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Micromachined Coulter counter for dynamic impedance study of time sensitive cells

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An Erratum to this article was published on 26 August 2012

Abstract

This paper describes the design, modeling, fabrication and characterization MEMS Coulter counter that can detect and monitor the dynamic cell impedance changes in situ as a function of time after mixing isolated cell populations with different extracellular media within 0.3 s from the start of mixing. The novelty of this design is the use of multi-electrodes with vertical sidewalls to enable the measurements of time sensitive cells with significantly enhanced sensitivity as well as the integration of passive mixing, focusing of cells in line and impedance detection using the vertical electrodes on a single chip that is made mainly using multilayer of SU-8, which has not been reported before. The devices were tested with both fluidic and electrical functionality using yeast cells in cryoprotectant agent (diluted dimethyl sulfoxide), red blood cells, microbeads with different dimensions, and dyed fluids. The results demonstrate rapid changes of cell volume within the first 0.6 s after mixing followed by a stable and a fixed cell volume. The micromixer was initially simulated using COMSOL finite element tool. Image processing technique was used to quantitatively evaluate mixing efficiency by analyzing color intensities variation of captured images of 2 dyed fluids mixed in the channel at flow rates between 0.1–0.4 μl/min, the mixing efficiencies were between 87 %–95 %, respectively.

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References

  • D.A. Ateya, J.S. Erickson, P.B. Howell Jr., L.R. Hilliard, J.P. Golden, F.S. Ligler, The good, the bad, and the tiny: a review of micro flow cytometry. Anal. Bioanal. Chem. 391, 1485–1498 (2008)

    Article  Google Scholar 

  • R. Bernini, E.D. Nuccio, F. Brescia, A. Minardo, L. Zeni, P.M. Sarro, R. Palumbo, M.R. Scarfi, Development and characterization of integrated silicon micro flow cytometer. Anal. Bioanal. Chem. 386, 1267–1272 (2006)

    Article  Google Scholar 

  • C.C. Chang, Z.X. Huang, R.J. Yang, Three-dimensional hydrodynamic focusing in two-layer polydimethylsiloxane (PDMS) microchannels. J. Micromech. Microeng. 17, 1479–1486 (2007)

    Article  Google Scholar 

  • H.T. Chen, Y.N. Wang, Fluorescence detection in a micro flow cytometer without on-chip fibers. Microfluid Nanofluid 4, 689–694 (2008)

    Article  Google Scholar 

  • H.T. Chen, Y.N. Wang, Optical microflow cytometer for particle counting, sizing and fluorescence detection. Microfluid Nanofluid 6, 529–537 (2009)

    Article  Google Scholar 

  • W.H. Coulter, US Patent 2,656,508 (1953)

  • L. Du, J. Zhe, J.E. Carletta, R.J. Veillette, Inductive Coulter counting: detection and differentiation of metal wear particles in lubricant. Smart Mater. Struct. 19, 057001 (2010)

    Article  Google Scholar 

  • J.M. England, M.C. Down, Measurement of the mean cell volume using electronic particle counters. Br. J. Haematol. 32, 403–410 (1975)

    Article  Google Scholar 

  • F.U. Gast, P.S. Dittrich, P. Schwille, M. Weigel, M. Mertig, J. Opitz, U. Queitsch, S. Diez, B. Lincoln, F. Wottawah, S. Schinkinger, J. Guck, J. Kas, J. Smolinski, K. Salchert, C. Werner, C. Duschl, M.S. Jager, K. Uhlig, P. Geggier, S. Howitz, The microscopy cell (MicCell), a versatile modular flow through system for cell biology, biomaterial research, and nanotechnology. Microfluid Nanofluid 2, 21–36 (2006)

    Article  Google Scholar 

  • S. Gawad, L. Schild, P. Renaud, Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing. Lab-on-a-Chip 1, 76–82 (2001)

    Article  Google Scholar 

  • S. Gawad, K. Cheung, U. Seger, A. Bertsch, P. Renaud, Lab Chip 4, 241–251 (2004)

    Article  Google Scholar 

  • D. Holmes, H. Morgan, N.G. Green, High throughput particle analysis: combining dielectrophoretic particle focusing with confocal optical detection. Biosens. Bioelectron. 21, 1621–1630 (2006)

    Article  Google Scholar 

  • F. Jiang, K.S. Drese, S. Hardt, M. Kupper, F. Schonfeld, Helical flows and chaotic mixing in curved micro channels. A.I.Ch.E. J 50, 2297 (2004)

    Article  Google Scholar 

  • M. Koch, A.G.R. Evans, A. Brunnschweiler, Design and fabrication of a micromachined Coulter counter. J. Micromech. Microeng. 9, 159–161 (1999)

    Article  Google Scholar 

  • D. Larsen, G.B. Lankenstein, J. Branebjerg, Microchip coulter particle counter. Transducers’97, 1319–1322 (1997)

    Google Scholar 

  • S.W. Levin, R.L. Levin, A.K. Solomon, A. Pandiscio, D.H. Kirkwood, Improved stop-flow apparatus to measure permeability of human red cells and ghosts. J. Biochem. Biophys. Meth. 3, 255–272 (1980)

    Article  Google Scholar 

  • C. Lin, G. Lee, L. Fu, B. Hwey, Vertical focusing device utilizing dielectrophoretic force and its application on microflow cytometer. IEEE Trans. J. MEMS 13, 923–932 (2004)

    Google Scholar 

  • A.D.C. Macknight, A. Leaf, Regulation of cellular volume. J. Physiology 57, 510–73 (1977)

    Google Scholar 

  • X. Mao, J.R. Waldeisena, T.J. Huang, Microfluidic drifting implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device. Lab-on-a-Chip 7, 1260–1262 (2007)

    Article  Google Scholar 

  • J.H. Milgram, A.K. Solomon, Membrane-permeability equations and their solutions for red-cells. J. Membr. Biol. 34, 103–144 (1977)

    Article  Google Scholar 

  • S. Murali, X. Xia, A.V. Jagtiani, J. Carletta, J. Zhe, Capacitive Coulter counting: detection of metal wear particles in lubricant using a microfluidic device. Smart Mater. Struct. 18, 037001 (2008)

    Article  Google Scholar 

  • T.N.T. Nguyen, M.C. Kimb, J.S. Park, N.E. Lee, An effective passive microfluidic mixer utilizing chaotic advection. Sensor Actuator B Chem. 132, 172–181 (2008)

    Article  Google Scholar 

  • J.H. Nieuwenhuis, F. Kohl, J. Bastemeijer, P.M. Sarro, M.J. Vellekoop, Integrated Coulter counter based on 2-dimensional liquid aperture control. Sensor Actuator B Chem. 102, 44–50 (2004)

    Article  Google Scholar 

  • T. Papanek, The water permeability of the human erythrocyte in the temperature range +25 C to −10 C, PhD thesis, Massachusetts Institute of Technology (1978)

  • O.A. Saleh, L.L. Sohn, An artificial nanopore for molecular sensing. Nano Lett. 3, 37–38 (2003)

    Article  Google Scholar 

  • R. Scott, P. Sethu, C.K. Harnett, Three-dimensional hydrodynamic focusing in a microfluidic Coulter counter. Rev. Sci. Instrum. 79, 046104 (2008)

    Article  Google Scholar 

  • M. Sridhar, D. Xu, Y. Kang, A.B. Hmelo, L.C. Feldman, D. Li, D. Li, Experimental characterization of a metal-oxide-semiconductor field-effect transistor-based Coulter counter. J. Appl. Phys. 103, 104701 (2008)

    Article  Google Scholar 

  • N. Sundararajan, M.S. Pio, L.P. Lee, A. Berlin, Three-dimensional hydrodynamic focusing in Polydimethylsiloxane (PDMS) microchannels. IEEE Trans. J. MEMS. 13, 559–567 (2004)

    Google Scholar 

  • C. Tsai, H. Hou, L. Fu, An optimal three-dimensional focusing technique for micro-flow cytometers. Microfluid Nanofluid 5, 827–836 (2008)

    Article  Google Scholar 

  • Z. Wang, O. Hansen, P.K. Petersen, A. Rogeberg, J.P. Kutter, D.D. Bang, A. Wolff, Dielectrophoresis microsystem with integrated flow cytometers for on-line monitoring of sorting efficiency. Electrophoresis 27, 5081–5092 (2006)

    Article  Google Scholar 

  • J. Zhe, A. Jagtiani, P. Dutta, H. Jun, J. Carletta, A micromachined high throughput Coulter counter for bioparticle detection and counting. J. Micromech. Microeng. 17, 304 (2007)

    Article  Google Scholar 

  • S. Zheng, Y.C. Tai, Design and fabrication of a micro coulter counter with thin film electrodes. Proceedings of 2006 International Conference on Microtechnologies in Medicine and Biology. 16–19 (2006)

  • S. Zheng, M. Liu, Y.C. Tai, Micro coulter counters with platinum black electroplated electrodes for human blood cell sensing. Biomed. Microdev. 10, 221–231 (2008a)

    Article  Google Scholar 

  • S. Zheng, M.S. Nandra, C.Y. Shih, W. Li, Y.C. Tai, Resonance impedance sensing of human blood cells. Sensor Actuator Phys. 145, 29–36 (2008b)

    Article  Google Scholar 

  • S. Zheng, Y.C. Tai, Design and fabrication of amicro coulter counter with thin film electrodes. Proceedings of 2006 International Conference on Microtechnologies in Medicine and Biology. 16–19 (2006c)

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Authors and Affiliations

  1. University of Missouri, Columbia, MO, USA

    Yifan Wu, James D. Benson & Mahmoud Almasri

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  1. Yifan Wu
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  2. James D. Benson
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  3. Mahmoud Almasri
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Correspondence to Mahmoud Almasri.

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Wu, Y., Benson, J.D. & Almasri, M. Micromachined Coulter counter for dynamic impedance study of time sensitive cells. Biomed Microdevices 14, 739–750 (2012). https://doi.org/10.1007/s10544-012-9655-6

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  • DOI: https://doi.org/10.1007/s10544-012-9655-6

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