Creation of highly functional thermal and fluids mechanism for micro cell processing

本研究的目的是开发一种新型的微细胞处理系统，通过利用微尺度固有的热和流体现象，在微通道中有效地混合，标记，分选和运输细胞。作为具体应用，设想了使用成体干细胞的再生医学，并且已经开发了可以从细胞混合物中有效提取稀有细胞的细胞分选系统。更具体地说，高精度的数值方案和一种新的成像方法已被开发用于理解微通道中的细胞/颗粒运动。通过对基于新型生物相容性材料的MEMS制造技术的发展以及对微细胞分选器原型的实验评价，获得了可用于未来临床应用的细胞分选系统的具体设计指导原则，并研制了一种叠层微混合器和一种基于该混合器的免疫磁性细胞分选系统。我们发现，吞吐量可以高于以前的微细胞分选仪，并且当采用编号方法时，可以处理临床使用所需的相对大量的细胞样品。此外，已经提出了利用通过在壁上的抗原-抗体相互作用来减速细胞滚动的新型基于粘附的细胞分选系统，并开发了其原型。利用该系统，可以消除靶细胞的标记。我们还提出了一种新的抗体固定化方法--氨基功能化聚对二甲苯。传统的细胞分选/孵育过程耗时长，需要大量人力资源。本研究提出的基于微尺度热和流体流动特性的细胞分选方法将降低细胞分选的成本和分析时间，最终为再生医学的发展做出贡献。

The objective of the present study is to develop a novel micro cell processing system for efficient mixing, labeling, sorting and transporting of cells in micro channels by using heat and fluid phenomena inherent in microscale. As a specific application, regenerative medicine using adult somatic stem cells is assumed, and cell sorting systems that can efficiently extract rare cells from cell mixture have been developed. More specifically, high-precision numerical scheme and a novel imaging methods have been developed for understanding cell/particle motions in micro channels. Specific design guiding principle for cell sorting system that can be used for future clinical application is obtained by development of MEMS fabrication technologies using new biocompatible materials and experimental evaluation of the prototype micro cell sorters.A lamination micro mixer and an immunomagnetic cell sorting system using the mixers have been developed. We found that the throughput can be higher than previous micro cell sorters, and that processing relatively-large amount of cell samples needed for clinical use is possible when the numbering-up approach is adopted. In addition, novel adhesion-based cell sorting systems that utilize deceleration of cell rolling by antigen-antibody interaction on the wall has been proposed, and its prototype is developed. With this system, one can eliminate labeling of the target cells. We also propose a new immobilization method of antibody with amino-functionalized parylene.Conventional cell sorting/incubation process is time consuming and requires a long time and much human resources. Cell sorting methods proposed in the present study based on characteristics of microscale heat and fluid flows will reduce cost and analysis time of cell sorting, and eventually make contribution to advances of regenerativie medicine.