Skip to main content
Log in

Development and characterization of hollow microprobe array as a potential tool for versatile and massively parallel manipulation of single cells

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

Parallel manipulation of single cells is important for reconstructing in vivo cellular microenvironments and studying cell functions. To manipulate single cells and reconstruct their environments, development of a versatile manipulation tool is necessary. In this study, we developed an array of hollow probes using microelectromechanical systems fabrication technology and demonstrated the manipulation of single cells. We conducted a cell aspiration experiment with a glass pipette and modeled a cell using a standard linear solid model, which provided information for designing hollow stepped probes for minimally invasive single-cell manipulation. We etched a silicon wafer on both sides and formed through holes with stepped structures. The inner diameters of the holes were reduced by SiO2 deposition of plasma-enhanced chemical vapor deposition to trap cells on the tips. This fabrication process makes it possible to control the wall thickness, inner diameter, and outer diameter of the probes. With the fabricated probes, single cells were manipulated and placed in microwells at a single-cell level in a parallel manner. We studied the capture, release, and survival rates of cells at different suction and release pressures and found that the cell trapping rate was directly proportional to the suction pressure, whereas the release rate and viability decreased with increasing the suction pressure. The proposed manipulation system makes it possible to place cells in a well array and observe the adherence, spreading, culture, and death of the cells. This system has potential as a tool for massively parallel manipulation and for three-dimensional hetero cellular assays.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • D.R. Albrecht, V.L. Tsang, R.L. Sah, S.N. Bhatia, Lab Chip 5, 111–118 (2005)

    Article  Google Scholar 

  • S. Bhatia, U. Balis, M. Yarmush, M. Toner, Biotechnol. Prog. 14, 378–387 (1998)

    Article  Google Scholar 

  • Y.-C. Chen, Y.-H. Cheng, H.S. Kim, P.N. Ingram, J.E. Nor, E. Yoon, Lab Chip 14, 2941–2947 (2014)

    Article  Google Scholar 

  • P.Y. Chiou, A.T. Ohta, M.C. Wu, Nature 436, 370–372 (2005)

    Article  Google Scholar 

  • K. Chun, G. Hashiguchi, H. Toshiyoshi, H. Fujita, Jpn. J. Appl. Phys. 38, L279–L281 (1999)

    Article  Google Scholar 

  • G.M. Cooper, The Cell: A Molecular Approach, 2nd edn. (Sinauer Associates Inc, Sunderland, 2000)

    Google Scholar 

  • L.S. De Clerck, C.H. Bridts, A.M. Mertens, M.M. Moens, W.J. Stevens, J. Immunol. Methods 172, 115–124 (1994)

    Article  Google Scholar 

  • E. Evans, B. Kukan, Blood 64, 1028–1035 (1984)

    Google Scholar 

  • J.-P. Frimat, M. Becker, Y.-Y. Chiang, U. Marggraf, D. Janasek, J.G. Hengstler et al., Lab Chip 11, 231–237 (2011)

    Article  Google Scholar 

  • D.S. Gray, J.L. Tan, J. Voldman, C.S. Chen, Biosens. Bioelectron. 19, 771–780 (2004)

    Article  Google Scholar 

  • O.T. Guenat, S. Generelli, M. Dadras, L. Berdondini, N. de Rooij, M. Koudelka-Hep, J. Micromech. Microeng. 15, 2372–2378 (2005)

    Article  Google Scholar 

  • A. Hofmann, U. Ritz, S. Verrier, D. Eglin, M. Alini, S. Fuchs et al., Biomaterials 29, 4217–4226 (2008)

    Article  Google Scholar 

  • S. Hong, Q. Pan, L.P. Lee, Integr. Biol. 4, 374–380 (2012)

    Article  Google Scholar 

  • L.C. Hsiung, C.H. Yang, C.L. Chiu, C.L. Chen, Y. Wang, H. Lee et al., Biosens. Bioelectron. 24, 869–875 (2008)

    Article  Google Scholar 

  • T. Hunt, R. Westervelt, Biomed. Microdevices 8, 227–230 (2006)

    Article  Google Scholar 

  • M.L. Juan, M. Righini, R. Quidant, Nat. Photonics 5, 349–356 (2011)

    Article  Google Scholar 

  • T. Kodama, T. Osaki, R. Kawano, K. Kamiya, N. Miki, S. Takeuchi, Biosens. Bioelectron. 47, 206–212 (2013)

    Article  Google Scholar 

  • P.J. Lee, P.J. Hung, R. Shaw, L. Jan, L.P. Lee, Appl. Phys. Lett. 86, 223902 (2005)

    Article  Google Scholar 

  • U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira et al., Lab Chip 8, 2174–2181 (2008)

    Article  Google Scholar 

  • J. Mitchison, M. Swann, J. Exp. Biol. 31, 443–460 (1954)

    Google Scholar 

  • H. Park, D. Kim, K.-S. Yun, Sensors Actuators B Chem. 150, 167–173 (2010)

    Article  Google Scholar 

  • S. Park, Y.-S. Kim, W.B. Kim, S. Jon, Nano Lett. 9, 1325–1329 (2009)

    Article  Google Scholar 

  • E. Peer, A. Artzy-Schnirman, L. Gepstein, U. Sivan, ACS Nano 6, 4940–4946 (2012)

    Article  Google Scholar 

  • M. Sato, D. Theret, L. Wheeler, N. Ohshima, R. Nerem, J. Biomech. Eng. 112, 263–268 (1990)

    Article  Google Scholar 

  • G.W. Schmid-Schönbein, K.L. Sung, H. Tözeren, R. Skalak, S. Chien, Biophys. J. 36, 243–256 (1981)

    Article  Google Scholar 

  • Q. Shen, S.K. Goderie, L. Jin, N. Karanth, Y. Sun, N. Abramova et al., Science 304, 1338–1340 (2004)

    Article  Google Scholar 

  • T. Shibata, S. Yamanaka, N. Kato, T. Kawashima, M. Nomura, T. Mineta et al., Microelectron. Eng. 86, 1439–1442 (2009)

    Article  Google Scholar 

  • A.M. Skelley, O. Kirak, H. Suh, R. Jaenisch, J. Voldman, Nat. Methods 6, 147–152 (2009)

    Article  Google Scholar 

  • D.P. Theret, M. Levesque, M. Sato, R. Nerem, L. Wheeler, J. Biomech. Eng. 110, 190–199 (1988)

    Article  Google Scholar 

  • M.A. Unger, H.-P. Chou, T. Thorsen, A. Scherer, S.R. Quake, Science 288, 113–116 (2000)

    Article  Google Scholar 

  • C.F. Wilson, G.J. Simpson, D.T. Chiu, A. Strömberg, O. Orwar, N. Rodriguez et al., Anal. Chem. 73, 787–791 (2001)

    Article  Google Scholar 

  • A. Yusof, H. Keegan, C.D. Spillane, O.M. Sheils, C.M. Martin, J.J. O’Leary et al., Lab Chip 11, 2447–2454 (2011)

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by KAKENHI 25820087 and the Tokai Foundation for Technology.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Moeto Nagai.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 3438 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nagai, M., Oohara, K., Kato, K. et al. Development and characterization of hollow microprobe array as a potential tool for versatile and massively parallel manipulation of single cells. Biomed Microdevices 17, 41 (2015). https://doi.org/10.1007/s10544-015-9943-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s10544-015-9943-z

Keywords

Navigation