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Downscaling screening cultures in a multifunctional bioreactor array‐on‐a‐chip for speeding up optimization of yeast‐based lactic acid bioproduction
Author(s) -
Totaro Damiano,
Rothbauer Mario,
Steiger Matthias G.,
Mayr Torsten,
Wang HsiangYu,
Lin YuSheng,
Sauer Michael,
Altvater Martin,
Ertl Peter,
Mattanovich Diethard
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27338
Subject(s) - bioprocess , bioreactor , bioproduction , biochemical engineering , laboratory flask , microfluidics , microbiology and biotechnology , process engineering , chemistry , nanotechnology , biology , materials science , engineering , paleontology , organic chemistry
A key challenge for bioprocess engineering is the identification of the optimum process conditions for the production of biochemical and biopharmaceutical compounds using prokaryotic as well as eukaryotic cell factories. Shake flasks and bench‐scale bioreactor systems are still the golden standard in the early stage of bioprocess development, though they are known to be expensive, time‐consuming, and labor‐intensive as well as lacking the throughput for efficient production optimizations. To bridge the technological gap between bioprocess optimization and upscaling, we have developed a microfluidic bioreactor array to reduce time and costs, and to increase throughput compared with traditional lab‐scale culture strategies. We present a multifunctional microfluidic device containing 12 individual bioreactors ( V t = 15 µl) in a 26 mm × 76 mm area with in‐line biosensing of dissolved oxygen and biomass concentration. Following initial device characterization, the bioreactor lab‐on‐a‐chip was used in a proof‐of‐principle study to identify the most productive cell line for lactic acid production out of two engineered yeast strains, evaluating whether it could reduce the time needed for collecting meaningful data compared with shake flasks cultures. Results of the study showed significant difference in the strains' productivity within 3 hr of operation exhibiting a 4‐ to 6‐fold higher lactic acid production, thus pointing at the potential of microfluidic technology as effective screening tool for fast and parallelizable industrial bioprocess development.