Research Paper | Published:

Experimental Methods for On–Line Mass Spectrometry in Fermentation Technology*

Bio/Technologyvolume 1pages181188 (1983) | Download Citation



It is shown here how mass spectrometry (MS) can be used for on–line data acquisition in fermentation. MS was applied in this work to analyze gas and liquid phases. Gas phase analysis allows fast and accurate measurement of all gases of interest (O2, N2, CO2, Ar, He etc.). Liquid phase analysis is possible with a steam sterilizable membrane probe and permits direct analysis of dissolved gases (O2, CO2, N2) and various volatiles. Automatic switching between gas inlet and membrane probe and the data reduction was accomplished by desk computer. Continuous yeast fermentation was monitored over long periods to study long–term stability, which seems to be adequate for fermentation processes.

*Parts of this work were presented at the 2nd European Congress Biotechnology in Eastbourne, U.K., 1981, and at the 9th International Mass Spectrometry Conference in Vienna, A, 1982.

**Symbols used in this paper appear preceding the reference section.

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  1. 1

    Norris, P.E. and Scrivens, J.H. 1981. On-line mass spectrometry evaluation and implementation, Dyn. Mass Spectrometry 6: 155–166.

  2. 2

    Fite, W.L., Patterson, T.A., Siegel, M.W., and Brackmann, R.T. 1981. Quadrupole mass spectrometry in process monitoring and control, Dyn. Mass Spectrometry 6: 167–180.

  3. 3

    Schuy, K.D. 1967. Der Beitrag der Massenspektrometrie zur Steuerung und Kontrolle industrieller Fertigungsprozesse. Z. Instr. 75: 190–195.

  4. 4

    Tailliez, B.Y., and Hume, S.H. 1981. The use of time-of-flight mass spectrometry (TOFMS) in process monitoring and control. Dyn. Mass Spectrometry. 6: 181–192.

  5. 5

    Crawford, R.W., Bedford, R.G., Wong, C.M., Brand, H.R., and Kishiyama, K.I. 1981. Use of an automated mass spectrometer for an underground coal gasification field test. Dyn. Mass Spectrometry 6: 195–211.

  6. 6

    Hunter, J.A., Stacy, R.W., and Hitchcock, F.A. 1949. A mass spectrometer for continuous gas analysis. Rev. Scient. Instrum. 20: 333–336.

  7. 7

    Muysers, K. and Smidt, U. 1972. p. 601–622. Clinical uses of mass spectrometry. In: Biochemical applications of Mass Spectrometry. Waller G. R. (ed.), Wiley Interscience, New York.

  8. 8

    Poll, A., Potter, C.J., and Tily, P.J. 1970. On-line analysis of reactor products by mass spectrometry. Chem. Eng. (London) N244: CE413–CE418.

  9. 9

    Cameresi, G.G. and Costa, B. 1978. Real time control of industrial processes by application of a quadrupole M.S. computer system. Adv. Mass Spectrometry 7B: 1062–1068.

  10. 10

    Tonge, G.M. 1980. Instrumentation and control in fermentation: The application of computer controlled mass spectrometry. 5th Intern. Ferm. Symp., London, Canada (abstr).

  11. 11

    Tal'roze, V.L., Gorodetsky, I.G., Zolotoy, N.B., Karpov, G.V., Skurat, V.E., and Maslennikova, V. Ya. 1978. Capillary system for continuous introducing of volatile liquids into analytical mass spectrometers and its applications. Adv. Mass Spectrometry 7B: 858–864.

  12. 12

    Pungor, E., Perley, C.R., Cooney, C.L., and Weaver, J.C. 1981. Continuous monitoring of fermentation outlet gas using a computer coupled MS. Biotechnol. Letters 2: 409–414.

  13. 13

    Matz, G. 1981. Ein mobiles Massenspektrometersystem zur Erfassung umweltbelastender Schadstoffe. Hochschule der Bundeswehr, Hamburg. (Ph.D. thesis).

  14. 14

    Ottley, T.W. 1981. A quadrupole system for atmospheric pollution monitoring. Dyn. Mass Spectrometry 6: 212–219.

  15. 15

    Hwang, S.T. and Kammermeyer, K. 1981. Membranes in Separations. Wiley and Sons (Wiley Interscience), New York.

  16. 16

    Ponte, J. and Durves, M.J. 1979. The use in physiology of a rapidly responding mass-spectrometer sensor. Recent Dev. Mass Spectrom. Biochem. Med. 6: 483–487.

  17. 17

    Woldring, S., Owens, G., and Woolford, D. 1966. Blood gases; continuous in vivo recording of partial pressures by mass spectrography. Science. 153: 885–887.

  18. 18

    Brantigan, J.W., Gott, V.L., Vestal, M.L., Fergusson, G.J., and Johnson, W.H. 1970. A non thrombogenic diffusion membrane for continuous in vivo measurement of blood gases by mass spectrometry. J. Appl. Physiol. 28: 375–377.

  19. 19

    Johnson, T.D., Watkins, G.M., Holsinger, J., Roberts, M.P., and Thomas, D.D. 1979. The development of a flexible mass spectrometer catheter. Recent Dev. Mass Spectrom. Biochem. Med. 5: 463–480.

  20. 20

    Reuss, M., Piehl, H., and Wagner, F. 1975. Application of mass spectrometry to the measurement of dissolved gases and volatile substances in fermentation. Europe. J. Appl. Microbiol. Biotechnol. 1: 323–325.

  21. 21

    Heinzle, E. and Lafferty, R.M. 1980. Continuous mass spectrometric measurement of dissolved H2, O2 and CO2 during chemolitho-autotrophic growth of Alcaligenes eutrophus strain H 16. Europ. J. Appl. Microbiol. Biotechnol. 11: 17–22.

  22. 22

    Pungor, E., Schaefer, E., Weaver, J.C., and Cooney, C.L. 1981. p. 393–398. Direct monitoring of a fermentation in a computer-mass spectrometer-fermentor system. In: Advances in Biotechnology. 1: M. MooYoung, C. W. Robinson, and C. Vezina (ed). Pergamon Press, Toronto.

  23. 23

    Jouanneau, Y., Kelly, B.C., Berlier, Y., Lespinat, P.A., and Vignais, P.M. 1980. Continuous monitoring, by mass spectrometry, of H2 production and recycling in Rhodopseudomonas capsulata. J. Bacteriol. 143: 628–636.

  24. 24

    Lundsgaard, J.S., Peterson, L.C., and Degn, H. 1976. p. 168–183. Mass spectrometric determination of oxygen kinetics in biochemical systems. In: Measurement of Oxygen. Proc. Interdisc. Symp., H. Degn and R. Brook (Ed.) Elsevier, Amsterdam.

  25. 25

    Doerner, P., Lehmann, J., Piehl, H., and Megnet, R. 1982. Process analysis of the acetone-butanol fermentation by quadrupole mass spectrometry. Biotechnol. Letters 4: 557–562.

  26. 26

    Weaver, J.C., Mason, M.K., Jarrell, J.A., and Peterson, J.W. 1976. Biochemical assay by immobilized enzymes and a mass spectrometer. p. 207–225. Biochem. Biophys. Acta 438: 296–303.

  27. 27

    Weaver, J.C. 1977. Possible biomedical applications of the volatile enzyme product method. In: Biomedical Applications of Immobilized Enzymes and Proteins. 2: T.M.S. Chang (ed.) Plenum Press.

  28. 28

    Weaver, J.C. and Abrams, J.H. 1979. Use of variable pH interface to a mass spectrometer for the measurement of dissolved volatile compounds. Rev. Sci. Instrum. 50: 478–481.

  29. 29

    Weaver, J.C., Perley, C.R., Reames, F.M., and Cooney, C.L. 1980. Temporarily immobilized microorganisms: rapid measurements using a mass spectrometer. Biotechnol. Letters 2: 133–137.

  30. 30

    Meyenburg, K. 1969. Katabolit-Repression und der Sprossungszyklus von Saccharomyces cerevisiae. Diss. ETH no. 4279, Zurich.

  31. 31

    Krasnobajev, V. Givaudan, Dubendorf, CH (private communication).

  32. 32

    Furukawa, K., Heinzle, E., Dunn, I.J., and Bourne, J.R. Influence of oxygen on the growth of Saccharomyces cerevisiae in continuous culture. Biotechnol. Bioeng. (in press).

  33. 33

    Heinzle, E., Furukawa, K., Tanner, R., and Dunn, I.J. 1982. Modelling of sustained oscillations observed in continuous culture of Saccharomyces cerevisiae. 1st Workshop on Modelling and Control of Biotechnical Processes. IFAC, Helsinki.

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  1. Technisch-chemisches Laboratorium ETH, CH-8092, Zurich, Switzerland

    • E. Heinzle
    • , K. Furukawa
    • , I. J. Dunn
    •  & J. R. Bourne


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