Macromolecules and Microsystems in Biology and Medicine (MMBM)

Keywords: lab on chips, magnetic tweezers, microfluidics, homologous recombination, chromatin, protein assays, mutation screening

Read the scientific activity report. (pdf 7.5Mo, last update 15th, april 2009)

MMBM is an interdisciplinary group of about 30 persons, dedicated to the application of physics and chemistry to biology and medicine. We develop both original methodologies for the study of DNA-protein transactions.
involved in cancer, and diagnosis methods directly relevant to cancer, such as mutation analysis, or the search and sorting of cancer cells. The group is also involved in the development of diagnosis tools for other types of pathologies, such as Alzheimer's disease, or infectious diseases.

Our group has three main lines of research :
The first is the development of bioanalytical tools and methods. Our group is a pioneer in microfluidics and lab on chips, developing in the area innovative technologies: magnetic and convective self-assembly, flow control, non-conventional microfabrication strategies and surface treatments, high throughput droplet microfluidics. Using these technologies, our group is developing several diagnosis-oriented projects in collaboration with clinicians, e.g.:

• Development of new media and strategies for mutation analysis (now in use in routine in several hospitals in France).
• Capture and molecular typing of tumour cells from patients, for the evaluation of metastatic relapse and treatment orientation. We are the coordinator of the European Project Caminems (cf charte d'aide à la lecture : un acronyme qui se lit comme un mot, sans l'épeler, s'écrit en minuscules) on this topic, and collaborating with several hospitals and research groups in France and abroad.
• Early diagnosis of neurodegenerative diseases (prion diseases, Alzheimer) by microfluidic methods, within the European consortium NeuroTAS
• Original systems for the oriented culture of neurones, and the study of neurons degenerescence
• Portable “point of care” microfluidic device for fast genetic analysis of pathogens, and the diagnosis of nosocomial infections (ANR project “Redloc”)

Fig. 1 

Our group is also involved in fundamental studies of molecular motors DNA-protein interactions and protein-protein interactions, at the single molecule and single cell level, developing for that novel nanomanipulation instruments. Currently we focus on the mechanisms of homologous recombination at the single molecule level, the organization and structural plasticity of chromatin, also studied by single molecule nanomanipulation, and the study of single molecular motors and trafficking at the single organelle level in vivo.

Fig. 2 

We also pursue projects using micrometric colloids to explore and engineer various biological cell or tissue functions and properties as T-cell activation. This cell plays a central role in mammalian immune response or single cell and collective bacterial adhesion which raises important public health problems.

In the next years, the group plans to intensify these research lines, with a particular focus on cell biology and cellular diagnosis.

Last update: April 2009

Key publications

2008

• Chabert M and Viovy JL
  Microfluidic high-throughput encapsulation and hydrodynamic self-sorting of single cells
  Proc Natl Acad Sci USA, 105(9):3191-6 - Abstract
  We present a purely hydrodynamic method for the high-throughput encapsulation of single cells into picoliter droplets, and spontaneous self-sorting of these droplets. Encapsulation uses a cell-triggered Rayleigh-Plateau instability in a flow-focusing geometry, and self-sorting puts to work two extra hydrodynamic mechanisms: lateral drift of deformable objects in a shear flow, and sterically driven dispersion in a compressional flow. Encapsulation and sorting are achieved on-flight in continuous flow at a rate up to 160 cells per second. The whole process is robust and cost-effective, involving no optical or electrical discrimination, active sorting, flow switching, or moving parts. Successful encapsulation and sorting of 70-80% of the injected cell population into drops containing one and only one cell, with <1% contamination by empty droplets, is demonstrated. The system is also applied to the direct encapsulation and sorting of cancerous lymphocytes from a whole blood mixture, yielding individually encapsulated cancer cells with a >10,000-fold enrichment as compared with the initial mix. The method can be implemented in simple “soft lithography” chips, allowing for easy downstream coupling with microfluidic cell biology or molecular biology protocols.

2006

• Courty S, Luccardini C, Bellaïche Y, Cappello G and Dahan M.
  Tracking Individual Kinesin Motors in Living Cells Using Single Quantum-Dot Imaging
  Nanoletters, 6:1491-1495
• Bancaud A, Conde e Silva N, Barbi M, Wagner G, Allemand JF, Mozziconacci J, Lavelle C, Croquette V, Victor JM, Prunell A, Viovy JL
  Structural plasticity of single chromatin fibers revealed by torsional manipulation
  Nature Struct. Mol. Biol, 13, 444-450

2002

• Doyle PS, Bibette J, Bancaud A, Viovy JL
  Self-assembled magnetic matrices for DNA separation chips
  Science, 295, (5563), 2237

2000

• Viovy JL
  Electrophoresis of DNA and Other Polyelectrolytes : Physical Mechanisms
  Review of Modern Physics, 72:813-872