Bulk Foam Destabilization through Local Heating

As chronic diseases become more prevalent globally, there is an increasing need for manufacturing and testing of drug and therapeutic treatments. Bioreactors are a commonly used tool in this process, from lab-scale strain and cell line development to large-scale manufacturing of for example monoclonal antibodies (mAbs), insulin, and human growth hormone. Gas is often introduced into the culture media for maintaining appropriate levels of dissolved gasses, such as oxygen. In this process of bubbling through the reactor a layer of foam is created, stabilized by the proteins and surfactants in the media. The foam is an unwanted side-effect as it decreases the productivity of the reactor due to cell entrapment and loss of valuable bioreactor space. Foam leads to a further decrease in efficiency through a reduction of gas transfer rates from the headspace, and significant downtime and loss of productivity required for careful handling of foam. The problem is exacerbated further by the constant need for higher cell densities and product yields, increasing the oxygen demand of the process and hence the foaming problem.

To combat this, anti-foaming agents are often added to the media. These are either oil-based solutions or hydrophobic particles meant to de-stabilize the foam and decrease the thickness of the foam layer. The addition of foreign chemicals and particles into the bioreactor has some significant side-effects. Firstly, anti-foaming agents have been shown to be toxic to cell health. Furthermore, anti-foaming agents can lead to a significant decrease in oxygen uptake by the cell, limiting the yield of the reactor. On a lab-scale, this can be detrimental to drug discovery. While on the production scale, it leads to an increase in cost and a decrease in productivity.

 

Due to the adverse impact on cell viability, productivity, and cost there is a clear need for an alternative to anti-foaming agents. We have developed a method of destabilizing foam through local heating of the bubble, leading to a combination of Marangoni flows and evaporation. First, we experimentally elucidate the mechanism and regime map of foam destabilization on a single-bubble model. The results here are supported through a COMSOL simulation. We then translate the results to a larger scale relevant system with sparging and continuous foam generation.