Development of the nano device for medical use based on the Biochemical IC

我们系统地研究了新型概念器件“生化集成电路芯片”，从基础材料阶段到可应用的细胞融合芯片阶段。本研究的目的是多样化和应用于生物学，使生物化学领域的各种合成和分析的所有距离都可以缩小到微尺寸领域。细胞- 5蛋白合成生化IC芯片，最初于2001年开发并验证用于萤光素酶（萤火虫的发光蛋白），经过长期的不断发展，成为合成通用的、众所周知的标记蛋白绿色荧光蛋白（Green fluorescence protein， GFP）。通过这一新的证据，验证了生物化学集成电路芯片组用于无剔除蛋白合成的实用性和通用性。作为内置细胞微型装置的一项基础技术，我们通过对几个方面的研究，找到了在规定时间内在微型装置中培养细胞的条件，寻找具有生物相容性、表面改性、表面结构、微观结构制作策略等方面的光固化树脂。这项基础研究是必不可少的，因为光引发剂，包含在光固化聚合物中，阻止细胞在设备表面生长。我们实现了小于10微米的加工分辨率，这是构建自由表面微立体光刻所需的高分辨率，是制造生物化学集成电路芯片混合结构的必要条件。这项新技术不仅有助于获得直径为10微米的微管，而且有助于提高细胞的粘附性。我们提出并开发了“光驱动纳米机器”，该机器具有可移动的元件，采用高速双光子吸收微立体光刻技术制造，可以提前在显微镜下实现细胞操作。并通过制作纳米镊子、2个角的纳米针、3个角的10微米长的纳米机械手等验证了其有效性。我们还开发了生物可降解聚合物的三维微加工系统，特别是聚乳酸，用于植入式生物化学集成电路的药物释放芯片。获得的分辨率为50微米，但制造的装置具有良好的生物相容性，因为我们没有使用有毒溶剂。少

We studied the novel conceptual device, "Biochemical IC chip," from the basic material stage to the applicable cell-fusion chip stage under systematic approach. The purposes of this research are diversification and application to biology, which all the distances of the various synthesis and analysis in the biochemistry area could downsize to micro-size domain.Biochemical IC chip for cell-five protein synthesis, originally developed and verified as use for luciferase, a luminous protein of firefly in the year of 2001, was evolved to be synthesized general and well known marker protein Green fluorescence protein (GFP) continuously for along-term period. Through this new evidence, utility and generality of the Biochemical IC chip-set for cull-free protein synthesis was verified. As a basic technology of a mien) device with a built-in cell, we found the condition which the cell could be cultivated in the micro device among the appointed time, by studying several point, hunt up the photocur … More able resin with biocompatibility, surface modification, surface structure, fabrication strategy of the microstructure, and so on.This basic study is essential because photo-initiator, containing in the photocurable polymers, prevent cell growth on the surface of the device. We achieved the processing resolution of less than 10 micrometer, which high-resolution is required to construct the free-surface microstereolithography, essential to fabricate hybrid structure for biochemical IC chip. This new technology is contributed to not only acquire 10-micrometer-diameter micro pipe, but also improvement of the cell adhesion.We proposed and developed "optically driven nano-machine," which is controlled by the laser trapping remotely The nano-machine has movable elements and is fabricated by high-speed two-photon-absorption microstereolithography to realize a cell operation under the microscope in advance. We also verified its availability by fabricating nano-tweezer, nano-needle of 2 D.O.F.,10 micrometer-length nano-manipulator of 3 D.O.F, and so on.We also developed three-dimensional microfabrication system for biodegradable polymers, especially poly (lactic acid), for the purpose of the implantable use as a drug release chip of the biochemical IC. The resolution attained are 50 micrometer, but the fabricated device has good biocompatibility, because we never employ toxic solvents. Less