mercredi 23 avril 2008

Kinetically-Driven Analysis And Separations In Microsystems: Applications To Chemical And Biological Complex Media

A Ph-D position (full salary incl. social charges) is available for 36 months at the Ecole Normale Supérieure de Paris, Dept. of Chemistry.

The consortium of three research groups involving C. Gosse (LPN, Marcoussis), L. Jullien (ENS, Paris), and A. Lemarchand (Paris 6 University) has recently introduced new approaches for identifying, quantifying, and sorting targeted substrates according to the topology and the dynamics of the reactive mechanism they obey. More precisely, our current strategy relies on maximizing the response of a given substrate (or network of substrates) to one or several appropriate periodic stimulations.

Our first approach is based on applying a periodic uniform electric field for sorting a given reactant submitted to a titration reaction: When the frequency of the field is tuned to match the reactive dynamics of the desired reactant, it exhibits a maximized dispersion coefficient. This dispersion can be easily controlled and allows us to collect the target product at the edges of the concentration distribution of the mixture. In alternative sorting protocols, the reactive mixture is exposed to two periodic excitations at the same frequency, again tuned to match the dynamics of the titration reaction for the reactant of interest. In the most selective protocol, we superimpose the modulation of a thermodynamic parameter such as the temperature to the oscillation of an electric field. For an appropriate phase delay between both modulations, we predict an oriented motion for the desired reactant which can then easily be extracted from the other mixture components (non mobile or slower). More recently, we have started to investigate how the modulation of the temperature alone can be used to evaluate the dynamics of a reactive system. We have shown that this non invasive approach is efficient to analyze mechanisms. We currently investigate this strategy to measure the concentration of a dynamically-addressed component in a reactive mixture. 12,324

We have already experimentally validated the first approach at the centimeter scale. Evaluating further approaches now requires to downsize the analytical and separation devices to the micrometer scale. In the present Ph. D. project, the student will be precisely concerned with the experimental implementation of the preceding concepts into the microdevices for which we have developed an expertise in relation to the measurement of dynamic parameters. In the first evaluation step, we intend to investigate model systems such as complementary oligonucleotides involved in various pairing reactions. In a second step, we would like to apply our approach to living reactive systems such as cultured cells. 567

This Ph-D will be interdisciplinary (collaboration between chemists, physicists, and biologists). It will imply systems (oligonucleotides, biological molecules,…), tools (fluorescence microscopy, two-photon excitation, FCS,...), and concepts (transport and diffusion of matter or heat). This Ph-D will be in the continuation of the Ph-D of André Estévez-Torres and will greatly benefit from our previous experience.

For further information and application, please contact:
Prof. Ludovic JULLIEN
Département de Chimie UMR 8640, Ecole Normale Supérieure
24, rue Lhomond, F-75231 Paris Cedex 05, France
Téléphone 00 33 (0)1 44 32 33 33
e-mail: Ludovic.Jullien@ens.fr
http://www.chimie.ens.fr

References
1 : L. Jullien, A. Lemarchand, H. Lemarchand, Diffusion of Reactive Species Tuned by Modulated External Fields : Application to High Performance Chromatography, J. Chem. Phys., 2000, 112, 8293-8301.
2 : A. Lemarchand, L. Jullien, Symmetry-Broken Reactant Motion upon Phase-Related Symmetrically Modulated Excitations: Application to Highly Selective Molecular Sorting, J. Phys. Chem. A, 2005, 109, 5770-5776.
3 : H. Berthoumieux, L. Jullien, A. Lemarchand, Temporal Modulation of a Spatially Periodic Potential for Kinetically Governed Oriented Motion, J. Phys. Chem. B, 2007, 111, 2045-2051.
4 : H. Berthoumieux, L. Jullien, A. Lemarchand, Response to a Temperature Modulation a Signature of Chemical Mechanisms, Phys. Rev. E, 2007, 76, 056112.
5 : D. Alcor, V. Croquette, L. Jullien, A. Lemarchand, Molecular Sorting by Stochastic Resonance, Proc. Natl. Acad. Sci. USA, 2004, 101, 8276-8280 ; D. Alcor, J.-F. Allemand, E. Cogné-Laage, V. Croquette, F. Ferrage, L. Jullien, A. Kononov, A. Lemarchand, Stochastic Resonance to Control Diffusion in Chemistry, J. Phys. Chem. B, 2005, 109, 1318-1328.
6 : A. Estévez-Torres, C. Gosse, T. Le Saux, J.-F. Allemand, V. Croquette, H. Berthoumieux, A. Lemarchand, L. Jullien, Fourier Analysis To Measure Diffusion Coefficients and Resolve Mixtures on a Continuous Electrophoresis Chip, Anal. Chem., 2007, 79, 8222-8231 ; A. Estévez-Torres, T. Le Saux, C. Gosse, A. Lemarchand, A. Bourdoncle, L. Jullien, Fourier Transform to Analyse Reaction Diffusion Dynamics in a Microsystem, Lab on Chip, 2008, in press
7 : A. Bourdoncle, A. Estévez Torres, C. Gosse, L. Lacroix, P. Vekhoff, L. Jullien, J.-L. Mergny, Quadruplex-based molecular beacons as tunable DNA probes, J. Am. Chem. Soc., 2006, 128, 11094-11105.