Microfluidics and Nanofluidics

, Volume 8, Issue 4, pp 509–519 | Cite as

Design and fabrication of microfluidic devices integrated with an open‐ended MEMS probe for single‐cell impedance measurement

  • Ling-Sheng Jang
  • Hsin-Hung Li
  • Jen-Yu Jao
  • Ming-Kun Chen
  • Chia-Feng Liu
Research Paper
First Online:
Received:
Accepted:

Abstract

When an electrical current with a low frequency is applied to a cell, the current passes through the outside of the cell. Thus, impedance measurements at low frequencies cannot be used to determine the pathological change of the cellular organelle taking place inside the cell. However, increasing the frequency of the electrical current makes the capacitive impedance of the cell decrease, allowing the electrical current to flow through the cell. This study presents the design and fabrication of a microfluidic device integrated with a coplanar waveguide open-ended micro-electro-mechanical-systems (MEMS) probe for the impedance measurement of the single HeLa cell in frequencies between 1 MHz and 1 GHz. The device includes a poly-dimethlysiloxane (PDMS) cover with a microchannel and microstructures to capture the single HeLa cell and a conductor-backed CPW fabricated using a silicon chip and two printed circuit boards (PCB). The effects of the substrate on the characteristic impedance of the conductor-backed coplanar waveguide (CBCPW) structure were investigated under three conditions by utilizing a time-domain reflectometer (TDR). Finally, impedance measurements using the proposed device and a vector network analyzer (VNA) are demonstrated for de-ionized (DI) water, alcohol, PBS, and a single HeLa cell.

Keywords

Single cell Cell impedance Microfluidics MEMS Coplanar waveguide Probe Conductor-backed coplanar waveguide (CBCPW) 
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Notes

Acknowledgments

This study was supported by the National Science Council, Taiwan, R.O·C., (NSC 96-2221-E-006-289), and made use of shared facilities provided under the Program of Top 100 Universities Advancement funded by the Ministry of Education in Taiwan. The authors would also like to thank the Center for Micro/Nano Science and Technology at National Cheng Kung University and the National Nano Device Laboratories for access granted to major equipment throughout the duration of this study and for their general technical support.

References

  1. Ayliffe HE, Frazier AB, Rabbitt RD (1999) Electric impedance spectroscopy using microchannels with integrated metal electrodes. J Microelectromech S 8:50–57CrossRefGoogle Scholar
  2. Bedair SS, Wolff I (1992) Fast, accurate and simple approximate analytic formulas for calculating the parameters of supported coplanar waveguides for MMIC’s. IEEE T Microw Theory 40(1):41–48CrossRefGoogle Scholar
  3. Beilenhoff K, Heinrich W, Hartnagel HL (1992) Finite-difference analysis of open and short circuits in coplanar MMIC’s including finite metallization thickness and mode conversion. IEEE MTT-S Int Microw Symp Dig 1:103–106Google Scholar
  4. Beilenhoff K, Klingbeil H, Heinrich W, Hartnagel HL (1993) Open and short circuits in coplanar MMIC’s. IEEE T Microw Theory 41(9):1534–1537CrossRefGoogle Scholar
  5. Bérubé D, Ghannouchi F, Savard P (1996) A comparative study of four open-ended coaxial probe models for permittivity measurements of lossy dielectric/biological materials at microwave frequencies. IEEE Trans Microw Theory Tech 44(10):1928–1934CrossRefGoogle Scholar
  6. Chmiola J, Yushin G, Dash RK, Hoffman EN, Fischer JE, Barsoum MW, Gogotsi Y (2005) Double-layer capacitance of carbide derived carbons in sulfuric acid. Electrodhem Solid St 8:A357–A360CrossRefGoogle Scholar
  7. Fouad HV (1980) Finite boundary corrections to coplanar stripline analysis. Electron Lett 16(15):604–606CrossRefGoogle Scholar
  8. Gawad S, Cheung K, Seger U, Bertsch A, Renaud P (2004) Dielectric spectroscopy in a micromachined flow cytometer: theoretical and practical considerations. Lab Chip 4:241–251CrossRefGoogle Scholar
  9. Ghione G, Naldi C (1983) Parameters of coplanar waveguides with lower ground plane. Electron Lett 19(18):734–735CrossRefGoogle Scholar
  10. Gomez R, Bashir R, Sarikaya A, Ladisch MR, Sturgis J, Robinson JP, Geng t, Bhunia AK, Apple HL, Wereley S (2001) Microfluidic bioship for impedance spectroscopy of biological species. Biomed Microdev 3:201–209CrossRefGoogle Scholar
  11. Heiskanen Arto R, Spegel Christer F, Natalie K, Tautgirdas R, Jenny E (2008) Monitoring of saccharomyces cerevisiae cell proliferation on thiol-modified planar gold microelectrodes using impedance spectroscopy. Langmuir 24:9066–9073CrossRefGoogle Scholar
  12. Hilberg W (1969) From approximations to exact relations for characteristic impedances. IEEE T Microw Theory 17(5):259–265CrossRefGoogle Scholar
  13. Hobbie RK (1997) Intermediate physics for medicine and biology, 3rd edn. American Institute of Physics, New YorkGoogle Scholar
  14. Huang Y, Wang XB, Holzel R, Beckert FF, Gascoynet PRC (1995) Electrorotational studies of the cytoplasmic dielectric properties of Friend murine erythroleukaemia cells. Phys Med Biol 40(11):1789–1806CrossRefGoogle Scholar
  15. Jang LS, Wang WH (2007) Microfluidic device for cell capture and impedance measurement. Biomed Microdevices 9(5):737–743CrossRefGoogle Scholar
  16. Kitazawa T, Hayashi Y (1987) Variational method for coplanar waveguide with anisotropic substrates. IEE Proc H Microw Antennas Propag 134(1):7–10CrossRefGoogle Scholar
  17. Lohndorf M, Schlecht U, Gronewold TMA, Malave A, Tewes M (2005) Microfabricated high-performance microwave impedance biosensors for detection of aptamer-protein interactions. Appl Phys Lett 87: 243902Google Scholar
  18. Markx GH, Davey CL (1999) The dielectric properties of biological cells at radiofrequencies: applications in biotechnology. Enzyme Microb Technol 25:161–171Google Scholar
  19. Messina TC, Dunkleberger LN, Mensing GA, Kalmbach AS, Weiss R, Beebe DJ, Sohn LL (2003) A Novel high-frequency sensor for biological discrimination. In: The 7th International Conference on Micro Total Analysis SystemsGoogle Scholar
  20. Olapinski M, Manus S, Fertig N, Simmel FC (2007) Probing whole cell currents in high-frequency electrical fields: identification of thermal effects. Biosens Bioelectron 23:872–878CrossRefGoogle Scholar
  21. Pething R, Kell DB (1987) The passive electrical properties of biological systems: their significance in physiology, biophysics and biotechnology. Phys Med Biol 32:933–970Google Scholar
  22. Ramo S, Whinnery JR, and Duzer TV (1994) Fields and waves in communication electronics. secs. 2.5, 3.16, 3.17, 3.18, and 5.11. Wiley, New YorkGoogle Scholar
  23. Rauch W, Gornik E, Solkner G, Valenzuela AA, Fox F, Bechner H (1993) Microwae properties of YBa2Cu3O7 − x Thin films studied with coplanar transmission line resonators. J Appl Phys 73:1866–1872CrossRefGoogle Scholar
  24. Schuy S, Janshoff A (2006) Microstructuring of phospholipid bilayers on gold surfaces by micromolding in capillaries. J Colloid Interface Sci 295(1):93–99CrossRefGoogle Scholar
  25. Simon RN (2001) Coplanar waveguide circuits, components, and systems. Wiley, New YorkGoogle Scholar
  26. Simons RN, Ponchak GE (1988) Modeling of some coplanar waveguide discontinuities. IEEE T Microw Theory 36(12):1796–1803CrossRefGoogle Scholar
  27. Sun T, Green NG, Morgan H (2007) Analytical and numerical modeling methods for impedance analysis of single cells on-chip. Nano 3(1):55–63CrossRefGoogle Scholar
  28. Templer RH, Ces O (2008) New frontiers in single-cell analysis. J R Soc Interface 5:S111–S112CrossRefGoogle Scholar
  29. Veyres C, Hanna VF (1980) Extension of the application of conformal mapping techniques to coplanar lines with finite dimensions. Int J Electron 48(1):47–56CrossRefGoogle Scholar
  30. Wei YZ, Sridhar S (1989) Technique for measuring complex dielectric constants of to 20 GHz. Rev sci Instrum 60(9):3041–3046CrossRefGoogle Scholar
  31. Wen CP (1969) Coplanar waveguide: a surface strip transmission line suitable for nonreciprocal gyromagnetic device applications. IEEE T Microw Theory 17(12):1087–1090CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ling-Sheng Jang
    • 1
  • Hsin-Hung Li
    • 1
  • Jen-Yu Jao
    • 1
  • Ming-Kun Chen
    • 1
  • Chia-Feng Liu
    • 1
  1. 1.Department of Electrical Engineering and Center for Micro/Nano Science and TechnologyNational Cheng Kung UniversityTainanTaiwan

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