BioSystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology Centre , Singapore 138602.
Pillar of Engineering Product Development, Singapore University of Technology and Design , Singapore 487372.
Anal Chem. 2018 Jan 2;90(1):912-919. doi: 10.1021/acs.analchem.7b03859. Epub 2017 Dec 11.
Mechanical properties of cells, reflective of various biochemical characteristics such as gene expression and cytoskeleton, are promising label-free biomarkers for studying and characterizing cells. Electrical properties of cells, dependent on the cellular structure and content, are also label-free indicators of cell states and phenotypes. In this work, we have developed a microfluidic device that is able to simultaneously characterize the mechanical and electrical properties of individual biological cells in a high-throughput manner (>1000 cells/min). The deformability of MCF-7 breast cancer cells was characterized based on the passage time required for an individual cell to pass through a constriction smaller than the cell size. The total passage time can be divided into two components: the entry time required for a cell to deform and enter a constriction, which is dominated by the deformability of cells, and the transit time required for the fully deformed cell to travel inside the constriction, which mainly relies on the surface friction between cells and the channel wall. The two time durations for individual cells to pass through the entry region and transit region have both been investigated. In addition, undeformed cells and fully deformed cells were simultaneously characterized via electrical impedance spectroscopy technique. The combination of mechanical and electrical properties serves as a unique set of intrinsic cellular biomarkers for single-cell analysis, providing better differentiation of cellular phenotypes, which are not easily discernible via single-marker analysis.
细胞的力学特性反映了各种生化特性,如基因表达和细胞骨架,是研究和表征细胞的有前途的无标记生物标志物。细胞的电学特性取决于细胞的结构和内容,也是细胞状态和表型的无标记指示。在这项工作中,我们开发了一种微流控装置,能够以高通量 (>1000 个/分钟) 的方式同时表征单个生物细胞的力学和电学特性。基于单个细胞通过小于细胞尺寸的收缩所需的通过时间来表征 MCF-7 乳腺癌细胞的可变形性。总通过时间可以分为两个组成部分:细胞变形并进入收缩所需的进入时间,这主要由细胞的可变形性决定,以及完全变形的细胞在收缩内行进所需的通过时间,这主要依赖于细胞和通道壁之间的表面摩擦力。已经研究了单个细胞通过入口区域和过渡区域的两个时间段。此外,通过电阻抗谱技术同时对未变形细胞和完全变形细胞进行了表征。机械和电学特性的结合为单细胞分析提供了一组独特的内在细胞生物标志物,更好地区分了细胞表型,这通过单标志物分析不易辨别。