Using microfluidics for drug discovery

A representation of microfluidics

The Merten group at the European Molecular Biology Laboratory is developing microfluidics technology for drug discovery and personalised medicine.

Dr Christoph Merten is the leader of the Merten group at the European Molecular Biology Laboratory (EMBL), Europe’s flagship laboratory for basic research in molecular biology. His group at EMBL develops microfluidic technology. SciTech Europa spoke with Merten about his group’s current work on drug discovery and use of microfluidics.

How does your group approach drug discovery and what have been the biggest benefits of
using microfluidics?

We approach drug discovery using droplet microfluidics. In these systems, we use tiny droplets that are so small that you can see them only under the microscope. We use those droplets as miniaturised test tubes, and they are surrounded by oil to keep them separated. By making the assay volumes much smaller, there are many benefits. For instance, we have a strongly increased throughput, meaning you can test hundreds of thousands of antibodies in a single experiment, you can use patient materials (when you take patient biopsies and want to run experiments directly, this material is not available in large quantities so you need small assay volumes, and this means that we are able to carry out large screens using patient material), and, of course, we also have cost savings based on these very small volumes.

The competitive advantage of the group stems from the fact that it is very interdisciplinary. For example, we have engineers, physicists, biologists, and bioinformaticians all working together, and this puts us in the unique position of being able to perform first of its kind screens because we build the hardware, we develop software to run our instruments, and then we directly apply this to bio-medical applications. This is nicely represented by the fact that we have 15 patents filed on technology and applications so far.

Given that microfluidics is a profoundly interdisciplinary area, as you have mentioned, have you experienced any challenges in bringing together experts from such diverse fields and working effectively together?

It is perhaps not as challenging as it might first appear. The interdisciplinary atmosphere is very exciting and stimulating for everybody, and it also allows people to pick up specialised additional skills. Sometimes, it only becomes apparent that people have very different problems when diving into new disciplines based on their primary training. We get around this by encouraging communication.

What makes EMBL such a great place to work and how does it support you?

We profit a lot from the EMBL, and it is fantastic for many reasons. Most of all, it has a very collaborative atmosphere, and we benefit from the different facilities EMBL has to offer. For instance, if we have engineers in the group and they need specialised electronic parts or maybe even just some advice, they can easily find the right people to talk to. We are also able to connect with our colleagues at EMBL’s Genomics Core Facility (GeneCore) and ‘Mouse House’ in order to take advantage of their expertise.

Can you tell me about your three future priority areas (therapeutic antibodies, personalised medicine and genomics)?

One big application we have successfully established is higher throughput screening platforms for therapeutic antibodies, and I believe current and future research will
mainly focus on increasing data content and enabling multi-plexing.

We have very clear ideas on how to discover therapeutic antibodies against multiple drug targets in parallel. In the field of personalised therapy, we have done quite a few proof of concept experiments and we are now aiming at translational steps. We are very keen to do initial first clinical trials, particularly with our collaboration partners at Heidelberg and Aachen University (Professors Saez-Rodriguez and Cramer), and I think these devices will enable personalised therapies at a lower cost than what patients currently spend on routine diagnostics such as MIT scans. As such, there is big translational potential.

How important is it to work closely with pharmaceutical companies? And how challenging is this? Do they want to guide you in certain directions?

We can learn a lot from the pharma industry about what is most needed in a clinical setting. Furthermore, we can strongly benefit from their expertise in assay development and target validation. When we collaborate with pharma, we insist that we have the rights to publish the results, and this makes the exchange with the industry very healthy.

What are your thoughts on the argument that Europe isn’t the most attractive place for big pharma companies to continue to develop?

There is an increased amount of collaboration between academia and the pharmaceutical industry in Europe, and so while Europe may not be and may not become the most competitive place, it is definitely getting better.

Your spin-off company, Velabs Therapeutics, has developed a droplet-based microfluidic screening technology which aims at the fast generation of antibodies against target molecules presented on cellular membrane surfaces or as soluble protein. What can the company offer to its users which they cannot find elsewhere, and what hurdles have you faced?

I have perhaps simply been lucky in the sense that I have had some very good people working with me in all aspects of the process. The business element is looked after by an experienced CEO (Dr Christoph Antz), for instance, while I work as the CSO, which is good fun. When difficult challenges arise, there are people who can help and who have helped previously.

Velabs offers its customers functional high throughput screening. We are particularly focusing on antibodies that modulate GCPRs and ion channels and our technology enables us to screen 100,000s of antibodies for such properties in a single experiment, rather than only selecting for binding – historically, the market has only offered screens for binding, but we can screen for function. And while there is typically a focusing problem here, for example depending on where the cell is inside the droplet you get stronger or weaker signals, we have developed proprietary technology that can overcome that.

In closing, what does the future hold for you both in regard to your research group at EMBL
and elsewhere?

In the personalised therapy sector, we are hoping to found another start-up company, which is very exciting. However, I still see my future as being in academia; I like to run an academic lab because of the freedom that is offered, meaning that I can dive into different topics to develop new technologies or to conduct basic research. However, I believe that it is important to have more than just a scientific paper resulting from my work, and so whenever there is a chance to commercialise something, to license something, or to fund a start-up, then I am always very interested.

Dr Christoph Merten
Group Leader Microfluidics
Genome Biology Unit
European Molecular Biology Laboratory (EMBL)
+49 6221 387 8557
merten@embl.de
Tweet @embl
www.merten.embl.de

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