Microbioreactors (MBRs)

Microbioreactors (MBRs) are miniaturized bioreactors designed for small-scale bioprocessing, cell culture, and microbial fermentation. They integrate essential bioreactor functions—such as mixing, aeration, pH and temperature control—into a compact system, enabling high-throughput and cost-efficient bioprocess development.

Key Features of Microbioreactors

1. Small Working Volume
   • Typically range from microliters (µL) to milliliters (mL).
   • Require minimal reagents, reducing costs and waste.
2. High-Throughput Capability
   • Often used in parallel (e.g., microtiter plates, microfluidic chips) to test multiple conditions simultaneously.
3. Automated and Real-Time Monitoring
   • Equipped with sensors for pH, dissolved oxygen (DO), temperature, biomass, and metabolite concentrations.
4. Integrated Control Systems
   • Allow automated feeding, gas exchange, and mixing, simulating larger-scale bioreactors.
5. Scalability
   • Data from MBRs can be used to optimize conditions for large-scale bioreactors (up to industrial-scale fermentation).

Types of Microbioreactors

1. Microfluidic Bioreactors

   • Use lab-on-a-chip technology with microchannels for cell culture and fermentation.
   • Require minimal reagents, enabling single-cell studies and precision bioprocessing.

2. Microtiter Plate Bioreactors

   • Common in 96-well or 384-well plates, ideal for high-throughput screening.
   • Often used in synthetic biology, drug development, and enzyme engineering.

3. Miniature Stirred-Tank Reactors

   • Scaled-down versions of conventional bioreactors with stirrers, spargers, and real-time monitoring.
   • Used for cell culture, protein production, and metabolic engineering.

4. Membrane-Based MBRs

   • Utilize semipermeable membranes for oxygen supply and waste removal.
   • Suitable for long-term cell culture and tissue engineering.

Applications of Microbioreactors

1. Biopharmaceutical Production

   • Used for optimizing monoclonal antibody (mAb) production, vaccine development, and recombinant protein expression.

2. Synthetic Biology & Metabolic Engineering

   • Enable rapid screening of genetically engineered microorganisms (e.g., E. coli, yeast, CHO cells).

3. Environmental Biotechnology

   • Applied in wastewater treatment and microbial ecology studies.

4. Biomedical Research

   • Used in organ-on-a-chip models, stem cell research, and personalized medicine.

5. Food & Beverage Industry

   • Help optimize fermentation processes for probiotics, enzymes, and alternative proteins.

Advantages of Microbioreactors

✔ Cost-Efficient – Uses minimal reagents and media.
✔ Rapid Data Acquisition – Speeds up process development.
✔ Better Process Control – Real-time monitoring ensures reproducibility.
✔ Scalability – Can predict large-scale bioprocessing performance.

Challenges

⚠ Oxygen & Nutrient Limitations – Small volumes can lead to depletion issues.
⚠ Shear Stress Sensitivity – Some designs may not mimic larger bioreactors perfectly.
⚠ Complex Data Analysis – High-throughput experiments generate large datasets.