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Electrical impedance tomographic imaging of a single cell electroporation

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Abstract

A living cell placed in a high strength electric field, can undergo a process known as electroporation. It is believed that during electroporation nano-scale defects (pores) occur in the membrane of the cell, causing dramatic changes to the permeability of its membrane. Electroporation is an important technique in biotechnology and medicine and numerous methods are being developed to improve the understanding and use of the technology. We propose to extend the toolbox available for studying electroporation by generating impedance distribution images of the cell as it undergoes electroporation using Electrical Impedance Tomography (EIT). To investigate the feasibility of this concept, we develop a mathematical model of the process of electroporation in a single cell and of EIT of the process and show simulation results of a computer-based finite element model (FEM). Our work is an attempt to develop a new imaging tool for visualizing electroporation in a single cell, offering a different temporal and spatial resolution compared to the state of the art, which includes bulk measurements of electrical properties during single cell electroporation, patch clamp and voltage clamp measurement in single cells and optical imaging with colorimetric dyes during single cell electroporation. This paper is a preliminary theoretic feasibility study.

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References

  • A. Adler, Measurement of pulmonary function with electrical impedance tomography, Ecole polytechnique de Montreal (1996)

  • H. Beving et al., Dielectric properties of human blood and erythrocytes at radio frequencies (0.2–10 MHz); dependence on cell volume fraction and medium composition. Eur. Biophys. J. 23(3), 207–215 (1994)

    Article  Google Scholar 

  • B. Brown, Electrical impedance tomography (EIT): a review. J. Med. Eng. Technol. 27(3), 97–108 (2003)

    Article  Google Scholar 

  • K.T.C. Chai et al., Electrical impedance tomography for sensing with integrated microelectrodes on a CMOS microchip. Sensors Actuators B Chem. 127, 97–101 (2007)

    Article  Google Scholar 

  • C. Chen et al., Membrane electroporation theories: a review. Med. Biol. Eng. Comput. 44(1–2), 5–14 (2006)

    Article  Google Scholar 

  • M. Cheney et al., Electrical impedance tomography. SIAM Rev. 41(1), 85–101 (1999)

    Article  MATH  MathSciNet  Google Scholar 

  • L.V. Chernomordik et al., The electrical breakdown of cell and lipid membranes: the similarity of phenomenologies. Biochim. Biophys. Acta 902(3), 360–373 (1987)

    Article  Google Scholar 

  • R.V. Davalos et al., A feasibility study for electrical impedance tomography as a means to monitor tissue electroporation for molecular medicine. Biomed. Eng. IEEE Trans. 49(4), 400–403 (2002)

    Article  Google Scholar 

  • R.V. Davalos et al., Tissue ablation with irreversible electroporation. Ann. Biomed. Eng. 33(2), 223–231 (2005)

    Article  Google Scholar 

  • R. Davalos, B. Rubinsky, Tissue ablation with irreversible electroporation. USPTO. USA, UC system (2011)

  • S. Dharia et al., Single cell electric impedance topography: mapping membrane capacitance. Lab Chip 9(23), 3370–3377 (2009)

    Article  Google Scholar 

  • R.E. Diaz-Rivera, B. Rubinsky, Electrical and thermal characterization of nanochannels between a cell and a silicon based micro-pore. Biomed. Microdevices 8(1), 25–34 (2006)

    Article  Google Scholar 

  • J.F. Edd et al., In vivo results of a new focal tissue ablation technique: irreversible electroporation. Biomed. Eng. IEEE Trans. 53(7), 1409–1415 (2006)

    Article  Google Scholar 

  • J.F. Edd et al., Imaging cryosurgery with EIT: tracking the ice front and post-thaw tissue viability. Physiol. Meas. 29(8), 899–912 (2008)

    Article  Google Scholar 

  • B. Ehrenberg et al., Membrane potential induced by external electric field pulses can be followed with a potentiometric dye. Biophys. J. 51(5), 833–837 (1987)

    Article  Google Scholar 

  • A.T. Esser et al., Towards solid tumor treatment by irreversible electroporation: Intrinsic redistribution of fields and currents in tissue. Technol. Cancer Res. Treat. 6(4), 261–273 (2007)

    MathSciNet  Google Scholar 

  • K.R. Foster et al., The electrical resistivity of cytoplasm. Biophys. J. 16(9), 991–1001 (1976)

    Article  Google Scholar 

  • P. O Gaggero, P. Thomann, Miniaturization and distinguishability limits of electrical impedance tomography for biomedical application, PhD Thesis, (2011)

  • N.G. Gencer et al., Electrical impedance tomography: induced-current imaging achieved with a multiple coil system. Biomed. Eng. IEEE Trans. 43(2), 139–149 (1996)

    Article  MathSciNet  Google Scholar 

  • R.W. Glaser et al., Reversible electrical breakdown of lipid bilayers: formation and evolution of pores. Biochim. Biophys. Acta 940(2), 275–287 (1988)

    Article  Google Scholar 

  • A. Golberg et al., Irreversible electroporation for microbial control of drugs in solution. Aaps Pharmscitech 10(3), 881–886 (2009)

    Article  Google Scholar 

  • Y. Granot et al., In vivo imaging of irreversible electroporation by means of electrical impedance tomography. Phys. Med. Biol. 54(16), 4927 (2009)

    Article  Google Scholar 

  • D.S. Holder, Electrical impedance tomography: methods, history and applications, CRC Press (2010)

  • Y. Huang, B. Rubinsky, Micro-electroporation: improving the efficiency and understanding of electrical permeabilization of cells. Biomed. Microdevices 2(2), 145–150 (1999)

    Article  Google Scholar 

  • Y. Huang, B. Rubinsky, Microfabricated electroporation chip for single cell membrane permeabilization. Sensors Actuators A Phys. 89(3), 242–249 (2001)

    Article  Google Scholar 

  • M. Khine et al., Single-cell electroporation arrays with real-time monitoring and feedback control. Lab Chip 7(4), 457–462 (2007)

    Article  Google Scholar 

  • K.J. Kinosita, T.Y. Tsong, Formation and resealing of pores of controlled sizes in human erythrocyte membrane. Nature 268(5619), 438–441 (1977)

    Article  Google Scholar 

  • T. Kotnik et al., Cell membrane electroporation - Part 1: the phenomenon. IEE Electr. Insul. Mag. 28(5), 14–23 (2012)

    Article  Google Scholar 

  • W. Krassowska, P.D. Filev, Modeling electroporation in a single cell. Biophys. J. 92(2), 404–417 (2007)

    Article  Google Scholar 

  • Y. Lee, P. Deng, Review of micro/nano technologies and theories for electroporation of biological cells. Sci. China Phys. Mech. Astron. 55(6), 996–1003 (2012)

    Article  Google Scholar 

  • D.W. Marquardt, An algorithm for least-squares estimation of nonlinear parameters. J. Soc. Ind. Appl. Math. 11(2), 431–441 (1963)

    Article  MATH  MathSciNet  Google Scholar 

  • L.M. Mir et al., Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur. J. Cancer 27(1), 68–72 (1991)

    Article  MathSciNet  Google Scholar 

  • E. Neumann, K. Rosenheck, Permeability changes induced by electric impulses in vesicular membranes. J. Membr. Biol. 29(10), 279–290 (1972)

    Article  Google Scholar 

  • E. Neumann et al., Gene transfer into mouse lymphoma cells by electroporation in high electric fields. EMBO J. 1(7), 841–845 (1982)

    Google Scholar 

  • E. Neumann et al. (eds.), Electroporation and electrofusion in cell biology (Plenum Press, New York, 1989)

    Google Scholar 

  • F. Riemann et al., Release and uptake of haemoglobin and ions in red blood cells induced by dielectric breakdown. Biochim. Biophys. Acta 394(3), 449–462 (1975)

    Article  Google Scholar 

  • F. Ryttsen et al., Characterization of single-cell electroporation by using patch-clamp and fluorescence microscopy. Biophys. J. 79(4), 1993–2001 (2000)

    Article  Google Scholar 

  • A.J.H. Sale, W.A. Hamilton, Effects of high electric fields on microorganisms. 1. Killing of bacteria and yeasts. Biochim. Biophys. Acta 148, 781–788 (1967)

    Article  Google Scholar 

  • A.J.H. Sale, W.A. Hamilton, Effects of high electric fields on microorganisms. 3. Lysis of erythrocytes and protopasts. Biochim. Biophys. Acta 163, 37–43 (1968)

    Article  Google Scholar 

  • G. Saulis et al., Kinetics of pore resealing in cell-membranes after electroporation. Bioelectrochem. Bioenerg. 26(1), 1–13 (1991)

    Article  Google Scholar 

  • M.E. Spira, A. Hai, Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotechnology 8(2), 83–94 (2013)

    Article  Google Scholar 

  • T. Sun et al., On-chip electrical impedance tomography for imaging biological cells. Biosens. Bioelectron. 25(5), 1109–1115 (2010)

    Article  Google Scholar 

  • J. Teissie et al., Mechanisms of cell membrane electropermeabilization: a minireview of our present (lack of?) knowledge. Biochim. Biophys. Acta (BBA)-Gen. Subj. 1724(3), 270–280 (2005)

    Article  Google Scholar 

  • A.V. Titomirov et al., In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim. Biophys. Acta 1088(1), 131–134 (1991)

    Article  Google Scholar 

  • S. Toepfl et al., Review: potential of high hydrostatic pressure and pulsed electric fields for energy efficient and environmentally friendly food processing. Food Rev. Int. 22, 405–423 (2006)

    Article  Google Scholar 

  • J.C. Weaver, Electroporation theory. Concepts and mechanisms. Methods Mol. Biol. 47, 1–26 (1995)

    MathSciNet  Google Scholar 

  • J.C. Weaver, Electroporation of biological membranes from multicellular to nano scales. Dielectr. Electr. Insul. IEEE Trans. 10(5), 754–768 (2003)

    Article  MathSciNet  Google Scholar 

  • J.T. Yorkey, J.G. Webster, A comparison of impedance tomographic reconstruction algorithms. Clin. Phys. Physiol. Meas. 8, 55–62 (1987)

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Graduate Program in Biophysics, UC Berkeley, 6124 Etcheverry Hall, Berkeley, CA, 94720, USA

    Arie Meir

  2. Department of Mechanical Engineering, UC Berkeley, 6124 Etcheverry Hall, Berkeley, CA, 94720, USA

    Boris Rubinsky

Authors
  1. Arie Meir
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  2. Boris Rubinsky
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Correspondence to Arie Meir.

Appendix

Appendix

Table 1 Model electric parameters used for numerical experiments
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Meir, A., Rubinsky, B. Electrical impedance tomographic imaging of a single cell electroporation. Biomed Microdevices 16, 427–437 (2014). https://doi.org/10.1007/s10544-014-9845-5

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