françoise Farace, Philippe Vielh, Laurent Malaquin, Jean-Louis Viovy (2010 Aug 2)

Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays.

Proceedings of the National Academy of Sciences of the United States of America : 14524-9 : DOI : 10.1073/pnas.1001515107
Christophe Lavelle, Pierre Recouvreux, Hua Wong, Aurélien Bancaud, Jean-Louis Viovy, Ariel Prunell, Jean-Marc Victor (2010 Jan 13)

Right-handed nucleosome: myth or reality?

Cell : 1216-7; author reply 1217-8 : DOI : 10.1016/j.cell.2009.12.014
All publications