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👩‍🔬Intro to Biotechnology

Bioreactor Types

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Why This Matters

Bioreactors are the workhorses of biotechnology—they're where the actual biological production happens. Whether you're growing bacteria to produce insulin, cultivating algae for biofuels, or engineering tissues for medical applications, the bioreactor you choose determines your success. You're being tested on your ability to match bioreactor design to specific applications, understanding why certain configurations work better for particular cell types, products, and scales.

The key concepts here revolve around mixing mechanisms, mass transfer efficiency, shear sensitivity, and operational modes (batch vs. continuous). Don't just memorize a list of bioreactor names—know what problem each design solves and when you'd choose one over another. If an exam question describes a production scenario, you should be able to recommend the appropriate bioreactor type and justify your choice.


Mechanically Agitated Systems

These bioreactors use physical components to actively mix the culture medium. Mechanical agitation creates turbulence that enhances oxygen transfer and nutrient distribution, but generates shear forces that can damage sensitive cells.

Stirred Tank Bioreactor

  • Impeller-driven mixing—the rotating blade creates turbulent flow that maintains homogeneity throughout the culture medium
  • Precise parameter control of pH, temperature, and dissolved oxygen makes this the industry standard for most microbial and mammalian cell cultures
  • High shear forces limit its use with fragile cells but make it excellent for robust microorganisms in pharmaceutical and industrial fermentation

Wave Bioreactor

  • Rocking motion creates gentle waves that promote mixing and gas exchange without mechanical impellers
  • Disposable bag design reduces contamination risk and eliminates cleaning validation—ideal for research and clinical-scale production
  • Shear-sensitive cell compatibility makes this perfect for mammalian cell cultures and small-scale process development

Compare: Stirred Tank vs. Wave Bioreactor—both achieve mixing and aeration, but stirred tanks use aggressive mechanical agitation while wave bioreactors use gentle rocking motion. Choose stirred tanks for robust microbes at large scale; choose wave bioreactors for sensitive mammalian cells at smaller scales.


Pneumatically Driven Systems

These bioreactors rely on gas flow rather than mechanical parts to achieve mixing. Rising bubbles or air-driven circulation creates movement without impellers, reducing shear stress and mechanical complexity.

Bubble Column Bioreactor

  • Gas sparging introduces bubbles at the bottom that rise through the liquid, creating mixing and oxygen transfer simultaneously
  • Simple design with low energy consumption—no moving parts means reduced maintenance and operating costs at large scale
  • Best for aerobic fermentation processes like biofuel production where gentle mixing is sufficient

Airlift Bioreactor

  • Draft tube circulation creates a defined flow pattern where liquid rises in one section and descends in another, driven entirely by air injection
  • Gentle handling of shear-sensitive cells—the controlled circulation pattern minimizes cell damage compared to mechanical agitation
  • Superior gas-liquid mass transfer efficiency makes this ideal for plant cell cultures, animal cell cultures, and oxygen-demanding processes

Compare: Bubble Column vs. Airlift Bioreactor—both use gas to drive mixing, but airlift bioreactors add a draft tube that creates organized circulation patterns. Airlift designs offer better mixing uniformity and gentler conditions, making them preferred for sensitive cell types.


Immobilized Cell Systems

These bioreactors attach cells to solid supports rather than suspending them freely. Immobilization increases effective cell density and allows continuous operation, but creates potential mass transfer limitations.

Packed Bed Bioreactor

  • Solid support matrix immobilizes microorganisms or cells, enabling extremely high cell densities in a compact volume
  • Continuous processing capability makes this ideal for wastewater treatment, bioconversion reactions, and enzyme production
  • Concentration gradients can develop due to limited mixing—requires careful monitoring of flow rates and nutrient distribution

Fluidized Bed Bioreactor

  • Suspended solid particles create a fluid-like bed when liquid flows upward, combining immobilization benefits with improved mass transfer
  • Large surface area for microbial attachment supports high-density cultures with better nutrient access than packed beds
  • Versatile bioprocessing applications including fermentation, wastewater treatment, and continuous production systems

Hollow Fiber Bioreactor

  • Hollow fiber membranes provide enormous surface area for cell attachment within a compact cartridge design
  • Efficient nutrient and gas exchange occurs across the fiber walls while products can be continuously harvested from the extracapillary space
  • Biopharmaceutical and tissue engineering applications—commonly used for monoclonal antibody production and growing 3D tissue constructs

Compare: Packed Bed vs. Fluidized Bed Bioreactor—both immobilize cells on solid supports, but fluidized beds suspend particles in flowing liquid while packed beds keep them stationary. Fluidized beds offer better mass transfer but require more energy to maintain particle suspension.


Membrane-Integrated Systems

These bioreactors incorporate membrane technology to separate cells from products or control the culture environment. Membranes enable selective retention or removal of components, supporting continuous high-density cultures.

Membrane Bioreactor

  • Combined biological treatment and filtration—membranes separate biomass from effluent in a single integrated system
  • High-quality effluent eliminates the need for secondary clarifiers, making this the gold standard for advanced wastewater treatment
  • Flexible operation in continuous or batch modes allows optimization for different treatment goals and facility constraints

Perfusion Bioreactor

  • Continuous medium exchange—fresh nutrients constantly added while spent medium and products are removed through retention devices
  • Sustained high cell densities over extended culture periods make this essential for producing therapeutic proteins and monoclonal antibodies
  • Reduced contamination risk and enhanced product yield compared to batch systems—critical for expensive biopharmaceutical production

Compare: Membrane Bioreactor vs. Perfusion Bioreactor—both use membranes to separate cells from liquid streams, but membrane bioreactors focus on wastewater treatment (removing cells from effluent) while perfusion bioreactors focus on cell culture (retaining cells while exchanging medium). Know the application context.


Specialized Energy Input Systems

These bioreactors are designed for organisms with unique energy requirements, particularly photosynthetic species. Light becomes the primary energy input rather than chemical substrates.

Photobioreactor

  • Light-driven cultivation supports photosynthetic organisms like algae and cyanobacteria that convert light energy and CO2CO_2 into biomass
  • Multiple configurations (tubular, flat-panel, vertical column) optimize light exposure and surface-to-volume ratios for different scales
  • Biofuel production and carbon capture applications leverage the ability of phototrophs to fix carbon dioxide while producing valuable lipids or pigments

Compare: Photobioreactor vs. Stirred Tank Bioreactor—photobioreactors prioritize light penetration and distribution, while stirred tanks prioritize oxygen transfer and mixing. You'd never grow algae efficiently in a standard stirred tank because light can't penetrate the dense, opaque culture.


Quick Reference Table

ConceptBest Examples
Mechanical agitationStirred Tank, Wave Bioreactor
Pneumatic mixingBubble Column, Airlift Bioreactor
Cell immobilizationPacked Bed, Fluidized Bed, Hollow Fiber
Shear-sensitive cellsAirlift, Wave, Hollow Fiber
Continuous operationPerfusion, Packed Bed, Membrane Bioreactor
Wastewater treatmentMembrane Bioreactor, Packed Bed, Fluidized Bed
Photosynthetic organismsPhotobioreactor
High cell densityPerfusion, Hollow Fiber, Packed Bed

Self-Check Questions

  1. Which two bioreactor types both use gas flow for mixing but differ in their circulation patterns? What structural feature accounts for this difference?

  2. A pharmaceutical company needs to produce a therapeutic antibody using mammalian cells that are sensitive to mechanical stress. Compare the suitability of a stirred tank bioreactor versus an airlift bioreactor for this application.

  3. Identify three bioreactor types that support immobilized cell cultures. What advantage does immobilization provide, and what challenge does it create?

  4. You're designing a system to cultivate microalgae for biofuel production. Why would a photobioreactor be preferred over a bubble column bioreactor, even though both can provide adequate mixing?

  5. Compare perfusion bioreactors and membrane bioreactors in terms of their primary applications and what the membrane accomplishes in each system.