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Foam Level in Bioreactor Vessels

Foam Level in Bioreactor Vessels
The pharmaceutical industry uses fermentation process in Bioreactor vessels to grow microorganisms that are used in antibiotics, vaccines, steroids, etc…

Typically, cell cultures and raw materials (called “broth”) are mixed by an agitator and then allowed to settle. As the broth settles, the fermentation process begins and the cells start to grow. CO² gases, produced by the fermentation process, are drawn through filters by a vacuum pump in the top of the fermentation vessel. The filters keep outside contaminants from getting into the vessel, and keep the microorganisms from getting out.

In many fermentation processes foam, or froth, is generated on top of the broth.

As the foam layer grows higher, de-foaming agent is sprayed into the vessel to knock it down before it reaches the outlet to the vacuum pump. If the foam gets into the outlet the filters will become fouled, blocking the exchange of gases. This forces the process to be shut down and the batch in progress to be ruined.

A ruined batch can often represent hundreds of thousands of dollars in lost product. Filters must then be cleaned or replaced prior to the next batch. If foam gets into the vacuum pump, the pump must be taken apart and sterilized. In some cases the foam will short circuit the pump requiring replacement.

The de-foaming agent is sometimes sprayed in on a timed basis to ensure the foam does not get too high. This method results in excessive use of the de-foaming agent. To prevent this, a point level switch is often used to activate the de-foaming spray at a fixed level. This can be a conductance, ultrasonic, or RF admittance type switch.

The de-foaming agent is typically a silicone-based oil that breaks down the foam. The de-foaming agent is very expensive so fermentation operators strive to use as little as possible, thus reducing cost. Additionally, excessive use of the de-foaming agent can upset the fermentation process, affecting mass and oxygen transfer. Anything added to the broth must eventually be processed out, so less is better.

Foam Level Measurement Technologies
The following is a review of the most common point level measurement devices used for foam detection in fermentation vessels.

Conductivity Switch
Conductivity switches are often used for foam detection in fermentation vessels. Unfortunately, conductivity switches are notorious for false level indication due to material bridging between the active electrode and ground. This condition will cause the de-foaming agent to be dispensed continuously until the false alarm is recognized.

In an automated process this will be extremely expensive and the excessive use of de-foaming agent is likely to upset the fermentation process resulting in a lost batch.

Also, the foam will often leave a hard, insulating coating on the electrode as it dries, insulating the conductivity switch and causing it to not “see” a high-level condition. This would result in fouling of the filters and possible damage to the vacuum pump.

Ultrasonic Gap Switch
Ultrasonic gap switches operate by sending an acoustic signal from a send crystal across an opening (gap) to a receive crystal. The acoustic signal is driven at a magnitude that is too low to travel across the gap when in air or gas. When a liquid fills the gap, the acoustic signal travels through the liquid to the receive crystal and indicates the presence of material.

Foam, being mostly gas, is not a good medium for conducting acoustic signals. The bubbles will attenuate the signal to a point where it will no longer traverse the gap. Also, coatings, left by the foam, will dry into a hard crust in the gap, which will further attenuate the acoustic signal. Either of these conditions will cause the foam level to pass the high-level control point, fouling the filters, and possibly damaging the vacuum pump.

RF Admittance
RF Admittance level switches provide the best possible solution to high-level foam detection. RF level switches will easily detect any water based (conductive) foam. Products such as the Intellipoint from Drexelbrook have driven shield circuitry which allows the sensor to ignore even heavy, crusty coatings left by the foam.

Sensors are available with sanitary, electropolished surfaces. RF Admittance level sensors can be used in applications from cryogenic to 2000 degrees Fahrenheit, Vacuum to 10,000 psi. The Intellipoint provides a continuous AutoVerify self-check that ensures the operational integrity of the switch at all times. The Intellipoint is also self-calibrating. Simply install the sensor into the vessel and power it up.

The microprocessor based electronic unit calibrates the switch for the optimum set point. Using the Intellipoint to automate the de-foaming process will ensure that foam does not reach the vent line preventing a lost batch due to clogged filters. Dispensing de-foaming agent only when necessary reduces cost and eliminates process upset condition due to excessive use.

Drexelbrook also offers the 401-700-035 Flash Programmer/interface Validation kit. The Flash Programmer allows an operator to read and store the capacitance values and alarm set point of the Intellipoint using a laptop computer. These recorded values are very important to plant personnel responsible for periodic Validation procedures. This information allows the operator to compare current values to stored values since the last validation period.