Automated Measurement and Monitoring of Bioprocesses: Key Elements of the M3C Strategy - Measurement, Monitoring, Modelling, and Control of Bioprocesses - page 10

Fig. 1 Phase-plane plot of CO 2 versus O 2 content (as molar fraction, y) in the exhaust gas during
a batch and a consecutive fed-batch cultivation of Saccharomyces cerevisiae. The time
information is lost in a phase-plane plot. Three typical ''straight lines''—almost linear domains—
are visible, and the negative slopes estimate the RQ: the steepest domain was observed during
oxido-reductive batch growth on glucose with concomitant ethanol excretion (RQ & 3), the
flattest domain characterizes the consecutive growth of the cells on ethanol (RQ & 0.5), and the
middle domain was recorded during the controlled glucose feed phase in the final fed-batch
(RQ & 1). Linear regression of the data domains must be applied with the objective of
minimizing the orthogonal distances of data points from the regression line (where transition
phases should be omitted since the RQ changes dynamically)
are often not trusted, even though good coincidence between actual but relative data
with those of approved reference cultivations should be sufficient indication of good
reproducibility (of the process). Obviously, many people rely on offline reference
methods only. Madrid and Felice [ 26 ] compiled a broad comparison of all those
methods and differentiated nicely what a method can and cannot detect.
3.1 Biomass
To my knowledge, no fully automatic version of the SOP for manual determina-
tion of cell dry weight has been commercialized to date. The sensors and instru-
ments useful to quantify biomass are either indirect methods—and deliver
estimates—or methods implementing counting of suspended particles—and these
deliver a cell number concentration rather than a cell mass concentration.