Real-Time Analysis of Cellular Response to Small-Molecule Drugs within a Microfluidic Dielectrophoresis Device

被引:15
作者
Park, In Soo [1 ]
Lee, Jaewoo [1 ]
Lee, Gyudo [1 ,5 ]
Nam, Kihwan [1 ]
Lee, Taewoo [1 ]
Chang, Woo-Jin [2 ,3 ]
Kim, Hansung [1 ]
Lee, Sei-Young [1 ]
Seo, Jongbum [1 ]
Yoon, Dae Sung [4 ]
Lee, Sang Woo [1 ]
机构
[1] Yonsei Univ, Dept Biomed Engn, Wonju 220710, South Korea
[2] Univ Wisconsin, Dept Mech Engn, Milwaukee, WI 53211 USA
[3] Univ Wisconsin, Great Lakes WATER Inst, Milwaukee, WI 53211 USA
[4] Korea Univ, Sch Biomed Engn, Seoul 136703, South Korea
[5] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA
基金
新加坡国家研究基金会;
关键词
B16F10; MELANOMA-CELLS; SEPARATION; COTRANSPORT; TRANSISTORS; INVASION; GROWTH; ARRAY;
D O I
10.1021/ac5041549
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Quantitative detection of the biological properties of living cells is essential for a wide range of purposes, from the understanding of cellular characteristics to the development of novel drugs in nanomedicine. Here, we demonstrate :that analysis of cell biological properties within a microfluidic dielectrophoresis device enables quantitative detection of cellular biological properties and simultaneously allows large-scale measurement in a noise-robust and probeless manner. Applying this technique, the static and dynamic biological responses of live B16F10 melanoma cells to the small-molecule drugs such as N-ethylmaleimide (NEM) and [(dihydronindenyl)oxy]alkanoic acid (DIOA) were quantitatively and statistically examined by investigating changes in movement of the cells. Measurement was achieved using subtle variations in dielectrophoresis (DEP) properties of the cell's, which were attributed to activation or deactivation of K+/Cl- cotransporter channels on the cell membrane by the small-molecule drugs, in a microfluidic device. On the basis of quantitative analysis data, we also provide the first report of the shift of the complex permittivity of a cell induced by the small-molecule drugs. In addition, we demonstrate interesting quantifiable parameters including the drug effectiveness coefficient, antagonistic interaction coefficient, kinetic rate, and full width at half-maximum, which corresponded to changes in biological properties of B16F10 cells over time when NEM and DIOA were introduced alone or in combination. Those demonstrated parameters represent very useful tools for evaluating the effect of small-molecule drugs on the biological properties of cells.
引用
收藏
页码:5914 / 5920
页数:7
相关论文
共 31 条
[1]   Dielectrophoretic Technique for Measurement of Chemical and Biological Interactions [J].
Baek, Sang Hyun ;
Chang, Woo-Jin ;
Baek, Ju-Yeoul ;
Yoon, Dae Sung ;
Bashir, Rashid ;
Lee, Sang Woo .
ANALYTICAL CHEMISTRY, 2009, 81 (18) :7737-7742
[2]   Graphene and Nanowire Transistors for Cellular Interfaces and Electrical Recording [J].
Cohen-Karni, Tzahi ;
Qing, Quan ;
Li, Qiang ;
Fang, Ying ;
Lieber, Charles M. .
NANO LETTERS, 2010, 10 (03) :1098-1102
[3]   Nanomechanical analysis of cells from cancer patients [J].
Cross, Sarah E. ;
Jin, Yu-Sheng ;
Rao, Jianyu ;
Gimzewski, James K. .
NATURE NANOTECHNOLOGY, 2007, 2 (12) :780-783
[4]  
Duan XJ, 2012, NAT NANOTECHNOL, V7, P174, DOI [10.1038/NNANO.2011.223, 10.1038/nnano.2011.223]
[5]   Outside Looking In: Nanotube Transistor Intracellular Sensors [J].
Gao, Ruixuan ;
Strehle, Steffen ;
Tian, Bozhi ;
Cohen-Karni, Tzahi ;
Xie, Ping ;
Duan, Xiaojie ;
Qing, Quan ;
Lieber, Charles M. .
NANO LETTERS, 2012, 12 (06) :3329-3333
[6]   Dielectrophoresis-based cellular microarray chip for anticancer drug screening in perfusion microenvironments [J].
Hsiung, Lo-Chang ;
Chiang, Chi-Ling ;
Wang, Chen-Ho ;
Huang, Yu-Hsu ;
Kuo, Ching-Te ;
Cheng, Ji-Yen ;
Lin, Ching-Hung ;
Wu, Victoria ;
Chou, Hsien-Yeh ;
Jong, De-Shien ;
Lee, Hsinyu ;
Wo, Andrew M. .
LAB ON A CHIP, 2011, 11 (14) :2333-2342
[7]   Single cell viability observation in cell dielectrophoretic trapping on a microchip [J].
Huang, Chengjun ;
Liu, Chengxun ;
Stakenborg, Josine Loo Tim ;
Lagae, Liesbet .
APPLIED PHYSICS LETTERS, 2014, 104 (01)
[8]   DC-Dielectrophoretic separation of biological cells by size [J].
Kang, Yuejun ;
Li, Dongqing ;
Kalams, Spyros A. ;
Eid, Josiane E. .
BIOMEDICAL MICRODEVICES, 2008, 10 (02) :243-249
[9]   The role of potassium chloride cotransporters in murine and human sperm volume regulation [J].
Klein, T. ;
Cooper, T. G. ;
Yeung, C. H. .
BIOLOGY OF REPRODUCTION, 2006, 75 (06) :853-858
[10]   Dielectrophoretic concentration and separation of live and dead bacteria in an array of insulators [J].
Lapizco-Encinas, BH ;
Simmons, BA ;
Cummings, EB ;
Fintschenko, Y .
ANALYTICAL CHEMISTRY, 2004, 76 (06) :1571-1579