Modeling, Simulation, and Performance Evaluation of a Novel Microfluidic Impedance Cytometer for Morphology-Based Cell Discrimination

The performance of a novel microfluidic impedance cytometer [1] for single-cell analysis is investigated in-silico by means of a finite element model. The main feature of the device is the ability to probe impedance of flowing cells along two orthogonal directions. As proved by means of numerical simulations involving spherical and ellipsoidal cells, this allows to extract information on cell morphology. In particular, simple anisotropy indices are devised, which are independent from cell volume and rather insensitive to small imperfections in the focusing system. In addition, simulations with budding yeasts show the capability of the device to identify the cell division stage.

[1]  Lilia Alberghina,et al.  Analysis and modeling of growing budding yeast populations at the single cell level , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[2]  Albert van den Berg,et al.  Single cells or large populations? , 2007, Lab on a chip.

[3]  Urban Seger,et al.  Dielectric spectroscopy in a micromachined flow cytometer: theoretical and practical considerations. , 2004, Lab on a chip.

[4]  S. Gawad,et al.  Impedance spectroscopy flow cytometry: On‐chip label‐free cell differentiation , 2005, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[5]  K Zouaoui Boudjeltia,et al.  Assessment of erythrocyte shape by flow cytometry techniques , 2006, Journal of Clinical Pathology.

[6]  J Hurley,et al.  Sizing particles with a Coulter counter. , 1970, Biophysical journal.

[7]  Hywel Morgan,et al.  Single-cell microfluidic impedance cytometry: a review , 2010 .

[8]  Ling-Sheng Jang,et al.  Single-cell trapping and impedance measurement utilizing dielectrophoresis in a parallel-plate microfluidic device , 2014 .

[9]  P Bisegna,et al.  An impedance-based flow microcytometer for single cell morphology discrimination. , 2014, Lab on a chip.

[10]  Lani F. Wu,et al.  Cellular Heterogeneity: Do Differences Make a Difference? , 2010, Cell.

[11]  Ling-Sheng Jang,et al.  Electrical characteristics analysis of various cancer cells using a microfluidic device based on single-cell impedance measurement , 2012 .

[12]  Federica Caselli,et al.  EIT-Inspired Microfluidic Cytometer for Single-Cell Dielectric Spectroscopy , 2010, Journal of Microelectromechanical Systems.

[13]  K. Asami,et al.  Dielectric modelling of cell division for budding and fission yeast , 2007 .

[14]  Che-Hsin Lin,et al.  Vertical focusing device utilizing dielectrophoretic force and its application on microflow cytometer , 2004 .

[15]  Subra Suresh,et al.  Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease , 2010, MRS bulletin.

[16]  Guillaume Mernier,et al.  Characterization of a novel impedance cytometer design and its integration with lateral focusing by dielectrophoresis. , 2012, Lab on a chip.

[17]  Jing-Juan Xu,et al.  Label-free electrical discrimination of cells at normal, apoptotic and necrotic status with a microfluidic device. , 2011, Journal of chromatography. A.

[18]  Maryam Tabrizian,et al.  Dielectric spectroscopy as a viable biosensing tool for cell and tissue characterization and analysis. , 2013, Biosensors & bioelectronics.

[19]  Yi Wang,et al.  A microfluidic impedance flow cytometer for identification of differentiation state of stem cells. , 2013, Lab on a chip.

[20]  Thomas Braschler,et al.  Label-free detection of Babesia bovis infected red blood cells using impedance spectroscopy on a microfabricated flow cytometer. , 2007, Acta tropica.

[21]  H Morgan,et al.  Discrimination and analysis of phytoplankton using a microfluidic cytometer. , 2007, IET nanobiotechnology.

[22]  G. Kovacs,et al.  Microfluidic impedance cytometer for platelet analysis. , 2013, Lab on a chip.

[23]  Arkadiusz Pierzchalski,et al.  Microfluidic impedance‐based flow cytometry , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[24]  S. Gawad,et al.  Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing. , 2001, Lab on a chip.

[25]  H. Shapiro,et al.  The evolution of cytometers , 2004, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[26]  Ling-Sheng Jang,et al.  Microfluidic device for cell capture and impedance measurement , 2007, Biomedical microdevices.

[27]  William R B Lionheart,et al.  A Matlab toolkit for three-dimensional electrical impedance tomography: a contribution to the Electrical Impedance and Diffuse Optical Reconstruction Software project , 2002 .

[28]  D. Isaacson,et al.  Electrode models for electric current computed tomography , 1989, IEEE Transactions on Biomedical Engineering.

[29]  J.A. Schwartz,et al.  A three-dimensional dielectrophoretic particle focusing channel for microcytometry applications , 2005, Journal of Microelectromechanical Systems.

[30]  Federica Caselli,et al.  A simple formula for the effective complex conductivity of periodic fibrous composites with interfacial impedance and applications to biological tissues , 2008 .

[31]  Hywel Morgan,et al.  Positional dependence of particles in microfludic impedance cytometry. , 2011, Lab on a chip.

[32]  K. Foster,et al.  Dielectric properties of tissues and biological materials: a critical review. , 1989, Critical reviews in biomedical engineering.

[33]  Christian H. Reccius,et al.  Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry. , 2009, Lab on a chip.

[34]  E. Somersalo,et al.  Existence and uniqueness for electrode models for electric current computed tomography , 1992 .

[35]  Sam Emaminejad,et al.  Microfluidic diagnostic tool for the developing world: contactless impedance flow cytometry. , 2012, Lab on a chip.