On-line Process Mass Spectrometry has been increasingly applied to industrial aerobic fermentations since the early 1980s.  It is now commonly used to provide reliable and accurate near-continuous estimates of culture oxygen uptake (OU), carbon dioxide evolution (CE), respiration quotient (RQ), and oxygen mass transfer coefficient (k_la).  A few researchers and companies have developed more sophisticated applications of this technology, such as using standard mass spectrometry based computed results (e.g. OU) as inputs to “virtual sensor” models, which estimate, on-line, other important fermentation parameters such as cell mass and substrate concentration. Other advanced applications use process mass spectrometry results for on-line control decisions and for scanning fermentation exhaust gas for any compounds of environmental concern.  Process Mass Spectrometry has clearly evolved to where it is a classic and proven example of the FDA’s endorsed Process Analytical Technology (PAT) initiative.
    This presentation will include a brief overview of process mass spectrometers used with bioreactors, summarize several standard and advanced applications, and conclude with a vision and perceived challenges regarding future use of this technology.