生物样品分离与生物分子持续纯化的电动流体装置研制

Mixing of two solutions, each containing a different solute, is a spontaneous process with a net increase in entropy. However, the reverse of the mixing process is usually impossible unless certain conditions are met. This project will design a novel platform, a two-dimensional microfluidic electro-fluid-dynamic (EFD) device, for highly efficient separation of biological samples and purification of biomolecules. With this device, a continuous solution stream containing a mixture of two compounds can be separated into two channels, each containing a pure compound, thus reversing the mixing process. When the electric field is strategically applied in the interconnecting channels of an EFD device, the pressure required to direct an analyte into a certain channel can be calculated by using the solutions of electric field and fluid dynamics in the mass balance equation. The EFD devices expand the spatial separatih containing a pure compound, thus reversing the mixing process, using a two-dimensional microfluidic electro-fluid-dynamic (EFD) device. When the electric field is strategically applied in the interconnecting channels of an EFD device, the pressure required to direct an analyte into a certain channel can be calculated by using the solutions of electric field and fluid dynamics in the mass balance equation. If the pressure and electric potential at various inlets and outlets satisfy these predetermined conditions, the reverse of a mixing process is observed. The EFD devices expand the spatial separation of analytes from one dimension to two using both differential migration behaviour of analytes and the velocity field distribution in different channel geometries. The devices designed according to these basic physicochemical principles can be used for complete processing of minute samples and to obtain pure chemical species from complex mixtures. We have demonstrated recently that with a simple "Y" shaped device or multiple-branched device, continuous purification can be achieved. In this work, we propose to continue this work by designing new structures so that a single voltage applied to the device can generate different electric fields in different locations of an EFD devise to achieve multi component purification simultaneously. This design will significantly reduce the complexity and cost for the operation of the EFD device. In addition, new sample introduction strategies will be developed, so that the entire sample can be delivered to go through the purification process. The successful development of this platform will provide a powerful approach for acquiring pure substance from complex biological samples.

不同物质的混合是一个熵增加的自发过程。相反，从混合物出发分离单一纯净物质的过程，却很难发生。为解决这一问题，本项目拟设计一种新型高效的分离纯化平台，即二维电动流体装置，并用于生物样品分离与生物分子的纯化。在这一装置中，电场和流体动压力同时施加在二维微控通道网络中,以驱动流体及流体内物质的定向迁移。装置内混合物中的不同物质可被导入不同的分离通道中，从而成功实现混合物的持续纯化分离。前期工作已验证其可行性。在本申请项目中，首先，设计一种新型的样品进样装置，并进一步提高装置的稳定性和可操作性，实现样品生物理化性质的保护；其次，将通过单一电源对装置进行控制，即通过调整微流控通道的几何尺寸来满足各收集通道内所需的电场强度；然后，对数值进行模拟优化，获得装置的细节和分离过程中控制条件的参数。这一研究目标的成功实现，将为生物样品的分离与生物分子的纯化提供强有力的工具。

随着生物制药工业的发展，对高性能分离纯化技术的需求越来越大。我们的研究主要通过将电泳分离和压力驱动技术相结合，以开发新的分离策略。在过去的四年中，我们根据提出的方案，设计和实施了我们的研究，圆满实现了既定目标。此外，我们还开发了一系列分离分析的新技术，研发了高速样品制备技术和高通量定量质谱技术。我们培养了许多硕士和博士生，并在我们领域的顶级期刊上发表了许多高质量的论文。