Microfluidic dielectrophoretic cell manipulation towards stable cell contact assemblies

Abstract

Cell contact formation, which is the process by which cells are brought into close proximity is an important biotechnological process in cell and molecular biology. Such manipulation is achieved by various means, among which dielectrophoresis (DEP) is widely used due to its simplicity. Here, we show the advantages in the judicious choice of the DEP microelectrode configuration in terms of limiting undesirable effects of dielectric heating on the cells, which could lead to their inactivation or death, as well as the possibility for cell clustering, which is particularly advantageous over the linear cell chain arrangement typically achieved to date with DEP. This study comprises of experimental work as well as mathematical modeling using COMSOL. In particular, we establish the parameters in a capillary-based microfluidic system giving rise to these optimum cell–cell contact configurations, together with the possibility for facilitating other cell manipulations such as spinning and rotation, thus providing useful protocols for application into microfluidic bioparticle manipulation systems for diagnostics, therapeutics or for furthering research in cellular bioelectricity and intercellular interactions.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. M.A. Abdul Razak, K.F. Hoettges, H.O. Fatoyinbo, F.H. Labeed, M.P. Hughes, Biomicrofluidics 7, 064110 (2013)

    Article  Google Scholar 

  2. Y. Abe, K. Nagamine, M. Nakabayashi, H. Kai, H. Kaji, T. Yamauchi, K. Yamasaki, M. Nishizawa, Biomed. Microdevices 18, 55 (2016)

    Article  Google Scholar 

  3. A.K. Adya, E. Canetta, G.M. Walker, FEMS Yeast Res. 6, 120 (2006)

    Article  Google Scholar 

  4. B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, J. Wilson, T. Hunt, Molecular Biology of the Cell (Garland Science, New York, 2008)

  5. A. Andryieuski, S.M. Kuznetsova, S.V. Zhukovsky, Y.S. Kivshar, A.V. Lavrinenko, Sci. Rep. 5, 13535 (2015)

  6. P. Benhal, J.G. Chase, P. Gaynor, B. Oback, W. Wang, Lab Chip 14, 2717 (2014)

    Article  Google Scholar 

  7. H. Berg, in Mod. Bioelectr., ed. by A.A. Marino (CRC Press, New York, 1988), p. 269

  8. M. Birle, C. Leu, in 18th Int. Symp. High Volt. Eng (Seoul, 2013), p. 1025

  9. D. Botstein, G.R. Fink, Genetics 189, 695 (2011)

    Article  Google Scholar 

  10. S. Burgarella, M. Di Bari, B. Sarah, B.M. Di, Electrophoresis 36, 1466 (2015)

    Article  Google Scholar 

  11. A. Castellanos, A. Ramos, A. González, N.G. Green, H. Morgan, J. Phys. D. Appl. Phys. 36, 2584 (2003)

    Article  Google Scholar 

  12. B. Çetin, D. Li, Electrophoresis 32, 2410 (2011)

    Article  Google Scholar 

  13. B. Çetin, M.B. Özer, M.E. Solmaz, Biochem. Eng. J. 92, 63 (2014)

    Article  Google Scholar 

  14. H.K. Chu, Z. Huan, J.K. Mills, J. Yang, D. Sun, in IEEE Int. Conf. Intell. Robot. Syst. (Chicago, 2014), p. 2003

  15. J. Coffel, E. Nuxoll, Int. J. Pharm. 544, 335 (2018)

    Article  Google Scholar 

  16. F. Dal Dosso, T. Kokalj, J. Belotserkovsky, D. Spasic, J. Lammertyn, Biomed. Microdevices 20, 44 (2018)

  17. D.S. Dimitrov, in Handb. Biol. Phys., ed. by R. Lipowsky and E. Sackmann (Elsevier, Amsterdam, 1995), p. 851

  18. H. Ding, J. Shao, Y. Ding, W. Liu, X. Li, H. Tian, Y. Zhou, Appl. Surf. Sci. 330, 178 (2015)

    Article  Google Scholar 

  19. L. Doh-Hyoung, Y. Chengjie, P. Elisabeth, F. Bakhtier, N.H. M, Electrophoresis 32, 2298 (2011)

    Google Scholar 

  20. V.A. Evans, N. Kumar, A. Filali, F.A. Procopio, O. Yegorov, J.P. Goulet, S. Saleh, E.K. Haddad, C. da Fonseca Pereira, P.C. Ellenberg, R.P. Sekaly, P.U. Cameron, S.R. Lewin, PLoS Pathog. 9, e1003799 (2013)

  21. R.E. Fernandez, B.J. Sanghavi, V. Farmehini, J.L. Chávez, J. Hagen, N. Kelley-Loughnane, C.-F. Chou, N.S. Swami, Electrochem. Commun. 72, 144 (2016)

    Article  Google Scholar 

  22. M. Ferrari, BioMEMS and Biomedical Nanotechnology (Springer, Boston, 2007)

    Book  Google Scholar 

  23. N. García, E. Benito, P. Tiemblo, M.M.B. Hasan, A. Synytska, M. Stamm, Soft Matter 6, 4768 (2010)

    Article  Google Scholar 

  24. M. Gel, Y. Kimura, O. Kurosawa, H. Oana, H. Kotera, M. Washizu, Biomicrofluidics 4, 022808 (2010)

    Article  Google Scholar 

  25. J.W. Gooch, in Encycl. Dict. Polym., ed. by J. W. Gooch (Springer, New York, 2011), p. 213 

  26. N. Gopalakrishnan, R. Hannam, G.P. Casoni, D. Barriet, J.M. Ribe, M. Haug, O. Halaas, Lab Chip 15, 1481 (2015)

    Article  Google Scholar 

  27. L. He, J. Huang, N. Perrimon, Proc. Natl. Acad. Sci. 114, 5467 (2017)

  28. N. Hu, J. Yang, S. Qian, S.W. Joo, X. Zheng, Biomicrofluidics 5, 34121 (2011)

    Article  Google Scholar 

  29. N. Hu, J. Yang, S.W. Joo, A.N. Banerjee, S. Qian, Sensors Actuators B Chem. 178, 63 (2013)

  30. M. Iwamoto, in Encycl. Nanotechnol., ed. by B. Bhushan (Springer, Dordrecht, 2012), p. 1276

  31. T.B. Jones, Electromechanics of Particles (Cambridge University Press, Cambridge; New York, 1995)

    Book  Google Scholar 

  32. S. Kakaç, Microfluidics Based Microsystems Fundamentals and Applications (Springer, Dordrecht, 2010)

    Book  Google Scholar 

  33. M. Kandušer, D. Miklavčič, in Electrotechnol. Extr. From Food Plants Biomater., ed. by E. Vorobiev and N. Lebovka (Springer, New York, 2008), p. 1

  34. A.A. Kayani, K. Khoshmanesh, T.G. Nguyen, G. Kostovski, A.F. Chrimes, M. Nasabi, D.A. Heller, A. Mitchell, K. Kalantar-zadeh, Electrophoresis 33, 2075 (2012a)

    Article  Google Scholar 

  35. A.A. Kayani, K. Khoshmanesh, S.A. Ward, A. Mitchell, K. Kalantar-zadeh, Biomicrofluidics 6, 031501 (2012b)

  36. E.W.M. Kemna, F. Wolbers, I. Vermes, A. van den Berg, Electrophoresis 32, 3138 (2011)

    Article  Google Scholar 

  37. J.C. Krebs, Y. Alapan, B.A. Dennstedt, G.D. Wera, U.A. Gurkan, Biomed. Microdevices 19, 20 (2017)

  38. J. Li, X. Yu, T.E. Wagner, Y. Wei, Oncol. Lett. 8, 198 (2014)

    Article  Google Scholar 

  39. J.H. Lienhard IV, J.H. Lienhard V, A Heat Transfer Textbook (Dover Publications, New York, 2011)

  40. A.P. Liu, O. Chaudhuri, S.H. Parekh, Integr. Biol. 9, 383 (2017)

    Article  Google Scholar 

  41. A. Longo, A. Baraket, M. Vatteroni, N. Zine, J. Baussells, RogerFuoco, F. Di Francesco, G.S. Karanasiou, D.I. Fotiadis, A. Menciassi, A. Errachid, Procedia Eng. 168, 97 (2016)

  42. X. Luo, J.J. He, J. Neuro-Oncol. 21, 66 (2015)

    Google Scholar 

  43. M.A. Md Ali, K. (Ken) Ostrikov, F.A. Khalid, B.Y. Majlis, A.A. Kayani, RSC Adv. 6, 113066 (2016)

  44. M. Mehdizadeh, Microwave/RF Applicators and Probes for Material Heating, Sensing, and Plasma Generation (Elsevier, Amsterdam; Boston, 2010)

    Google Scholar 

  45. K. Menon, R.A. Joy, N. Sood, R.K. Mittal, Bionanoscience 3, 356 (2013)

    Article  Google Scholar 

  46. H. Morgan, N. Green, in Encycl. Microfluid. Nanofluidics, ed. by D. Li (Springer, New York, 2015), p. 563

  47. O.T. Nedelcu, Rom. J. Inf. Sci. Technol. 14, 309 (2011)

    Google Scholar 

  48. E. Neumann, A.E. Sowers, C.A. Jordan, Electroporation and Electrofusion in Cell Biology (Plenum Press, New York, 1989)

    Book  Google Scholar 

  49. J.A. Nickoloff, Animal Cell Electroporation and Electrofusion Protocols (Humana Press, Totowa, 1995)

    Google Scholar 

  50. S. Nishimura, H. Matsumura, K. Kosuge, T. Yamaguchi, Langmuir 26, 10357 (2010)

    Article  Google Scholar 

  51. J. L. Nitiss, J. Heitman, Yeast as a Tool in Cancer Research (Springer, Dordrecht, 2007)

  52. E. Nuxoll, Adv. Drug Deliv. Rev. 65, 1611 (2013)

    Article  Google Scholar 

  53. B.M. Ogle, M. Cascalho, J.L. Platt, Nat Rev Mol Cell Biol 6, 567 (2005)

    Article  Google Scholar 

  54. A. Otsuki, T. Sagawa, in Chemeca 2010 Eng. Edge (South Australia, 2010), p. 2568

  55. D.T. Pathak, X. Wei, A. Bucuvalas, D.H. Haft, D.L. Gerloff, D. Wall, PLoS Genet. 8, 1 (2012)

    Article  Google Scholar 

  56. R. Pethig, Biomicrofluidics 4, 022811 (2010)

  57. R. Pethig, Y. Huang, X. Wang, J.P.H. Burt, J. Phys. D. Appl. Phys. 25, 881 (1992)

  58. P. Piyasena, C. Dussault, T. Koutchma, H.S. Ramaswamy, G.B. Awuah, Crit. Rev. Food Sci. Nutr. 43, 587 (2003)

    Article  Google Scholar 

  59. R. Plonsey, R.C. Barr, Bioelectricity (Springer, Boston, 2007)

  60. H.A. Pohl, Dielectrophoresis : The Behavior of Neutral Matter in Nonuniform Electric Fields (Cambridge University Press, Cambridge, 1978)

    Google Scholar 

  61. C. Qian, H. Huang, L. Chen, X. Li, Z. Ge, T. Chen, Z. Yang, L. Sun, Int. J. Mol. Sci. 15, 18281 (2014)

    Article  Google Scholar 

  62. A. Ramos, Electrokinetics and Electrohydrodynamics in Microsystems (Springer, New York, 2011)

    Book  Google Scholar 

  63. A. Ramos, H. Morgan, N.G. Green, A. Castellanos, J. Phys. D. Appl. Phys. 31, 2338 (1998)

    Article  Google Scholar 

  64. L. Rems, M. Ušaj, M. Kandušer, M. Reberšek, D. Miklavčič, G. Pucihar, Sci. Rep. 3, 3382 (2013)

    Article  Google Scholar 

  65. T. Robinson, P.E. Verboket, K. Eyer, P.S. Dittrich, Lab Chip 14, 2852 (2014)

    Article  Google Scholar 

  66. B. Salim, M.V. Athira, A. Kandaswamy, M. Vijayakumar, T. Saravanan, T. Sairam, Biomed. Microdevices 19, 89 (2017)

  67. J. Schaper, Development of a Technology for Arranged Electrofusion of Mammalian Cells: Applicability in Breast Cancer Immunotherapy, Bielefeld University, 2007

  68. F.I. Schmidt, P. Kuhn, T. Robinson, J. Mercer, P.S. Dittrich, Biophys. J. 105, 420 (2013)

    Article  Google Scholar 

  69. R.M. Schoeman, E.W.M. Kemna, F. Wolbers, A. van den Berg, Electrophoresis 35, 385 (2014)

    Article  Google Scholar 

  70. M. Şen, K. Ino, J. Ramón-Azcón, H. Shiku, T. Matsue, Lab Chip 13, 3650 (2013)

    Article  Google Scholar 

  71. B. Shaparenko, The Thermal Dielectrophoretic Force on a Dielectric Particle in Electric and Temperature, University of Pennsylvania, 2015

  72. Q. Shi, J. Wang, D. Chen, J. Chen, J. Li, K. Bao, Biomed. Microdevices 16, 859 (2014)

    Article  Google Scholar 

  73. A.V. Shutko, V.S. Gorbunov, K.G. Guria, K.I. Agladze, Biomed. Microdevices 19, 72 (2017)

  74. M.G. Smith, M. Snyder, in Curr. Protoc. Hum. Genet. (Wiley, New York, 2001), p. 15.6.1

  75. R. Soffe, S.-Y. Tang, S. Baratchi, S. Nahavandi, M. Nasabi, J.M. Cooper, A. Mitchell, K. Khoshmanesh, Anal. Chem. 87, 2389 (2015)

  76. R. Soltanzadeh, E. Afsharipour, C. Shafai, N. Anssari, B. Mansouri, Z. Moussavi, Biomed. Microdevices 20, 1 (2017)

  77. G. Stéphane, F. Eric, G. Patrick, Biotechnol. Bioeng. 92, 403 (2005)

    Article  Google Scholar 

  78. W.-H. Tan, S. Takeuchi, Lab Chip 6, 757 (2006)

    Article  Google Scholar 

  79. J. Tesarik, Z.P. Nagy, C. Mendoza, E. Greco, Hum. Reprod. 15, 1149 (2000)

    Article  Google Scholar 

  80. G. Tresset, S. Takeuchi, Biomed. Microdevices 6, 213 (2004)

    Article  Google Scholar 

  81. A. Troiano, E. Pasero, L. Mesin, in New Adv. Veh. Technol. Automot. Eng., ed. by J. P. Carmo and J. E. Ribeiro (IntechOpen, Rijeka, 2012), p. 231

  82. H.-H. Tsai, C.-F. Lin, Y.-Z. Juang, I.-L. Wang, Y.-C. Lin, R.-L. Wang, H.-Y. Lin, Sensors Actuators B Chem. 144, 407 (2010)

    Article  Google Scholar 

  83. M. Usaj, K. Flisar, D. Miklavcic, M. Kanduser, Bioelectrochemistry 89, 34 (2013)

    Article  Google Scholar 

  84. N. Van Pham, J. Villemejane, F. Hamdi, G. Mottet, C. Dalmay, M. Woytasik, E. Martincic, E. Dufour-Gergam, O. Français, L.M. Mir, B. Le Pioufle, Procedia Eng. 5, 49 (2010)

    Article  Google Scholar 

  85. M. Verduyckt, H. Vignaud, T. Bynens, J. Van den Brande, V. Franssens, C. Cullin, J. Winderickx, in Syst. Biol. Alzheimer’s Dis., ed. by J. I. Castrillo and S. G. Oliver (Springer, New York, 2016), p. 197

  86. J. Voldman, Annu. Rev. Biomed. Eng. 8, 425 (2006)

    Article  Google Scholar 

  87. T. Wasilewski, J. Gębicki, W. Kamysz, Sensors Actuators B Chem. 257, 511 (2018)

    Article  Google Scholar 

  88. J. Wu, Y. Ben, D. Battigelli, H.C. Chang, Ind. Eng. Chem. Res. 44, 2815 (2005)

    Article  Google Scholar 

  89. W. Wu, Y. Qu, N. Hu, Y. Zeng, J. Yang, H. Xu, Z.Q. Yin, PLoS One 10, 1 (2015)

    Google Scholar 

  90. L. Xiong, Y. Yan, M. Jiahao, Z. Yanhang, W. Qian, Z. Zhaohua, R. Tianling, J. Semicond. 36, 64009 (2015)

  91. S. Yan, Y. Zhu, S.-Y. Tang, Y. Li, Q. Zhao, D. Yuan, G. Yun, J. Zhang, S. Zhang, W. Li, Electrophoresis 39, 957 (2018)

    Article  Google Scholar 

  92. J. Yang, M. H. Shen, in Nucl. Reprogramming Methods Protoc., ed. by S. Pells (Humana Press, Totowa, 2006), p. 59

  93. L. Yang, T. Hong, Y. Zhang, J.G.S. Arriola, B.L. Nelms, R. Mu, D. Li, Biomed. Microdevices 19, 38 (2017)

    Article  Google Scholar 

  94. S. Youssefian, N. Rahbar, C.R. Lambert, S. Van Dessel, J. R. Soc. Interface 14, 20170127 (2017)

    Article  Google Scholar 

  95. X. Zhang, Z. Zhu, Z. Ni, N. Xiang, H. Yi, Biomed. Microdevices 19, 21 (2017)

    Article  Google Scholar 

  96. K. Zhu, A.S. Kaprelyants, E.G. Salina, G.H. Markx, Biomicrofluidics 4, 022809 (2010)

    Article  Google Scholar 

  97. U. Zimmermann, Biochim. Biophys. Acta - Rev. Biomembr 694, 227 (1982)

    Article  Google Scholar 

  98. U. Zimmermann, in Methods Hybrid Form, ed. by A. H. Bartal and Y. Hirshaut (Humana Press, Totowa, 1987), p. 97

Download references

Acknowledgements

We thank the Ministry of Higher Education of Malaysia (MOHE) for support under Fundamental Research Grant Scheme (FRGS) FRGS/2/2013/TK03/UKM/01/1 and FRGS/1/2015/TK04/MMU/02/9 and the Ministry of Education of Malaysia (MOE) for support under the Higher Institution Centre of Excellence (HiCOE) Grant, AKU-95. Dr. Adam Chrimes acknowledges the support of the Victorian Government through the 2015 Victorian Postdoctoral Research Fellowship program. Professor Leslie Yeo is grateful to the Australian Research Council for a Future Fellowship (FT130100672).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Aminuddin Bin Ahmad Kayani.

Electronic supplementary material

Online Resource 1

(DOCX 4.46 mb)

Online Resource 2

(MPG 3340 kb)

Online Resource 3

(MPG 3517 kb)

Online Resource 4

(MPG 5698 kb)

Online Resource 5

(MPG 3760 kb)

Online Resource 6

(MPG 4112 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Md Ali, M.A., Kayani, A.B.A., Yeo, L.Y. et al. Microfluidic dielectrophoretic cell manipulation towards stable cell contact assemblies. Biomed Microdevices 20, 95 (2018). https://doi.org/10.1007/s10544-018-0341-1

Download citation

Keywords

  • Dielectrophoresis
  • Cell contact
  • Cell chain
  • Spinning
  • Rotation
  • Microfluidics