Research interests

Acousto-fluidic interactions

This theme concerns the design and implementation of microdevices- (sensors and actuators) based on acousto- fluidic interactions. The field of application mainly concerns devices for biomedical applications. The work focuses on:

  • Acoustofluidic interactions for sensing applications (resonant sensors, diphasic fluids…)
  • Acoustophoresis (manipulation of droplets, acoustic mixing…)

 

GaAs Device and Experimental setup with electrical and fluidic connectionsAln/Si Lamb Wave Gas flow sensor (velocity and orientation)LGS microsensors

 

Nano-bio Characterization

The global performances of a biosensor depend on the sensitivity of the transducer, but the main bottleneck is governed by the biospecific interface which guarantees the ability of the biochip to operate in a real biological world and reach the required specificity. Finally, and perhaps surprisingly, to investigate onto large library of samples of patients, an investigation at the nanoscale of the biochemical architecture is crucial for developing functional biosensors. The team has been exploring this nanoworld for biological and clinical purposes with the Clinical Innovation Proteomic Platform (CLIPP) since 2008. Atomic force microscopy (AFM) is a technique which enables to assess changes in surface topography, biofilm homogeneity, protein surface coverage and protein 3D structure without any need of labeling. Also, Mass Spectrometry (MS), engaged directly on the biochip (without elution) by MALDI-TOFF approach, or after elution of biological material captured on the chip by Electrospray, enables the molecular proteomic profile of the biological objects selectively and spatially captured on the biochip through microarrays. Thus, the coupling of the transduction system like Surface Plasmon Resonance using a microarrayed biochip with the MS and/or AFM is a promising way to perform a correlation between an average measurement at the macroscale of biological activity on the chip and the in situ visualization and characterization of nanoscale biological events.

 

On Chips MALDI Imaging of peptidic fragment of LAG3 protein capture at the fmole level from Human plasma. Biacore chips in microchanels  (left) & Horiba Scientific chips in spots (right).

In collaboration with CLIPP

 


Nucleotide binding influence on the tubulin protofilament conformationAdherent T24 cells on glass
AFM images obtained in buffer and at 37°C

 

 

 Surface & Molecule Bio-Engineering

 

Our team combines diverse interdisciplinary and multiphysical approaches to design and implement new features coupled with high level instrumentations (SPR, AFM and MS) to better control realization of biochips and biospecific interfaces. The objective is to respond to biological/biochemical or medical questions, to improve life understanding and to develop diagnostics for better treatment of diseases. Surface bioengineering of biochips produced at FEMTO-ST allow us to control the interface between a sensitive layer and complex biological samples over the manufacture of the materials, their chemical functionalization and biomolecule grafting. Different approaches of functionalization using physical, bioaffinity and covalent and noncovalent chemistries are used with a special care to full retention of protein conformation and activity in order to improve global performances in terms of sensitivity & specificity. Our miniaturized systems allow us to optimize capture of trace proteins, cells and microorganisms in complex biologic fluids and are used for in vitro diagnosis and screening of biomarkers of human pathologies.

In addition, a new program of biomolecular engineering has recently started based on expression of proteins in bacterial expression systems and in particular of membrane proteins in the lactic acid bacterium, Lactococcus lactis. We plan to develop new functional and structural characterizations of these type of proteins involved in many vital process and major targets of pharmaceutical drugs.

 

 

 Lactococcus lactis and nisin used for controlled gene expression Lactococcus lactis as an expression system for custom protein production

 

Biomedical optics and translational research

 

This theme is clearly oriented towards clinical applications of biomedical optics. The goal is not only to study optical instrumentation meant to address well identified clinical needs at an international level, but also, and more importantly, to translate these instrumentations as close as possible to the patients. To do this, systems must be rethought in order to take into account constraints related to the use of biological sample obtained by patients in the operating theater.
In order to address the challenges, integrated conception of the devices is required. Researches in this theme are therefore highly multi-disciplinary and are in line with work conducted in the frame of the Biom’@x transversal axis of the Institute (Biom’@x: sciences and technologies for a translational medicine) which is headed by a member of the BMD group. Therefore, we have first strong collaborations with the other research department at FEMTO-ST and second with the Clinical Investigation Center of the Besançon University Hospital. It must be noted that a member of the BMD group holds a supplementary position atthis investigation center where he is the technological supervisor and the head of the “microsystem and biological qualification” team.