Electrical properties characterization of single yeast cells by dielectrophoretic motion and electro-rotation

Abstract

The electrical parameters of single cells are label-free and intrinsic properties that can reflect the physiological characteristics. In recent years, many measurement methods based on impedance spectroscopy and rotation spectrum analysis have been developed. However, most of these works need to measure the response at whole frequency range to obtain DEP spectra and estimate the electrical parameters by fitting method, which are time-consuming and limit the measurement throughput. Therefore, improving the measurement throughput for single cells is an essential problem to be solved addressed. In this paper we present a microfluidic chip that combines dielectrophoretic motion and electro-rotation technology for single-cell electrical properties characterization. Since the movement and rotation speed of single cell in mediums are related to the electrical parameters of itself, electric signals and medium, the electrical properties can be obtained by measuring and analyzing the movement trajectory and rotation speed of the cell. Numerical simulations were performed to analyze the electric field distribution of the chip under different signal configurations, which predict the movement trajectory and rotation state, and determine the values of electric field on the cells. Based on the simulation results, cell focusing, dielectrophoretic motion and electro-rotation were successfully realized. By analyzing the movement trajectory and rotation speed, the conductivity of wall and the permittivity of membrane of yeast cells were characterized. The measurement method avoids the time-consuming of the traditional rotational spectra method, and can realize rapid and efficiency and single-cell electrical characterization.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. F. Alnaimat, S. Ramesh, A. Alazzam, A. Hilal-Alnaqbi, W. Waheed, B. Mathew, Dielectrophoresis-based 3D-focusing of microscale entities in microfluidic devices. Cytome. Part A 93(8), 811–821 (2018)

    Article  Google Scholar 

  2. A. Alrifaiy, J. Borg, O.A. Lindahl, K. Ramser, A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy- first investigations of single biological cells. Biomed. Eng. Online 14, 36 (2015)

    Article  Google Scholar 

  3. R.K. Anand, E.S. Johnson, D.T. Chiu, Negative dielectrophoretic capture and repulsion of single cells at a bipolar electrode: the impact of faradaic ion enrichment and depletion. J. Am. Chem. Soc. 137(2), 776–783 (2015)

    Article  Google Scholar 

  4. K. Asami, T. Yonezawa, Dielectric behavior of wild-type yeast and vacuole-deficient mutant over a frequency range of 10 kHz to 10 GHz. Biophy. J. 71(4), 2192–2200 (1996)

    Article  Google Scholar 

  5. L. Chen, X. Liu, X. Zheng, X. Zhang, J. Yang, T. Tian, Y. Liao, Dielectrophoretic separation of particles using microfluidic chip with composite three-dimensional electrode. Micromachines 11(7), 700 (2020)

    Article  Google Scholar 

  6. Y. Feng, L. Huang, P. Zhao, F. Liang, W. Wang, A microfluidic device integrating impedance flow cytometry and electric impedance spectroscopy for high-efficiency single-cell electrical property measurement. Anal. Chem. 91(23), 15204–15212 (2019)

    Article  Google Scholar 

  7. F.J. Garcia-Diego, M. Rubio-Chavarria, P. Beltran, F.J. Espinos, Characterization of simple and double yeast cells using dielectrophoretic force measurement. Sensors 19(17), 3813 (2019)

    Article  Google Scholar 

  8. N. Haandbæk, S.C. Bürgel, F. Rudolf, F. Heer, A. Hierlemann, Characterization of single yeast cell phenotypes using microfluidic impedance cytometry and optical imaging. ACS Sensors 1(8), 1020–1027 (2016)

    Article  Google Scholar 

  9. M. Habaza, M. Kirschbaum, C. Guernth-Marschner, G. Dardikman, I. Barnea, R. Korenstein, C. Duschl, N.T. Shaked, Rapid 3D refractive-index imaging of live cells in suspension without labeling using dielectrophoretic cell rotation. Adv. Sci. 4(2), 1600205 (2017)

    Article  Google Scholar 

  10. S.I. Han, Y.D. Joo, K.H. Han, An electrorotation technique for measuring the dielectric properties of cells with simultaneous use of negative quadrupolar dielectrophoresis and electrorotation. Analyst 138(5), 1529–1537 (2013)

    Article  Google Scholar 

  11. L. Huang, W. He, W. Wang, A cell electro-rotation micro-device using polarized cells as electrodes. Electrophoresis 40(5), 784–791 (2019)

    Article  Google Scholar 

  12. L. Huang, F. Liang, Y. Feng, A microfluidic chip for single-cell 3D rotation enabling self-adaptive spatial localization. J. Appl. Phys. 126(23), 234702 (2019)

    Article  Google Scholar 

  13. L. Huang, P. Zhao, W. Wang, 3D cell electrorotation and imaging for measuring multiple cellular biophysical properties. Lab Chip 18(16), 2359–2368 (2018)

    Article  Google Scholar 

  14. M.P. Hughes, Computer-aided analysis of conditions for optimizing practical electrorotation. Phys. Med. Biol. 43(12), 3639–3648 (1998)

    Article  Google Scholar 

  15. M.P. Hughes, X.B. Wang, F.F. Becker, P.R.C. Gascoyne, R. Pethig, Computer-aided analyses of electric fields used in electrorotation studies. J. Phys. D Appl. Phys. 27(7), 1564–1570 (1994)

    Article  Google Scholar 

  16. J.M. Irish, N. Kotecha, G.P. Nolan, Mapping normal and cancer cell signalling networks: towards single-cell proteomics. Nat. Rev. Cancer 6(2), 146–155 (2006)

    Article  Google Scholar 

  17. A. Jaffe, J. Voldman, Multi-frequency dielectrophoretic characterization of single cells. Microsyst. Nanoeng. 4, 23 (2018)

    Article  Google Scholar 

  18. C.P. Jen, T.W. Chen, Selective trapping of live and dead mammalian cells using insulator-based dielectrophoresis within open-top microstructures. Biomed. Microdevices 11, 597–607 (2009)

    Article  Google Scholar 

  19. T.B. Jones, Basic theory of dielectrophoresis and electrorotation. IEEE Eng. Med. Biol. 22(6), 33–42 (2003)

    Article  Google Scholar 

  20. T. Lannin, W.W. Su, C. Gruber, I. Cardle, C. Huang, F. Thege, B. Kirby, Automated electrorotation shows electrokinetic separation of pancreatic cancer cells is robust to acquired chemotherapy resistance, serum starvation, and EMT. Biomicrofluidics 10(6), 064109 (2016)

    Article  Google Scholar 

  21. Y.L. Liang, Y.P. Huang, Y.S. Lu, M.T. Hou, J.A. Yeh, Cell rotation using optoelectronic tweezers. Biomicrofluidics 4(4), 043003 (2010)

    Google Scholar 

  22. A. Mansoorifar, A. Koklu, A.C. Sabuncu, A. Beskok, Dielectrophoresis assisted loading and unloading of microwells for impedance spectroscopy. Electrophoresis 38(11), 1466–1474 (2017)

    Article  Google Scholar 

  23. S. Patel, D. Showers, P. Vedantam, T.R. Tzeng, S. Qian, X. Xuan, Microfluidic separation of live and dead yeast cells using reservoir-based dielectrophoresis. Biomicrofluidics 6(3), 034102 (2012)

    Article  Google Scholar 

  24. P. Pathak, H. Zhao, Z. Gong, F. Nie, T. Zhang, K. Cui, Z. Wang, S.T. Wong, L. Que, Real-time monitoring of cell viability using direct electrical measurement with a patch-clamp microchip. Biomed. Microdevices 13(5), 949–953 (2011)

    Article  Google Scholar 

  25. C.C.H. Petersen, Whole-cell recording of neuronal membrane potential during behavior. Neuron 95(6), 1266–1281 (2017)

    Article  Google Scholar 

  26. M. Schwarz, M. Jendrusch, I. Constantinou, Spatially resolved electrical impedance methods for cell and particle characterization. Electrophoresis 41(1–2), 65–80 (2020)

    Article  Google Scholar 

  27. H. Shafiee, J.L. Caldwell, M.B. Sano, R.V. Davalos, Contactless dielectrophoresis: a new technique for cell manipulation. Biomed. Microdevices 11(5), 997–1006 (2009)

    Article  Google Scholar 

  28. M.J.T. Stubbington, O. Rozenblatt-Rosen, A. Regev, S.A. Teichmann, Single-cell transcriptomics to explore the immune system in health and disease. Science 358(6359), 58–63 (2017)

    Article  Google Scholar 

  29. J. Sun, Y. Gao, R.J. Isaacs, K.C. Boelte, P.C. Lin, E.M. Boczko, D. Li, Simultaneous on-chip DC dielectrophoretic cell separation and quantitative separation performance characterization. Anal. Chem. 84(4), 2017–2024 (2012)

    Article  Google Scholar 

  30. S.Y. Tang, P. Yi, R. Soffe, S. Nahavandi, R. Shukla, K. Khoshmanesh, Using dielectrophoresis to study the dynamic response of single budding yeast cells to Lyticase. Anal. Bioanal. Chem. 407(12), 3437–3448 (2015)

    Article  Google Scholar 

  31. C.I. Trainito, E. Bayart, F. Subra, O. Francais, B. Le Pioufle, The electrorotation as a tool to monitor the dielectric properties of spheroid during the permeabilization. J. Membr. Biol. 249(5), 593–600 (2016)

    Article  Google Scholar 

  32. A. Valero, T. Braschler, P. Renaud, A unified approach to dielectric single cell analysis: Impedance and dielectrophoretic force spectroscopy. Lab Chip 10(17), 2216–2225 (2010)

    Article  Google Scholar 

  33. Y. Xu, X. Xie, Y. Duan, L. Wang, Z. Cheng, J. Cheng, A review of impedance measurements of whole cells. Biosens. Bioelectron. 77, 824–836 (2016)

    Article  Google Scholar 

  34. L. Zhang, S. Wan, Y. Jiang, Y. Wang, T. Fu, Q. Liu, Z. Cao, L. Qiu, W. Tan, Molecular elucidation of disease biomarkers at the interface of chemistry and biology. J. Am. Chem. Soc. 139(7), 2532–2540 (2017)

    Article  Google Scholar 

  35. Z. Zhang, T. Zheng, R. Zhu, Characterization of single-cell biophysical properties and cell type classification using dielectrophoresis model reduction method. Sensor. Actuat. B-Chemical 304, 127326 (2020)

    Article  Google Scholar 

  36. Y. Zhao, D. Chen, Y. Luo, F. Chen, X. Zhao, M. Jiang, W. Yue, R. Long, J. Wang, J. Chen, Simultaneous characterization of instantaneous Young’s modulus and specific membrane capacitance of single cells using a microfluidic system. Sensors 15(2), 2763–2773 (2015)

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Fundamental Research Funds for the Central Universities (JZ2019HGBZ0165)

Author information

Affiliations

Authors

Corresponding author

Correspondence to Liang Huang.

Ethics declarations

Conflict of interest

The authors have declared no conflict of interest.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 6020 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huang, L., Fang, Q. Electrical properties characterization of single yeast cells by dielectrophoretic motion and electro-rotation. Biomed Microdevices 23, 11 (2021). https://doi.org/10.1007/s10544-021-00550-7

Download citation

Keywords

  • Dielectrophoresis
  • Electro-rotation
  • Electrical properties
  • Microfluidic