Improving the cell culture workflow
In this interview, Dr Daniel Wehrhahn, Director of the Cell Handling Applications team at Eppendorf (Hamburg, Germany), discusses the challenges in developing cell culture consumables and the importance of observing the cell culture lab environment to create a product that will allow safer, more reproducible research.
Dr Daniel Wehrhahn
Daniel Wehrhahn is the Director of the Cell Handling Applications team at Eppendorf Headquarters in Hamburg, Germany. The team consists of experienced field and technical application specialists responsible for application concepts, trainings and support of consumables and instruments of the Eppendorf Cell Handling portfolio. Before taking over this responsibility he worked as a product specialist for automated liquid handling and global product manager for cell culture consumables. He joined Eppendorf in February 2005 after working as a Genomics Scientists in a pharmaceutical biotech company working on transgenic zebrafish models and high-throughput sequencing. Structure–function studies on cobra venom factor and recombinant protein expression in the Baculovirus system were the major part in his PhD research at the University of Hamburg, where he also gained several years of experience with different cell culture systems.
Could you tell us a little about your career to date and what your current role at Eppendorf entails?
Initially I studied chemistry focusing on the aspects of life in this discipline, so for my PhD I changed to a molecular biology and biochemistry topic. I did structure–function studies on cobra venom factor, which is a protein that has the potential to deplete the complement system and therefore may be interesting as a therapy for specific autoimmune diseases. After my PhD, I worked in a small pharmaceutical biotech startup company on a genome-wide screen on zebrafish as a model to find promising target genes in the areas of CNS diseases, diabetes and cancer.
My time at Eppendorf started in 2005 in the product support group, where I performed support for automated liquid handling developing applications. After that I worked as a product manager for consumables. For the past year I have been leading a team of experienced food and technical applications specialists. We are responsible for application concepts for training and support of the consumables and instruments that Eppendorf offers in the cell handling and cell culture portfolio.
Eppendorf has recently developed a new line of cell culture consumables. How did you go about developing this?
The Eppendorf portfolio already consists of a variety of products for use in cell culture laboratories such as CO2 incubators, pipettes, pipette tips, tubes in general, centrifuges and spectrometers, and also the Eppendorf Cell Technology products: micromanipulators for microinjection into cells. So, in a way the next logical step was to offer researchers consumables for cell culture to unite these two competencies together: on the one hand the development and production of high-quality consumables and on the other hand the development of instruments for cell expansion. The extension of the product portfolio into consumables is a strategic decision offering synergy for the researchers so that we can make the products work well together and they can acquire products from a single source. In this way we can improve process safety and quality of the whole process. Of course we also benefit as this an attractive market and we can offer a more comprehensive solution.
Once we decided to develop these new products we developed a market entry strategy since culture consumables are relatively established products and have been on the market for many years already. We designed a whole range of cell culture consumables for different application needs and equipped them with new and superior features and benefits for our customers. The goal was not to limit the users in the way they ordinarily work, but to improve the handling significantly, in order to improve the overall safety. In the end we achieved this with a significantly improved grip structure of the products for safe manual gripping, high stability, easy identification of products, improved orientation while working with the products, optimized optical performance of the vessels and the secure storage of unused materials in open packages. These are the aspects that we found are most important to customers and left us room for improvement.
You met scientists in hundreds of cell culture laboratories worldwide and analyzed their work processes, practices and preferences in the daily use of traditional cell culture dishes. How important was speaking to users about their needs and ideas for improvements?
It was very important because during the first 12 months after the project started we visited users all over the world and asked them questions to find out which individual steps in the workflows haven’t been resolved to their satisfaction. Sometimes we even stood together in the cell culture laboratories and discussed individual steps and details, so within this process a few things became clear. Even small steps in a workflow can have a significant impact on the results. In cell culture it’s also important to note that manual work still predominates, with hardly any steps in the process being fully automated. This means that aspects such as grip or the ability to hold and stack vessels securely, plays a much more important role compared with automated processes, because improvement decreases the danger if something falls down or is contaminated, the loss of cell material in general or if a vessel is opened inadvertently during transport. In addition, cell culture work is physically demanding owing to the number of tasks that are performed manually. In line with our PhysioCare concept, an ongoing initiative to continuously improve ergonomic workflow in our products, we aim to support improvements in cell culture workflow to create a direct difference in quality and reproducibility of results.
Did you find much consistency in approach between different laboratories, or was there a lot of variation in practices/processes?
We saw quite a difference from lab to lab in the way that the general cell culture workflows are performed. Many scientists learn cell culture from experienced colleagues and not every lab uses standardized procedures, for instance for cell authentication and contamination detection. Another aspect was local difference and the standard workflows. In India for example there are labs that are well equipped, but the climatic conditions mean that they deal frequently with contamination, whereas in Western countries the danger of microorganisms being spread through air conditioning is lower. Another factor is that the local suppliers of consumables, instruments and reagents are different, which may also influence the individual lab processes along with their training materials or standard textbooks on analysis and testing.
Therefore, what we first had to find out was which of these local differences were relevant and would lead to significant variation in the requirements of our customers. In the end we came to the conclusion that the essential requirements of the cell culture users in the labs are practically similar, such as ease of use, process safety, production quality of the products they are using and the surface characteristics; these were all relevant all over the world.
Also, we noticed that the users of cell culture products tend to stick to a protocol for a long time. Once processes are established they tend to be kept for a long time, sometimes generations, even when they are awkward and not very comfortable to do. If you ask users about the challenges they face, they tend to say everything works fine. However when you really look into the processes and analyze, which takes some time and effort, you usually see there are things that could be improved to achieve higher reproducibility.
We have touched on this already, but what differences do you specifically hope this new line of products will have on laboratory workflows in cell research?
Of course these consumables will not change cell research in total but our goal is to help increase safety and reduce contamination and to offer products that are ergonomic to work with. If they can help scientists to obtain more reproducible results every day in cell research and at the same time make their work easier and more enjoyable, that will make a difference for us. Many customers have tried the products already and the feedback on the results has been positive, so I think we are heading in the right direction.
What are the biggest outstanding challenges in developing cell culture consumables?
With respect to individual cell culture consumable formats, at present there is still need to increase the cell yield and growth area in a small space to the maximum and at the same time retain good quality control and imaging of the cells. Of course there are multi-layer flasks and other technologies already on the market, but they are sometimes not ideal for scientists and we get feedback from customers that they would like a more efficient use of media and better possibility for imaging and quality control of cells.
In a more general, not product-dependent view on cell culture, I would say that still a challenge for many scientists and technicians is to give the individual cell system the optimal growth conditions within the incubation and culturing process. Growth factors, nutrients and the right surface to grow on: there are thousands of different cell types out there such as primary cells and of course stem cells so this whole matrix can become pretty complicated and not easy for the user to choose the best conditions. When we do our cell culture training we still get many questions on contamination and passaging techniques, which are the basis of cell culture techniques. Therefore I would say that there is still a level of uncertainty and an opportunity for us to look at the processes and try to give practical and helpful recommendations.
What advances do you envisage with respect to cell culture for cell therapies and regenerative medicines in the coming years?
I imagine that I have the same opinion that many other scientists have too; the rise of iPSC technology is a great promise in the field of regenerative medicine and cell therapy. They can propagate almost indefinitely and differentiate into almost any cell type in the body, such as heart, neurons, and pancreas, therefore potentially replace damaged or lost cells. They are derived from adults so they represent an unlimited supply without the risk of immune rejection and also without the obvious ethical concerns you face when you work with fetal or embryonic stem cells for example. Even though the different methods of reprogramming have been demonstrated to work, there are still a lot of challenges such as low efficiency, genomic insertions, introduced oncogenes, especially when you work with viruses, or tumor development in general, so think the task of producing safe iPSCs for therapeutic use is a challenge. I believe that we will see a lot of progress in the area, especially to increase safety and efficiency in the next couple of years.
What are you looking forward to working on over the coming year?
I’m looking forward to work with our customers and the team at Eppendorf to make more workflow steps easier, safer, quicker and more ergonomic, as we have begun to do already with general cell culture procedures. We are currently developing new training and support materials dealing with what we think are important aspects of cell handling techniques, and as a first step we will launch a training course in the beginning of 2016, showing how the right pipetting technique can advance the reliability of culture processes.