Microscale and miniscale fermentation and screening.

Area of Science:

• Biotechnology
• Biochemical Engineering
• Microfluidics

Background:

• Small-scale bioreactors (microliter to milliliter) are increasingly important for bioprocess development.
• Characterization of mass transfer, including volumetric mass transfer coefficient (kLa) and maximum oxygen transfer rate (OTRmax), is critical.
• kLa values up to 1440 h⁻¹ have been reported for these systems.

Purpose of the Study:

• To review advancements in small-scale bioreactor technology.
• To highlight methods for characterizing mass transfer and monitoring cultivation parameters.
• To discuss the application of single-cell microfluidics and fed-batch techniques for process optimization.

Main Methods:

• Utilizing optical on-line methods (fluorescence, scattered light) for monitoring pH, dissolved oxygen tension (DOT), product formation, and biomass.
• Employing single-cell microfluidics to study microbial behavior under varying conditions.
• Implementing novel fed-batch strategies to bridge screening and production scales.

Main Results:

• High kLa values demonstrate efficient oxygen transfer in small-scale bioreactors.
• OTRmax is significantly affected by liquid film thickness and viscosity.
• Optical methods and microfluidics provide real-time data for process understanding.
• Fed-batch techniques facilitate the assimilation of cultivation conditions across scales.

Conclusions:

• Small-scale bioreactors offer powerful tools for bioprocess characterization and optimization.
• Integrated monitoring and advanced techniques like microfluidics enhance insights into microbial processes.
• Bridging the gap between lab-scale screening and industrial production is achievable with novel cultivation strategies.