Nowadays biology research is faced with a considerable amount of genomic data which has to be functionally characterised in order to bring new concepts, which will lead to new therapies. These studies approach molecular-based mechanisms, and need high-throughput and parallel data management. The multidisciplinary work presented here has allowed the development of a miniaturised technology of cell culture in liquid drops, matrixed on a plane solid substrate, to test the action of molecules or conditions on the cells behaviour. After the macroscopic demonstration of nucleic acid molecule transfection in living cells on such a device, we have developed a fabrication protocol for a miniaturised support, able to maintain 100 nano-drops per cm², based on differential surface tensions. A picoliter dispensing robot was integrated to make the cell culture drops automatically. The cells' behaviour in the drops is analysed by high-content fluorescence microscopy after fixation. Each cell of each drop is characterised by tenths of parameters individually. This new analytical approach, which has triggered the development of new bio-statistical tools, has been applied to a multipartner project of siRNA screening, aimed at studying the impact of genes on glioblastoma cells chemoresistance. We have also shown the use of mass spectrometry as a multiparametric phenotyping method. This cell-on-chip technology seems particularly well suited for the study of the precise behaviour of cells among a population at high-throughput. It will be the base of new lab-on-chip technologies.
Development of a new cell-on-chip format for high-content phenotyping