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Microfluidic Picoliter Bioreactor for Microbial Single-cell Analysis: Fabrication, System Setup, and Operation
Published on: December 6, 2013
Bioprocess control in microscale: scalable fermentations in disposable and user-friendly microfluidic systems
Matthias Funke1, Andreas Buchenauer, Wilfried Mokwa
1AVT-Biochemical Engineering, RWTH Aachen University, Worringerweg 1, D-52074 Aachen, Germany.
Microbial Cell Factories
|November 16, 2010
Summary
This study introduces a novel microfluidic system for high-throughput bioprocess development. The system enables scalable, controlled fermentations in microtiter plates, accelerating drug development.
Area of Science:
- Biotechnology
- Microbial Fermentation
- Bioprocess Engineering
Background:
- Biotechnological production efficiency relies on strain selection and optimal cultivation conditions, often requiring extensive experimentation.
- High-throughput devices are crucial for accelerating drug development by enabling rapid bioprocess optimization.
- Existing systems like the BioLector use microtiter plates (MTPs) as small-scale fermenters, but integration with advanced control is needed.
Purpose of the Study:
- To combine microfluidic bioprocess control with BioLector technology in MTPs for enhanced microbioreactor applications.
- To develop a user-friendly, disposable microfluidic system for routine laboratory use in bioprocess development.
- To enable rapid, reliable, and scalable fermentations with precise control.
Main Methods:
- Integration of microfluidic liquid dosing with the BioLector fiber-optic online-monitoring system in disposable MTPs.
- Pneumatic hardware actuation for user-friendly control of microfluidic MTPs.
- Testing of pH-controlled batch and fed-batch fermentations of Escherichia coli with precise parameter control.
Main Results:
- Successful implementation of pH-controlled batch and fed-batch fermentations in microfluidic MTPs.
- Precise pH control within a narrow dead band (0.03) using automated dosing of acid and base.
- Demonstrated scale-up potential by maintaining a constant volumetric mass transfer coefficient (kLa) of 460 1/h, showing comparable E. coli growth kinetics to laboratory-scale fermenters.
Conclusions:
- A user-friendly, disposable microfluidic system for microbioreactors has been successfully established.
- The system allows for scalable, fully controlled, and fully monitored fermentations in volumes under 1 milliliter.
- This technology significantly advances high-throughput bioprocess development and drug discovery pipelines.
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