Skip to main content
SpringerLink
Log in

Integration of a pump and an electrical sensor into a membrane-based PDMS microbioreactor for cell culture and drug testing

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

To the extent possible, artificial organs should have characteristics that match those of the in vivo system. To this end, microfabrication techniques allow us to create microenvironments that can help maintain cell organization and functionality in in vitro cultures. We present three new microbioreactors, each of which allows cells to be cultured in a perfused microenvironment similar to that found in vivo. Our microbioreactors use new technology that permits integration onto the chip (35 mm × 20 mm) of an electrical sensor, in addition to one or more pumping systems and associated perfusion circuitry. The monitoring of Caco-2 cell cultures using electrical impedance spectroscopy (EIS) has allowed us to measure the effects of cell growth, cellular barrier formation and the presence of chemical compounds and/or toxins. Specifically, we have investigated the ability of the electrical sensor to maintain appropriate sensitivity and precision. Our results show that the sensor was very sensitive not only to the presence or the absence of the cells, but also to changes in cell state. Our perfused microbioreactors are highly efficient miniaturized tools that are easy to operate. We anticipate that they will offer promising new opportunities in many types of cell culture research, including drug screening and tissue engineering.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • M. Adolphe, G. Barlovatz-Meimon, Culture de Cellules Animales, Methodologies Applications. Editions (INSERM, Paris, France,, 1988)

  • H. Andersson, A. van den Berg, Lab-on-Chips for Cellomics, Micro and Nano Technologies for Life Sciences (Kluwer, Dordrecht, 2004)

    Google Scholar 

  • P. Artursson, J. Karlsson, Biochem. Biophys. Res. Commun. 175(3), 880–885 (1991)

    Article  Google Scholar 

  • F. Asphahani, M. Zhang, Analyst 132, 835–841 (2007)

    Article  Google Scholar 

  • E. Barsoukov, J.R. Macdonald, Impedance Spectroscopy, 2nd edn. (Wiley, Hoboken, 2005), p. 595

    Book  Google Scholar 

  • H. Blankson, I. Holen, P.O. Seglen, Exp. Cell Res. 218, 522–530 (1995)

    Article  Google Scholar 

  • N. Bowden, S. Brittain, A.G. Evans, J.W. Hutchinson, G.M. Whitesides, Nature 393, 146–149 (1998)

    Article  Google Scholar 

  • Y. Cho, H.S. Kim, A.B. Frazier, Z.G. Chen, D.M. Shin, A. Han, J. Microelectromech. Syst. 18, 808–816 (2009)

    Article  Google Scholar 

  • A.D. De Lorenzo, A. Andreoli, Curr. Opin. Clin. Nutr. Metab. Care 6, 551–555 (2003)

    Article  Google Scholar 

  • E. Ekue Creppy, A. Traore, I. Baudrimont, M. Cascante, M.-R. Carratu, Toxicology 181–182, 433–439 (2002)

    Article  Google Scholar 

  • D. Erickson, D. Li, Anal. Chim. Acta 507, 11–26 (2004)

    Article  Google Scholar 

  • Y. Feldman, Y. Hayashi, Dielectric Spectroscopy of Biological Systems; from Amino Acids to Cells. XII International conference on Electrical Bio Impedance, 20–24 June. (Gdansk, Poland, 2004), p. 13–16

  • S. Ferruzza, M.-L. Scarino, G. Rotilio, M.R. Cirilio, P. Santaroni, A. Onetti Muda, Y. Sambuy, Am. J. Physiol.–Gastrointest. 277, 1138–1148 (1999)

    Google Scholar 

  • S. Ferruzza, M. Scacchi, M.L. Scarino, Y. Sambuy, Toxicol. in Vitro 16, 399–404 (2002)

    Google Scholar 

  • K.R. Foster, Annu. Rev. Biomed. Eng. 4, 1–27 (2002)

    Article  Google Scholar 

  • S. Gawad, L. Schild, P. Renaud, Lab Chip 1, 76–82 (2001)

    Article  Google Scholar 

  • S. Gawad, K. Cheung, U. Seger, A. Bertsch, P. Renaud, Lab Chip 4, 241–251 (2004)

    Article  Google Scholar 

  • G.O. Gey, Am J Cancer 17, 752–756 (1933)

    Google Scholar 

  • I. Giaever, C.R. Keese, PNAS 88, 7896–7900 (1991)

    Article  Google Scholar 

  • I. Giaever, C.R. Keese, Nature 366, 591–592 (1993)

    Article  Google Scholar 

  • R. Gudivaka, D.A. Schoeller, R.F. Kushner, M.J. Bolt, J. Appl. Physiol. 87, 1087–1096 (1999)

    Google Scholar 

  • A. Han, L. Yang, A.B. Frazier, Clin. Cancer Res. 13, 139–143 (2007)

    Article  Google Scholar 

  • D. Holmes, D. Pettigrew, C.H. Reccius, J.D. Gwyer, C.V. Berkel, J. Holloway, D.E. Davie, H. Morgan, Lab Chip 9, 2881–2889 (2009)

    Article  Google Scholar 

  • C.D. James, N. Reuel, E.S. Lee, R.V. Davalos, S.S. Mani, A. Carroll-Portillo, R. Rebeil, A. Martino, C.A. Apblett, Biosens. Bioelectron. 23, 845–851 (2008)

    Article  Google Scholar 

  • L.-S. Jang, M.-H. Wang, Biomed. Microdevices 9, 737–743 (2007)

    Article  Google Scholar 

  • E. Katz, I. Willner, Electroanalysis 15(11), 913–947 (2003)

    Article  Google Scholar 

  • C.R. Keese, J. Wegener, S.R. Walker, I. Giaever, PNAS 101, 1554–1559 (2004)

    Article  Google Scholar 

  • S. Kumar, C. Wittman, E. Heinzle, Biotechnol. Lett. 26, 1–10 (2004)

    Article  Google Scholar 

  • C. Kuttel, E. Nascimento, N. Demierre, T. Silva, T. Braschler, P. Renaud, A.G. Oliva, Acta Trop. 102, 63–68 (2007)

    Article  Google Scholar 

  • U.G. Kyle, I. Bosaeus, A.D. De Lorenzo, P. Deurenberg, M. Elia, J.M. Gomez, B.L. Heitmann, L. Kent-Smith, J.C. Melchior, M. Pirlich, H. Scharfetter, A.M.W.J. Schols, C. Pichard, Clin. Nutr. 23, 1226–1243 (2004)

    Article  Google Scholar 

  • E.L. LeCluyse, P.L. Bullock, A. Parkinson, Adv. Drug Deliv. Rev. 22, 133–186 (1996)

    Article  Google Scholar 

  • F. Leira, C. Alvarez, A.G. Gabado, J.M. Vieites, M.R. Vieytes, L.M. Botana, Anal. Biochem. 317, 129–135 (2003)

    Article  Google Scholar 

  • P. Linderholm, T. Braschler, J. Vannod, Y. Barrandon, M. Brouard, P. Renaud, Lab Chip 6, 1155–1162 (2006)

    Article  Google Scholar 

  • D. Malleo, J.T. Nevill, L.P. Lee, H. Morgan, Microfluid Nanofluid 9, 191–198 (2010)

    Article  Google Scholar 

  • J.C. Mc Donald, D.C. Duffy, J.R. Anderson, D.T. Chiu, H. Wu, O.J.A. Schueller, G.M. Whitesides, Electrophoresis 21, 27–40 (2000)

    Article  Google Scholar 

  • S. Miret, L. Abrahamse, E.M. Groene, J. Biomol. Screen. 9(7), 598–606 (2004)

    Article  Google Scholar 

  • H. Morgan, T. Sun, D. Holmes, S. Gawad, N.G. Green, J. Phys. D: Appl. Phys. 40, 61–70 (2007)

    Article  Google Scholar 

  • A. Moscona, Exp. Cell Res. 3, 535–539 (1952)

    Article  Google Scholar 

  • Y. Murakami, Y. Oshima, T. Yasumoto, Bull. Jap. Soc. Sci. Fish. 48, 69–72 (1982)

    Google Scholar 

  • T. Okada, A. Narai, S. Matsunaga, N. Fusetani, M. Shimizu, Toxicol. in Vitro 14, 219–226 (2000)

    Google Scholar 

  • S. Ostrovidov, J. Jiang, Y. Sakai, T. Fujii, Biomed. Microdevices 6(4), 279–287 (2004)

    Article  Google Scholar 

  • S. Ostrovidov, J. Mizuno, H. Nakamura, H. Inui, Y. Sakai, T. Fujii, Proceedings of MicroTas 2005, volume 1. (Boston, Massachussetts USA, October 9 – 13, 2005), p. 361

  • S. Perichon Lacour, S. Wagner, Z. Huang, Z. Suo, Appl. Phys. Lett. 82(15), 2404–2406 (2003)

    Article  Google Scholar 

  • G. Ranaldi, R. Consalvo, Y. Sambuy, M.L. Scarino, Toxicol. in Vitro 17, 761–767 (2003)

    Google Scholar 

  • K. Rissanen, S. Ostrovidov, E. Lennon, V. Senez, J. Kim, B. Kim, K. Sakai Furukawa, T. Ushida, Y. Sakai, T. Fujii, Proceedings of 3rd International IEEE EMBS Special Topic Conference on Microtechnologies. (Ohau, Hawai USA, May 12 – 15, 2005), pp. 201–204

  • R. Rodriguez-Trujillo, O. Castillo-Fernandez, M. Garrido, M. Arundell, A. Valencia, G. Gomila, Biosens. Bioelectron. 24, 290–296 (2008)

    Article  Google Scholar 

  • G. Schade-Kampmann, A. Huwiler, M. Hebeisen, T. Hessler, M. Di Berardino, Cell Prolif. 41, 830–840 (2008)

    Article  Google Scholar 

  • H.P. Schwan, Electrical properties of tissue and cell suspensions, in Advances in Biological and Medical Physics, 5, ed. by J.H. Lawrence, C.A. Tobias (Academic, New-York, 1957), pp. 147–209

    Google Scholar 

  • V. Senez, E. Lennon, S. Ostrovidov, T. Yamamoto, H. Fujita, Y. Sakai, T. Fujii, IEEE Sensor J. 8, 548–557 (2008)

    Article  Google Scholar 

  • T. Sun, H. Morgan, Microfluid Nanofluid 8, 423–443 (2010)

    Article  Google Scholar 

  • K. Tachibana, P.J. Scheurer, Y. Tsukitani, H. Kikuchi, D.V. Engen, J. Clardy, Y. Gopichand, F.J. Schimitz, J. Am. Chem. Soc. 103, 2469–2471 (1981)

    Article  Google Scholar 

  • A. Thomasset, Lyon Med. 209, 1325–1352 (1963)

    Google Scholar 

  • A. Traore, I. Baudrimont, S. Dano, A. Sanni, Y. Larondelle, Y.J. Schneider, E. Ekue Creppy, Arch. Toxicol. 77(11), 657–662 (2003)

    Article  Google Scholar 

  • C. Vale, L.M. Botana, FEBS J. 275, 6060–6066 (2008)

    Article  Google Scholar 

  • C.H. Von Bonsdorff, S.D. Fuller, K. Simons, EMBO J. 4, 2781–2792 (1985)

    Google Scholar 

  • A.L. Wang, F.L. Wang, H. Yin, W. Xing, Z. Yu, M. Guo, J. Cheng, Biosens. Bioelectron. 25, 990–995 (2010)

    Article  Google Scholar 

  • B. Xi, N. Yu, X. Wang, X. Xu, Y.A. Abassi, Biotechnol. J. 3, 484–495 (2008)

    Article  Google Scholar 

  • S. Yamashita, T. Furubayashi, M. Kataoka, T. Sakane, H. Sezaki, H. Tokuda, Eur. J. Pharm. Sci. 10, 195–204 (2000)

    Article  Google Scholar 

  • J.H. Yeon, J.-K. Park, Anal. Biochem. 341, 308–315 (2005)

    Article  Google Scholar 

Download references

Acknowledgments

This project was supported in part by LIMMS (the Laboratory for Integrated Micro Mechatronic Systems) in Tokyo, which is a joint effort of the Communication and Information Science and Technology Department of CNRS (CNRS-STIC, France) and the Institute of Industrial Science (IIS) at the University of Tokyo. It was supported by the CNRS, the MEXT (Japanese Ministry of Education, Culture, Sports, Science and Technology), and the JSPS (Japanese Society for the Promotion of Science). The authors wish to thank Pentax Corporation for their support. We also acknowledge Dr Poleni for his fruitful insights into fluorescence observations with Hoescht and Calcein-AM dyes.

Author information

Authors and Affiliations

  1. Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153–8505, Japan

    Serge Ostrovidov, Yasuyuki Sakai & Teruo Fujii

Authors
  1. Serge Ostrovidov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuyuki Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teruo Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Serge Ostrovidov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ostrovidov, S., Sakai, Y. & Fujii, T. Integration of a pump and an electrical sensor into a membrane-based PDMS microbioreactor for cell culture and drug testing. Biomed Microdevices 13, 847–864 (2011). https://doi.org/10.1007/s10544-011-9555-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-011-9555-1

Keywords

Search

Navigation