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Dr. Fabrice Turlais is Vice-President Sample Management at Evotec in Toulouse, France. He has a distinguished track record in highly-automated Drug Discovery, including 15 years with Cancer Research Technology (CRT) in the UK where he was Group Leader, Screening & Compound Management. He holds a PhD in Biochemistry from the University of Hertfordshire and has been a Board member of both ELRIG-UK and ELRIG-Fr, helping to advanced Laboratory Robotics in the field of high-throughput drug discovery. Fabrice is also a long-term user of Ziath equipment for tracking samples in 2D-barcoded tubes.
So, who better to ask about today’s challenges in digital sample management?
A major issue in using today’s databases for storing sample and compound inventory information is the diverse nature of the samples available. Especially as Drug Discovery moves away from solely-chemical-based libraries towards biologicals in libraries, the existing database software may not be able to record all the correct parameters, or tracking tags, for biological samples. This leads to biological reagents and samples being stored in multiple databases, which makes the process of ordering and booking out material far more complicated. Ten years ago, only chemical compounds were tracked through large relational databases such as those now available from Dotmatics and Titian.
Biologics were manufactured and used on an ad hoc basis, as required, and frequently there was no storage for these compounds in Drug Discovery libraries. The compound stores were optimized for storing purified solids or compounds in solution, such as DMSO, in 2D-barcoded tubes. But with the development of high throughput, high content screens involving RNA, DNA, antibodies and proteins, the need to store these biologics and keep them in good condition and be able to find them easily has become paramount. Unfortunately, there is no easy way of registering these in chemical-dedicated databases.
Samples being removed from low temperature storage
So, what could be done to improve this?
“Ideally, there would be a unique registration i.d. for each biological that covers how it should be stored, for example at +4, -18, -80 or -196C, and be able to track back to what it is and how it was made, it’s associated properties, such as its clone generation or culture passage for example.
Where the chemical-based databases are excellent at storing compound properties such as chiral centres, molecular weights, number of carbon atoms and functional groups, right now there is no agreed schema for delineating what biological information is relevant and what should be searchable in an inventory management programme, for example for plasmids or RNA samples which will have a different set of properties. It would be very good to have a selection of these attributes in the database, ready to be used, even if not required for all samples, as at the moment we need several different databases to track all the relevant properties.
With elegant chemical compound libraries such as those you have mentioned already available, why are there no databases for biological entities?
Many years ago, the SBS (Now SLAS) set American Standards for microplates – the so-called SBS standard) that meant that Screeners around the world agreed on what size and format a microplate or 2D-barcoded tube rack should be. That was very helpful, because it meant that everyone – researchers and manufacturers – were working to the same set of standards and the automation, the instrumentation, was inter-changeable between projects and labs. We now need some new standards in this age of “rich information” sharing that allow us to agree on nomenclature for biological materials, for example, as well as which features are important for biological screening. Unfortunately, when Lab Automation merged with SBS to form SLAS, the biology part of the organisation was relatively small and that lead to a focus on chemical compound management. We lost out on standards setting for the nascent biologics sector. New bottlenecks have since been discovered further up the R&D chain. At the time Big Pharma were selling off their vaccines research units as they were making no money. Twenty years have passed and now CRISPR/CAS9 technology has moved that research back into fashion and importance, but we still do not have the tools for high-speed, high-density research in biology in the way that they exist in chemistry.
What are the dangers of having no agreed standards in this area?
When siRNA studies began, it highlighted what a mess we were in as far as drug discovery biology was concerned. We had no quality measurements for the rigour or efficiency of siRNA screens. Because there were no agreed standards, you could not compare results from one trial to another. Everyone was reporting different parameters and bench-marking the studies became impossible. It’s important as we move into the era of CRISPR screening that we don’t make those mistakes again, we must have new standards for data analysis. Modern inventory management systems must be designed to handle these features, as we are not just trying to replicate what we did with small molecules, but transforming the way we store information about more complex entities and reagents that may include living cells and tissues.
How confident are you of future developments?
I think working through the cross-industry bodies such as ELRIG, SLAS and even SiLA, they can help to set new standards.
Then software companies will need to develop the big databases that can be configured for use by the biologist. We have already seen how using standardised 2D-barcoded tubes has helped enormously to keep track of large sample libraries – there are great tools out there from companies like Ziath to track and select tubes and you can buy refrigerated stores from bench-top size to whole buildings! Integrating these digitally with the big data storage platforms and using wireless technology to allow full database access at the point of retrieval of a sample from a store will be important too. But we must be able to identify and categorize the things we have made that will form the basis of our next-generation medicines and especially in personalised medicine, where antibody therapies will play such a huge part.
Dr Turlais was speaking in a personal capacity and his views on the challenges may not necessarily reflect the policies of Evotec SA.
For further information on new products addressing today’s challenges in digital sample management please contact Steve Knight at firstname.lastname@example.org or visit www.ziath.com