Stiffness Dependent Separation of Cells in a Microfluidic Device

被引:89
作者
Wang, Gonghao [1 ]
Mao, Wenbin [1 ]
Byler, Rebecca [2 ]
Patel, Krishna [2 ]
Henegar, Caitlin [1 ]
Alexeev, Alexander [1 ]
Sulchek, Todd [1 ,2 ,3 ]
机构
[1] Georgia Inst Technol, Woodruff Sch Mech Engn, Atlanta, GA 30332 USA
[2] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA
[3] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA
基金
美国国家科学基金会;
关键词
CONTINUOUS-FLOW; CANCER-PATIENTS; CYTOCHALASIN-D; SINGLE CELLS; WHOLE-BLOOD; DEFORMABILITY; CHIP; DIELECTROPHORESIS; FLUID; MICROCAPSULES;
D O I
10.1371/journal.pone.0075901
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Abnormal cell mechanical stiffness can point to the development of various diseases including cancers and infections. We report a new microfluidic technique for continuous cell separation utilizing variation in cell stiffness. We use a microfluidic channel decorated by periodic diagonal ridges that compress the flowing cells in rapid succession. The compression in combination with secondary flows in the ridged microfluidic channel translates each cell perpendicular to the channel axis in proportion to its stiffness. We demonstrate the physical principle of the cell sorting mechanism and show that our microfluidic approach can be effectively used to separate a variety of cell types which are similar in size but of different stiffnesses, spanning a range from 210 Pa to 23 kPa. Atomic force microscopy is used to directly measure the stiffness of the separated cells and we found that the trajectories in the microchannel correlated to stiffness. We have demonstrated that the current processing throughput is 250 cells per second. This microfluidic separation technique opens new ways for conducting rapid and low-cost cell analysis and disease diagnostics through biophysical markers.
引用
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页数:10
相关论文
共 55 条
[31]   Hydrodynamic sorting of microparticles by size in ridged microchannels [J].
Mao, Wenbin ;
Alexeev, Alexander .
PHYSICS OF FLUIDS, 2011, 23 (05)
[32]   Exploiting mechanical biomarkers in microfluidics [J].
Mao, Xiaole ;
Huang, Tony Jun .
LAB ON A CHIP, 2012, 12 (20) :4006-4009
[33]   ASCITIC FLUID FROM HUMAN OVARIAN-CANCER PATIENTS CONTAINS GROWTH-FACTORS NECESSARY FOR INTRAPERITONEAL GROWTH OF HUMAN OVARIAN ADENOCARCINOMA CELLS [J].
MILLS, GB ;
MAY, C ;
HILL, M ;
CAMPBELL, S ;
SHAW, P ;
MARKS, A .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (03) :851-855
[34]   Isolation of tumor cells using size and deformation [J].
Mohamed, Hisham ;
Murray, Megan ;
Turner, James N. ;
Caggana, Michele .
JOURNAL OF CHROMATOGRAPHY A, 2009, 1216 (47) :8289-8295
[35]  
Moreno-Flores S, 2010, NANOTECHNOLOGY, P21
[36]   Stress relaxation microscopy: Imaging local stress in cells [J].
Moreno-Flores, Susana ;
Benitez, Rafael ;
Vivanco, Maria dM ;
Luis Toca-Herrera, Jose .
JOURNAL OF BIOMECHANICS, 2010, 43 (02) :349-354
[37]   Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis [J].
Pamme, Nicole ;
Wilhelm, Claire .
LAB ON A CHIP, 2006, 6 (08) :974-980
[38]   Microfluidic-based cell sorting of Francisella tularensis infected macrophages using optical forces [J].
Perroud, Thomas D. ;
Kaiser, Julia N. ;
Sy, Jay C. ;
Lane, Todd W. ;
Branda, Catherine S. ;
Singh, Anup K. ;
Patel, Kamiesh D. .
ANALYTICAL CHEMISTRY, 2008, 80 (16) :6365-6372
[39]   Free flow acoustophoresis:: Microfluidic-based mode of particle and cell separation [J].
Petersson, Filip ;
Aberg, Lena ;
Sward-Nilsson, Ann-Margret ;
Laurell, Thomas .
ANALYTICAL CHEMISTRY, 2007, 79 (14) :5117-5123
[40]   Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels [J].
Pommer, Matthew S. ;
Zhang, Yanting ;
Keerthi, Nawarathna ;
Chen, Dong ;
Thomson, James A. ;
Meinhart, Carl D. ;
Soh, Hyongsok T. .
ELECTROPHORESIS, 2008, 29 (06) :1213-1218