Parallel use of shake flask and microtiter plate online measuring devices (RAMOS and BioLector) reduces the number of experiments in laboratory-scale stirred tank bioreactors.
BACKGROUND
Conventional experiments in small scale are often performed in a 'Black Box' fashion, analyzing only the product concentration in the final sample. Online monitoring of relevant process characteristics and parameters such as substrate limitation, product inhibition and oxygen supply is lacking. Therefore, fully equipped laboratory-scale stirred tank bioreactors are hitherto required for detailed studies of new microbial systems. However, they are too spacious, laborious and expensive to be operated in larger number in parallel. Thus, the aim of this study is to present a new experimental approach to obtain dense quantitative process information by parallel use of two small-scale culture systems with online monitoring capabilities: Respiration Activity MOnitoring System (RAMOS) and the BioLector device.


RESULTS
The same 'mastermix' (medium plus microorganisms) was distributed to the different small-scale culture systems: 1) RAMOS device; 2) 48-well microtiter plate for BioLector device; and 3) separate shake flasks or microtiter plates for offline sampling. By adjusting the same maximum oxygen transfer capacity (OTRmax), the results from the RAMOS and BioLector online monitoring systems supplemented each other very well for all studied microbial systems (E. coli, G. oxydans, K. lactis) and culture conditions (oxygen limitation, diauxic growth, auto-induction, buffer effects).


CONCLUSIONS
The parallel use of RAMOS and BioLector devices is a suitable and fast approach to gain comprehensive quantitative data about growth and production behavior of the evaluated microorganisms. These acquired data largely reduce the necessary number of experiments in laboratory-scale stirred tank bioreactors for basic process development. Thus, much more quantitative information is obtained in parallel in shorter time.
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
S J
SJ
Wewetzer
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
M
M
Kunze
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
T
T
Ladner
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
B
B
Luchterhand
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
S
S
Roth
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
N
N
Rahmen
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
R
R
Kloß
University of Minho, CEB - Centre of Biological Engineering, Campus de Gualtar, 4700-057 Braga, Portugal.
A
A
Costa E Silva
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
L
L
Regestein
RWTH Aachen University, AVT - Biochemical Engineering, Worringer Weg 1, 52074 Aachen, Germany.
J
J
Büchs
BioLector; High-throughput; Microtiter plates; Online measurement; Oxygen limitation; Parallel cultivation; RAMOS; RoboLector; Shake flasks; Small-scale cultivation