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Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

机译:集成单细胞阱和3D稳定旋转操纵的微流控芯片的研究

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摘要

Single cell manipulation technology has been widely applied in biological fields, such as cell injection/enucleation, cell physiological measurement, and cell imaging. Recently, a biochip platform with a novel configuration of electrodes for cell 3D rotation has been successfully developed by generating rotating electric fields. However, the rotation platform still has two major shortcomings that need to be improved. The primary problem is that there is no on-chip module to facilitate the placement of a single cell into the rotation chamber, which causes very low efficiency in experiment to manually pipette single 10-micron-scale cells into rotation position. Secondly, the cell in the chamber may suffer from unstable rotation, which includes gravity-induced sinking down to the chamber bottom or electric-force-induced on-plane movement. To solve the two problems, in this paper we propose a new microfluidic chip with manipulation capabilities of single cell trap and single cell 3D stable rotation, both on one chip. The new microfluidic chip consists of two parts. The top capture part is based on the least flow resistance principle and is used to capture a single cell and to transport it to the rotation chamber. The bottom rotation part is based on dielectrophoresis (DEP) and is used to 3D rotate the single cell in the rotation chamber with enhanced stability. The two parts are aligned and bonded together to form closed channels for microfluidic handling. Using COMSOL simulation and preliminary experiments, we have verified, in principle, the concept of on-chip single cell traps and 3D stable rotation, and identified key parameters for chip structures, microfluidic handling, and electrode configurations. The work has laid a solid foundation for on-going chip fabrication and experiment validation.
机译:单细胞操作技术已广泛应用于生物学领域,例如细胞注射/去核,细胞生理学测量和细胞成像。近来,通过产生旋转电场已经成功地开发了具有用于细胞3D旋转的电极的新颖配置的生物芯片平台。但是,旋转平台仍然有两个主要缺点需要改进。主要的问题是,没有芯片上的模块可以方便地将单个细胞放入旋转腔中,这在手动将单个10微米规模的细胞移入旋转位置的实验中,效率非常低。其次,腔室内的电池可能会遭受不稳定的旋转,其中包括重力感应下沉到腔室底部或电动感应平面运动。为了解决这两个问题,本文提出了一种具有单细胞陷阱和单细胞3D稳定旋转操作能力的新型微流控芯片,它们都在一个芯片上。新的微流控芯片由两部分组成。顶部捕获部分基于最小流动阻力原理,用于捕获单个细胞并将其传输到旋转腔。底部旋转部分基于介电电泳(DEP),用于在旋转室内以增强的稳定性3D旋转单个单元格。将这两个部分对齐并结合在一起以形成用于微流体处理的封闭通道。使用COMSOL仿真和初步实验,我们从原则上验证了芯片上单细胞陷阱和3D稳定旋转的概念,并确定了芯片结构,微流体处理和电极配置的关键参数。这项工作为正在进行的芯片制造和实验验证奠定了坚实的基础。

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