Design challenges for single-use fermentorsThe construction of single-use bioreactors suitable for fermentation processes poses significant engineering challenges. One such challenge is reduction in culture heat load caused by the insulating properties of the single-use film. The net heat load in a fermentor is the sum of the agitation power, metabolic heat from the culture, evaporative cooling at liquid surface, sensible heat in the gas stream, and heat loss to the environment . For microbial systems, however, sensible heat and evaporative cooling can be neglected as they are relatively low. Heat loss to the environment is also low because of the outer vessel wall insulation. Consequently, heat from agitation and culture metabolism contribute the most to the culture heat load. As a single-use polymeric liner has a lower heat transfer coefficient compared with stainless steel, the heat transfer rate of single-use fermentors is significantly lower compared with conventional stainless steel fermentors. Depending on the liner thickness and formulation, the heat transfer coefficients of single-use fermentors are approximately half the ones of traditional stainless steel bioreactors. The reduced heat transfer rates pose an increased challenge to maintain a suitable temperature for fast growing microbial cultures in single-use fermentor systems. Lower surface area-to-volume ratios at larger scales further aggravate the heat removal challenge. To compensate, the following points can be considered:
- Adequate agitation to provide convective turbulent flow to all heat transfer surfaces.
- Include additional design solutions for cooling, such as spiral-baffled or segmented tank jackets, jacketed bottom and top dishes, and auxiliary heat-removal surfaces.
- Increase vessel height-to-diameter ratio to concomitantly increase the surface-to-volume ratio.
- Use of low-temperature coolants such as ethylene glycol.
- Pre-cooling of the sparge gases (not very effective, though, as gases have a relatively low thermal heat capacity compared with liquid coolants).
- Decrease growth rate to reduce metabolic heat generation by limiting carbon source feed rate. This solution has a dual effect. As the oxygen demand will be lower, the agitation needed (and heat generated) to maintain a sufficient level of dissolved oxygen will be decreased.
- Apply continuous culture. This solution reduces the fermentor size and consequently maximizes the heat transfer surface-to-fermentor volume ratio.
- Increasing power of the agitation system 
- Oxygen enrichment of sparger gas
- Use of microporous spargers (addition of antifoam agent might be necessary)
- Increasing head pressure (will require a hardware support structure to hold the single-use bag, but might be redundant with today’s design solutions)
ConclusionThe engineering challenges in terms of heat removal and oxygen transfer delayed the entry of disposable stirred-tank fermentors. Since 2007, however, when the first single-use microbial systems were introduced, successful high-cell density cultivations of both E.coli and Pseudomonas have been reported . By applying general bioengineering principles and designs, high oxygen transfer rates can be achieved also in disposable fermentors. Augmented designs and operational methods compensate for the low heat transfer rates in these systems. Although pressurizable single-use stirred-tank fermentors are within the realm of technical feasibility, this feature might not be necessary as sufficient oxygen transfer can be achieved through a variety of mechanical and process control designs and techniques.
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3. Application note: Microbial fermentation in single-use Xcellerex fermentor system. GE Healthcare, 29-0564-39, Edition AB (2014)