Advertisement

How to improve the sensitivity of coplanar electrodes and micro channel design in electrical impedance flow cytometry: a study

  • Jonathan CottetEmail author
  • Alexandre Kehren
  • Harald van Lintel
  • François Buret
  • Marie Frénéa-Robin
  • Philippe Renaud
Research Paper
  • 143 Downloads
Part of the following topical collections:
  1. 2018 International Conference of Microfluidics, Nanofluidics and Lab-on-a-Chip, Beijing, China

Abstract

This paper describes a comprehensive analysis of the geometrical parameters influencing the sensitivity of a coplanar electrode layout for electrical impedance flow cytometry. The designs presented in this work have been simulated, fabricated, and tested. 3D finite element method was applied to simulate and improve the sensitivity of the coplanar designs for two spacings between electrodes. The proposed model uses conditional expressions to define spatially dependent material properties. The vertical and lateral sensitivities were evaluated for all the designs. The experimental results obtained with polystyrene beads show good agreement with the simulations. Precentering particles with dielectrophoresis allowed to control their position in the microchannel. The optimized designs are envisioned to be used for sizing and characterizing particles from single cells to cell aggregates.

Keywords

Lab-on-a-Chip Impedance spectroscopy Flow cytometry Electrode design 

Notes

Acknowledgements

The authors acknowledge the support from the CMi staff at EPFL for their technical assistance. The Ampere lab would like to acknowledge support from the Institut National de la Santé et de la Recherche Médicale (INSERM, Plan Cancer, Physicancer Program, Dynamo project). The authors also acknowledge the support of the Programme d’Avenir Lyon Saint-Etienne (PALSE mobility Grant) and the Laboratoire d’Excellence iMUST (ANR-10-LABX-0064/ANR-11-IDEX-0007) from University of Lyon as well as the Doctoral school 160 EEA of the University of Lyon for the mobility grants allocated.

Compliance with ethical standards

Conflict of interest

There are no conflicts to declare.

Supplementary material

10404_2018_2178_MOESM1_ESM.pdf (1.6 mb)
Supplementary material 1 (PDF 1629 KB)

References

  1. Allen T (1997) Volume 1: powder sampling and particle size measurement. Particle size measurement. Springer, Amsterdam, pp 335Google Scholar
  2. Ayliffe HE, Frazier AB, Rabbitt RD (1999) Electric impedance spectroscopy using microchannels with integrated metal electrodes. J Microelectromech Syst 8:50–57.  https://doi.org/10.1109/84.749402 CrossRefGoogle Scholar
  3. Benazzi G, Holmes D, Sun T, Mowlem MC, Morgan H (2007) Discrimination and analysis of phytoplankton using a microfluidic cytometer. IET Nanobiotechnol 1:94–101.  https://doi.org/10.1049/iet-nbt:20070020 CrossRefGoogle Scholar
  4. Braschler T, Demierre N, Nascimento E, Silva T, Oliva AG, Renaud P (2008) Continuous separation of cells by balanced dielectrophoretic forces at multiple frequencies. Lab Chip 8:280–286.  https://doi.org/10.1039/b710303d CrossRefGoogle Scholar
  5. Brazey B, Cottet J, Bolopion A, Van Lintel H, Renaud P, Gauthier M (2018) Impedance-based real-time position sensor for lab-on-a-chip devices. Lab Chip 18:818–831.  https://doi.org/10.1039/c7lc01344b CrossRefGoogle Scholar
  6. Caselli F, Bisegna P (2017) Simulation and performance analysis of a novel high-accuracy sheathless microfluidic impedance cytometer with coplanar electrode layout. Med Eng Phys.  https://doi.org/10.1016/j.medengphy.2017.04.005 CrossRefGoogle Scholar
  7. Chen J et al (2011) Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells. Lab Chip 11:3174–3181.  https://doi.org/10.1039/c1lc20473d CrossRefGoogle Scholar
  8. Chen J, Xue C, Zhao Y, Chen D, Wu MH, Wang J (2015) Microfluidic impedance flow cytometry enabling high-throughput single-cell electrical property characterization. Int J Mol Sci 16:9804–9830.  https://doi.org/10.3390/ijms16059804 CrossRefGoogle Scholar
  9. Cheung K, Gawad S, Renaud P (2005) Impedance spectroscopy flow cytometry: on-chip label-free cell differentiation. Cytom Part A 65:124–132.  https://doi.org/10.1002/cyto.a.20141 CrossRefGoogle Scholar
  10. Clausen C, Skands G, Bertelsen C, Svendsen W (2014) Coplanar electrode layout optimized for increased sensitivity for electrical impedance spectroscopy. Micromachines 6:110–120.  https://doi.org/10.3390/mi6010110 CrossRefGoogle Scholar
  11. Cottet J, Vaillier C, Buret F, Frenea-Robin M, Renaud P (2017) A reproducible method for mum precision alignment of PDMS microchannels with on-chip electrodes using a mask aligner. Biomicrofluidics 11:064111.  https://doi.org/10.1063/1.5001145 CrossRefGoogle Scholar
  12. Cottet J, Kehren A, Lasli S, van Lintel H, Buret F, Frénéa-Robin M, Renaud P (2019) Dielectrophoresis-assisted creation of cell aggregates under flow conditions using planar electrodes. Electrophoresis (under revision)Google Scholar
  13. Coulter WH (1953) Means for counting particles suspended in a fluid. US PatentGoogle Scholar
  14. Coulter WH, Hogg WR (1970) Signal modulated apparatus for generating and detecting resistive and reactive changes in a modulated current path for particle classification and analysisGoogle Scholar
  15. Coulter WH, Rodriguez CM, (1988) Particle analyzer for measuring the resistance and reactance of a particleGoogle Scholar
  16. De Ninno A, Errico V, Bertani FR, Businaro L, Bisegna P, Caselli F (2017) Coplanar electrode microfluidic chip enabling accurate sheathless impedance cytometry. Lab Chip 17:1158–1166.  https://doi.org/10.1039/C6LC01516F CrossRefGoogle Scholar
  17. Demierre N (2008) Continuous-flow separation of cells in a lab-on-a-chip using “liquid electrodes” and multiple-frequency dielectrophoresis. Dissertation, EPFL.  https://doi.org/10.5075/epfl-thesis-4099
  18. Demierre N, Braschler T, Linderholm P, Seger U, van Lintel H, Renaud P (2007) Characterization and optimization of liquid electrodes for lateral dielectrophoresis. Lab Chip 7:355–365.  https://doi.org/10.1039/b612866a CrossRefGoogle Scholar
  19. Demierre N, Braschler T, Muller R, Renaud P (2008) Focusing and continuous separation of cells in a microfluidic device using lateral dielectrophoresis. Sens Actuators B Chem 132:388–396.  https://doi.org/10.1016/j.snb.2007.09.078 CrossRefGoogle Scholar
  20. Evander M, Ricco AJ, Morser J, Kovacs GTA, Leung LLK, Giovangrandi L (2013) Microfluidic impedance cytometer for platelet analysis. Lab Chip 13:722–729.  https://doi.org/10.1039/c2lc40896a CrossRefGoogle Scholar
  21. Gawad S, Schild L, Renaud PH (2001) Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing. Lab Chip 1:76–82.  https://doi.org/10.1039/b103933b CrossRefGoogle Scholar
  22. Haandbaek N, With O, Burgel SC, Heer F, Hierlemann A (2014a) Characterization of subcellular morphology of single yeast cells using high frequency microfluidic impedance cytometer. Lab Chip 14:3313–3324.  https://doi.org/10.1039/c3lc50866h CrossRefGoogle Scholar
  23. Haandbaek N, Burgel SC, Heer F, Hierlemann A (2014b) Resonance-enhanced microfluidic impedance cytometer for detection of single bacteria. Lab Chip 14:369–377.  https://doi.org/10.1039/c4lc00576g CrossRefGoogle Scholar
  24. Haandbaek N, Burgel SC, Rudolf F, Heer F, Hierlemann A (2016) Characterization of single yeast cell phenotypes using microfluidic impedance cytometry and optical imaging. ACS Sen 1:1020–1027.  https://doi.org/10.1021/acssensors.6b00286 CrossRefGoogle Scholar
  25. Han XJ, van Berkel C, Gwyer J, Capretto L, Morgan H (2012) Microfluidic lysis of human blood for leukocyte analysis using single cell impedance cytometry. Anal Chem 84:1070–1075.  https://doi.org/10.1021/ac202700x CrossRefGoogle Scholar
  26. Holmes D, Morgan H (2010) Single cell impedance cytometry for identification and counting of CD4 T-cells in human blood using impedance labels. Anal Chem 82:1455–1461.  https://doi.org/10.1021/ac902568p CrossRefGoogle Scholar
  27. Holmes D et al (2009) Leukocyte analysis and differentiation using high speed microfluidic single cell impedance cytometry. Lab Chip 9:2881–2889.  https://doi.org/10.1039/b910053a CrossRefGoogle Scholar
  28. Kuttel C, Nascimento E, Demierre N, Silva T, Braschler T, Renaud P, Oliva AG (2007) Label-free detection of Babesia bovis infected red blood cells using impedance spectroscopy on a microfabricated flow cytometer. Acta Trop 102:63–68.  https://doi.org/10.1016/j.actatropica.2007.03.002 CrossRefGoogle Scholar
  29. Morgan H, Spencer D (2015) Microfluidic impedance cytometry for blood cell analysis. Microfluidics for medical applications. The Royal Society of Chemistry, London, pp 213–241Google Scholar
  30. Petchakup C, Li KHH, Hou HW (2017) Advances in single cell impedance cytometry for biomedical applications. Micromachines.  https://doi.org/10.3390/mi8030087 CrossRefGoogle Scholar
  31. Reale R, De Ninno A, Businaro L, Bisegna P, Caselli F (2018) Electrical measurement of cross-sectional position of particles flowing through a microchannel. Microfluid Nanofluid.  https://doi.org/10.1007/s10404-018-2055-3 CrossRefGoogle Scholar
  32. Shaker M, Colella L, Caselli F, Bisegna P, Renaud P (2014) An impedance-based flow microcytometer for single cell morphology discrimination. Lab Chip 14:2548–2555.  https://doi.org/10.1039/c4lc00221k CrossRefGoogle Scholar
  33. Song HJ, Wang Y, Rosano JM, Prabhakarpandian B, Garson C, Pant K, Lai E (2013) A microfluidic impedance flow cytometer for identification of differentiation state of stem cells. Lab Chip 13:2300–2310.  https://doi.org/10.1039/c3lc41321g CrossRefGoogle Scholar
  34. Song HJ et al (2016) Identification of mesenchymal stem cell differentiation state using dual-micropore microfluidic impedance flow cytometry. Anal Methods UK 8:7437–7444.  https://doi.org/10.1039/c6ay01377e CrossRefGoogle Scholar
  35. Spencer D, Morgan H (2011) Positional dependence of particles in microfludic impedance cytometry. Lab Chip 11:1234–1239.  https://doi.org/10.1039/c1lc20016j CrossRefGoogle Scholar
  36. Spencer D, Hollis V, Morgan H (2014) Microfluidic impedance cytometry of tumour cells in blood. Biomicrofluidics.  https://doi.org/10.1063/1.4904405 CrossRefGoogle Scholar
  37. Sun T, Morgan H (2010) Single-cell microfluidic impedance cytometry: a review. Microfluid Nanofluid 8:423–443.  https://doi.org/10.1007/s10404-010-0580-9 CrossRefGoogle Scholar
  38. Zhao Y et al (2014) Tumor cell characterization and classification based on cellular specific membrane capacitance and cytoplasm conductivity. Biosens Bioelectron 57:245–253.  https://doi.org/10.1016/j.bios.2014.02.026 CrossRefGoogle Scholar
  39. Zhao Y et al (2016a) Electrical property characterization of neural stem cells in differentiation. PLoS One.  https://doi.org/10.1371/journal.pone.0158044 CrossRefGoogle Scholar
  40. Zhao Y et al (2016b) Single-cell electrical phenotyping enabling the classification of mouse tumor samples. Sci Rep 6:19487.  https://doi.org/10.1038/srep19487 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Univ Lyon, Ecole Centrale de Lyon, Université Claude Bernard Lyon 1, INSA Lyon, CNRS, AmpèreEcullyFrance
  2. 2.École Polytechnique Fédérale de Lausanne, EPFL-STI-IMT-LMIS4LausanneSwitzerland

Personalised recommendations