Macromolecules and Microsystems in Biology and Medicine (MMBM)

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

Group leader : Jean-Louis Viovy

Macromolecules and Microsystems in Biology and Medicine (MMBM)

Read the activity report  (pdf 1,7Mo, last update 19th, april 2011) 

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”)

 

FIG1: Capture and analysis of circulating tumour cells. Upper panel: sketch of the technology we have developed for the capture and study of tumour cells. 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 (red and blue) are captured, whereas negative cells (blue) are not. The captured cells can be stained with different biomarkers, observed and studied with high accuracy after their capture. The lower panel displays a real image of cancer cells from a lymphoma patient, with multiple immunostaining (green, yellow and red antibodies, and blue DNA marker), imaged by confocal microscopy in situ after capture.FIG1: Capture and analysis of circulating tumour cells. Upper panel: sketch of the technology we have developed for the capture and study of tumour cells. 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 (red and blue) are captured, whereas negative cells (blue) are not. The captured cells can be stained with different biomarkers, observed and studied with high accuracy after their capture. The lower panel displays a real image of cancer cells from a lymphoma patient, with multiple immunostaining (green, yellow and red antibodies, and blue DNA marker), imaged by confocal microscopy in situ after capture.

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.

FIG2: In-vivo tracking of single myosin V molecules labelled with Qdots. Each Qdot is visible as a single red point in the upper image (A. Tubulin is labelled in green. The track of a single motor, showing for the first time in vivo individual steps, speed and processivity in vivo, is shown in the lower panel (B)FIG2: In-vivo tracking of single myosin V molecules labelled with Qdots. Each Qdot is visible as a single red point in the upper image (A. Tubulin is labelled in green. The track of a single motor, showing for the first time in vivo individual steps, speed and processivity in vivo, is shown in the lower panel (B)

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.

Key publications

Year of publication : 2010

Year of publication : 2009

Year of publication : 2008

  • 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.