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用于捕获和操控细胞的基于互补金属氧化物半导体的介电泳芯片实验室平台

Dielectrophoretic lab-on-CMOS platform for trapping and manipulation of cells.

作者信息

Park Kyoungchul, Kabiri Shideh, Sonkusale Sameer

机构信息

Nano Lab, Department of Electrical and Computer Engineering, Tufts University, Medford, MA, 02155, USA.

出版信息

Biomed Microdevices. 2016 Feb;18(1):6. doi: 10.1007/s10544-016-0030-x.

DOI:10.1007/s10544-016-0030-x
PMID:26780441
Abstract

Trapping and manipulation of cells are essential operations in numerous studies in biology and life sciences. We discuss the realization of a Lab-on-a-Chip platform for dielectrophoretic trapping and repositioning of cells and microorganisms on a complementary metal oxide semiconductor (CMOS) technology, which we define here as Lab-on-CMOS (LoC). The LoC platform is based on dielectrophoresis (DEP) which is the force experienced by any dielectric particle including biological entities in non-uniform AC electrical field. DEP force depends on the permittivity of the cells, its size and shape and also on the permittivity of the medium and therefore it enables selective targeting of cells based on their phenotype. In this paper, we address an important matter that of electrode design for DEP for which we propose a three-dimensional (3D) octapole geometry to create highly confined electric fields for trapping and manipulation of cells. Conventional DEP-based platforms are implemented stand-alone on glass, silicon or polymers connected to external infrastructure for electronics and optics, making it bulky and expensive. In this paper, the use of CMOS as a platform provides a pathway to truly miniaturized lab-on-CMOS or LoC platform, where DEP electrodes are designed using built-in multiple metal layers of the CMOS process for effective trapping of cells, with built-in electronics for in-situ impedance monitoring of the cell position. We present electromagnetic simulation results of DEP force for this unique 3D octapole geometry on CMOS. Experimental results with yeast cells validate the design. These preliminary results indicate the promise of using CMOS technology for truly compact miniaturized lab-on-chip platform for cell biotechnology applications.

摘要

细胞的捕获和操控是生物学和生命科学众多研究中的关键操作。我们讨论了一种基于互补金属氧化物半导体(CMOS)技术的片上实验室(Lab-on-a-Chip)平台的实现,该平台用于通过介电泳捕获和重新定位细胞及微生物,我们在此将其定义为片上CMOS实验室(Lab-on-CMOS,LoC)。LoC平台基于介电泳(DEP),介电泳是任何介电粒子(包括生物实体)在非均匀交流电场中所受的力。DEP力取决于细胞的介电常数、其大小和形状,还取决于介质的介电常数,因此它能够根据细胞表型进行选择性靶向。在本文中,我们探讨了一个重要问题,即用于DEP的电极设计,为此我们提出了一种三维(3D)八极几何结构,以创建用于捕获和操控细胞的高度受限电场。传统的基于DEP的平台单独实现在与电子和光学外部基础设施相连的玻璃、硅或聚合物上,这使其体积庞大且成本高昂。在本文中,使用CMOS作为平台为真正小型化的片上CMOS实验室或LoC平台提供了一条途径,其中DEP电极使用CMOS工艺的内置多层金属层进行设计,以有效捕获细胞,并带有用于原位监测细胞位置阻抗的内置电子设备。我们展示了这种独特的3D八极几何结构在CMOS上的DEP力电磁仿真结果。酵母细胞的实验结果验证了该设计。这些初步结果表明,使用CMOS技术构建用于细胞生物技术应用的真正紧凑小型化片上实验室平台具有广阔前景。

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