Research Based on Parallel Fermentation
Reducing costs while developing efficient bioprocesses as fast as possible is a rigorous task. Intensive screenings, including a vast number of different experiments regarding strains, media composition and process conditions, have to be conducted in order to create high yields and product titers. High-throughput fermentation in microliter scale is the method of choice, as it generates high data output while cutting costs due to savings on time and workforce, automation and low material input. The BioLector microbioreactor is a powerful tool for full process control in microliter scale.
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The BioLector XT microbioreactor suits the trends in bioprocess development. It can run up to 48 cultivations in parallel, while measuring up to six parameters at a time, including biomass, pH, dissolved oxygen, and fluorescence. The gassing lid fully seals the microtiter plate from the environment so that the microbioreactor itself can be placed in usual lab atmosphere without compromising on the maintenance of anaerobic conditions in the gassing lid. Compatibility with the microfluidic module allows also for anaerobic fed-batch and pH-regulated processes.
For microaerophilic organisms the use of the O2 down-regulating module is recommended in order to achieve defined atmospheric conditions of between 1% to 21% oxygen content.
The BioLector XT device is hence a valuable tool for the screening of anaerobic or microaerophilic strains, as for instance in the microbiome or food & beverage research.
Traditional methods of screening and process development often have limitations. These include poor scalability, low throughput, and small amount of bioprocess parameter information.
The BioLector XT microbioreactor is an advanced tool tackling all these issues. With the geometry of the FlowerPlate microtiter plate and the shaking capabilities of the microbioreactor, a broad range of defined oxygen transfer rates can be achieved, facilitating scalability to bench and pilot scales.
While bench-scale fermentors can produce a large amount of bioprocess information, throughput is limited. Using methods like shake flask experiments can increase the number of simultaneous cultivations, however, little process information will be gained due to missing sensor technology. Cultivations also must be paused for sampling, which can negatively affect gas transfer and culture performance.
The BioLector XT microbioreactor can run up to 48 cultivations in parallel, while measuring up to six parameters at the same time, including biomass, pH, dissolved oxygen, and fluorescence, such as proteins or dyes. While measuring, the plate continues to shake, in order to avoid any pause in gas transfer. Time between measurements is very short in a few-minute-range, allowing for small inflections in the biomass profile, which may indicate metabolic changes, to be observed.
The screening of clones from large libraries often is tedious and subject to random factors at least to a certain degree. Consequentially, the more clones that can be screened, the better your chances are to find the desired optimization. Traditional screening methods however may either lack a good enough throughput or data amount so that favorable clones remain undetected or the reason for certain improvements stays unknown.
The BioLector XT microbioreactor addresses this problem by allowing you to perform a high-throughput screening of clones as well as the detection of relevant metabolic information, including biomass, pH value, dissolved oxygen, and fluorescence. The level of throughput and data collection of the microbioreactor facilitates rapid clone screening in relevant conditions and insight into the reason for certain steps of optimization, which paves the way for timely and reliable development of strains.
When applying conventional methods for media optimization, measurements are performed only every couple of hours as the process is limited by sampling. Inherent to this approach is the risk of missing small changes in, for example, the biomass or DO signals, which in turn might lead to wrong or lacking conclusions based on the few data collected. The BioLector XT microbioreactor, however, measures cultivation parameters online, which mostly obsoletes the need of drawing samples and increases data density. Due to the high-throughput nature of the device it is suitable for the design of experiments (DoE). Not only many nutrient components can be examined individually, but their interactions can also be monitored in order to optimize the most productive and cost-efficient media.
A key application of synthetic biology is the design of new metabolic pathways in microbial expression systems towards innovative products, such as biofuels and new chemical building blocks. These modern bioprocesses utilize renewable feedstocks as substrates and are creating a novel sustainable industry, which is known as bioeconomy.
BioLector technology can be applied in this field in order to study the physiological behavior of synthetic bugs. By changing metabolic pathways, growth behavior and acidification of the microorganism can also be affected, which has to be studied in detail before designing a new bioprocess. The microbioreactor technology processes all of these new bugs under different cultivation or media conditions in a high-throughput manner, with online-monitoring process parameters.
The producers generated can easily be characterized and compared by specific growth rates, acidification rates, oxygen consumption, or by product formation rates. In addition, by using fluorescent proteins (e.g. GFP) as reporters, the BioLector XT microbioreactor is frequently used for the basic characterization of new promoters or even whole libraries of synthetic promoters.