Insulator‐based dielectrophoretic single particle and single cancer cell trapping

Trapping of individual cells at specific locations in a microfluidic lab‐on‐a‐chip platform is essential for single cell studies, especially those requiring individual stimulation followed by downstream analysis. To this aim, we have designed microdevices based on direct current (DC) insulator‐based dielectrophoresis (iDEP) acting as individual single cell traps. We present both the design of a negative iDEP trap and a positive iDEP trap using insulating posts integrated at microchannel intersections. We obtained electric field distributions via numerical simulations adapted to the intersection and trap geometry with which we predict single particle pathlines. With polystyrene particles of 10 μm diameter, we demonstrated an effective design for a single particle trap in the case of negative dielectrophoresis. The onset trapping voltage shows an inverse relation to the buffer conductivity, thus indicating the influence of electrokinetic effects on the trapping behavior. Additionally, we demonstrated the proof‐of‐principle of single MCF‐7 breast cancer cell trapping in a positive iDEP trap. Our single particle trapping experiments were further in very good agreement with numerical simulations. To ensure that no significant damage occurred to the cells during the experiment, we further optimized medium conditions to ensure viability of the cells for at least 1 h, more than sufficient for microfluidic trapping experiments. Our results thus indicated the successful design of DC iDEP traps, which can easily be integrated into a variety of microchip operations for single cell analysis.

[1]  R. M. Westervelt,et al.  Dielectrophoresis tweezers for single cell manipulation , 2006, Biomedical microdevices.

[2]  Hywel Morgan,et al.  Trapping single human osteoblast-like cells from a heterogeneous population using a dielectrophoretic microfluidic device. , 2010, Biomicrofluidics.

[3]  Chun-Ping Jen,et al.  Selective trapping of live and dead mammalian cells using insulator-based dielectrophoresis within open-top microstructures , 2009, Biomedical microdevices.

[4]  R Guerrieri,et al.  Dielectrophoretic trapping in microwells for manipulation of single cells and small aggregates of particles. , 2009, Biosensors & bioelectronics.

[5]  Thomas Braschler,et al.  Continuous separation of cells by balanced dielectrophoretic forces at multiple frequencies. , 2008, Lab on a chip.

[6]  P. Renaud,et al.  Focusing and Continuous Separation of Cells in a Microfluidic Device using Lateral Dielectrophoresis , 2007, TRANSDUCERS 2007 - 2007 International Solid-State Sensors, Actuators and Microsystems Conference.

[7]  Jaydev P Desai,et al.  Engineering approaches to biomanipulation. , 2007, Annual review of biomedical engineering.

[8]  J. Voldman.  Electrical forces for microscale cell manipulation. , 2006, Annual review of biomedical engineering.

[9]  S. Kalams,et al.  DC-Dielectrophoretic separation of biological cells by size , 2008, Biomedical microdevices.

[10]  Gregory T. Roman,et al.  Single-cell manipulation and analysis using microfluidic devices , 2006, Analytical and bioanalytical chemistry.

[11]  Blanca H. Lapizco-Encinas,et al.  Simultaneous concentration and separation of microorganisms: insulator-based dielectrophoretic approach , 2010, Analytical and bioanalytical chemistry.

[12]  D. Grier.  A revolution in optical manipulation , 2003, Nature.

[13]  Thomas Schnelle,et al.  Contact-free single-cell cultivation by negative dielectrophoresis , 2008 .

[14]  Y. Huang,et al.  Cell separation by dielectrophoretic field-flow-fractionation. , 2000, Analytical chemistry.

[15]  F F Becker,et al.  Separation of human breast cancer cells from blood by differential dielectric affinity. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  S. Martínez-Chapa,et al.  Performance characterization of an insulator‐based dielectrophoretic microdevice , 2008, Electrophoresis.

[17]  A. Ros,et al.  Poly(oxyethylene) based surface coatings for poly(dimethylsiloxane) microchannels. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[18]  Byungkyu Kim,et al.  Separation of malignant human breast cancer epithelial cells from healthy epithelial cells using an advanced dielectrophoresis-activated cell sorter (DACS) , 2009, Analytical and bioanalytical chemistry.

[19]  B. Lapizco-Encinas,et al.  Controlled microparticle manipulation employing low frequency alternating electric fields in an array of insulators. , 2010, Lab on a chip.

[20]  P. D. Grossman.  CHAPTER 4 – Free-Solution Capillary Electrophoresis , 1992 .

[21]  E. Cummings,et al.  Dielectrophoretic concentration and separation of live and dead bacteria in an array of insulators. , 2004, Analytical chemistry.

[22]  Separation of viable and nonviable animal cell using dielectrophoretic filter , 2010, Biotechnology progress.

[23]  Thomas Braschler,et al.  A miniaturized continuous dielectrophoretic cell sorter and its applications. , 2010, Biomicrofluidics.

[24]  C. Jen,et al.  Trapping of cells by insulator-based dielectrophoresis using open-top microstructures , 2009 .

[25]  R. Davalos,et al.  An insulator-based (electrodeless) dielectrophoretic concentrator for microbes in water. , 2005, Journal of microbiological methods.

[26]  Myung-Suk Chun,et al.  Improvement of microchannel geometry subject to electrokinesis and dielectrophoresis using numerical simulations , 2008 .

[27]  E. Cummings,et al.  Insulator‐based dielectrophoresis for the selective concentration and separation of live bacteria in water , 2004, Electrophoresis.

[28]  K. Lim,et al.  Pillar array microtraps with negative dielectrophoresis. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[29]  Martin A. M. Gijs,et al.  Magnetic bead handling on-chip: new opportunities for analytical applications , 2004 .

[30]  Ling-Sheng Jang,et al.  Single-cell trapping utilizing negative dielectrophoretic quadrupole and microwell electrodes. , 2009, Biosensors & bioelectronics.

[31]  A. Singh,et al.  Dielectrophoresis in microchips containing arrays of insulating posts: theoretical and experimental results. , 2003, Analytical chemistry.

[32]  G. Gradl,et al.  A 3-D microelectrode system for handling and caging single cells and particles , 1999 .

[33]  Joel Voldman,et al.  Quantitative modeling of dielectrophoretic traps. , 2006, Lab on a chip.

[34]  R. Pethig.  Review article-dielectrophoresis: status of the theory, technology, and applications. , 2010, Biomicrofluidics.

[35]  S. Martínez-Chapa,et al.  Prediction of trapping zones in an insulator-based dielectrophoretic device. , 2009, Lab on a chip.

[36]  Hywel Morgan,et al.  Negative DEP traps for single cell immobilisation. , 2009, Lab on a chip.

[37]  Joel C. Colburn,et al.  Capillary electrophoresis : theory & practice , 1992 .

[38]  Nancy L Allbritton,et al.  CRITICAL REVIEW www.rsc.org/loc | Lab on a Chip Analysis of single mammalian cells on-chip , 2006 .

[39]  F F Becker,et al.  Dielectric properties of human leukocyte subpopulations determined by electrorotation as a cell separation criterion. , 1999, Biophysical journal.

[40]  M. Sano,et al.  Contactless dielectrophoresis: a new technique for cell manipulation , 2009, Biomedical microdevices.

[41]  S. Martínez-Chapa,et al.  Characterization of electrokinetic mobility of microparticles in order to improve dielectrophoretic concentration , 2009, Analytical and bioanalytical chemistry.

[42]  Ching-Te Huang,et al.  Hydrodynamic separation of cells utilizing insulator-based dielectrophoresis , 2009, 2009 Symposium on Design, Test, Integration & Packaging of MEMS/MOEMS.

[43]  P. Reimann,et al.  Acceleration of absolute negative mobility. , 2007, Journal of separation science.

[44]  Patrick Camilleri,et al.  Capillary electrophoresis : theory and practice , 1993 .

[45]  J. Cooper,et al.  Lab-on-a-chip technologies for proteomic analysis from isolated cells , 2008, Journal of The Royal Society Interface.

[46]  Marco Rito-Palomares,et al.  Dielectrophoresis for the manipulation of nanobioparticles , 2007, Electrophoresis.

[47]  J. Voldman,et al.  Holding forces of single-particle dielectrophoretic traps. , 2001, Biophysical journal.

[48]  M. Sano,et al.  Selective isolation of live/dead cells using contactless dielectrophoresis (cDEP). , 2010, Lab on a chip.

[49]  F F Becker,et al.  Differential analysis of human leukocytes by dielectrophoretic field-flow-fractionation. , 2000, Biophysical journal.

[50]  Alexandra Ros,et al.  Microfluidic single-cell analysis of intracellular compounds , 2008, Journal of The Royal Society Interface.

[51]  Thomas B. Jones,et al.  Electromechanics of Particles , 1995 .

[52]  H Morgan,et al.  The dielectrophoretic levitation and separation of latex beads in microchips , 2001, Electrophoresis.

[53]  H. P. Schwan,et al.  Surface conductance and other properties of latex particles measured by electrorotation , 1987 .

[54]  C. Culbertson,et al.  Chemical analysis of single mammalian cells with microfluidics. Strategies for culturing, sorting, trapping, and lysing cells and separating their contents on chips. , 2007, Analytical chemistry.

[55]  M. McClain,et al.  Microfluidic devices for the high-throughput chemical analysis of cells. , 2003, Analytical chemistry.

[56]  Ralf Eichhorn,et al.  Brownian motion: Absolute negative particle mobility , 2005, Nature.