Biomedical Microdevices

, Volume 1, Issue 2, pp 131–138 | Cite as

Microfabricated Biocapsules Provide Short-Term Immunoisolation of Insulinoma Xenografts

  • Tejal A. Desai
  • Wen Hwa Chu
  • Guido Rasi
  • Paola Sinibaldi-Vallebona
  • Enrico Guarino
  • Mauro Ferrari


This study examines the viability and functionality of two insulinoma cell lines, RIN (1048) and βTC6F7, encapsulated within microfabricated biocapsules. Surface and bulk micromachining are integrated in the biocapsule fabrication process, resulting in a diffusion membrane with uniform pore size distribution as well as mechanical and chemical stability, surrounded by an anisotropically-etched silicon wafer, which serves as the encapsulation cavity. Insulinoma cells (4500 cells/biocapsule) were enclosed within these microfabricated biocapsules and subjected to a static incubation study after either implantation in BALB-C mice or incubation in vitro. Examination of retrieved microfabricated biocapsules revealed an insulin stimulatory index of approximately 1.5 for encapsulated RIN cells and 3.6 for encapsulated βTC6F7 cells for biocapsules with 18 nm pore sized microfabricated membranes, similar to indices of biocapsules incubated in vitro. There was an 80% decrease in cell stimulatory response between in vitro and in vivo 66 nm-biocapsules as compared to 20% for 18 nm-biocapsules, indicating that the immunoisolatory effectiveness depends greatly on achieving uniform pore sizes in the size range of 18 nm or smaller. The present study demonstrates the feasibility of using microfabricated biocapsules for the immunoisolation of insulinoma cells lines. The microfabricated biocapsule may serve as an alternative to conventional polymeric based biocapsules for possible use as in vivo insulin secreting bioreactor.

BioMEMS microfabricated biocapsule; immunoisolation insulinoma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    R.P. Lanza and W.L. Chick, Scientific American Science & Medicine 2(4), 16–25 (1995).Google Scholar
  2. 2.
    C.K. Colton, Cell Transplantation 4(4), 415–436 (1995).MathSciNetCrossRefGoogle Scholar
  3. 3.
    W.H. Chu, T. Huen, J. Tu, and M. Ferrari, Silicon-micromachined Direct-pore Filters for Ultrafiltration. In: P.L. Gourley, ed. Micro and Nanofabricated Electro-Optical-Mechanical Systems for Biomedical and Environmental Application, SPIE 2978 111–122 (1997).Google Scholar
  4. 4.
    T.A. Desai, W.H. Chu, J. Tu, P. Shrewsbury, and M. Ferrari, Microfabricated Biocapsules for Cell Xenografts: A Review. In: P.L. Gourley, ed. Micro and Nanofabricated Electro-Optical-Mechanical Systems for Biomedical and Environmental Application. SPIE 2978 216–226 (1997).Google Scholar
  5. 5.
    T.A. Desai, W.H. Chu, J.K. Tu, G.M. Beattie, A. Hayek, and M. Ferrari, Biotechnology and Bioengineering 57(1), 118–120 (1998).CrossRefGoogle Scholar
  6. 6.
    T.A. Desai, M. Ferrari, and G. Mazzoni, Silicon Microimplants: Fabrication and Biocompatibility, Materials and Design Technology. Ed. T. Kozik ASME: 97–103. (1995).Google Scholar
  7. 7.
    J.P. Benson, K.K. Papas, I. Constantinidis, and A. Sambanis, Cell Transplantation 6(4), 395–402 (1997).CrossRefGoogle Scholar
  8. 8.
    H. Hayashi, K. Inoue, T. Aung, T. Tun, G. Yuanjun, W. Wenjing, S. Shinohara, H. Kaji, R. Doi, and H. Setoyama, et al. Cell Transplantation 5(5 Suppl 1), S65–9 (1996).CrossRefGoogle Scholar
  9. 9.
    H. Ohgawara, J. Miyazaki, Y. Nakagawa, S. Sato, S. Karibe, and T. Akaike, Cell Transplantation 5(5 Suppl 1), S71–3 (1996).CrossRefGoogle Scholar
  10. 10.
    D. Hansford, T.A. Desai, and M. Ferrari, “Biocompatible Silicon Wafer Bonding for Biomedical Microdevices,” In: P.L. Gourley, ed. Micro and Nanofabricated Electro-Optical-Mechanical Systems for Biomedical and Environmental Applications, SPIE, 164–168 (1998).Google Scholar
  11. 11.
    S.A. Clark, C. Quaade, H. Constandy, P. Hansen, P. Halban, S. Ferber, C.B. Newgard, and K. Normington, Diabetes 46(6), 958–967 (1997).Google Scholar
  12. 12.
    S. Efrat, M. Leiser, M. Surana, M. Tal, D. Fusco-Demane, and N. Fleischer, Diabetes 42(6), 901–907 (1993).Google Scholar
  13. 13.
    D. Knaack, D.M. Fiore, M. Surana, M. Leiser, M. Laurance, D. Fusco-DeMane, O.D. Hegre, N. Fleischer, and S. Efrat, Diabetes 43(12), 1413–1417 (1994).Google Scholar
  14. 14.
    P.E. Lacy and M. Kostianovsky, Diabetes 16, 35–39 (1967).Google Scholar
  15. 15.
    C.K. Colton and E. Avgoustiniatos, Transactions of the ASME 113, 152–170 (1991).Google Scholar
  16. 16.
    D.L. Eizirik, L. Jansson, M. Flodstrom, C. Hellerstrom, and A. Andersson, Journal of Clinical Endocrinology and Metabolism 82(8), 2660–3 (1997).CrossRefGoogle Scholar
  17. 17.
    T. Wasada, K. Aoki, T. Babazono, H. Kuroki, H. Arii, A. Saeki, and Y. Omori, Endocrine Journal 42(6), 747–752 (1995).Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Tejal A. Desai
    • 1
  • Wen Hwa Chu
    • 2
  • Guido Rasi
    • 3
    • 4
  • Paola Sinibaldi-Vallebona
    • 1
  • Enrico Guarino
    • 1
  • Mauro Ferrari
    • 2
  1. 1.Department of BioengineeringUniversity of IllinoisChicagoUSA
  2. 2.Biomedical Microdevices CenterUniversity of CaliforniaBerkeleyUSA
  3. 3.Istituto di Medicina SperimentaleRomeItaly
  4. 4.Istituto di Medicina SperimentaleRomaItaly

Personalised recommendations