TY - JOUR
T1 - Inertial Microfluidic Cell Stretcher (iMCS)
T2 - Fully Automated, High-Throughput, and Near Real-Time Cell Mechanotyping
AU - Deng, Yanxiang
AU - Davis, Steven P.
AU - Yang, Fan
AU - Paulsen, Kevin S.
AU - Kumar, Maneesh
AU - Sinnott DeVaux, Rebecca
AU - Wang, Xianhui
AU - Conklin, Douglas S.
AU - Oberai, Assad
AU - Herschkowitz, Jason I.
AU - Chung, Aram J.
N1 - Funding Information:
This work was supported by Rensselaer Polytechnic Institute (RPI), NSF-1444104, DoD-W81XWH-15-1-0495, and NIH-R00CA166815. Device fabrication for this work was performed in part at the Micro and Nano Fabrication Clean Room (MNCR) at RPI.
Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/7/26
Y1 - 2017/7/26
N2 - 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.
AB - 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.
KW - deformability cytometry
KW - high-throughput cell screening
KW - inertial cell stretcher
KW - mechanophenotype
KW - microfluidics
UR - http://www.scopus.com/inward/record.url?scp=85019593451&partnerID=8YFLogxK
U2 - 10.1002/smll.201700705
DO - 10.1002/smll.201700705
M3 - Article
C2 - 28544415
AN - SCOPUS:85019593451
VL - 13
JO - Small
JF - Small
SN - 1613-6810
IS - 28
M1 - 1700705
ER -