Inertial Microfluidic Cell Stretcher (iMCS): Fully Automated, High-Throughput, and Near Real-Time Cell Mechanotyping.

Inertial Microfluidic Cell Stretcher (iMCS): Fully Automated, High-Throughput, and Near Real-Time Cell Mechanotyping.
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惯性微流体电池担架(IMC):完全自动化,高通量和接近实时的细胞机械分型。

DOI:
10.1002/smll.201700705
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发表时间:
2017-07
期刊:
Small (Weinheim an der Bergstrasse, Germany)
影响因子:
--
通讯作者:
Chung AJ
Chung AJ
中科院分区:
其他
文献类型:
--
作者:
Deng Y;Davis SP;Yang F;Paulsen KS;Kumar M;Sinnott DeVaux R;Wang X;Conklin DS;Oberai A;Herschkowitz JI;Chung AJ

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据报道,与细胞骨架结构相关的机械生物标志物是强大的无标记细胞状态标识符。为了测量细胞力学特性,主要采用传统的生物物理(例如原子力显微镜、微移液管抽吸、光学担架)和微流控方法;然而,它们严重受到低通量、低灵敏度和/或耗时和劳动密集型过程的影响,不允许技术实际用于细胞生物学研究应用。在这里,提出了一种新型惯性微流控细胞担架(iMCS),能够近乎实时地表征大量单细胞变形能力。该平台惯性地控制微通道中的细胞位置,并在 T 形接头处发生大应变碰撞时使细胞变形。记录细胞伸长运动,并与传统流式细胞术类似,近乎实时地可视化数千个细胞变形信息。整个细胞机械分型过程完全自动化,无需任何人为干预,实现了用户友好且稳健的操作。通过 iMCS,报告了乳腺癌进展和上皮间质转化中明显的细胞硬度变化,并且还展示了该平台在快速癌症药物发现中的用途。该平台即时返回大量具有高统计意义的单细胞定量机械特性(例如剪切模量),从而能够在临床和生物物理研究中实际使用。提出了一种新型惯性微流控细胞担架(iMCS),能够以全自动方式近乎实时地对大量单细胞变形能力进行表征和分类。通过这种方法,报告了乳腺癌进展和上皮间质转化中统计上稳健的细胞变形性测量,并且还证明了癌症药物发现的平台用途。
Mechanical biomarkers associated with cytoskeletal structures have been reported as powerful label-free cell state identifiers. In order to measure cell mechanical properties, traditional biophysical (e.g., atomic force microscopy, micropipette aspiration, optical stretchers) and microfluidic approaches were mainly employed; however, they critically suffer from low-throughput, low-sensitivity, and/or time-consuming and labor-intensive processes, not allowing techniques to be practically used for cell biology research applications. Here, a novel inertial microfluidic cell stretcher (iMCS) capable of characterizing large populations of single-cell deformability near real-time is presented. The platform inertially controls cell positions in microchannels and deforms cells upon collision at a T-junction with large strain. The cell elongation motions are recorded, and thousands of cell deformability information is visualized near real-time similar to traditional flow cytometry. With a full automation, the entire cell mechanotyping process runs without any human intervention, realizing a user friendly and robust operation. Through iMCS, distinct cell stiffness changes in breast cancer progression and epithelial mesenchymal transition are reported, and the use of the platform for rapid cancer drug discovery is shown as well. The platform returns large populations of single-cell quantitative mechanical properties (e.g., shear modulus) on-the-fly with high statistical significances, enabling actual usages in clinical and biophysical studies. A novel inertial microfluidic cell stretcher (iMCS) capable of characterizing and classifying large populations of single-cell deformability near real-time in a fully automated manner is presented. Through this method, statistically robust cell deformability measurements in breast cancer progression and epithelial mesenchymal transition are reported, and the platform usage for cancer drug discovery is also demonstrated.
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