Les technologies de criblage sans marquage

After more than a decade focusing on large scale screens and increasing throughput, it has emerged that there is a need for a more rational and biologically relevant approach to facilitate the drug discovery process.

In addition to conventional technologies (reporter gene assays, automated fluorescence microscopy…), label-free technologies present valuable alternatives.  Such alternatives include sensors based on changes in impedance or optical properties or image-based techniques such as digital holographic microscopy or phase contrast image processing.

Target-unbiased screens have concurrently reinforced the importance of post-screen target identification and validation.  This has been demonstrated by directly probing molecular interactions to elucidate the mechanism of action of active compounds identified by primary screens.  In addition, this has led to improved characterization of active chemical compounds at an early stage, including compound quality and the quantitative determination of thermodynamic and kinetic constants.

Many biophysical label-free approaches have been successfully implemented, examples of which include light scattering, surface plasmon resonance, calorimetry, or more recently, microscale thermophoresis. In the context of screening, emphasis will be placed upon mass spectrometry, one of the oldest label-free technologies.

Case studies will be presented that employ both cutting-edge technology and the challenges associated with robust large scale implementation. Taking together these considerations, changes in interactions between the academic, pharmaceutical and biotechnical industries will also be addressed.

From 04.06.2014

In Lausanne