1. ¹Institut National de la Santé et de la Recherche Médicale (INSERM), U603, Paris, France
2. ²Centre National de la Recherche Scientifique (CNRS), UMR 8154, Paris, France
3. ³Laboratory of Neurophysiology and New Microscopies, University Paris Descartes, Paris, France

Correspondence: Dr M Oheim, Institut National de la Santé et de la Recherche Médicale (INSERM, U603) and Centre National de la Recherche Scientifique (CNRS, UMR 8154), Molecular and Cellular Biophysics of the Synapse (MCBS), Laboratory of Neurophysiology and New Microscopies, University Paris Descartes, 45 rue des Saints Pères, F-75006 Paris, France. E-mail: martin.oheim@univ-paris5.fr

⁴MO is a member of the AUTOSCREEN consortium for cell-based high-throughput and high-content analysis and drug discovery screens.

Received 27 April 2007; Revised 24 May 2007; Accepted 24 May 2007; Published online 2 July 2007.

Abstract

Knowledge gained from the revolutions in genomics and proteomics has helped to identify many of the key molecules involved in cellular signalling. Researchers, both in academia and in the pharmaceutical industry, now screen, at a sub-cellular level, where and when these proteins interact. Fluorescence imaging and molecular labelling combine to provide a powerful tool for real-time functional biochemistry with molecular resolution. However, they traditionally have been work-intensive, required trained personnel, and suffered from low through-put due to sample preparation, loading and handling. The need for speeding up microscopy is apparent from the tremendous complexity of cellular signalling pathways, the inherent biological variability, as well as the possibility that the same molecule plays different roles in different sub-cellular compartments. Research institutes and companies have teamed up to develop imaging cytometers of ever-increasing complexity. However, to truly go high-speed, sub-cellular imaging must free itself from the rigid framework of current microscopes.