Microfabricated analytical systems for integrated cancer cytomics.

Abstract

Tracking and understanding cell-to-cell variability is fundamental for systems biology, cytomics and computational modelling that aids e.g. anti-cancer drug discovery. Limitations of conventional cell-based techniques, such as flow cytometry and single cell imaging, however, make the high-throughput dynamic analysis on cellular and subcellular processes tedious and exceedingly expensive. The development of microfluidic lab-on-a-chip technologies is one of the most innovative and cost-effective approaches towards integrated cytomics. Lab-on-a-chip devices promise greatly reduced costs, increased sensitivity and ultrahigh throughput by implementing parallel sample processing. The application of laminar fluid flow under low Reynolds numbers provides an attractive analytical avenue for the rapid delivery and exchange of reagents with exceptional accuracy. Under these conditions, the fluid flow has no inertia, enabling the precise dosing of drugs, both spatially and temporally. In addition, by confining the dimensions of the microfluidic structure, it is possible to facilitate the precise sequential delivery of drugs and/or functional probes into the cellular systems. As only low cell numbers and operational reagent volumes are required, high-throughput integrated cytomics on a single cell level finally appears within the reach of clinical diagnostics and drug screening routines. Lab-on-a-chip microfluidic technologies therefore provide new opportunities for the development of content-rich personalized clinical diagnostics and cost-effective drug discovery. It is largely anticipated that advances in microfluidic technologies should aid in tailoring of investigational therapies and support the current computational efforts in systems biology.