A chip-based system for cell manipulation and cellular function analysis

A thorough understanding of cellular functions is a prerequisite for realizing biological applications such as medical diagnostics, drug discovery, and tissue engineering. Therefore, we have been developing novel MEMS devices for massively parallel manipulation and analysis of single cells. They include (1) an array of out-of-plane, hollow SiO2 microneedles capable of introducing desired biomolecules (DNA, proteins, etc.) into living cells and extracting biomolecules expressed in the cells, (2) a micromanipulator array capable of massively parallel trapping and manipulation of single living cells for 2 D/3 D cell patterning applicable to in vitro patterned cell culture, and (3) a cell culture microdevice actuated by piezoelectric thin film for on-chip regulation of cell functions. Furthermore, we have been developing a newly designed probe for atomic force microscope (AFM) , named bioprobe, which is integrated with a sharp-tipped, hollow SiO2 nanoneedle (Fig.1) for analyzing cellular functions in a single living cell with high spatial and temporal resolution; it can be used to perform AFM measurements at the molecular level under near-physiological conditions but also to deliver biomolecules into living cells and to extract target biomolecules in the cells. The MEMS devices proposed here will be powerful tools for addressing fundamental issues in cell biology, neurobiology, pharmacology, and tissue engineering.