On-chip cell measurement in closed space using multi-scale manipulation

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We studied on fundamental methods for understanding of unknown function of cells based on stimulation of individual cells in a closed space.1. Three-dimensional laser manipulation: By using two-dimensional scanning of laser with Galvano mirrors and vertical motion of the objective lens, we controlled focus of laser in 3D. Then, we realized three-dimensional laser manipulation of microscopic objects in high speed. Here, CCD shutter timing and lens motion was synchronized and the blur was eliminated successfully.2. Three-dimensional laser manipulation with microtools: By using thermal gel which can be made by local heating of focused laser, we succeeded in manipulating cells with the gel-bead. Moreover, 3D manipulation of an organic nanotube was possible by suing laser trapped microtools. We made microtools by photolithography. Then we can manipulate cells without direct laser irradiation to the cells.3. Fabrication of on-chip closed space: We made a closed space (cage) in the microchip by using photo crosslinkable resin. The cage is made is made of permeable membrane. Individual cells are transported in the cage. We also made a pH sensitive surface in the microchannel.4. Individual cell measurement in the chip using 3D multi-scale manipulation: We made a microchip having microchannels and cages by photolithography. The cell was transported in the cage. Environmental condition around the cell was controlled and the cell was rnonitored stably for long time.