Development of Biological Sample Separation/Extraction and Preparation Microsystems for High Performance Biosensing

DNA、蛋白质的分析方法和装置是近年来微全分析系统（μTAS）或芯片实验室（Lab-on-a-Chip，LC-MS）研究的热点之一。然而，在许多情况下，需要在分析之前进行传统的样品制备。为了实现μTAS的高速、高通量分析，要求在微流控装置/系统中实现样品的分离/提取。我们应用MEMS技术和纳米技术，大量制备了nl或pl的微流控器件和系统，研制了以温敏水凝胶的溶胶-凝胶转化为载液的生物分子分选系统。通过优化通道结构和流动特性，实现了单进双出高速分选。还实现了在5毫秒内的非常快速的排序。利用微机控制DMD投射的红外光照明，在矩阵微通道中实现了一进九出的分选系统。研制了一种集成有超低死体积试剂注入器的微室，用于活细胞的实时监测。为了实现试剂的具体引入，我们还开发了3D鞘流扫描仪。对于高通量分析，具有被动分布的8个诊断微室的原型有助于同时进行细胞注射。另一方面，还开发了在微通道中使用鞘流行为用于生物细胞分选的微流体系统。流动系统可以将两种不同的细胞分选到16个出口微室。为了实现DNA和蛋白质的高效反应，提出了有机物/水两相微滴和有机物/水/空气三相微滴两种通用型微流控装置。

In recent one of the most active area of Micro Total Analysis Systems (μTAS) or Lab-on-a-Chip (LOC), DNA, Protein analysis methods and devices have been improved. However, traditional sample preparations before analysis are required in many cases. In order to realize high speed and high throughput analysis in μTAS, sample separations/extractions are requested to be obtained in microfluidic devices/systems. We applied MEMS technologies and nano technologies and fabricated micro fluidic devices and systems of nl or pl in volume.Biomolecules sorting systems using so-gel transformation of the thermo-sensitive hydrogel as the carrier fluid were developed. High speed one inlet and two outlets sorter is realized by optimizing the channel structures and the flow behaviors. Very fast sorting within 5 msec was also realized. One inlet and 9 outlets sorting system is realized in a matrix microchannel using IR light illumination projected by the PC controlled DMD. A micro chamber integrated with an extremely low dead volume reagent injector for real-time monitoring of living cell was developed. In order to realize specific introduction of the reagent, we also developed the 3D sheath flow scanner. For high throughput analysis, a prototype of 8 diagnostic micro chambers having passive distributing facilitates simultaneous cell injection. On the other hand, microfluidic systems using sheath flow behavior in the microchannel for biological cell sorting were also developed. The flow system can sort two different cells to 16 outlet microchambers. To realize high efficient reaction of DNA and protein, two phase micro droplets of organic/water and three phase micro droplets of organic/water/air genelation fluidic devices were proposed.