Enhanced wave bioreactor design for highly aerobic fermentation processes

生物反应器是生物过程中使用的设备，用于生产各种有价值的生物产品，如药物，食品配料，可生物降解的塑料材料和清洁的运输燃料。有许多类型的生物反应器。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物的治疗剂。这些培养物所需的通气是通过将其置于塑料袋中进行摇摆运动而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钢罐装置的生物反应器相比具有成本效益。然而，它们的应用仅限于低水平曝气混合的情况。本研究的目标之一是修改通用波生物反应器的设计，使其能够用于需要更高通气混合能力的微生物发酵过程。通过在摇袋中添加填料来强化通用设计，并将其与通用设计和传统搅拌槽设计进行了比较。将在各种操作条件的工程相关性中建立掺气-混合标准。在设计表征之后，将对两种具有商业利益的高度好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，使用我们的新基因修饰微生物，和（B）我们最近开发的重组蛋白产品（hCD 83 ext），作为预防器官移植排斥反应的新的潜在治疗剂。这些发酵过程将测试与其他两种设计相比的增强型生物反应器设计的一系列生物处理能力。* 在短期内，更好地理解新的增强型波生物反应器设计的工程性能应导致波生物反应器的各种生物处理机会的显著扩展能力。从长远来看，我们打算在案例研究中为新的制造企业展示高效处理高好氧发酵的方法。分拆企业应导致医疗保健成本的降低。同时培训学生将确保有效地向市场转让技术。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. **