Dr. Günter Roth is head of the “Microarray Copying“ research group at the Center for Biological Systems Analysis (ZBSA) at the University of Freiburg. Roth, who studied physics and biochemistry, has developed a biomolecule copier that he plans to use to establish his own company. The company will be called BioCopy, and the planned product lines, AptaSWIFT and immune2day, have already won numerous prizes for Roth and his team. In an interview with Mia Kühn from BIOPRO Baden-Württemberg, Roth explains how the copier works and also talks about his start-up plans.
We are building a kind of biomolecule copier that works very much like a photocopier. We use a chip that has a large number of small cavities, i.e. depressions, on its surface. They resemble honeycombs except for the fact that each cavity is just 50 µm in diameter, in other words, the thickness of a hair. Separate biomolecular reactions take place in each of the cavities: polymerase chain reactions (PCR) can, for example, be used to produce exact copies of the DNA strand in the cavity. These copies then bind directly to the surface of the cavity cover. Each cavity thus creates a pixel DNA on the cover; so we can copy a DNA microarray. The copying process can be repeated many times. As well as making DNA-to-DNA copies, we can also produce DNA-to-protein and DNA-to-RNA copies. We produce biomolecule copies with standard biomolecule mixes that biologists have been using for 3 or 4 decades: PCR mixes (DNA copies), transcription mixes (RNA copies) and cell-free protein expression mixes (protein copies). These mixes are our "ink". The combination of these small cavities with biochemistry results in a copier that is able to copy up to 100,000 different pixels, i.e. biomolecules, on an area of the size of a thumb nail.
Exactly, BioCopy is the copier, our basic tool so to speak. The individual projects – or future product lines – are based on our ability to adapt the copying processes for specific applications. The AptaSWIFT project, for example, deals with the identification and copying of aptamers, i.e. oligonucleotides that bind with high specificity to a target structure. Aptamers are seen as the next generation of antibodies and it is still quite difficult to find good ones. Our array identifies aptamers through different oligonucleotides. We then use microfluidics to bring the oligonucleotides into contact and bind with a molecule we are interested in. We then identify, recover and amplify the strongest binders.
The copier can also be used to develop vaccines. The immune2day project will involve using the cDNA of a virus or bacterium to make a DNA copy. We will then generate corresponding proteins from the DNA template in the copier, which can subsequently be used to identify potential vaccine targets with the help of antibodies present in the blood of infection survivors. The proteins that have been identified can then be copied and used as a vaccine for active immunisations. One of the major benefits of the new method is the time it saves. The entire process from identification of the vaccine target, to vaccine development and approval currently takes around a year. With immune2day, we can reduce the time required to develop the vaccine by a third or even a half. We also want to offer antibodies for passive immunisations. We can use our microfluidics methods to obtain cells from the blood of infection survivors. These cells produce protective antibodies against the pathogen. As we are able to find these cells relatively quickly, it only takes a week or so to produce antibodies with cell cultures. The vaccine can then protect people who work in conflict zones for a few weeks or increase the probability of survival of people who are already infected.
We are currently developing many different projects, all involving our copier. We have already come up with 40 different uses for our copier, but I am sure we will find more. We have enough work to keep us going for several years. The Freiburg team is taking part in this year's international iGEM competition, using the copier for testing blood. The procedure will be similar to immune2day. However, the team's DiaCHIP can copy already existing vaccines, and can therefore be used to analyse an individual's blood to find out whether he or she has already been exposed to a certain pathogen.
The growing attention that the method is receiving makes it much easier as far as contacts with investors are concerned. After the video of the pitch we presented at the regional Elevator Pitch in Stuttgart was posted on YouTube, we were very quickly contacted by people who wanted to invest a few thousand euros into our business and others that wanted to give us close to one million euros. We are now in contact with the latter group so that we can get our company up and running quickly. We are also discussing whether crowdfunding would be worth trying. Many private business angels and smaller investors have contacted us, because they heard about our projects from competitions we've taken part in. If it were up to us, and if we manage to acquire our objective of 4 million euros, we will set up the company at the end of 2015.
I am pretty sure that we will be able to gain a foothold with our aptamers. However, we can't foresee how fast we will grow. Although the aptamer copier is generally seen as a solid business project, it might not grow as fast as some investors hope. Vaccine investors usually hope to make big money. A company like us that is commercialising its first-ever vaccine, can potentially make around 100 million euros. However, some investors also accept that it takes longer to achieve return on investment. Such investors tend to see the social value, in other words saving human lives, as more important than the millions of euros in potential profits.
As part of my PhD thesis at the IMTEK (Department of Microsystems Engineering at the University of Freiburg), I printed rather than copied DNA microarrays. It was rather like printing newspapers. When I started the PhD, I thought that one day I might further develop the method into a copying process. So I filed my first patent. I was really lucky that the University recognised the potential of what I wanted to patent and decided to fund the patent application. The patent was then filed jointly: I wrote the application, we discussed it with the patent attorneys, and the University of Freiburg did the paperwork. I consider myself extremely lucky, because it was our project that the University picked from the large number of patent applications. We have had a lot of support from the University with all the patent applications we have submitted. And I am delighted that that has been the case. The patents make an important contribution to setting up our company.
Of course, it is good to know a lot of people. A good network can open many doors. But you also need a lot of luck. I met one of my best business contacts on the train from Berlin to Freiburg. It was pure coincidence that we were sitting in the same compartment. Since then, this chance meeting has led to a collaborative EU project. However, the best way to get yourself known is through the prizes you win, trade fairs, meetings and presentations, such as the one at BIOPRO's Healthcare Forum in 2014. BIOPRO's Biotech Guide that presents all the biotech companies in Baden-Württemberg has also been quite helpful. The University of Freiburg's iGEM team, which I am supervising with some other colleagues, used the Biotech Guide to identify companies that the team could contact for an antibody or blood sample analysis.
I am very happy. The team is excellent, the experiments are going well, and the majority of what we are doing works rather well. We still have to optimise the method to make it work every time. It is like what happened to the photocopier. A prototype of a photocopier developed by Xerox's Chester Carlson caught fire on the evening it was due to be presented to the public. Not a good start. But Xerox carried on and made it. Think about how photocopiers were around 20 years ago. People worried that it would not work even though the device had been under development for 60 years. With our biomolecule copier, we are at the stage that the Xerox copier was at around 25 years ago. There are a few things that still need to be optimised. But we are still just starting out.
Once we have the number of investors we need, we hope to be able to present a copier that can be used by anyone who works in a laboratory in about two to three years' time. The method has enormous potential and I would be delighted if everything goes to plan and every laboratory has its biomolecule copier, just like every office has its photocopier.