Digital microfluidics with impedance sensing for integrated cell culture and analysis

被引:101
作者
Shih, Steve C. C. [1 ,2 ]
Barbulovic-Nad, Irena [1 ,2 ]
Yang, Xuning [3 ]
Fobel, Ryan [1 ,2 ]
Wheeler, Aaron R. [1 ,2 ,4 ]
机构
[1] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada
[2] Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada
[3] Univ Toronto, Dept Engn Sci, Toronto, ON M5S 1A4, Canada
[4] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
Digital microfluidics; Cell impedance; Multiplexing; Adherent cells; Electrowetting; SINGLE-CELL; REAL-TIME; MAMMALIAN-CELLS; CANCER-CELLS; DIELECTRIC-SPECTROSCOPY; ELECTRICAL-IMPEDANCE; BARRIER FUNCTION; FLOW-CYTOMETRY; DEVICE; BIOSENSOR;
D O I
10.1016/j.bios.2012.10.035
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
We report the first digital microfluidic (DMF) system capable of impedance sensing of mammalian cells. The new system was validated in three assays: calibration, proliferation, and serum sensing. In the first assay, three cell lines (HeLa, CHO-K1, and NIH-3T3) were seeded at different densities to determine the relationship between impedance and cell number, which was found to be linear for each type of cell. In the proliferation assay, cells were grown for four days and their proliferation rates were determined by regular impedance measurements. In the serum sensing assay, a dilution series of cell media containing different concentrations of serum was evaluated using impedance measurements to determine the optimum conditions for proliferation. The DMF impedance system is label-free, does not require imaging, and is compatible with long-term cell culture. We propose that this system will be useful for the growing number of scientists who are seeking methods other than fluorescence or cell sorting to analyze adherent cells in situ. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:314 / 320
页数:7
相关论文
共 64 条
[41]   Effects of Fetal Bovine Serum deprivation in cell cultures on the production of Anticarsia gemmatalis Multinucleopolyhedrovirus [J].
Mengual Gomez, Diego L. ;
Belaich, Mariano N. ;
Rodriguez, Vanina A. ;
Ghiringhelli, Pablo D. .
BMC BIOTECHNOLOGY, 2010, 10
[42]   On-chip micro-biosensor for the detection of human CD4+ cells based on AC impedance and optical analysis [J].
Mishra, NN ;
Retterer, S ;
Zieziulewicz, TJ ;
Isaacson, M ;
Szarowski, D ;
Mousseau, DE ;
Lawrence, DA ;
Turner, JN .
BIOSENSORS & BIOELECTRONICS, 2005, 21 (05) :696-704
[43]   Single cell dielectric spectroscopy [J].
Morgan, Hywel ;
Sun, Tao ;
Holmes, David ;
Gawad, Shady ;
Green, Nicolas G. .
JOURNAL OF PHYSICS D-APPLIED PHYSICS, 2007, 40 (01) :61-70
[44]   Microphysiological testing for chemo sensitivity of living tumor cells with multiparametric microsensor chips [J].
Otto, AM ;
Brischwein, M ;
Niendorf, A ;
Henning, T ;
Motrescu, E ;
Wolf, B .
CANCER DETECTION AND PREVENTION, 2003, 27 (04) :291-296
[45]   Improved method for impedance measurements of mammalian cells [J].
Ruemenapp, Christine ;
Remm, Margarete ;
Wolf, Bernhard ;
Gleich, Bernhard .
BIOSENSORS & BIOELECTRONICS, 2009, 24 (09) :2915-2919
[46]   Specific binding and magnetic concentration of CD8+T-lymphocytes on electrowetting-on-dielectric platform [J].
Shah, Gaurav J. ;
Veale, Jeffrey L. ;
Korin, Yael ;
Reed, Elaine F. ;
Gritsch, H. Albin ;
Kim, Chang-Jin CJ .
BIOMICROFLUIDICS, 2010, 4 (04)
[47]   EWOD-driven droplet microfluidic device integrated with optoelectronic tweezers as an automated platform for cellular isolation and analysis [J].
Shah, Gaurav J. ;
Ohta, Aaron T. ;
Chiou, Eric P. -Y. ;
Wu, Ming C. ;
Kim, Chang-Jin .
LAB ON A CHIP, 2009, 9 (12) :1732-1739
[48]   A feedback control system for high-fidelity digital microfluidics [J].
Shih, Steve C. C. ;
Fobel, Ryan ;
Kumar, Paresh ;
Wheeler, Aaron R. .
LAB ON A CHIP, 2011, 11 (03) :535-540
[49]   Capacitance cytometry: Measuring biological cells one by one [J].
Sohn, LL ;
Saleh, OA ;
Facer, GR ;
Beavis, AJ ;
Allan, RS ;
Notterman, DA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (20) :10687-10690
[50]   A digital microfluidic platform for primary cell culture and analysis [J].
Srigunapalan, Suthan ;
Eydelnant, Irwin A. ;
Simmons, Craig A. ;
Wheeler, Aaron R. .
LAB ON A CHIP, 2012, 12 (02) :369-375