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Immobilization of suspended mammalian cells: Analysis of hollow fiber and microcapsule bioreactors

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Vertrebrate Cell Culture I

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 34))

Abstract

Model equations of substrate mass transfer and uptake have been formulated for two bioreactor systems: microcapsules and a hollow fiber reactor. Assumptions include time independence, Fickian diffusion, homogenous cell suspension, and kinetics described by the zero and first order limits of the Monod equation. Glucose and oxygen were the substrates chosen for investigation of the kinetic and diffusion limitations. For microcapsules, the resulting radial concentration profiles indicated the possibility of a necrotic core due to insufficient substrate in those cases where diffusion is low and/or uptake is high. The model equations provide a means of estimating the maximum capsule radius which will allow adequate diffusion of nutrients to all of the contained cells. The simulated concentration gradients developed for a hollow fiber reactor demonstrate that diffusion limitations may exist at the far end of the reactor. Concentration gradients are shown both in the fiber lumens (in the axial direction) as well as in the shell space (in the radial direction). Variation of model parameters provides information on system specifications to avoid these diffusion limitations.

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Abbreviations

A:

radius of membrane fiber (cm)

B:

microcapsule radius or hollow fiber annulus radius (cm)

C0 :

bulk substrate concentration (moles ml−1)

C(r):

concentration as a function of radius (moles ml−1)

C(z):

concentration as a function of axial distance (moles ml−1)

De :

effective diffusivity (cm2 s−1)

I0(x):

modified Bessel fuction of the first kind, order zero

I1(x):

modified Bessel function of the first kind, order one

K0(x):

modified Bessel function of the second kind, order zero

K1(x):

modified Bessel function of the second kind, order one

Km :

Michaelis constant (moles ml−1)

L:

hollow fiber length (cm)

n:

number of hollow fibers

N:

substrate flux (moles cm2 s−1)

r:

radius (cm)

R:

outer radius of microcapsule or hollow fiber module (cm)

R:

uptake of substrate (moles ml−1 s−1)

Vk :

Vm/Km(s−1)

Vm :

maximum reaction rate (moles ml−1 s−1)

Vz :

axial fluid velocity (cm s−1)

z:

axial distance (cm)

References

  1. Abramowitz, M., Stegun, I. A., (eds.): Handbook of Mathematical Functions. Dover, New York 1972

    Google Scholar 

  2. Amicon literature: 17 Cherry Hill Drive, Danvers, MA 01923 (1985)

    Google Scholar 

  3. Altshuler, G. L.: unpublished results (1985)

    Google Scholar 

  4. Altshuler, G. L., Dziewulski, D. M., Sowek, J. A., Belfort, G.: Biotech. Bioeng. 28, 646 (1986)

    Google Scholar 

  5. Bailey, J. E., Ollis, D. F.: Biochemical Engineering Fundamentals. McGraw Hill, New York 1977

    Google Scholar 

  6. Bird, R. B., Stewart, W. E., Lightfoot, E. N.: Transport Phenomena, Wiley, New York 1960

    Google Scholar 

  7. Calabresi, P., McCarthy, K. L., Dexter, D. L., Cummings, F. J., Rotman, B.: Proc. Am. Assoc. Cancer Res. 22, 302 (1981)

    Google Scholar 

  8. David, G. S., Reisfeld, R. A., Chino, T. H.: J. Natl. Cancer Inst. 60, 303 (1978)

    Google Scholar 

  9. Davis, M. E., Watson, L. T.: Biotech. Bioeng. 27, 182 (1985)

    Google Scholar 

  10. Ehrlich, K. C., Stewart, E., Klein, E.: In Vitro 14, 443 (1978)

    Google Scholar 

  11. Fleischaker, R. J., Giard, D. J., Weaver, J., Sinskey, A. J.: Adv. Biotechn. 1, 425 (1980)

    Google Scholar 

  12. Freyer, J. P., Sutherland, R. M.: Adv. Exper. Med. Biol. 159, 463 (1983)

    Google Scholar 

  13. Georgakis, C., Chan, P. C. H., Aris, R.: Biotech. Bioeng. 17, 99 (1975)

    Google Scholar 

  14. Glacken, M. W., Fleischaker, R. J., Sinskey, A. J.: Ann. NY Acad. Sci. 413, 355 (1983)

    Google Scholar 

  15. Hopkinson, J.: Bio/Technology 3, 225 (1985)

    Google Scholar 

  16. Horvath, C., Shendalwan, L. H., Light, R. T.: Chem. Eng. Sci. 28, 375 (1973)

    Google Scholar 

  17. Inloes, D. S., Taylor, D. P., Cohen, S. N., Michaels, A. S., Robertson, C. R.: Appl. Envir. Microb. 46, 264 (1983)

    Google Scholar 

  18. Jarvis, A. P., Grdina, T. A.: Biotechniques 1, 22 (1983)

    Google Scholar 

  19. Kan, J. K., Shuler, M. L.: Biotech. Bioeng. 20, 217 (1978)

    Google Scholar 

  20. Karel, S. F., Libicki, S. B., Robertson, C. R.: Chem. Eng. Sci. 40, 1321 (1985)

    Google Scholar 

  21. Kim S., Cooney, D. O.: Chem. Eng. Sci. 31, 289 (1976)

    Google Scholar 

  22. Kleinstreuer, C., Poweigha, T.: Adv. Biochem. Eng./Biotech. 30, 91 (1984)

    Google Scholar 

  23. Knazek, R. A., Gullino, P. M., Kohler, P. O., Dedrick, R. L.: Science 178, 65 (1972)

    Google Scholar 

  24. Knazek, R. A., Kohler, P. O., Gullino, P. M.: Exp. Cell Res. 84, 251 (1974)

    Google Scholar 

  25. Knazek, R. A.: Fed. Proc. Am. Soc. Fed. Biol. 33, 1978 (1979)

    Google Scholar 

  26. Ku, K., Kuo, M. J., Delente, J., Wildi, B. S., Feder, J.: Biotech. Bioeng. 23, 79 (1981)

    Google Scholar 

  27. Lim, F., Moss, R. D.: J. Pharm. Sci. 70, 351 (1981)

    Google Scholar 

  28. Lydersen, B. K., Pugh, G. G., Paris, M. S., Sharma, B. P., Noll, L. A.: Bio/Technology 3, 63 (1985)

    Google Scholar 

  29. Margaritis, A., Wallace, J. B.: Bio/Technology 2, 447 (1984)

    Google Scholar 

  30. Prenosil, J. E., Pedersen, H.: Enzyme Microb. Technol. 5, 323 (1983)

    Google Scholar 

  31. Ratner, P. L., Cleary, M. L., James E.: J. Virol. 26, 536 (1978)

    Google Scholar 

  32. Reisfeld, R. A., David, G. S., Ferrone, S., Pellegrino, M. A., Holmes, E. C.: Cancer Res. 37, 2860 (1977)

    Google Scholar 

  33. Research and Education Assn.: Handbook of Mathematical Formulas, Tables, Functions, Graphs, Transforms. Research and Education Assn., New York 1980

    Google Scholar 

  34. Reuveny, S., Velez, D., Miller, L., MacMillan, D.: J. Immunol. Meth., in press (1986)

    Google Scholar 

  35. Rony, P. R.: Biotech. Bioeng. 13, 431 (1971)

    Google Scholar 

  36. Rutzky, L. P., Tomita, J. T., Calenoff, M. A., Kahan, B. D.: J. Natl. Cancer Inst. 63, 893 (1979)

    Google Scholar 

  37. Schonberg, J. A., Belfort, G.: Enhanced nutrient transport in hollow fiber bioreactors: A theoretical analysis. Submitted (1986)

    Google Scholar 

  38. Sowek, J.: private communication (1985)

    Google Scholar 

  39. Tharakan, J. P., Chau, P. C.: Biotech. Bioeng. 28, 329 (1986)

    Google Scholar 

  40. van Heuven, J. W., van Maanen, H. C. H. J., Ligtermoet, R.: Characteristics of immobilized enzyme systems. In: Innovations in Biotechnology, (Houwink, E. H. and van der Meer, R. R., eds.) p. 53. Elsevier Science, Amsterdam 1984

    Google Scholar 

  41. Waterland, L. R., Michaels, A. S., Robertson, C. R.: AIChE J. 20, 50 (1974)

    Google Scholar 

  42. Waterland, L. R., Robertson, C. R., Michaels, A. S.: Chem. Eng. Commun. 2, 37 (1975)

    Google Scholar 

  43. Webster, I. A., Shuler, M. L.: Biotech. Bioeng. 20, 1541 (1978)

    Google Scholar 

  44. Webster, I. A., Shuler, M. L., Rony, P. R.: Biotech. Bioeng. 21, 1725 (1979)

    Google Scholar 

  45. Webster, I. A., Shuler, M. L.: Biotech. Bioeng. 23, 447 (1981)

    Google Scholar 

  46. Wei, J., Russ, M. B.: J. Theor. Biol. 66, 775 (1977)

    Google Scholar 

  47. Wiemann, M. C., Ball, E. D., Fanger, M. W., Dexter, D. L., Mclntyre, O. R., Bernier, G., Calabresi, P.: Clin. Res. 31, 511A (1983)

    Google Scholar 

  48. Wolf, C. F. W., Munkelt, B. E.: Trans. Am. Soc. Artif. Int. Organs 21, 16 (1975)

    Google Scholar 

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© 1987 Springer-Verlag

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Heath, C., Belfort, G. (1987). Immobilization of suspended mammalian cells: Analysis of hollow fiber and microcapsule bioreactors. In: Vertrebrate Cell Culture I. Advances in Biochemical Engineering/Biotechnology, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0000671

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  • DOI: https://doi.org/10.1007/BFb0000671

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  • Print ISBN: 978-3-540-17626-8

  • Online ISBN: 978-3-540-47725-9

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