Biotechnological research and development would be virtually impossible without instrumental analytics. This is also true at BRAIN, where Dr Simon Seibert coordinates the Analytics Technology Platform. As well as having a state-of-the art pool of equipment, its special strengths lie in its close interlinkage with specific research projects, its methodological flexibility and the curiosity of its staff.
The core task that BRAIN has set itself with success for a number of years now is to make industrial processes that are based on natural substances, enzymes and microorganisms more profitable, resource-saving or possible in the first place in order to bring forth new products. Often, this involves pursuing entirely new avenues in biology and chemistry, and trying out several different approaches at the same time. There are no limits to the variety of issues concerned: Can new, custom-tailored biocatalysts be developed with improved and precisely defined properties for speciality markets? Which currently unknown natural substances are naturally sweet and might offer a healthy alternative to sugar? Can microorganisms be used to extract precious metals from waste incineration ash, or microbes “trained” to make greater use of specific biochemical metabolic pathways in order to provide high yields of valuable building blocks for bioplastics?
BRAIN browses through its proprietary BioArchive (“nature’s toolbox”) to answer such questions using sophisticated biological search engines. Instrumental analytics is a cross-cutting discipline that plays a key role in almost all projects, even though it works in the background. In brief, chemical analysis is used to answer the following question: which substances does a specific sample contain, and how much of each? From establishing whether the new enzyme exclusively produces the target product or creates undesired side products; whether the potential new sweetener is pure enough for tasting; whether a specific bacterium can really extract gold from electronic waste, and how efficiently the new production strain produces a chemical building block, instrumental analytics is essential for answering all these questions.
Dr Simon Seibert coordinates the Analytics Technology Platform at BRAIN and characterises his unit as follows: “The two most important features of analytics at BRAIN are its close interlinkage with specific R&D projects and its methodological flexibility. This is reflected both in our range of equipment and the methods we use, and in our most valuable resource: our staff. They also work on non-analytical tasks and have a comprehensive influence on the genesis of samples and the achievement of the research target. We have established an integrated system for that purpose that perfectly fits our corporate structure and will be continuously developed over the years.” Seibert believes these are unique selling points that set BRAIN apart from the analytics labs run by many other companies.
Flexible project support
To ensure the required flexibility when it comes to supporting research projects, the analytics team at BRAIN relies on well-established and widely deployable detection methods as the basis for its work. High performance liquid chromatography (HPLC)1 and gas chromatography (GC)2 are the methods mainly used to separate complex mixtures of substances. Both methods can be optimally adjusted to individual projects. Mass spectrometry (MS) in its various forms is the most important in a large range of detection methods for molecules. It also serves to clearly identify them.
The team that works on these and other items of equipment, tries out methods and evaluates data consists of BRAIN staff most of whom were not originally involved in analytics but have biological training. This gives them another string to their bow as researchers at the company and moves them from one project team to another. Simon Seibert is convinced that this organisational form promotes interdisciplinary thinking and fast, target-oriented work on solving problems: “We want to answer precisely those analytical questions that arise in project teams at a given time. Staff overlap is extremely useful in this context. Even when we carry out tests in the project itself, this helps us select conditions that ensure that samples can later be analysed in the best possible way. This way of working calls for an intensive exchange between project managers and our technology platform, for instance to plan staff deployment together.”
Valuable analytical potential was harnessed when AnalytiCon Discovery was incorporated into the BRAIN Group.
New analytical subjects
Given the variety of subjects, the analytics team members are used to familiarising themselves with new tasks all the time. Traditionally, BRAIN focuses on organic molecules3 such as proteins and small metabolic products of microorganisms. However, parallel to the set-up of the urban & green mining development programme, which uses microbes to extract precious metals from waste streams and ores, sound expertise has also been acquired in inorganic4 analytical procedures and investments have been made in state-of-the-art equipment in recent years.
ICP mass spectrometry (ICP-MS)56 is now used for the highly sensitive detection of individual elements such as gold or silver. With this method, the elements in a sample are electrically charged in a plasma7 that is heated to several thousand degrees Celsius. Afterwards they are separated and detected based on their mass, which is specific for the elements. Putting it simply, this approach weighs whether the particles that reach the detector are gold, silver or palladium, and how much of each is present in the sample.
If a bacterial culture is processed and measured for urban mining, it can be determined whether and to what extent the bacterium succeeded in separating a valuable element selectively from the waste stream. The analytical examination of the samples also provides statements on the expected yield and with it the economic efficiency of the chosen biological process. This is essential for deciding whether to pursue the approach in a pilot or demonstration plant such as BRAIN’s BioXtractor8.
“In elementary analytics too, it is the details that pose a challenge,” says Simon Seibert: “How reliably can an element be detected? Does the biological matrix perhaps influence the determination of content? Is there any interference?” We validate our methods in response to such uncertainties. In so doing, we prove that the method always gives the same, correct results under the same conditions, and how precisely the content can be determined. That is often hard work for the team. But the team members appreciate the need to test, develop and validate our approaches.” After all, that’s exactly what makes working at a research company so exciting, he adds.
A comprehensive documentation system that describes methods clearly for all research colleagues ensures that know-how is retained once a project has been successfully completed. If a special analytical technique is needed and it does not need to become established within the company or is unprofitable, the team also falls back on external service providers.
Valuable analytical potential was also harnessed when AnalytiCon Discovery was incorporated into the BRAIN Group. Seibert says: “AnalytiCon Discovery and BRAIN complement each other excellently in terms of analytical experience and the equipment pool. BRAIN’s particular strength lies in analysing primary metabolites9, sugars, fatty acids, elements and proteins. AnalytiCon has years of experience with secondary metabolites10. The special focus is on rapidly identifying natural substances that are already known and on clarifying the structure of unknown substances. I stay in close touch with our colleagues in Potsdam and hardly a week goes by in which we do not exchange samples for analysis or simply share analytical experience.”
What does the future of analytics at BRAIN look like? Simon Seibert sees the following scenario: “We will stay flexible and support all the new analytical requirements faced by the BRAIN Group. At the moment, we are bringing more of our own product candidates from our development programmes to market. During this phase and also later, when our developments go into production, new details and issues will become the focus of attention. The detection and documentation of constant high product quality will be an important additional field of application for analytical techniques.”