Interview with Philip Denner, Ph.D, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)

Since 2010, the DZNE has been using CellVoyager™ series as the High-Content Analysis system of a highly sophisticated screening platform in the Core Facility for Laboratory Automation Technologies (LAT). Dr. Philip Denner is the leader of LAT.

DZNE/Frommann

Q1. Tell us about your research

I've been in the High-Content Screening business since 2003. It's 20 years now. I'm a biochemist by training and immediately after my diploma, I went into pharmaceutical industry. I did my PhD at Schering AG in Berlin and there I got involved into automated microscopy and quantitative imaging. It was really in the early days of High-Content Screening. After my PhD, I worked for Schering AG and later Bayer AG as a research scientist and developed a lot of image-based assays for preclinical drug development, from target identification and validation to full library screening. We were one of the first laboratories implementing HCS into the drug development process. That’s in brief my background. In 2011, I joined DZNE. Here I got the opportunity to set up an automation lab for screening application, but also for all other kinds of automation processes. During that time, we installed the CellVoyager 6000 in a fully automated platform with more than 30 different instruments and used it a lot for High-Content Screening.
Now we have two CellVoyager CV8000 fully implemented in our robotic platform, so that we can truly run unattended workflows and measurements overnight or over weekends.

 

Q2. What role does the CellVoyager play in your research? Why you choose CellVoyager into your platform?

Implementing the CellVoyager within the screening process means that we are able to take images during an assay process,  so we can do snapshots of the cellular status at different timepoints. You seed the cells, examine the status of the cells prior to treatment, then add a specific treatment, take a snapshot of the cellular response in live cell mode, then finish the assay and do the immunofluorescence staining for selected markers and finally image the cellular markers in the CellVoyager again.
When I started working with Yokogawa in 2011, the Yokogawa system was the state-of-the-art HCS microscope, the most advanced instrument at that time. We saw the potential of what Yokogawa could develop. I remember that we had a meeting with Yokogawa in 2013. During that time, we developed together some hardware and software tools for the CV6000 and I wanted to say something very positive. I said, “Well, I have calculated that we only have one autofocus error in every 60,000 images". And then Yokogawa answered, "What! Still one?" I just wanted to highlight, that the Yokogawa autofocus error rate was amazingly good, because in the earlier days it was quite normal, that you had some autofocus errors in every plate with other microscopes. 

 

Q3. If someone wants to start a powerful High-Content Analysis automation system, what could be the tips?

The complete system we have here is quite large. Certainly, not everyone needs all these instruments for all types of assays. My recommendation is to start with a smaller system. We currently have over 30 instruments in our screening automation and when you initialize the whole system, any small error on any instrument will stop the whole system and that can be a pain.
If you like to do fully automated assay plate processing, you will need a good liquid handler, a 37°C incubator, an imager and a good system to transport the labware in between. When you need higher throughput, using many assay plates, you have to implement plate processing tools as well, e.g. barcode readers, printers, labelers, centrifuges, and dispensers etc. In addition to all the hardware, you will need a dedicated software, which is able to control all instruments in a robust way. Nowadays, there is different integration software available. Some are more closed, that means you have to do modifications of the process together with technical support and some are more open, which means you can modify protocols on your own. You have to choose based on your level of experience. 
At the end you will need a good IT infrastructure to store, transfer and share images and at the end do image and data analysis. For the beginning, a workstation might be sufficient, but from my experience higher computational power will be needed soon. If you have put a lot of effort in developing a state-of-the-art screening assay, you will ask quickly for more computational power to do deeper analysis of your system. 

 

-How do you start of to assay for sensitive cells, especially like stem cells?

Initially, we have done all the cell culture protocols manually. Today, we have installed an automation platform just for automated cell culture. We use it for long iPS cell differentiation and cell culture protocols. The aim here is to really standardize the protocols and to limit the variance as much as possible. A standardized cell model is absolutely required for reliable HCS.

 

Q4. What do you plan to research in the future?

2D and 3D iPS cell models and the organ/tissue-on-a-chip technology will definitely be a part of it. Many authorities changed their regulations to encourage the use of in vitro models over in vivo models with the aim to reduce or replace animal experiments. We can support this by developing new human iPS cell-derived cell models or organoids in more complex arrangements. And, of course, by developing new imaging approaches and corresponding image and data analysis tools using AI.

 

About Dr. Philip Denner

Dr. Denner is a highly experienced High-Content Analysis researcher who has worked extensively in both the pharmaceutical industry and academia. He was also one of the first users to integrate CellVoyager into a large fully automated system. He provided invaluable advice and contributed significantly to the development of the CellVoyager series. As a CellVoyager user and a pioneer in High-Content Analysis automation, Dr. Denner's insights and feedback have been invaluable to us throughout our joint development. 

 

About DZNE

The German Center for Neurodegenerative Diseases (German: Deutsches Zentrum für Neurodegenerative Erkrankungen, (DZNE)) is a research institution that investigates neurodegenerative disease. DZNE was founded in 2009 as a member of the Helmholtz Association and the first member of the German Centers for Health Research (DZG).

About LAT: Laboratory Automation Technologies (LAT) is a Core Research Facility (CRF) at DZNE in Bonn and was initiated in 2010.