Quantitative Flow Measurements in Bioreactors by Nuclear Magnetic Resonance Imaging

Abstract

We have developed nuclear magnetic resonance (NMR) flow imaging techniques to measure fluid flow in a cell-free hollow fiber bioreactor (HFBR). Using 1H NMR we track the motion of protons and obtain velocity distributions as a function of position and time. These measurements enable the visualization of flow patterns needed for module design and for establishing desired operating conditions. Uneven flow in the cell-containing region of an HFBR can result in concentration gradients and uneven cell distribution that may lead to reduced cell viability. Results from this non-invasive method could be used to design more efficient cell bioreac-tors or membrane separation devices.

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References

  1. 1

    Belfort, G. 1989. Membranes and bioreactors: A technical challenge in biotechnology. Biotechnol. Bioengr. 33: 1047–1066.

  2. 2

    Knazek, R.A., Gullino, P.M., Kohler, P.O. and Dedrick, R.L. 1972. Cell culture on artificial capillaries: An approach to tissue growth in vitro. Science 178: 65–67.

  3. 3

    Starling, E.H. 1896. On the absorption of fluids from the connective tissue spaces. J. Physiol. 19: 312–326.

  4. 4

    Moran, P.R. 1982. A flow velocity zeugmatographic interlace for NMR imaging in humans. Magn. Reson. Imag. 1: 197–203.

  5. 5

    Gullberg, G.T., Simons, M.A. and Wehrli, F.W. 1988. A mathematical model for signal from spins flowing during the application of spin echo pulse sequences. Mag. Reson. Imag. 6: 437–461.

  6. 6

    Edelstein, W.A., Hutchinson, J.M.S., Johnson, G. and Redpath, T. 1980. Spin warp NMR imaging and applications to human whole body imaging. Phys. Med. Biol. 25: 751–765.

  7. 7

    Apelblat, A., Katzir-Katchalsky, A. and Silberberg, A. 1974. A mathematical analysis of capillary-tissue fluid exchange. Biorheology. 11: 1–49.

  8. 8

    Heath, C.A., Hammer, B.E., Mirer, S.D., Pimbley, J.M. and Belfort, G. 1990. Magnetic resonance imaging and modeling of convec-tive leakage flows in hollow fiber bioreactors. AIChE. J. In press.

  9. 9

    Alderman, D.W. and Grant, D.M. 1979. An efficient decoupler coil design which reduces heating in conductive samples. J. Mag. Reson. 36: 447–451.

  10. 10

    Fernandez, E.J., Mancuso, A. and Clark, D.S. 1988. NMR spectroscopy studies of hybridoma metabolism in a simple membrane reactor. Biotech. Prog. 4: 173–183.

  11. 11

    Gilles, R.J., MacKenzie, N.E. and Dale, B.E. 1989. Analysis of bioreactor performance by nuclear magnetic resonance spectroscopy. Bio/Technology 7: 50–54.

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Hammer, B., Heath, C., Mirer, S. et al. Quantitative Flow Measurements in Bioreactors by Nuclear Magnetic Resonance Imaging. Nat Biotechnol 8, 327–330 (1990). https://doi.org/10.1038/nbt0490-327

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