Use of reaction calorimetry to monitor and control microbial cultures producing industrially relevant secondary metabolites

Voisard, D.; Claivaz, C.; Menoud, L.; Marison, I. W.; Stockar, Urs von

doi:10.1016/s0040-6031(97)00370-5

Cited by 11 publications

(5 citation statements)

References 14 publications

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“…The heat balance model presented in Equation ( 1) was adapted from works published by von Stockar (1989), Voisard (1998, Biener (2010Biener ( , 2012, Sivaprakasam (2011), Schuler (2012) and Mohan (2017) [11,[13][14][15][19][20][21]30]. q stir + q cal + q dos − q ex − q loss − q gas − q CO 2 + q r = q acc (1) As the uncertainty of the level sensor was too high (±25 mL) for an accurate estimation of the reaction medium volume, it was decided to use mass units instead of volumetric units.…”

Section: Heat Balance Modelmentioning

confidence: 99%

“…This property allowed Larsson et al (1991) to control fed-batch cultures of S. cerevisiae by biocalorimetry using an on/off-controller, and adding glucose only when the growth rate (hence the heat flow) was equal to zero [18]. Voisard et al (1998) used reaction calorimetry to monitor and control both batch and fed-batch microbial cultures to produce two chemicals [19]. In a further work (2002), scale-up studies performed using a 300 L biocalorimeter proved that pilot-scale calorimetric measurements were possible with precisely characterised heat transfers [15].…”

Section: Introductionmentioning

confidence: 99%

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Novel Strategy for the Calorimetry-Based Control of Fed-Batch Cultivations of Saccharomyces cerevisiae

2021

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Typical controllers for fed-batch cultivations are based on the estimation and control of the specific growth rate in real time. Biocalorimetry allows one to measure a heat signal proportional to the substrate consumed by cells. The derivative of this heat signal is usually used to evaluate the specific growth rate, introducing noise to the resulting estimate. To avoid this, this study investigated a novel controller based directly on the heat signal. Time trajectories of the heat signal setpoint were modelled for different specific growth rates, and the controller was set to follow this dynamic setpoint. The developed controller successfully followed the setpoint during aerobic cultivations of Saccharomyces cerevisiae, preventing the Crabtree effect by maintaining low glucose concentrations. With this new method, fed-batch cultivations of S. cerevisiae could be reliably controlled at specific growth rates between 0.075 h−1 and 0.20 h−1, with average root mean square errors of 15 ± 3%.

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Section: Heat Balance Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Strategy for the Calorimetry-Based Control of Fed-Batch Cultivations of Saccharomyces cerevisiae

2021

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“…Biocalorimetry has been used in many different applications, including to monitor culture metabolism and control the feed of nutrients and hence the growth rate. By doing so, respiro-fermentative metabolism caused by overflow metabolism in Crabtree positive organisms could be avoided [34][35][36][37][38]. In addition, a study was performed in the RC1 to determine the existence of endothermic bacterial strains [39].…”

Section: Bench Scale Biocalorimetry Applicationsmentioning

confidence: 99%

The Application of Dielectric Spectroscopy and Biocalorimetry for the Monitoring of Biomass in Immobilized Mammalian Cell Cultures

2015

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Abstract:The purpose of this study was to introduce dielectric spectroscopy and biocalorimetry as monitoring methods to follow immobilised Chinese Hamster Ovary (CHO) cell culture development. The theory behind both monitoring techniques is explained and perfusion cultures are performed in a Reaction Calorimeter (eRC1 from Mettler Toledo) as an application example. The findings of this work show that dielectric spectroscopy gives highly reliable information upon the viable cell density throughout the entire culture. On the other hand, the RC1 could only provide accurate data from day 5, when the cell density exceeded 4 × 10 , a viable cell density commonly achieved in fed-batch and the early stages of a perfusion culture. This work suggests that biocalorimetry should be possible to implement at industrial scale to monitor CHO cell cultures.

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“…Developed ®rst for chemical processes (Karlsen and Villadsen, 1987;Landau, 1996;Regenass, 1985;Stockton et al, 1986), several researchers have adapted this technique to the study of living organisms (Cooney et al, 1969;Marison et al, 1998;Marison and von Stockar, 1985;Meier-Schneiders et al, 1992;van Klee et al, 1993). As a result they have become very powerful tools for quantitative thermodynamic studies (Duboc and von Stockar, 1995;Schill and von Stockar, 1995) and for the reliable monitoring and control of many bioprocesses (Birou et al, 1987;Duboc et al, 1999;Liu et al, 1999;Marison and von Stockar, 1986;Meier-Schneiders et al, 1995a;Randolph et al, 1989;van Klee et al, 1996;Voisard et al, 1998;von Stockar et al, 1997von Stockar et al, , 1995.…”

Section: Introductionmentioning

confidence: 99%

“…To achieve this, an industrially relevant fed-batch bioprocess for the production of biopesticides using Bacillus sphaericus was used because it has been studied calorimetrically at the laboratory-scale (Voisard et al, 1998) and shown to exhibit a number of challenging features, including protease secretion, inducing foam formation with accompanied variations in stirring power. The industrial interest in this aerobic, sporulating bacterium is for the production of binary toxins speci®cally active against mosquito larvae of the Culex and Anopheles species responsible for the transmission of ®larial parasites and malaria (Davidson, 1985;Lacey, 1984;Priest, 1992;Singer, 1980).…”

Section: Introductionmentioning

confidence: 99%

Development of a large‐scale biocalorimeter to monitor and control bioprocesses

Voisard

Pugeaud

Kumar

et al. 2002

Biotech & Bioengineering

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Calorimetry has shown real potential at bench-scale for chemical and biochemical processes. The aim of this work was therefore to scale-up the system by adaptation of a standard commercially available 300-L pilot-scale bioreactor. To achieve this, all heat flows entering or leaving the bioreactor were identified and the necessary instrumentation implemented to enable on-line monitoring and dynamic heat balance estimation. Providing that the signals are sufficiently precise, such a heat balance would enable calculation of the heat released or taken up during an operational (bio)process. Two electrical Wattmeters were developed, the first for determination of the power consumption by the stirrer motor and the second for determination of the power released by an internal calibration heater. Experiments were designed to optimize the temperature controller of the bioreactor such that it was sufficiently rapid so as to enable the heat accumulation terms to be neglected. Further calibration experiments were designed to correlate the measured stirring power to frictional heat losses of the stirrer into the reaction mass. This allows the quantitative measurement of all background heat flows and the on-line quantitative calculation of the (bio)process power. Three test fermentations were then performed with B. sphaericus 1593M, a spore-forming bacterium pathogenic to mosquitoes. A first batch culture was performed on a complex medium, to enable optimization of the calorimeter system. A second batch culture, on defined medium containing three carbon sources, was used to show the fast, accurate response of the heat signal and the ability to perfectly monitor the different growth phases associated with growth on mixed substrates, in particular when carbon sources became depleted. A maximum heat output of 1100 W was measured at the end of the log-phase. A fed-batch culture on the same defined medium was then carried out with the feed rate controlled as a function of the calorimeter signal. A maximum heat output of 2250 W was measured at the end of the first log-phase. This work demonstrates that real-time quantitative calorimetry is not only possible at pilot-scale, but could be readily applied at even larger scales. The technique requires simple, readily available devices for determination of the few necessary heat flows, making it a robust, cost-effective technique for process development and routine monitoring and control of production processes.

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Use of reaction calorimetry to monitor and control microbial cultures producing industrially relevant secondary metabolites

Cited by 11 publications

References 14 publications

Novel Strategy for the Calorimetry-Based Control of Fed-Batch Cultivations of Saccharomyces cerevisiae

Novel Strategy for the Calorimetry-Based Control of Fed-Batch Cultivations of Saccharomyces cerevisiae

The Application of Dielectric Spectroscopy and Biocalorimetry for the Monitoring of Biomass in Immobilized Mammalian Cell Cultures

Development of a large‐scale biocalorimeter to monitor and control bioprocesses

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