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

近年来最活跃的领域之一是微全量分析系统（μTAS）或芯片实验室（Lab-on-a-Chip， LOC）， DNA、蛋白质的分析方法和设备得到了改进。然而，在许多情况下，需要在分析前进行传统的样品制备。为了实现μTAS的高速、高通量分析，需要在微流体装置/系统中进行样品分离/提取。我们应用MEMS技术和纳米技术，批量制造了nl或pl微流体器件和系统。开发了以热敏水凝胶为载体的生物分子分选系统。通过对通道结构和流动特性的优化，实现了高速一进两出分选机。还实现了5毫秒内的快速排序。利用PC控制的DMD投影的红外光照明，在矩阵微通道中实现了1进9出的分选系统。研制了一种集成极低死体积试剂注射器的微室，用于实时监测活细胞。为了实现试剂的具体导入，我们还开发了三维护套流量扫描仪。对于高通量分析，具有被动分布的8个诊断微室的原型便于同时注射细胞。另一方面，利用微通道鞘层流动特性进行生物细胞分选的微流体系统也得到了发展。流动系统可以将两个不同的细胞分选到16个出口微室。为实现DNA与蛋白质的高效反应，提出了两相有机/水微滴和三相有机/水/空气微滴生成流体装置。

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.