The Port-a-Patch: Pioneering the Field of Semi- Automated Patch Clamp
For the 20th anniversary of the Port-a-Patch, we are delighted to present an exclusive interview with our CEO, Niels Fertig. A visionary leader and innovator, Niels will take us on a voyage through time, unraveling the story behind this revolutionary patch clamp system that has transformed the field of electrophysiology.
“Thank you for joining us today, Niels. As we celebrate the 20th anniversary of the Port-a-Patch, we thought it would be great if you could walk us through the journey of how the Port-a-Patch came to be. How did the idea for the Port-a-Patch come about, and what were the challenges you encountered along the way?”
Thank you, it’s always a pleasure for me to talk about our Port-a-Patch. So, the foundation for the Port-a-Patch was the chip-based patch clamp, which originated from my PhD work around a planar patch clamp technique. And I think it’s important to acknowledge here that the fundamental concept of the planar patch clamp was first developed at the Bogomoletz Institute of Physiology in Kyiv, Ukraine, by the renowned Ukrainian biophysicists Kostyuk, Kryshtal and Pidoplichko. So, those scientists were role models for us at that time. They were our heroes. My PhD advisor, Jan Behrends, and I had a great appreciation for the entire group at the Bogomoletz Institute, all those really cool people who built everything themselves and did some great electrophysiology very early on.
So, in their pioneering experiments, Kostyuk and others used, if I recall correctly, a polymer film (as a substrate) with a 40-micron pore, so much larger than what we use now. And they also used much larger snail cells, not mammalian cells. But they did get that to work and then did some beautiful recordings. And so, that was the basis, the basic idea, which we further developed to apply it to mammalian cells.
“So, you decided to revive a long-forgotten idea and adapt it to mammalian cells. But why planar patch clamp? What are the advantages of the planar patch clamp compared to conventional patch clamp?”
Well, we believed that replacing the traditional patch pipette with a planar structure chip would provide a number of advantages in terms of the experimental parameters. We figured that using a chip would result in lower capacitance and better access resistance compared to a pipette. This would result in a lower RC constant, which would enable higher time resolution, reduced noise, and the ability to capture fast events and record tiny currents. So that was the main idea.
And in 2002 we had what I would consider our major scientific contribution – our publication on the planar patch clamp technique in the Biophysical Journal. In that publication, we showed for the first time whole-cell, as well as single-channel, recordings conducted with a microstructured chip.
But I realized that while that is true and the chip greatly improves experimental conditions, that wasn’t necessarily the main advantage of it. The real high potential that I could see was not only scientific but also technical. Using the chip, you can automate the procedure of capturing a cell, avoiding the manual labor-intensive process and facilitating the experimental procedure. Also, by using a chip, you can potentially have multiple recording sites on one substrate, allowing for scalability. So, it quickly became clear to me that I wanted to not only focus on scientific development but also utilize the chip to build a device and make it accessible as a technology for other people to enable them to do their research in an easier fashion. And that is basically what led to the decision to start a company around that.
We started Nanion in January 2002, towards the end of my PhD. We raised some money, assembled a team, and got started.
“And what did your team look like back then?”
We had a small team at the time. The first two employees were Michael George, our CTO, who was working on the software, and I. Then there was Matthias Beckler, who is now our Head of Production, and he basically made the suction control unit for the Port-a-Patch. Andrea Brüggemann joined us in March 2003, and she brought, of course, a lot of expertise on the cell electrophysiology side. Then Sonja Stölzle-Feix came along pretty early on, and Juergen Steindl as well. Those were the core people at the time. And we also had some scientific advisors working with us, including Jan Behrends. Those were the few people we had in the beginning, when we started making the Port-a-Patch.
Of course, we have further developed it over the years, and naturally, there have been many more people who contributed to that. Patrick Mumm, for example, is a big part of the later developments, and Ali Obergrussberger and many others…
“So, from the very beginning, it was just you and Michael who founded the company and started developing the prototype of the future Port-a-Patch…”
Well, the original idea wasn’t really to create the Port-a-Patch. Our initial business plan envisioned an automated system with 16 recording sites and automated liquid handling, a much larger and more complex project. However, after about a year, we realized that this would require more time, resources, and manpower than we had available. So, we had a discussion with our small team where we decided to pivot away from the automated robotic patch clamp system and make what nowadays would be called an MVP, minimum viable product, which is essentially the core essence of the idea that could be achieved in a shorter time and with fewer resources. This way, we wouldn’t run out of money and could bring something to the market.
That’s when we came up with the idea of the Port-a-Patch – the simplest approach making use of chip-based patch clamp. One chip, one aperture, one cell at a time, small benchtop device with just an automated suction control to run our experiments automatically, while still doing the addition of cells and the liquid handling manually. Really, the minimum viable product from our perspective.
So, very quickly we put together a prototype that we wanted to show at the Biophysics in 2003. Our prototype didn’t look like the Port-a-Patch looks today. It was a bit of a rush job, and it looked pretty terrible, to be honest. So, we took it to a small company that usually paints cars and asked if they could make it shiny and add some color. So, we had that all done, and it was very raw, but we brought that piece and showed it for the first time at the biophysics conference. It was quite a big achievement because now we had something tangible to showcase to people. And the system we had was compact and easy to transport for demonstrations. Hence, we called it the Port-a-Patch – the Portable Patch.
“And how was the conference? What did people say about your shiny and colorful Portable Patch?”
It was good, we received pretty good feedback at the Biophysics, which encouraged us to keep going and improve the device further. We started visiting some of our prospects who were interested, and we could show them the instrument, which was really nice. But I have to say that we also met a lot of people who were very critical of what we considered to be a great idea. Many times, we’ve heard “This will never work”, “I don’t think this will be a great product”, “I don’t think I will need it because we have PhD students who do patch clamping for us”, “It won’t work.” And I think that was a very good learning experience for us because we got to understand what people were interested in, and also received some feedback that we could use early on to improve our product. It didn’t take too long: we were able to have a real product by the end of the year and we got our first orders shortly after.
“Oh, you found your first clients pretty quickly…”
Well, it wasn’t all that smooth. By the end of 2003, we were almost out of money. We had only received seed financing and hadn’t secured a large venture capital round. We didn’t have the resources to build a big machine, and we could only provide a small one. So, we started talking to several venture capital companies to raise a Series A round and secure more significant investment. But it wasn’t an easy time to find funding in 2003-2004. The heyday of early-stage financing had passed, and venture capital was drying up after the burst of the dot-com bubble.
Fortunately, in 2004, things started looking up. We were able to do enough business with our Port-a-Patch to bring in some revenue. It was a bit of a shift from our original plan of a large system, but we managed to break even as a company in 2004. We were still a small team and didn’t pay ourselves high salaries, so selling Port-a-Patches fully covered our costs for the year.
Yes, it took us a little while to catch up in order to build larger instrumentation and develop our product portfolio, but I think that was a success factor for us as a company. We couldn’t have done it all in parallel or started with a larger machine. Port-a-Patch was just the right instrument for us.
“That’s quite impressive – breaking even within two years of existence. It sounds like the Port-a-Patch has been a great success.”
Yes, that was a fantastic experience! With the Port-a-Patch we didn’t need to raise more venture capital, we were able to grow organically through our revenue and reinvest those resources into developing the larger machine, which eventually became the Patchliner. Normally, we would have done it the other way around, but the Port-a-Patch turned out to be a huge success and a valuable learning experience for us.
We had the opportunity to get early access to the market and interact with real customers, which was incredibly helpful. It wasn’t just about developing our own stuff; receiving feedback from customers played a crucial role.
You know, looking back, I believe there’s a bit of a first principles approach in our journey. Although I didn’t know the term at the time, we essentially followed the concept of a minimum viable product. And even today, after 20 years, our Port-a-Patch still garners significant interest. This minimum viable product remains meaningful and adds value to our customers. Yes, it’s not for everyone and over time, we have developed other products to complement it, like Patchliner or SyncroPatch 384. However, if your application doesn’t need high throughput or an automated workflow, our Port-a-Patch still shines. Of course, we have made improvements along the way, adding new features, enhancing perfusion, and implementing temperature control. We even managed to make it smaller and integrated the amplifier, making it a sleek and appealing instrument that still finds a market.
“Is Port-a-Patch considered the world’s first automated patch-clamp system?”
I would claim that we were the first on the market with a small benchtop automated or semi-automated planar patch clamp instrument, however you want to call it. The Port-a-Patch was the first product that provided high fidelity Giga seals on a chip. Yes, there were some other automated patch-clamp systems at the time, including NeuroPatch/Apatchi-1, AutoPatch, and Flyscreen. However, they were all pipette-based, and as far as I know, they never achieved commercial success. There was also IonWorks system from Molecular Devices, which used planar patch clamp technology, but it didn’t provide Giga seals. Later, the PatchXpress machine from Axon Instruments was introduced to the market. It was capable of forming Giga seals, but that was after the Port-a-Patch.
“Do you think Port-a-Patch revolutionized the field of electrophysiology?”
Yes, I really do think so. Patch-clamp electrophysiology today is often considered as more of an art rather than a hard science. You need a highly skilled person, a scientist with a ton of experience, to get things right. It’s challenging for many people, both from an experimental procedure point of view and because the physics part of it is a little bit hard for many people oriented towards biology and biochemistry. So, I think having a device that automates the process for you was really enabling for many people. And I think it was a bit of a revolution. Maybe not for the whole world, but within the small field of electrophysiology, I think the Port-a-Patch was a revolutionary product. It put something into people’s hands that even a non-expert could use to answer scientific questions related to their research without needing to go to a super expert who has been doing patch clamp for 20 years and collaborate with them. You could use it to get answers very quickly.
“So, what is next for the Port-a-Patch? Are there any upcoming developments or add-ons in the pipeline that we can look forward to?”
Well, the very concept of Port-a-Patch is quite mature. But yes, we keep developing it and there are further developments related to amplifier electronics, for example, that are coming up. So, stay tuned.