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Process Worldwide-PharmaTEC 02-2004
Frustrating foam
What makes foam, and how to control it

Foam can be a serious problem in fermentation processes. It can be controlled by adding chemicals, broken up by mechanical devices, and sometimes avoided altogether by careful design. This article describes how to choose the best method for a particular process.

We are surrounded by foam. Sometimes it’s fun—think of bubble bath, cappuccino and beer. Sometimes it’s useful: examples are the froth-flotation processes used in wastewater treatment and minerals processing, and foams used in the food industry to produce dried fruit juice and instant mashed potato. Often, though, foam is just a nuisance. A classic example which forms the subject of this article is foam produced during fermentation processes. Foams consist of liquid lamellas filled with gas. Their formation depends on the presence of surfactants, which are found preferentially on liquid surfaces. If air is sparged into a liquid containing a surfactant, the surfactant molecules form a double layer around the air bubble. The result is a spherical foam lamella. Foam is stable if the energy of the system is low and the forces within the foam are in equilibrium. Spherical lamellae are not stable because of their high liquid content. Surface tension and other mechanical stresses therefore cause spherical lamellae to link together so that they share surfaces, and the result is a “polyhedral” foam that is more stable. Total equilibrium is energetically impossible, however, so even polyhedral foam will sooner or later self-destruct. The collapse of foam has three stages: drainage of liquid from between the lamellae, rupture of the lamellae, and the diffusion of gas out of the foam cells. Foaming fermenters In biotechnology, surfactants are almost always present, as both raw materials such as peptides, and substances such as proteins released by the growing micro-organisms. Add aeration and agitation, and the result can be a foam problem. The amount and nature of the foam is likely to change during the course of the fermentation. In addition, there is never a clear borderline between liquid and foam; instead there is usually a significant density gradient. Foam in bioreactors can carry away fermentation broth, leading to product losses and blocked filters downstream. As well as being troublesome to clean or replace, blocked filters can increase the pressure in the bioreactor, leading to slow growth and reduced productivity. In extreme cases, blocked filters can burst the filters or the reactor’s rupture disk, leading to product spills and even the release of pathogenic micro-organisms. Even if the reactor does not overflow, foam can still cause problems. Without foam control, the working volume of the reactor may be significantly reduced so as to allow room for the foam. Foam can affect the flow properties of the broth, leading to poor mixing, and organisms trapped in the foam may be deprived of oxygen and nutrients. In all cases the result is lost productivity.
Detect and destroy Before foam can be destroyed effectively it is necessary to detect it. Foam is easy to see, of course, and most bioreactors are equipped with a sightglass—but no operator can be expected to watch the fermenter continuously for hours or days. The answer is a foam detector linked to either a dosing system for chemical antifoam agents or a mechanical foam breaker. It is also possible to destroy foam by freezing or heating it, the latter typically using infrared or microwaves. Thermal defoaming is not used in biotechnology, however, because of the risk of killing the micro-organisms. In the simplest type of foam-detecting probe, a small voltage is placed between the vessel wall and the probe, which is insulated from the vessel. As soon as the conductive foam touches the probe, a current flows and is detected by the controller. If the system is prone to biofouling, however, a conducting layer of micro-organisms can bridge the gap from electrode to vessel, triggering the anti-foam system unnecessarily. An admittance probe overcomes this problem by using a high-frequency signal instead of a DC voltage between the probe and the vessel. A wide-band measuring bridge with an amplifier determines the electrical admittance of the probe, and this can be used to detect foam even in the presence of biofilms. Both types of probes are available from Bioengineering. Whichever type is used, and whether the anti-foam system is chemical or mechanical, it is a good idea to add a small time lag to the control system. This helps prevent the dosing of too much chemical anti-foam agent, or constant stop-and-go operation of a mechanical system. Chemical defoaming Having been detected, the foam is then destroyed by chemical or mechanical means; which one is better depends on the process. If chemicals are preferred, in most cases it is enough to inject a shot of anti-foam agent to destroy the foam as soon as it forms. However, chemical anti-foam agents can be used to stop foam from forming, as well as to destroy it. For foam prevention, the anti-foam agent is added to the broth before fermentation starts. This method stops foaming during the sterilization and cooling phases, as well as during the fermentation itself, and can make further dosing unnecessary. Foam prevention is ideal for certain difficult fermentations, in which foaming must be strictly avoided because substances in the broth are rendered corrosive by the high oxygen levels in the foam. Chemical anti-foam agents are surface-active substances which replace foam-forming components and also reduce the surface tension. They contain insoluble particles which reduce the viscosity of the foam lamellae. This causes the bubbles to drain, and so severely reduces the foam stability. Ingredients of anti-foam agents include silicone oils, polyalcohols, block copolymers and natural oils such rapeseed oil. Chemical defoaming has low capital costs compared to mechanical foam-breaking, but the operating costs can become important. This is especially true when the foaming potential is severe, and in high-flow continuous fermenters. There can be other disadvantages too. Chemical anti-foam agents can lower oxygen mass transfer rates by up to 60%, because by their nature they change the properties of gas bubbles. This can leave the micro-organisms short of oxygen, or require extra aeration—which can worsen the foam problem as well as increasing costs. Other characteristics such as cell density, growth rate or product concentration can also be negatively influenced by the use of chemicals. The micro-organism Helicobacter, for instance, cannot be cultivated in the presence of common chemical anti-foam agents. Their surface-active properties also cause chemical anti-foam agents to accumulate on micro-filtration membranes. This leads to fouling and destruction of the membranes, and hence to considerable losses in time and money. Mechanical defoaming The most effective mechanical defoaming systems use rotating elements—discs, bladed wheels or stirrers—to knock down the foam. Another approach is to use suction or air jets to break up the foam. In contrast to fermenters that rely on chemical defoaming, vessels with mechanical defoamers suffer hardly any biofouling because the constant impact of foam and liquid keeps the walls clean. Mechanical defoamers with rotating parts work by a combination of direct mechanical destruction of foam lamellas, centrifugal forces in the foam as it is thrown outwards from the spinning blade, and impact as this flying foam hits stationary patches of foam. The latter effect, in particular, can make the problem worse by creating secondary foam, so it is important that the foam-breaker has the right geometry and rotor speed. Once the foam has been broken down, effective recycling stops secondary foam forming and increases the destruction of primary foam. Bioengineering has developed a foam separator that incorporates a cyclone. The cyclone acts primarily not as a foam destroyer but as a way to separate liquid and gas. The liquid is recycled to the fermenter, sometimes with the aid of a pump, and the dry exhaust gas can be vented without fear of blocking filters downstream. This is a very gentle way to remove foam, and is ideal for fermentations where large amounts of cells or products are present in the foam. Foam prevention Some fermentations are so delicate that they are poisoned by chemical anti-foam agents and disrupted by mechanical defoamers. If foaming is still a problem, some other solution is needed. Since air sparging is the main cause of foam, another aeration system may help. For cultures with low oxygen demands, surface gassing—supplying air or oxygen to the vessel headspace, without sparging—may work. If the oxygen demand is such that sparging cannot be avoided, operating the vessel under slight positive pressure can suppress foam formation. Many cell cultures cannot survive either elevated pressures or forceful sparging, yet still have high oxygen demands. The answer here is to use small, gentle bubbles created by injecting air or oxygen through materials such as glass sinters or hoses with porous walls. For cultures with no tolerance for gas bubbles at all, Bioengineering has developed “bubble-free” aeration. Here the gas is supplied through a system of special porous hoses contained in a basket. The very large surface area of the hose allows enough oxygen to be transferred to satisfy the needs of most cell cultures, without bubbles.
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