Large-Scale Bioreactors Lecture

Question-and-answer flashcards covering applications, reactor types, operating modes, design considerations, and examples from the lecture on large-scale bioreactors.

What are the two largest global cell-culture fermentation activities?

Brewing and wine making.

Name three industrial or consumer products made via large-scale cell cultivation besides alcoholic beverages.

Enzymes, amino acids, and vaccines/therapeutic proteins.

Which Australian company recently gained approval to sell a cultured meat quail product, and what size fermenter do they use?

Val Foods; a 20,000-litre fermenter.

What does GMP stand for in bioprocessing?

Good Manufacturing Practice.

List three environmental parameters most bioreactors actively control.

Temperature, dissolved oxygen, and pH.

Why might photon delivery need to be controlled in a bioreactor?

To support growth of phototrophic organisms such as microalgae.

Give two reasons why sterility is critical in most cell-culture bioreactors.

To prevent contamination by unwanted organisms and to ensure product purity/safety.

Which two reactor types have no internal moving parts and rely on gas sparging for mixing?

Airlift (or tower) fermenters.

What unique bottom shape characterises lager beer fermenters and why?

A conical bottom to allow flocculated yeast to settle for harvest and beer clarification.

Identify four common construction materials for bioreactors.

Plastic, glass, stainless steel, mild steel (concrete for some waste systems).

What is the typical volume range for industrial bioreactors?

From millilitres to over one million litres.

Define batch culture.

A closed operation where medium and inoculum are added at start, no further input/withdrawal until harvest.

During a batch culture, what are the three classic growth phases?

Lag (adjustment), log (exponential), and stationary.

State one common reason stationary phase occurs in batch fermentations.

Nutrient limitation or accumulation of an inhibitory product (e.g., ethanol for yeast).

How is a continuous culture kept at constant volume?

By matching sterile feed inflow rate with effluent outflow rate (Fin = Fout).

In a chemostat, what relationship holds at steady state between specific growth rate (µ) and dilution rate (D)?

µ = D.

What is the purpose of cell recycle in continuous ethanol production?

To intensify fermentation by retaining high yeast biomass while continuously removing ethanol.

Why might two continuous reactors be operated in series?

To separate growth and production phases (e.g., different temperatures, inducers, or pH).

What nutrient does the depicted two-stage wastewater system primarily remove?

Phosphate.

Differentiate between aerobic digester and anaerobic digester in waste treatment.

Aerobic digesters use oxygen to break down waste; anaerobic digesters operate without oxygen and often produce methane.

Name one key challenge in scaling aerobic high-density cultures.

Achieving adequate oxygen transfer.

Describe the main goal of a perfusion cell-culture system.

To continuously supply fresh nutrients and remove inhibitory metabolites while retaining high cell density.

Which two metabolites most commonly inhibit mammalian cell cultures and are targeted by perfusion?

Lactic acid and ammonia.

What principal limitation dictates the design of photobioreactors?

Cell access to photons (light penetration).

Contrast open pond and closed photobioreactor systems on contamination control.

Closed systems provide containment and better exclusion of contaminants, whereas open ponds are more exposed to environmental contamination.

Give one advantage and one disadvantage of open-pond algal cultivation.

Advantage: low construction cost. Disadvantage: poorer process control and higher contamination risk.

Why are raceway ponds typically no deeper than ~30 cm?

To ensure sufficient light penetrates the culture for photosynthesis.

State two commercial products obtained from microalgae.

Omega-3 oils and natural pigments (e.g., astaxanthin or dunaliella β-carotene).

What is the major argument driving adoption of single-use bioreactor systems in therapeutics?

Reduction of cleaning/validation time, costs, and associated environmental load.

Name three common single-use bioreactor formats.

Roller bottles, wave-rocking bags, and stirred single-use bag reactors.

Which early blockbuster biologic was manufactured in large numbers of roller bottles?

Erythropoietin (by Amgen).

How is mixing achieved in a wave bioreactor?

By rocking the disposable bag back and forth to create fluid waves.

State one environmental benefit of EarthPower’s Camellia food-waste plant.

Diverts organic waste from landfills while producing renewable methane and fertiliser.

What is produced alongside ethanol in grain-based bioethanol plants and can be sold as a beverage gas?

Food-grade carbon dioxide.

How tall was the ICI single-cell protein bioreactor, and what organism type did it cultivate?

Approximately 60 m tall; it cultivated methylotrophic bacteria.

Why was methanol sparged at multiple heights in the ICI airlift bioreactor?

To supply substrate gradually because methanol is toxic at high local concentrations.

Which three cell attributes must be considered when choosing a bioreactor design?

Cell size/morphology, fragility/shear sensitivity, and growth mode (suspended vs. surface-attached).

Give two examples of fungal or yeast processes in which mycelial or budding morphology matters.

Fungal secondary metabolite production (mycelial) and baker’s yeast biomass production (budding).

What are the three most monitored parameters in large-scale bioreactors?

Temperature, dissolved oxygen, and pH.

Explain ‘clean-in-place’ (CIP) and its relevance.

Automated internal cleaning of reusable stainless-steel bioreactors between batches; essential for sterility and GMP compliance.