Enhanced wave bioreactor design for highly aerobic fermentation processes

生物反应器是用于生物过程的装置，用于生产各种有价值的生物制品，如药品、食品配料、可生物降解的塑料材料和清洁的运输燃料。生物反应器有很多种类型。几年前，一种新型的生物反应器设计被引入，用于生产来自动物细胞培养的治疗药物。这些培养物所需的通气量是通过在放在塑料袋中的培养物摇摆运动在培养物表面产生波浪来获得的。这些所谓的“波浪生物反应器”与传统的基于机械搅拌式钢槽设备的生物反应器相比，成本效益更高。然而，它们的应用仅限于低曝气-混合水平的情况。本研究的目的之一是修改普通波式生物反应器的设计，使其能够用于对曝气-混合能力要求更高的微生物发酵过程。*在摇床中增加一个辅助曝气器，对普通设计进行改进，并与普通设计和传统的搅拌池设计进行比较，以提高其生物处理能力。曝气-混合标准将建立在不同运行条件的工程关联式中。在设计表征之后，将对两种具有商业意义的高需氧发酵工艺进行概念验证研究，以生产：(A)透明质酸，一种用于医疗应用的商业产品，与我们新的转基因微生物一起；以及(B)我们最近开发的一种重组蛋白产品(HCD83ext)，作为预防器官移植排斥反应的新的潜在治疗方法。与其他两种设计相比，这些发酵过程将测试增强型生物反应器设计的一系列生物处理能力。*短期内，对新的增强型波浪生物反应器设计的工程性能的更好了解应该会使波浪生物反应器的能力显著扩展到各种生物处理机会。从长远来看，我们打算以案例研究为例，为新的制造企业展示高需氧发酵的有效处理。剥离企业应该导致医疗成本的降低。同时培训学生将确保有效地将技术转移到市场。他们获得的多学科知识将有助于加拿大和其他地方日益增长的生物制造需求。**

Bioreactors are devices used in bioprocesses to produce a variety of valuable biological products such as pharmaceuticals, food ingredients, biodegradable plastic materials and clean transportation fuels. There are many types of bioreactors. A few years ago, a new type of bioreactor design was introduced for the production of therapeutics derived from animal-cell cultures. The required aeration for these cultures is obtained by creating waves at the surfaces of the culture by a rocking motion of it placed in a plastic bag. These so-called "wave bioreactors" are cost-effective compared to the traditional ones based on mechanically-stirred steel-tank devices for those applications. However their applications are limited to cases for low levels of aeration-mixing. One of the objectives of this research is to modify the generic wave bioreactor design to allow its use in microbial fermentation processes which require higher aeration-mixing capabilities.*** The generic design will be enhanced with a supplementary aerator in the rocking bag, then compared with the generic design and the traditional stirred tank design for its bioprocessing enhancement. The aeration-mixing criteria will be established in engineering correlations for various operating conditions. The design characterization would be followed by proof-of-concept studies on two highly aerobic fermentation processes of commercial interest in production of: (a) hyaluronic acid, a commercial product used in medical applications, with our new genetically modified microorganism and (b) a recombinant protein product (hCD83ext) recently developed by us, as a new potential therapeutic for prevention organ-transplant rejection. These fermentation processes would test a range of bioprocessing capabilities of the enhanced bioreactor design compared to the other two designs. *** In the short term, the better understanding of the engineering performance of the new enhanced wave bioreactor design should lead to a significant extended capability of wave bioreactors to various bioprocessing opportunities. In a long term, we intend to demonstrate the efficient handling of highly-aerobic fermentations for new manufacturing enterprises exemplified in case studies. Spin-off enterprises should lead to the reduction of healthcare costs. The concurrent training of students would ensure efficient technology transfer to the market place. Their acquired multidisciplinary knowledge would help in the growing bio-manufacturing needs in Canada and elsewhere. **