Bioreactor culture
A glass or single-use tank with one or more impellers, a sparger and probes for DO, pH and temperature. It scales well because power per volume, gas flow and tip speed can be matched across sizes, and its oxygen supply can be raised by agitation, gas flow and oxygen enrichment.
Our ruleSimulations prepare you for the bench but don't replace hands-on practice.
Stirred tank
A glass or single-use tank with one or more impellers, a sparger and probes for DO, pH and temperature. It scales well because power per volume, gas flow and tip speed can be matched across sizes, and its oxygen supply can be raised by agitation, gas flow and oxygen enrichment.
How it differs from the standard method
- Microspargers give small bubbles and high kLa but strip CO₂ poorly; open-pipe spargers the reverse.
- Pluronic F-68 and antifoam are part of the medium design.
- Scale-up keeps P/V, kLa or tip speed constant, never all of them at once.
1A flask that controls itself
A bioreactor is a culture vessel that measures and controls the conditions cells live in: temperature, pH, dissolved oxygen, mixing and, in tissue engineering, the flow and mechanical loads the cells feel. A flask in an incubator can only exchange gas through its surface and relies on the incubator's air; at high cell density or large volume that is not enough.
Impeller and sparger
The workhorse of biomanufacturing. An impeller mixes, gas bubbled through a sparger supplies oxygen and removes CO₂, and the same design scales from 1 L to 20,000 L.
Rocking, surface-aerated
A single-use bag on a rocking platform; the wave renews the liquid surface, which takes up oxygen from the headspace. No bubbles and no impeller, and nothing to clean, but limited oxygen transfer at high density.
Medium through the tissue
For 3D constructs, pumping medium through the scaffold replaces diffusion with convection, so oxygen reaches cells millimetres deep, and the flow adds a shear stimulus.
Loading the construct
Compression, stretch or pressure applied in cycles, because cartilage, bone, tendon and muscle cells build matrix in response to the loads they would feel in the body.
2Oxygen is usually the limit
Oxygen dissolves poorly in water, about 0.2 mM from air at 37 °C, so a culture holds only seconds to minutes of supply at any time and must be fed continuously. The supply is the oxygen transfer rate, OTR = kLa·(C* − C), where kLa is the vessel's volumetric transfer coefficient and C* the saturation concentration.
3How it goes wrong
The fixes for oxygen create their own problems. Bubbles bursting at the surface kill cells caught in their films, which is why media for sparged culture contain Pluronic F-68.
Key terms
Practise these as flashcards →Volumetric oxygen transfer coefficient (per hour); oxygen transfer per unit driving force.
Oxygen transfer rate into the liquid and oxygen uptake rate by the cells, both in mmol/L/h.
Oxygen in the medium, usually given as % of air saturation; controlled at a set point by a cascade.
The order in which the controller raises oxygen supply: agitation, gas flow, then oxygen fraction in the gas.
Gas flow in vessel volumes per minute.
Speed of the impeller tip, π·D·N; a common, if crude, measure of how hard a tank is stirred.
The size of the smallest turbulent eddies; cells are damaged when it approaches their own size.
A non-ionic surfactant that protects cells from bubble rupture at the gas–liquid interface.
A culture started in batch and then fed concentrated nutrients without removing medium, to extend growth and production.
Constructs cultured alongside loaded ones without loading, to separate the effect of load from time in culture.
When to use it
- Producing recombinant proteins or antibodies from mammalian cells at litre to production scale, where density and productivity must be controlled.
- Expanding cells for a seed train or a cell therapy, in single-use bags that avoid cleaning and cross-contamination.
- Growing thick tissue constructs whose interior would die under static culture.
- Asking whether mechanical loading changes the matrix cells build, under defined strain, frequency and duty.
Compared with alternatives
Flasks and shake flasks are enough below about a litre and a few million cells per mL.
The microbial counterpart: higher oxygen demand, faster growth, and fed-batch strategies built around overflow metabolism.
Perfusion seeding uses the same chambers as perfusion culture, just for hours instead of weeks.
What happens to the harvest: viability and debris at harvest set the load on clarification and purification.
Microscale perfusion and stretch for tissue models, with far smaller volumes and imaging in situ.
Sub-techniques
Choosing one here switches the whole page, including the protocol and the lab, to it.
A glass or single-use tank with one or more impellers, a sparger and probes for DO, pH and temperature. It scales well because power per volume, gas flow and tip speed can be matched across sizes, and its oxygen supply can be raised by agitation, gas flow and oxygen enrichment.
- Microspargers give small bubbles and high kLa but strip CO₂ poorly; open-pipe spargers the reverse.
- Pluronic F-68 and antifoam are part of the medium design.
- Scale-up keeps P/V, kLa or tip speed constant, never all of them at once.