Parallel bioreactor system

申请联合体处理新工艺的发现，合成，结构阐明和生产的生物活性天然产物的微生物来源的发展。近年来，在该联盟中发现了100多种新的生物活性天然物质，包括几种新型支架。然而，新发现的天然物质往往只能少量生产。分离的少量通常仅足以进行新的天然物质的结构解析，而不足以进行详细的生物活性研究，作为评估潜力和可能的进一步药物开发的必要步骤。在较高的毫克范围内的数量是需要的成分的发展。到目前为止，这些数量是在非优化摇瓶培养中大量并行产生的。这需要多达200个平行批次，烧瓶体积为100 - 1000 mL。通过进一步增加工作体积来增加分离的材料量，在现有的基础设施下是不可能的。因此，在可控生物反应器中优化生产这些物质对于研究的有效实施和进一步发展至关重要。工作组有两个单独的发酵罐（4升和8升），原则上适合生产，但由于缺乏优化生产条件的基础设施，只能在次优状态下使用。将生产条件从摇瓶直接转移到这种生物反应器是不可能的。因此，需要一个包含几个小型发酵罐的系统进行优化和工艺开发，从而能够在实验中系统地调整培养参数。各工作组没有这种设施，而且由于要进行大量的实验，也不能通过合作获得这种设施。为了弥补这一设备缺口，要求购买一个有8个平行生物反应器的系统。单个反应器的数量是由于需要能够在一次实验中研究几种培养条件对生产的影响，并且需要有足够的生物重复。应用的发酵系统应具有标准和必要的设备部件，如温度，pH值和液位控制，溶解氧和氧化还原电位的测量以及发酵气体，带质量流量计的气体和泵模块，用于喂入影响过程的各种化合物（碱液，酸，消泡剂）和营养物质。

The applying consortium deal with the development of novel processes for the discovery, synthesis, structure elucidation and production of bioactive natural products of microbial origin. In recent years, more than 100 new bioactive natural substances have been discovered within the consortium, incuding several novel scaffolds. However, the newly discovered natural substances can often only be produced in small quantities. The isolated small amounts are usually only sufficient for carrying out the structural elucidation of a new natural substance, but not for detailed bioactivity studies as an essential step in evaluating the potential and possible further pharmaceutical development. Quantities in the higher milligram range are required for the componds development. So far, these quantities have been produced by massive parallelization in non-optimized shake flask cultures. This requires up to 200 parallel batches with a flask volume of 100 – 1000 mL. An increase in the isolated amounts of material by further increasing the working volumes is not possible with the existing infrastructure. Therefore, an optimized production of the substances in controlled bioreactors is essential for the efficient implementation and further development of research. The working groups have two individual fermenters (4 and 8 liters), which are in principle suitable for production, but can only be used suboptimal due to the lack of an infrastructure for optimizing the production conditions. A direct transfer of the production conditions from a shake flask to such a bioreactor is not possible. A system with several small fermenters is therefore required for optimization and process development, which enables the systematic adjustment of cultivation parameters in an experiment. Such a facility is not available in the working groups and, due to the large number of the experiments to be carried out, is also not accessible through cooperation. In order to close this equipment gap, the purchase of a system with 8 parallel bioreactors is requested. The number of individual reactors results from the need to be able to investigate the influence of several cultivation conditions on production in one experiment and to have sufficient biological replicates available. The fermentation system applied for should have standard and essential equipment parts such as temperature, pH and level controls, measurement of dissolved oxygen and redox potential as well as fermentation gases, gassing with mass flow meter and pump modules for feeding of various compounds, which impact the process (lye, acid, antifoam agent) and nutrients.