Bioreactors Design

What is a Bioreactor?
An apparatus for growing organisms (yeast,
bacteria, or animal cells) under controlled
conditions.
Used in industrial processes to produce
pharmaceuticals, vaccines, or antibodies
Also used to convert raw materials into useful
byproducts such as in the bioconversion of
corn into ethanol.

What is a Bioreactor?
Bioreactors supply a homogeneous (same
throughout) environment by constantly
stirring the contents.
Bioreactors give the cells a controlled
environment by ensuring the same
temperature, pH, and oxygen levels.

Types of Bioreactors

Batch: Media and cells are added to the reactor and it is run until a predetermined set point
(i.e. time, concentration). The bioreactor has a constant volume (the initial volume).

Fed-Batch: The bioreactor is a batch process in the beginning and after a certain point a feed
input is introduced and the volume of the vessel increases.

Continuous: The bioreactor starts with an initial volume and media is constantly introduced
and product is constantly taken out. The inputs and outputs are at the same rate, so the
volume always remains the same.

Types of Bioreactors
Bioreactors come in many different sizes
and configurations.

Bioreactor Components

Bioreactors consist of:

Vessel
Agitator
Sparger
Baffles
Probes
Temperature
Dissolved Oxygen
pH
Pressure Gauge

Cooling Jacket
Ports for input and output
of material
Condenser
Back Pressure Valve
Inlet Filters and Exhaust
Filters
Valves
Load Cell

Bioreactor - Vessel
The bioreactor vessel is a container which holds the media
and the cells
Vessels can be made of glass, stainless steel, or a durable
plastic.
The durable plastic vessels are disposable (single-use).
All the additional parts of a bioreactor connect to the vessel.
The top of the vessel is called a head plate. On glass reactors,
most additional parts are located on the head plate.

Bioreactor - Vessel
Head Plate

Vessel

Bioreactor - Agitator

An agitator is required to mix the contents in

the vessel to ensure a homogeneous
environment.
Agitators consist of a shaft and impellers.
Mixing of the bioreactor is crucial in order to
supply nutrients and oxygen to the culture
and to maintain a constant pH and
temperature.

Bioreactor Agitators

Impellers come in many different shapes

and sizes depending on what type of
mixing is needed.

Bioreactor Agitators

Agitator Shaft

Impellers

Bioreactor - Sparger

The sparger is an apparatus used to introduce

gasses into the vessel.
Spargers are located at the bottom of the
vessel and consist of a tube with tiny holes for
the gas to escape through into the culture.
The gas coming out of the sparger helps to
aerate and mix the contents in the vessel, as
well as supply oxygen to the cells.

Bioreactor - Sparger

Ring Sparger

Openings on Ring Sparger

Micro Sparger

Bioreactor - Baffles

Baffles are obstructions on the side of the

vessel that generate turbulence in the flow of
the culture.
Baffles are made out of stainless steel and are
welded to the inside of the vessel.
Baffles help to mix the culture by creating a
more turbulent flow.

Bioreactor - Baffles

Baffles obstruct the flow in the

vessel to help mix the contents.

Baffle

Bioreactor - Probes

Bioreactors require probes to monitor the

culture in the vessel.
The probes are found at different locations on
the vessel: head plate, top probe belt, bottom
probe belt.
Useful probes include temperature, pH, DO
(dissolved oxygen), and CO2

Bioreactor - Probes

Probe Belt
Probes on head plate

Probes

Bioreactor Cooling Jacket

Cells give off heat when growing and dividing.
To maintain a constant temperature in the reactor, the vessel
is covered by a cooling jacket.
Coolant (cold water or glycol) flows through the cooling jacket
to regulate the temperature.
The temperature is controlled by the flow rate of the coolant.

Bioreactor Cooling Jacket

Stainless Steel Cooling Jacket

surrounds the vessel.

Bioreactor - Ports
Bioreactors require addition ports, where material is either
introduced or removed from the vessel.
Ports are needed to add the media (media port), cells
(inoculation port), and nutrients (feed ports).
Ports are also used for the addition of acid and base for pH
control.
A sample port is also located on each vessel to remove
culture for off-line investigation.

Bioreactor - Ports

Ports

Bioreactor - Condenser

A condenser is an apparatus that captures

saturated air leaving the vessel.
The condenser is cooler than the saturated air
allowing it to condense on the surface and
return to the vessel as a liquid.
Condensers help to minimize the loss of
material out of the reactor due to
evaporation.

Bioreactor - Condenser

Bioreactor - Filters

Bioreactors need inlet filters to ensure the

gasses entering the vessel are sterile.
They require exhaust filters to keep the
reactor sterile and allow gas to escape to
regulate pressure.
Filters require a filter housing a stainless
steel cabinet to hold and sterilize the filter.

Bioreactor - Filters

Filter Housing
Filter

Bioreactor Back Pressure Valve

A bioreactor must remain under constant pressure; we want
the pressure in the reactor to be higher than the pressure
surrounding it
Constant pressure helps to ensure sterility of the reactor by
keeping microbes out (they are less likely to overcome the
pressure gradient)
Pressure is added to the reactor by the introduction of air at
the top of the reactor (head space).
The pressure is regulated using a back pressure valve.

Bioreactor Back Pressure Valve

Bioreactor - Valves

Valves are used to control the flow of either

gas or liquid
Bioreactors use many different types of
valves.
Manual Valves open and close the valves with your hand.
Pneumatic Valves automatic valve which opens and closes with
the use of high pressured air (instrument air).
Steam Lock Valves (so called block and bleed valves) a two valve
assembly so you can allow a fluid to flow through a portion of the
valve and then close and use the other portion of the valve to
sterilize the valve assembly after use to reduce contamination.
These valves can be manual or pneumatic.

Bioreactor - Valves

Valves are used at many different locations on

the bioreactor
Sample valve where a sample from the bioreactor can be
obtained.
Harvest valve location where the tank can be drained for
harvest.
Ports contain an automatic steam lock valve, so liquid
can be added to the vessel (the port can be sterilized after
use to prevent contamination)

Bioreactor - Valves

Pneumatic (Automatic) Valve

Steam Lock Valves

Manual Valve

Bioreactor Load Cell

A load cell is a scale that measures the weight

of the bioreactor.
The bioreactor sits on a series of load cells
that compress when weight is added to the
vessel.
The weight of the bioreactor can be correlated
to the volume of liquid in the vessel by using
the density of the cell culture medium.
Weight = Density x Volume

Bioreactor Load Cell

Compact
Compression
Load Cells

Spacing of
Load Cells

Bioreactor Utilities

Bioreactors require utilities:

Gasses
Air
Oxygen
Carbon Dioxide
Nitrogen
Clean Steam - for sterilization of the reactor (condensed
clean steam equals WFI (water for injection) that is clean
enough to be injected)
Coolant (cold water or glycol) for cooling jacket
Instrument Air - to operate pneumatic valves