title: Robotic platform for parallelized cultivation and monitoring of microbial growth parameters in microwell plates.
abstract: The enormous variation possibilities of bioprocesses challenge process development to fix a commercial process with respect to costs and time. Although some cultivation systems and some devices for unit operations combine the latest technology on miniaturization, parallelization, and sensing, the degree of automation in upstream and downstream bioprocess development is still limited to single steps. We aim to face this challenge by an interdisciplinary approach to significantly shorten development times and costs. As a first step, we scaled down analytical assays to the microliter scale and created automated procedures for starting the cultivation and monitoring the optical density (OD), pH, concentrations of glucose and acetate in the culture medium, and product formation in fed-batch cultures in the 96-well format. Then, the separate measurements of pH, OD, and concentrations of acetate and glucose were combined to one method. This method enables automated process monitoring at dedicated intervals (e.g., also during the night). By this approach, we managed to increase the information content of cultivations in 96-microwell plates, thus turning them into a suitable tool for high-throughput bioprocess development. Here, we present the flowcharts as well as cultivation data of our automation approach.
authors.affiliation: Chair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Knepper
authors.affiliation: Chair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heiser
authors.affiliation: Chair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Glauche
authors.affiliation: Chair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany peter.neubauer@tu-berlin.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Neubauer
mesh_terms: D000085:Acetates / Q000032:analysis; D057205:Automation, Laboratory / Q000379:methods*; D018533:Biomass; D003470:Culture Media / Q000737:chemistry; D004926:Escherichia coli / Q000254:growth & development; D005947:Glucose / Q000032:analysis; D057166:High-Throughput Screening Assays / Q000379:methods; D006863:Hydrogen-Ion Concentration; D007778:Lactobacillus / Q000254:growth & development; D008828:Microbiological Techniques / Q000379:methods*; D012371:Robotics / Q000379:methods*; D013053:Spectrophotometry
chemical_list: D000085:Acetates; D003470:Culture Media; D005947:Glucose
keywords: assays; consistent bioprocess development; high throughput; laboratory automation; microliter scale; monitoring; scale-down; scale-up; screening