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

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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.

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References

  • Ayliffe HE, Frazier AB, Rabbitt RD (1999) Electric impedance spectroscopy using microchannels with integrated metal electrodes. J Microelectromech S 8:50–57

    Article  Google Scholar 

  • 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):41–48

    Article  Google Scholar 

  • 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 1:103–106

    Google Scholar 

  • Beilenhoff K, Klingbeil H, Heinrich W, Hartnagel HL (1993) Open and short circuits in coplanar MMIC’s. IEEE T Microw Theory 41(9):1534–1537

    Article  Google Scholar 

  • 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):1928–1934

    Article  Google Scholar 

  • 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–A360

    Article  Google Scholar 

  • Fouad HV (1980) Finite boundary corrections to coplanar stripline analysis. Electron Lett 16(15):604–606

    Article  Google Scholar 

  • Gawad S, Cheung K, Seger U, Bertsch A, Renaud P (2004) Dielectric spectroscopy in a micromachined flow cytometer: theoretical and practical considerations. Lab Chip 4:241–251

    Article  Google Scholar 

  • Ghione G, Naldi C (1983) Parameters of coplanar waveguides with lower ground plane. Electron Lett 19(18):734–735

    Article  Google Scholar 

  • 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 3:201–209

    Article  Google Scholar 

  • 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 24:9066–9073

    Article  Google Scholar 

  • Hilberg W (1969) From approximations to exact relations for characteristic impedances. IEEE T Microw Theory 17(5):259–265

    Article  Google Scholar 

  • Hobbie RK (1997) Intermediate physics for medicine and biology, 3rd edn. American Institute of Physics, New York

    Google Scholar 

  • 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):1789–1806

    Article  Google Scholar 

  • Jang LS, Wang WH (2007) Microfluidic device for cell capture and impedance measurement. Biomed Microdevices 9(5):737–743

    Article  Google Scholar 

  • Kitazawa T, Hayashi Y (1987) Variational method for coplanar waveguide with anisotropic substrates. IEE Proc H Microw Antennas Propag 134(1):7–10

    Article  Google Scholar 

  • 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: 243902

    Google Scholar 

  • Markx GH, Davey CL (1999) The dielectric properties of biological cells at radiofrequencies: applications in biotechnology. Enzyme Microb Technol 25:161–171

    Google Scholar 

  • 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 Systems

  • Olapinski M, Manus S, Fertig N, Simmel FC (2007) Probing whole cell currents in high-frequency electrical fields: identification of thermal effects. Biosens Bioelectron 23:872–878

    Article  Google Scholar 

  • Pething R, Kell DB (1987) The passive electrical properties of biological systems: their significance in physiology, biophysics and biotechnology. Phys Med Biol 32:933–970

    Google Scholar 

  • 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 York

  • 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 73:1866–1872

    Article  Google Scholar 

  • Schuy S, Janshoff A (2006) Microstructuring of phospholipid bilayers on gold surfaces by micromolding in capillaries. J Colloid Interface Sci 295(1):93–99

    Article  Google Scholar 

  • Simon RN (2001) Coplanar waveguide circuits, components, and systems. Wiley, New York

  • Simons RN, Ponchak GE (1988) Modeling of some coplanar waveguide discontinuities. IEEE T Microw Theory 36(12):1796–1803

    Article  Google Scholar 

  • Sun T, Green NG, Morgan H (2007) Analytical and numerical modeling methods for impedance analysis of single cells on-chip. Nano 3(1):55–63

    Article  Google Scholar 

  • Templer RH, Ces O (2008) New frontiers in single-cell analysis. J R Soc Interface 5:S111–S112

    Article  Google Scholar 

  • Veyres C, Hanna VF (1980) Extension of the application of conformal mapping techniques to coplanar lines with finite dimensions. Int J Electron 48(1):47–56

    Article  Google Scholar 

  • Wei YZ, Sridhar S (1989) Technique for measuring complex dielectric constants of to 20 GHz. Rev sci Instrum 60(9):3041–3046

    Article  Google Scholar 

  • Wen CP (1969) Coplanar waveguide: a surface strip transmission line suitable for nonreciprocal gyromagnetic device applications. IEEE T Microw Theory 17(12):1087–1090

    Article  Google Scholar 

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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.

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  1. Department of Electrical Engineering and Center for Micro/Nano Science and Technology, National Cheng Kung University, 1 University Road, Tainan, 701, Taiwan

    Ling-Sheng Jang, Hsin-Hung Li, Jen-Yu Jao, Ming-Kun Chen & Chia-Feng Liu

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  1. Ling-Sheng Jang
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  2. Hsin-Hung Li
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  3. Jen-Yu Jao
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  4. Ming-Kun Chen
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  5. Chia-Feng Liu
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Correspondence to Ling-Sheng Jang.

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Jang, LS., Li, HH., Jao, JY. et al. Design and fabrication of microfluidic devices integrated with an open‐ended MEMS probe for single‐cell impedance measurement. Microfluid Nanofluid 8, 509–519 (2010). https://doi.org/10.1007/s10404-009-0480-z

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  • DOI: https://doi.org/10.1007/s10404-009-0480-z

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