Boost Fermenter Productivity with Oxygen
By Alan T.Y. Cheng, Praxair Inc.
Introduction
Air Based Fermentation and Limitations
Simple Oxygen Enrichment Techniques
Direct Oxygen Injection Technique
Airlift Versus Mechanically Agitated Fermenters
Process Economics
Conclusion
Introduction (Back to Top)
Many valuable chemical, food, beverage, pharmaceutical, and farm products are produced by aerobic fermentation. Worldwide demand for antibiotics and other fermentation products has been increasing steadily. To satisfy the demand for additional products without investing in new plants, manufacturers are trying to run high strength broth to improve productivity. With heavier biomass, additional oxygen supply is necessary to satisfy the additional oxygen demand. Otherwise, the growth of the biomass may deteriorate.
Oxygen demand is highest during the exponential growth phase. In this phase, extensive primary metabolite production creates a very high oxygen demand, stimulating cell growth. Viscosity increases rapidly during this phase and into the stationary phase, where secondary metabolite is produced. High viscosity in this phase inhibits oxygen transfer, resulting in an oxygen-starved condition.
Air Based Fermentation and Limitations (Back to Top)
Air is often used as the sole oxygen source in fermentation. Air can also strip off the carbon dioxide. However, air contains 21% oxygen, 78% nitrogen, and other minor gases or minor components. Most of the oxygen available from air remains undissolved and vents from the fermenters to the atmosphere, making it difficult to obtain even the minimal dissolved oxygen level required to sustain organism growth and maintain desired production level.
The simplest way to increase the oxygen supply to an air-based fermentation system is to increase the airflow. This will reduce the oxygen starvation problem at moderate oxygen demand. However, at higher oxygen uptake rates, the air will start flooding the impellers in the mechanically agitated fermenters. In an airlifted fermenter, excess air can fluidize the entire fermenter and blow the contents out of the fermenter.
Installing large agitators and motors may improve the oxygen transfer rate but it is an expensive proposition. Even if high capital expenditure is no object, larger agitators and more powerful motors can provide only incremental oxygen transfer rate improvements.
Simple Oxygen Enrichment Techniques (Back to Top)
Using oxygen to enrich the air stream is one way to avoid oxygen-starved conditions. This is usually done by adding oxygen directly to the air stream prior to the biological filter. It will allow a higher equilibrium driving force for the oxygen transfer without high capital investment. However, the air compressor must be oil free or it can create a fire hazard and precautions must be taken to avoid oxygen back-flow into the air line.
Since the enriched air will be using the same sparger for aeration, the dissolution efficiency is just as poor as the conventional air sparging system. With poor utilization, the conventional oxygen enrichment technique is generally only marginally economically attractive.
Direct Oxygen Injection Technique (Back to Top)
Praxair (Danbury, CT) has developed several direct oxygen injection techniques to improve the oxygen utilization efficiency. The direct oxygen injection technology, combined with air injection, provides safe, controlled dissolution of high-purity oxygen in fermenters. Air and oxygen are injected separately in the fermenter, fulfilling vital, distinct roles.
Figure 1 shows the typical fermentation cycle at which the oxygen demand is fairly low at the beginning of process. After a certain lag time, the growth becomes exponential and the oxygen demand increases rapidly. Praxair has developed a proprietary process to avoid oxygen starvation at this stage. Oxygen is injected directly into the broth, separate from the air. Since pure oxygen bubbles have an oxygen concentration five times higher than that of air, a very high oxygen dissolution rate can be achieved. When the growth of the biomass enters a stationary phase, the amount of oxygen injected can be reduced accordingly.
By injecting pure oxygen separately from air, the air retains its effectiveness as the most economical agent for stripping the fermentation broth of carbon dioxide and the other undesirable reaction byproducts that impede metabolite activity in most organisms. On the other hand, the high-purity oxygen used with the Praxair direct oxygen injection technology allows superior control of dissolved oxygen levels when processing primary and secondary metabolic products.
Without the constraint of handling a large volume of compressed air, the direct oxygen injection technique allows the oxygen sparger to be optimized separately. Subsequently, Praxair's direct injection technology increases efficiency of oxygen usage by as much as 100% compared to air injection. This increase is accomplished without needing additional power input.
Airlift Versus Mechanically Agitated Fermenters (Back to Top)
There are major differences between mechanically agitated fermenters and airlifted fermenters. In airlifted fermenters, air has the dual role of oxygenation and mixing of the entire fermenter. The size of the aas bubbles is influenced by the sparger design and the bubble coalescence rate. On the other hand, the agitator in a mechanically agitated fermenter usually controls the mixing and the bubble formation. In this case, air has very little to do with the bulk mixing of the fermentation broth.
It is necessary to supply very high air flow to an airlifted fermenter to provide adequate mixing, suspension of solids, and transfer of oxygen. For a commercial scale fermenter, the flow rate usually exceeds a superficial velocity of 0.05 m/sec. Therefore, the air bubble flow is heterogeneous—large bubbles are mixed with small bubbles. The coalescence rate is very high. Large bubbles are needed to provide sufficient mixing as the terminal velocity increases with bubble diameter. However, the mass transfer rate deteriorates with large bubbles, as large bubbles have lower surface area to volume ratio.
The Praxair direct oxygen injection technology allows the oxygen to be injected independently of the air. Hence, the oxygen is injected through a specially designed injector to disperse very small gas bubbles. The fine oxygen bubbles will rise in a homogeneous fashion. Very few large bubbles will be present or needed. The oxygen transfer efficiency is much higher in the homogeneous flow of the direct oxygen injection. Therefore, the overall cost of using pure oxygen in fermentation is reduced substantially. Figure 2 shows Praxair's patented method for injecting oxygen into an airlifted fermenter (U.S. Patent No. 5,798,254).
Figure 3 shows the difference in mass transfer coefficients between a Praxair direct oxygen injection system and simple oxygen enrichment from mixing pure oxygen with air. The test was conducted in a 110-gallon fermenter using simulated broth with sodium sulfite as reactant.
For the mechanically agitated fermenter, the gas dispersion turbines control the bubble sizes and coalescence rate of the of the gas bubbles. Praxair provides several proprietary oxygen injection methods to minimize the coalescence of oxygen bubbles with air bubbles. Using this technology, a high level of dissolved oxygen can be sustained throughout the fermenter. Any undissolved oxygen bubbles are easily vented with spent air. The oxygen uptake rate can be increased by as much as 100%, which is very difficult to achieve with other means. Replacing the agitation system can generally achieve only a small incremental increase in oxygen transfer rate before flooding occurs, while it may cost millions of U.S. dollars for a single fermenter.
Process Economics (Back to Top)
With direct oxygen injection, the oxygen usage rate improves as much as 100% over simple air enrichment. The efficient use of oxygen changes the economic incentive of using oxygen to supplement air in fermentation processes. The typical operating and cost-saving benefits resulting from complementing air injection with high-purity oxygen injection deliver a significant net benefit. There are direct economic benefits and indirect benefits brought by the Praxair direct oxygen injection technologies, such as:
- An increase in production yields from existing fermenters. Commercial fermenters experienced yield increases to 65%.
- Better control over oxygen dissolution throughout the entire fermentation cycle.
- The higher dissolved oxygen level required to satisfy the oxygen demand in the fermentation broth.
- More efficient use of oxygen.
- Reduced air compression cost.
- No capital outlay for new fermenters to provide additional production capacities.
New oxygen generating techniques also reduce the total cost of using oxygen in fermentation. An oxygen generating system using Vacuum Pressure Swing Adsorption (VPSA) technology using zeolites produces oxygen that is 90–93% pure. The development of ultra-efficient advanced adsorbents, improved process and systems designs, and optimized component packaging have led to the commercialization of an advanced VPSA system that supplies oxygen at a low price.
With an efficient oxygen dissolution technique and the availability of low-cost oxygen, an oxygen-based fermenter is even more economical to operate than it was previously. Figure 4 shows the comparative cost figures between the Praxair direct oxygen injection technology plus VPSA oxygen and conventional oxygen enrichment techniques. The operating cost of a conventional process with simple enrichment and liquid bulk oxygen is set at 100%. Using VPSA oxygen, the operating cost is reduced by 40–50%. Using direct oxygen injection, the cost is reduced by another 40–50%.
The economics of a direct oxygen injection process can be quantified in terms of product cost. As the yield or productivity of a fermenter increases while the fermenter size and number of batches remain constant, the product cost decreases accordingly. Similar benefits from the use of oxygen can be realized in terms of batch time reduction. The equation for product cost can be expressed as:
Cost of Product = [Cost of Media + {(Processing Cost) x (Cycle Length)}] / Yield
Where…
Cost of Product:......$/Kg
Media Cost:............$/Cycle (Equivalent to $/Batch)
Processing Cost:......$/Day (Including Turnaround Time)
Cycle Length:..........Days/Fermentation Cycle (Including Turnaround Time)
Yield:......................Kg/Cycle (Equivalent to Kg/Batch)
It has been shown that the yield of a fermenter can be increased by eliminating the oxygen starvation situation. Since the number of fermenters remains constant and the cycle time is unchanged, the cost of product is reduced accordingly. The cost of oxygen and additional media will add on only a small amount to the total cost. It can be shown that a fermentation plant can save millions of dollars in using the Praxair direct oxygen injection technique to increase yield and productivity.
Conclusion (Back to Top)
In contrast to the conventional technique of simple oxygen enrichment and bulk liquid oxygen supply, Praxair offers the direct oxygen injection technique for fermentation in both airlifted and mechanically agitated fermenters. With the cheaper source of VPSA oxygen, it is possible to cut the cost of using oxygen for fermentation by 50–70%. Therefore, oxygen can be an economical means to substantially improve productivity of a fermenter without major capital for plant expansion. The Praxair direct oxygen injection technology is being used commercially in North and South America, Europe, and Asia.
Reprinted with permission, from Praxair Technology Inc., copyright, 1998, 1999.
For more information: Eric Jones, Manager, Marketing Communications, Praxair Inc., 39 Old Ridgebury Rd., Danbury, CT 06810. Tel: 203-837-2705. Fax: 203-837-2454. Email: eric_jones@praxair.com.