Study of healthcare chips for the prompt test of tiny amounts of whole bloods

开展这一研究项目是为了建立制造保健芯片的基本技术，使我们能够从对体液(如少量血液和尿液)的分析中迅速收集各种生理信息。保健芯片是一种集成化、小型化的生化分析系统，可以被称为Micro TAS或Lab-on-a-Chip。由于用于生化分析的微芯片通常通过与光学测量或观察系统相结合来发挥作用，因此通常采用透明玻璃和塑料作为衬底材料，而不是LSI和/或MEMS中经常使用的硅。因此，本研究首先从玻璃基板的微细加工和组装技术的发展入手，然后应用这些技术发展到新型微细分析芯片的开发。本项目取得的主要研究成果有：(1)石英刻蚀技术…的应用更涉及到微毛细管电泳片的制造，(2)在高密度氟基等离子体中深蚀硼硅酸盐玻璃，(3)在硼硅酸盐玻璃上制作微毛细管电泳器并评价它们的操作特性，(4)使用阳极键合制造多层微流控器件，(5)用于通过阻抗谱检测活体样本的微流控器件的表面处理，(6)在具有完全埋入的微电极的微毛细管芯片上通过阻抗谱检测简单细胞，(7)使用介电对血细胞的芯片分离和操作技术，(8)在微毛细管电泳片上的血细胞的免疫电泳，(9)利用排斥介质电泳力开发细胞分选芯片，(10)通过在多晶硅薄膜中掺杂杂质将微电极集成到微流控器件中，以及(11)通过自对准电极形成工艺制造纳米分选芯片。较少

This research project was carried out in order to establish basic technologies for creating the healthcare chips that will enable us to collect various, physiologic information promptly from the analysis of the body fluid such as a small amount of blood and urine. The healthcare chip is a kind of the integrated and miniaturized biochemical analysis system that might be called micro TAS or Lab-on-a-chip. Since microchips for the biochemical analysis often function by the combination with an optical measurement or the observation system, not silicon as often used in LSI and/or MEMS but the transparent glass and plastic are often adopted as the substrate material. Therefore, at first this research started from the development of microfabrication and the assembly technology of the glass substrate, and then advanced to the development of new micro analysis chips by applying these technologies. Major research results obtained in this projects are (1) application of quartz etching technology … More to the fabrication of microcapillary electrophoresis chips, (2) deep etching of borosilcate glass in high density fluorine-based plasmas, (3) fabrication of microcapillary electrophoresis devices on borosilicate glass and evaluation of their operation characteristics, (4) fabrication of multilayer microfluidic devices using anodic bonding, (5) surface treatment in microfluidic device for the detection of living body sample by impedance spectroscopy, (6) detection of simple cells by impedance spectroscopy on a microcapillary chip with completely buried microelectrodes, (7) on chip separation and operation technology of blood cells using dielectrophoresis, (8) immunoelectrophoresis of blood cells on a microcapillary electrophoresis chip, (9) development of cell sorter chips using repulsive dielectrophoretic force, (10) microelectrode integration to microfluidic devices by impurity doping into polycrystalline silicon films, and (11) fabrication of nano sorter chips by self-aligned electrode formation process. Less