Abstract

Abstract : The advent of the genome facilitated by the advances in micro- and nanotechnology has revolutionized our understanding of living systems. DNA microarrays, catalytic RNA arrays, and protein arrays are all a consequence of innovations in engineering at the micro- and nanoscales. Here, we extend this paradigm to the fabrication of live mammalian cell arrays that can be used to investigate the state of the cell at the level of an integrated system. Specifically, we describe an electro-optical system that utilizes physical properties of mammalian cells (charge, dielectric permittivity) rather than receptor-mediated adhesion to rapidly pattern and manipulate cells in a microarray format. The platform we describe is an electro-optical method that employs two complementary methods of cell manipulation: (1) electrophoretic arraying of cells in a dc field due to their intrinsic negative surface charge and (2) remote optical manipulation of individual cells by vertical-cavity surface emitting laser driven infrared optical tweezers. The platform is optically transparent and thus enables monitoring of fluorescent reporters of cellular events (e.g., expression of green fluorescent protein) and allows remote optical manipulation of arrayed cells without risk of breaching the aseptic environment. In addition to the experimental manipulation of mammalian cells, we also present a theoretical framework to establish the limitations of the platform we describe. The ability to probe dynamic cellular events in parallel may offer insights into unforeseen biological mechanisms of cellular function and find applications in drug discovery, functional genomics, and tissue engineering.

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