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基于阻抗的无相机式细胞内力学测量法。

Impedance-Enabled Camera-Free Intrinsic Mechanical Cytometry.

机构信息

State Key Laboratory of Precision Measurement Technology and Instrument, Department of Precision Instrument, Tsinghua University, Beijing, 100084, P. R. China.

Department of Automation, Tsinghua University, Beijing, 100084, P. R. China.

出版信息

Small Methods. 2022 Jul;6(7):e2200325. doi: 10.1002/smtd.202200325. Epub 2022 May 20.

Abstract

Mechanical properties of single cells are important label-free biomarkers normally measured by expensive and complex imaging systems. To unlock this limit and allow mechanical properties comparable across different measurement platforms, camera-free intrinsic mechanical cytometry (CFIMC) is proposed for on-the-fly measurement of two major intrinsic mechanical parameters, that is, Young's modulus E and fluidity β, of single cells. CFIMC adopts a framework that couples the impedance electrodes with the constriction channel spatially, so that the impedance signals contain the dynamic deformability information of the cell squeezing through the constriction channel. Deformation of the cell is thus extracted from the impedance signals and used to derive the intrinsic mechanical parameters. With reasonably high throughput (>500 cells min ), CFIMC can successfully reveal the mechanical difference in cancer and normal cells (i.e., human breast cell lines MCF-10A, MCF-7, and MDA-MB-231), living and fixed cells, and pharmacological perturbations of the cytoskeleton. It is further found that 1 µM level concentration of Cytochalasin B may be the threshold for the treated cells to induce a significant cytoskeleton effect reflected by the mechanical parameters. It is envisioned that CFIMC provides an alternative avenue for high-throughput and real-time single-cell intrinsic mechanical analysis.

摘要

单细胞的力学特性是重要的无标记生物标志物,通常需要使用昂贵且复杂的成像系统进行测量。为了突破这一限制,并允许在不同的测量平台上进行可比的力学特性测量,提出了无相机固有力学细胞术(CFIMC),用于实时测量单细胞的两个主要固有力学参数,即杨氏模量 E 和流动性β。CFIMC 采用了一种将阻抗电极与收缩通道在空间上耦合的框架,从而使阻抗信号包含细胞通过收缩通道挤压时的动态变形信息。因此,从阻抗信号中提取细胞的变形,并用于推导固有力学参数。CFIMC 的高通量(>500 个细胞/分钟)可以成功揭示癌症和正常细胞(即人乳腺细胞系 MCF-10A、MCF-7 和 MDA-MB-231)、活细胞和固定细胞以及细胞骨架药理学干扰之间的力学差异。进一步发现,1µM 水平的细胞松弛素 B 浓度可能是处理细胞诱导细胞骨架效应的阈值,这种效应反映在机械参数中。可以预见,CFIMC 为高通量和实时单细胞固有力学分析提供了另一种途径。

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