基于微流控技术的生物材料片上低温保存方法研究

作为细胞等生物材料最有效甚至唯一的长期保存方法，低温保存在国民经济的众多领域都具有不可替代的作用。随着干细胞等材料在临床和科研中的广泛应用，低温保存中面临着越来越多的微小体积对象。为解决传统方法难以有效处理此类对象的问题，本项目提出基于微流控技术的片上低温保存方法，并立足于微尺度下的流动和传热传质机理对其中的基本问题展开创新研究，包括：应用微通道换热原理，研究降复温系统的设计和优化方法，实现灵活的慢速至超高速降复温；通过对降复温过程的建模仿真，形成降复温速率控制方法，减小降复温过程中的低温损伤；应用膜分离技术，研究低温保护剂处理系统的设计和优化方法，实现平稳可控的添加或去除低温保护剂；通过对处理过程的建模和仿真，建立处理程序的优化方法，在保证细胞安全的前提下提高处理效率。研究成果将形成片上低温保存方法体系，提高微小体积生物材料的保存效果和处理效率，具有广阔的应用前景和重要的社会价值。

As the principal method for long-term storage of biomaterials, cryopreservation is of great significance for both scientific research and clinic application. Considering the difficulties for traditional devices and methods in processing mini volume samples (i.e., stem cell preparations), a noval on-chip cryopreservation method is proposed herein, and several fundamental issues are investigated based on studying the mechanism of the conjugate fluid flow and heat/mass transfer inherent in each stage of cryopreservation process. By introducing of microchannel heat transfer principle and techniques, methods for design and optimization of the cooling/thawing system will be studied to achieve slow to ultra-rapid cooling/thawing of samples. Then the approach for accurate control of the cooling/thawing rate will be set up by modeling and simulating of the process, to reduce the cell inury cause by intracelluar ice formation or recrystallization. Moreover, methods for design and optimization of the cryoprotectant processing system will also be set up based on membrane separation technology and transmembrane mass transfer theory, to reduce the cell injury caused by osmotic cell volume excursion during adding or removing of cryoprotectants. And an approach to optimize the operation protocols will also be analyzed by modeling and simulating of the process, to achieve best operation efficiency without causing additional cell loss. By means of the studies above, it is hopeful to establish a systematic and advanced on-chip cyopreservation technology, which has good application prospect in clinic as well as scientific research.