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Wave Bioreactor Animation

The Wave Mixer provides rapid mixing:
The photo sequence on the left shows an actual experiment in real-time where dye was introduced into 10 liters in a 20 liter bag. Complete dispersion of the tracer dye occurs in just 6.5 seconds!

10 liters liquid in 20 liter bag run at 25 rpm.

Fluid Movement Diagram

Mixing requires fluid movement
Q = fluid pumped (lpm)
T = Q/V where V is the fluid volume

Mixing time to uniform mixing requires about 5 turnovers (T).

How does the Wave Mixer work?

First a little mixing theory:

Mixing requires the movement of fluid. The greater the flow, the quicker the time to get complete homogeneity. In addition, high fluid velocity is required to disperse solid particles and dissolve powders. The classic mixing tank accomplishes mixing by pumping fluid using an impeller.

Impeller Mixers Diagram

Impeller Mixers:
Q = aND^3
where N = RPM and
D is the diameter

For efficient mixing the impeller must be at least 1/5 the tank diameter so the opening for the agitator must be quite large.

To mix 100 liters in a stirred tank with a turnover T = 10 requires:

Impeller diameter 1 inch 8 inch
Speed 122,000 rpm 240 rpm

With an impeller mixer, a bag can only be used as a liner, precluding sterile operation.

Pumparound Loops:
Pumparound Loops Diagram
The Pumparound Loop
Flowrate is limited by shear in tube and collapse of the bag and tube inlet. Practical limit of 10 lpm.

Using a pumparound loop to mix 100 liters at a flowrate of 10 lpm only gives a turnover of 0.1. This is 100 fold less than a stirred tank. The pumparound loop is a very inefficient mixer and of little practical use. Its only advantage is that used with a peristaltic pump, it is a closed system.

Wave Bioreactor Animation

The Wave Mixer provides efficient mixing in a sealed bag by using a new approach.

Instead of using a pump or impeller to induce circulation flow, it uses waves generated by rocking motion. Wave motion moves large volumes of fluid and disperses solids. The rocking motion is very efficient at generating waves because it essentially uses gravity to accelerate the wave.

Wave Mixer Design Parameters
Computer models have been developed that determine the optimum operating parameters:

Container geometry
Bag support
Volume filled in bag
Tilt angle
Rocking rate
Fluid acceleration
Characteristics of the contents – solids, foaming etc.

Scalable Technology
Standard systems are available for 20 liter and 50 liter bags. These can be used to mix volumes from 1 to 35 liters of liquid. Larger systems up to 500 liters liquid volume have been tested and can be custom manufactured.

For the system to mix efficiently, it is critical that waves are propagated in the bag. For this reason, the bag must not be completely full. Typically, about 75% of the total bag volume can be filled with liquid. The remaining volume can be left empty or filled with inert gas or air. In addition, the bag must be made of fatigue-resistant materials and mounted so as to minimize creasing. Practical considerations limit the technology to maximum 1000 liter batch size.

The Wave Mixer principle has also been used for the mixing of materials in odd-shaped rigid containers. For example, a custom Wave Mixer was developed to thaw 500 x 1 liter square serum bottles. Unlike previous unagitated operation, the thawed serum was completely uniform with no precipitation. The thawing was also accomplished in a much shorter time.