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In this interview, Thomas told me about his career, marketing to scientists, automated patch clamp (APC) robots, APC instrumentation market, Sophion’s favorite competitor, and more. I learned a lot about Sophion’s story and instruments from Thomas, and if you want to know more about the APC robots and their use in industry and academia, this interview will be a good source of information for you.

Have a good read.

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So, Thomas, why don’t you just tell me a little bit about your academic background and career trajectory?

Sure. I did my Ph.D. in plant ecophysiology, mostly studying photosynthesis and oxygen dynamics in algae. You might think that there is a chasm between these topics and the ion channel field, but the interesting part is that to carry out my studies, I was using electrochemical microsensors and … glass micropipettes. Of course, it’s not the same as patch clamping, but still, there are many similarities.

Right after my Ph.D. I moved to the industry and joined Unisense (ed. a world-leading manufacturer of microsensors for environmental and medical research) as a marketing and product manager. After that, I have had several marketing and scientific communication roles at Thermo Fisher Scientific, Dako, and Agilent Technologies before joining Sophion in 2015.

And the fun part is that my story with Sophion goes back to my master’s degree. In the late 1990’s I was in the Study Council for Biology at the University of Copenhagen, and after one of the meetings, I remember Dr. Niels J. Willumsen, an electrophysiologist, telling me he was offered to join a startup, and whether he should leave the university and go to a startup or not. I didn’t know back then that I was talking with one of the future founders of Sophion. So, 15 years later, I joined Sophion as Director of Marketing and continue working for this great company to this day.

So, you said that right after your Ph.D., you started working as a marketing and product manager at Unisense. I’m curious about how a company can hire a basic scientist as a marketing manager? Did you have any previous experience in marketing or business? How did you convince them?

Actually, I didn’t have to convince them, they asked me. During my master’s and Ph.D. studies, and also in between, when I was working on different EU projects, I’ve always been teaching and writing a lot. So, the communication part came very naturally to me, and I always thought it’s really fun to work in this area. I mean, what is science if you don’t have the communication? What is science if you cannot tell people about it? So, at Unisense, they knew that I could do science communication and they saw the value in that. Later, when I worked at Thermo Fisher, Dako, and Agilent, and also now at Sophion, I continue working in the cross fields between science and marketing, making sure we use scientific information in our marketing efforts. In the end, we are marketing to scientists, so we need to speak the scientific language to ensure that people understand the value our products can bring.

It’s a very interesting point. Could you tell me more about science marketing? Is there anything special about marketing to scientists compared to other consumer types?

I think one of the key things when working with complex topics, like we are doing, is that you must use information that resonates with the users. In our case, the users are highly educated electrophysiologists… experts in their field. So, it doesn’t help only to use fancy words; you need to go down to the substance, which is the science, the performance, the facts. That’s why most, if not all, companies working with/for scientists focus a lot on application reports and scientific publications. Also, at Sophion, we have done the “Ion Channel Modulation Symposium” (ICMS) for the last five years, where we gather the pharma industry, CROs, and academics to discuss the science of ion channel modulation in a symposium style event. I think it has been important for the success of ICMS that it is science- and content-based so that scientists could get all the specific information they need to make their decisions, but also enabling communication between industry and academia.

Well, obviously, content marketing is not at all unique for our field and is something that had been a buzzword for many years, but I’m convinced that it is essential that we use science, performance, and facts to advertise our products… the glossy papers cannot do the trick here. It is fine that our products look good, which they do, but our users can easily see through that if the products do not have the quality and performance.

So, your current role is directly related but not limited to marketing. You are VP R&D and Marketing at Sophion. It sounds like a big role. So, what’s it like to be a VP of R&D and Marketing?

Well, it is indeed a large role with a lot of responsibility. It is also an interesting combination of roles because we, in marketing, are talking to our users and potential users and continuously learning from them about new things and new ideas. What they want now, and what they want in the future. And then, based on all that input, we are carrying the ideas to the R&D department and prioritize things so that they can be developed in the direction where we believe the market is going.

In many companies, there is a high degree of separation between Marketing and R&D, which makes it difficult to prioritize and act on customer input. Having R&D and Marketing under the same umbrella makes it easier and faster for us to move on market needs and customer wishes.

THOMAS BINZER

In many companies there is a very high degree of separation between Marketing and R&D, which makes it difficult to prioritize and act on customer wishes. Having both hats (R&D and Marketing) under the same umbrella makes it a lot easier and faster for us to control that flow of information and action. It’s simply faster for us to move on customer wishes and market wishes. And obviously, I’m not alone and I’m supported by a super team, both in R&D and in Marketing. I have never worked in a company where R&D scientists and engineers are so aware of customer needs. Many of our R&D engineers have, if not daily, then weekly discussions with our users.

Well, to be honest, it’s not that easy to find information about your team on the Internet. The same is true for Sophion’s story. Could you tell me more about Sophion?

Oh, sure. So, for those who know nothing about us, Sophion Biosciences is a small-medium sized company with a worldwide presence, focused on making automated electrophysiology equipment for research, early drug discovery, and cardiac safety profiling. Currently, we have demo labs in Boston, Tokyo, and Copenhagen and offices in greater London and Beijing, as well as distribution partners, mainly in the Asia Pacific region.

Sophion was founded in 2000 by a group of passionate electrophysiologists, with the shared purpose of making patch clamping objective and independent of user skills to provide faster, more accurate, and objective patch clamping results. Or as we like to say “take the voodoo out of patch clamping”. It was founded as a spinoff of the danish pharma company Neurosearch, that established Sophion since they needed the capabilities of higher throughput patch clamp.

So basically Sophion was born based on three needs: 1) The need for faster turnaround and higher throughput. 2) The need to take the subjectivity and personal skills out of patch clamping. 3) and the need to make it easier and more accessible to every laboratory to record and analyze patch clamp data.

Our first automated patch clamp system, QPatch, was launched in 2005 and had a fast uptake, especially in pharma and CROs, which raised some interest from investors. So in 2011, Sophion Bioscience was acquired by Biolin Scientific, a Swedish Biotech owned by Ratos, a Swedish private equity company listed on the Stockholm Stock Exchange. In 2017 we got the chance to make a management buyout and since then, we have been ‘master in our own house’. The management buyout has been received well by customers, that still, after 3 years, tell us that they have experienced a huge change to the better for both innovation, support, and service after the changes. That was the goal, so it makes us both proud and happy.

As you might know, at Sophion we develop everything ourselves. All the key components of our systems, like the pressure system or amplifiers, are designed by ourselves. So, in our team, we have hardware engineers, software engineers, electrophysiologists, microfluidic experts, cell culture experts, business professionals. I think it’s a key aspect that allows us to advance in the right direction. And for those who are interested, I will make sure we add some info on the board and management team on our website.

So, Sophion manufactures automated patch clamp devices, and currently, you have two products with different configurations, QPatch II and Qube 384. Could you tell me about the capabilities of these systems?

Sophion QPatch and Qube cover everything from basic research to high throughput screening.

THOMAS BINZER

Our QPatch and Qube cover, more or less, everything from basic research to high throughput screening. The QPatch is a very versatile medium-throughput system that is mostly used for cardiac safety, advanced electrophysiology, and medium-throughput screens (we’ve done 10 to 20,000 compound screens on a QPatch). QPatch has two configurations, QPatch 16 and QPatch 48, allowing for 16 or 48 simultaneous individually controlled patch-clamp recordings. QPatch is also the only available platform on the market that enables true-gigaseal recordings in physiological solutions, without the need for seal enhancers or fluoride to enable better seals. So, it’s a great system for academic labs, for CROs, for medicinal chemistry projects, lead optimization, and everywhere where the workflow does not require testing of thousands of compounds in a day.

But if you want to do large screens, then we have the Qube 384, which is a 384-well platform. It uses block-pipetting, like all the other 384 platforms on the market. It means that, unlike QPatch, where you can individually control each well for pressure, cell status, and liquid-additions, here you simply run 384 cells at the same time. Great for the purpose.

Both Qube and QPatch use plates or chips (single- or multi-hole) with built-in microfluidic flow channels, which means that compounds can be 100% exchanged, which is especially crucial for ligand-gated experiments. Also, all our plates are built with integrated individual electrode sets per well, which means no electrode maintenance is needed and no risk of drift due to lack of chlorination.

Also, both platforms are designed to run unattended, so they can run overnight routinely. That means you can run 12-16 plates during your workday and the same overnight. At Charles River in the UK, for example, they’re running routinely 8 to 12 plates every night while they’re home sleeping, which increases throughput a lot. How many plates you can run depends on how long the cells are in good condition. However, with our patented cell hotel, where cells are stored in growth media and prepared just before the experiment, 8 hours of cell viability can often be achieved.

OK. You are talking about plates, wells, holes, and pipettes here. For those unfamiliar with your products, could you describe in more detail the whole process of patch clamping using Sophion’s systems?

Well, the first thing to understand is that we are talking about planar patch clamp. It means that instead of using glass pipettes to patch the cell, we use holes at the bottom of wells on a plate. So, we have 16- and 48-well plates for QPatch and 384-well plates for Qube, and at the bottom of each well, we have one patch hole or multiple patch holes. All we need to do is to put our empty plate of choice inside the machine, add cell suspension into the special tank, add solutions, and push the ‘RUN’ button. QPatch and Qube will take care of everything else. By using liquid-handling pipettes, our machines will add solutions to the wells, add the cells to the wells, make seals, rupture cell membranes (if you want to go into the whole-cell mode), change solutions, record signals, and perform some kinds of data analysis for you. OK, I simplified it a bit. Obviously, you need to design your experiment, create protocols, and find the optimal conditions for the cells in advance. But overall, the whole process is not very different from what I just described.

It sounds good, almost like a patch-clamper’s dream. And when you are talking about these multi-hole wells, do you mean population patch-clamp?

Exactly. Our default QPlates (QChips for Qube) are single-hole, but we also have multi-hole plates with ten patch holes per recording site. These multi-hole plates allow for simultaneous recording of ten cells in parallel per recording site, thereby increasing the signal to noise ratio and the success rate. But if single-hole or ten-hole plates are not what you need, we can produce plates with a custom-made number of holes for you. So, it’s highly customizable.

Also, if you want to go into a large screen, it’s nice to optimize your assay in all possible ways before you go into production with that screen. And for this reason, we also have what we call Assay Development QChips (or “rainbow plates”) for the Qube, where you have four columns, each with 1, 2, 6, 10, 16, 36 holes in one plate. So, you can optimize and see where is the optimal between success rates, current level, and relevance, depending on what it is you are looking for.

OK. And I cannot help but ask you: Why Q? All Sophion’s products have Q as the first letter in their names. What does this first letter Q mean?

We often get the question of what the letter Q means…and it is not that easy and might have been lost in translation somewhere. It depends on who you are asking. I get three different explanations:

1) ‘Q’ reminds of IQ and thus intelligence and/or intelligent. We believe that the QPatch back in the days was, and still is, the only real intelligent APC robot that thinks for you. It is, to this day, still the only APC platform with build-in intelligence in the control software that allows for online and real-time evaluation of cell performance. QPatch will only advance experiments and add compounds if the cell(s) comply with a set of customizable quality criteria like seal level, capacitance, etc. We call it ‘online quality control’ and ‘intelligent compound handling’. Very similar to manual patch clamping and a great feature for saving time and compounds.

2) ‘Q’, as a letter, resembles a cell (the circle) with a pipette protruding from it. Choose some different fonts and you will see what I mean.

3) ‘Q’ is the first letter in Question, Quality, and Quantity. You can ask complex questions, and get an answer using the high quantity and quality of data.

Which one is true, I do not know, maybe a bit of each.

And what about the birds? Your Qube software releases are named after birds: Eagle, Falcon. Why is that?

Well, in order to discriminate between different releases, each new Qube software release comes with a new bird name next in line from the alphabet. Albatros, Blue-footed Booby, Condor, Duck, Eagle, Falcon….the next one is Goldcrest (‘Birds king’ in Danish).

But, for QPatch it was cities from A to Z, and for QPatch II it is planets orbiting the Sun…which I agree is slightly more complicated. Not all remember whether it is Jupiter or Saturn that comes after Mars….

OK. Let’s talk about your competitors now. Which is your favorite?

Oh, our favorite competitor is Nanion. We have been competing with them for many years. More or less neck and neck we’ve launched our 384 platforms, Qube and SyncroPatch. They’ve had the Patchliner for many years, we’ve had the QPatch. So, it’s absolutely Nanion. But we like Fluxion as well. Fluxion has a very ingenious product that is very well suited for ligand-gated assays because it has a unique liquid exchange system based on microflow channels, which enables 100% compound exchange/wash, the same way as the QPatch and Qube. So, Fluxion is also on our radar. But, Nanion is likely our favorite.

And who is the leader in the APC instrumentation market now: Sophion, Nanion, or Fluxion?

It depends on where you are looking. If you look at the pharma industry and the CROs, it’s absolutely Sophion who is the market leader. It has also been our focus for many years. If you look into academia, I think that Nanion might be the market leader there. They have their Port-a-Patch, which they place in a lot of the smaller labs, and overall, they’ve been more focusing on the academic segment and building their academic profile.

But now, we experience an increased interest in our systems from the academic labs and so we’re moving towards academia, whereas Nanion tries to move towards CROs and pharma. That’s why I call Nanion our favorite competitor.

OK. And how do you differentiate yourselves in this competitive market? What do you think your advantages over your competitors are?

I think, Sophion, no doubt, is the pride of high-quality APC systems that are, first of all, easy to use, but also can run unattended in any lab setting. You can learn to use QPatch or Qube in an hour or two, so it’s easy for companies and labs to go into production with our systems. Our development philosophy is that you shouldn’t use five to eight years of education, being a highly-skilled electrophysiologist, to stand beside a machine and operate it. Electrophysiologists should think all the big thoughts, design the assays, and analyze the data. They should not move plates around. Our idea is that it should be so easy to use APC equipment that anyone with a bit of laboratory training can operate it.

During our QPatch II development, we took a 17-year old high school student who had never been in a lab before, we brought him to the lab and asked him to set up a QPatch run. He had a quick-guide and we prepared the cells and solutions for him in advance. It took him eight minutes to start a patch-clamp job. It took eight minutes for a high school student to start patching cells with our QPatch on his first try.

That is our objective when we develop APC equipment: it should be that easy. It will make it easier when you have staff rotation or many users in a lab, which we see more and more both in pharma, CRO, and in the core labs in academia.

So, usability is one point, and another point is unattended operation. Our devices are designed in such a way that you don’t have to be present throughout the experiment and so you can have more time to focus on experimental design or data analysis.

“We think of Automated Patch Clamp like an iPhone. It might not be cheap to buy one, but when you have it, it doesn’t require much training and it will make your life a whole lot easier.”

THOMAS BINZER

And yet another important point is that all key components of our instruments (except liquid-handling robots from Tecan and Dynamic Devices) are designed by ourselves. We don’t use off-the-shelf amplifiers from other vendors, we have designed our amplifiers ourselves, so these are designed for automated patch-clamp. And that makes a difference. This is one of the reasons why we can introduce some of the new features, like online V1/2 estimation or online Vx estimation. Our hardware engineers improve our amplifiers and pressure systems and our software engineers make better our software to meet our clients’ needs. We have full control, and I think it’s a clear advantage.

I’m curious, why don’t you produce smaller-sized equipment, like Nanion’s Port-a-Patch, for example, to target academic labs? I think about your patent for a handheld patch-clamp device.

That’s interesting, of course. Maybe we will. It has simply not been our focus until now. We do see a lot more interest in our products from academia, as I mentioned before. So maybe… and fun you know about our patent on the handheld patch-clamp device, the QPette. I think it would make Chris Mathes happy if we finalized that idea (see the recent interview with Chris Mathes here).

OK. Sophion and academia. You said that it had not been your focus. Why is that? And how are things going now in this regard?

Well, as I told you before, Sophion has been owned by a Swedish Capital Fund for six years. When owned by a corporate that looks more at the business than at the science, it’s much more difficult to think long term. While academia has a large potential, the number of plates used is minimal compared to pharma, so we kept our focus. Since the Sophion management buyout in 2017, a lot of things became easier. So, we can now look more towards scientific collaborations and academia as an interesting segment.

At present, about 20-25% of our installs are in academia and we see a lot of interest in our systems from academic scientists, especially in the QPatch II. Due to our continuously growing academic interactions, we have recently appointed Damian Bell as Director of Scientific Affairs, who will, among others, help drive Sophion’s collaborations with academia (see Damian’s recent interview to the IonChannelLibrary here).

We are placing more and more instruments at the academic site. We have just installed both a Qube and a QPatch II at Steven Waxman’s lab at Yale University. Irina Vetter, Glen King, and Richard Lewis are all very active using our QPatch in their research at the University of Queensland. Heike Wulff at UC Davis has been a long-term user, George Chandy at Nanyang, Sarah Lilley at Sussex, but also McGill, Fudan, Dublin, Guizhou, Peking, etc etc. Many more to mention, but it is a global trend that academia is adopting APC. For us, it is super exciting that we get more adoption of true APC in academia (all due respect to the Nanion Port-a-Patch, but it is not APC) because academic scientists are often the ones that are spawning the good ideas and have the time and focus for breakthrough discoveries.

We also have more collaborative projects with academia now. Fredrik Elinder from Linkoping University, for example, told you about one such project in his recent interview. But we have for many years also worked with Aamir Ahmed and Jonathan Ashmore from UCL and KCL on ion channels in oncology.

By collaborating with scientists and making sure they have the results, we help them to build the case that they can show to their boards or funding bodies, and prove that our systems are suitable for their research.

THOMAS BINZER

We have what we call a “Technology Access Program” for people who want to buy a system, for people who don’t know the system, for people who cannot afford the system. Usually, scientists come to our lab, work with us, and the whole idea is, of course, to expand the market and the knowledge about automated patch clamp. Also, by collaborating with scientists and making sure they have the results, we help them to build the case that they can show to their boards or funding bodies, and prove that our systems are suitable for their research. This could potentially help them in getting funding to buy our systems in the future.

Also important, is that our collaborations with academia keep our application scientists stimulated and challenged. Some of the decisions to collaborate have been based on the fact that our application scientists thought it was interesting.

The automated patch clamp is a fantastic supplement to the manual patch clamp, and so, I’m sure that it will get more popularity in academia over time.

THOMAS BINZER

You know, QPatch has been pushing the boundaries of automated patch clamp for the past 20 years, and it is as close to manual patch clamp as it gets. It’s the only platform that can run totally without seal enhancers. Also, when you put your cells on, it measures individually which cells are in whole-cell and which are not. It can apply individual pressure protocols and if something happened with the cell, so it doesn’t go into whole-cell, then you can set your criteria, and you will never add any compound to that cell because it’s failed. So, you have all these advantages that make it close to manual patch clamp. It’s not to say that our QPatch is an alternative to manual patch clamp, but automated patch clamp is a fantastic supplement to manual patch clamp. So, I’m sure that automated patch clamp will get more popularity in academia over time.

I think it’s a shame that some people have the feeling that the automated patch clamp is not working well… because it is.

THOMAS BINZER

I know that some academic scientists are still skeptical about automated patch clamp, especially those having some negative experience with automated patch clamp in the past. And now, those scientists are kind of scared away from adopting new technologies. But I want to say that anyone who had a bad experience with APC should give us a call. And then, they can come for a demo, we can do a live demo, or we can do on-site demos, or sometimes we even ship a system, install it, and then they can run on it for a few months. Because I think it’s a shame that some people have the feeling that the automated patch clamp is not working well… because it is. You just have to select the right system. A lot of things have happened in the field over the past 10 years.

Adopting APC technologies is taking care of the future of Ph.D. students and postdocs.

THOMAS BINZER

Another motivation for lab directors and faculty staff to bring APC technologies to their labs is to take care of the future of their Ph.D. students and postdocs. The number of positions in the Universities is limited, so many postdoc-electrophysiologists will be looking for a job in pharma or biotech companies. One of the key skills for them will be to know about automated patch clamp, which is widely adopted there. Some laboratories are now adopting automated patch clamp to equip their students and postdocs for the future by allowing them to learn about APC technologies so that it’s not a new thing for them if they decide to leave academia.

Great. Let’s imagine that I want to buy an APC system. What criteria are the most important for me to consider, and what equipment would you recommend me buying?

First of all, I think it’s very important to understand what the throughput is that you need. If you only want to screen 10,000 compounds, or to do a medicinal chemistry program, to do basic science, or cardiac safety experiments, I would always recommend one of the smaller throughput systems. But it also depends on your workflow. If you get 25 compounds a day every day, then it could make sense with a medium-throughput system like QPatch, but if you get the 250 compounds every second Monday, it might be an easier workflow with a 384 platform.

Secondly, what are you working with? Is it ligand-gated channels, is it voltage-gated channels? For example, when you are working on ligands, it’s important to have a full compound exchange. And if you need that, then I would look for the microflow systems from Fluxion or Sophion.

The number of users? Will it be one expert-user or 5-10 different users? Do you expect that there will be new people coming in to use the system all the time? If you have 10 different users, then the operation should be easy to use. Complexity means human errors, which means downtime or more need for training.

But then, there are loads of other things that depend on the scope of your research or your topics. Data quality, voltage control, reproducibility and repeatability, software for data analysis, need for unattended operation, usability, level of application support, and…… of course, price.

And where are we in terms of price?

In general, pricing is from 300,000 euros and upwards. But sometimes we get older systems in, that we refurb and sell them. The price for such systems could be as low as 100,000 euros, so, comparable to a new manual patch clamp rig. We prefer to sell these to academic labs.

Oh, that’s interesting. So, one can buy a used-refurbished system from you for a fraction of the price. Are there many used APC systems on sale and in what condition are they?

No, you rarely see our used instruments on sale. Many of our systems that are still operating are 10-15 years old. Prices are very dependent on age and how good a shape the system is in.

The obvious problem when buying a used system is that you don’t know how well it has been tended. So usually, we are involved when a used system is changing owners to evaluate what shape it is in. Some key components need special attention, especially the robot. If the robot is not in good shape, then it’s a big problem. If the system has been standing idle for two-three years in a damp environment, then it’s likely not a system I would invest in, to be honest. Even though we have a good collaboration with both Tecan and Dynamic Devices, and we usually support the robots for a long time, there are limits to what our Field Service Engineers can do.

Is there a possibility to rent or to lease your equipment for those who cannot afford to pay the full price at once?

Of course. You can rent it, you can lease it, or you can rent-to-buy it. It depends on what your financial situation is. Sometimes we also sell a system where half is paid this year and another half is paid next year.

Also, some users start by buying a refurbished system for the first one to two years before they kind of get acquainted with APC and see the real value. And then they upgrade and buy either a new system, a QPatch II, or a Qube afterwards. There are many ways to get into the game.

For an institution that wants to adopt automated patch clamp, the key is to show the relevance somehow. So if you don’t have access to a system – reach out and make sure to create those relevant data with us so that you can show to your funding bodies, your boards, that this is the instrument you need.

APC is mostly used by Pharma and CROs for ion channel screening. But what we see now is that other screening technologies for ion channels are being developed, including fluorescence and luminescence-based, radiometric, optogenetic, cell-free, or label-free image-based assays. So, what do you think about the future of automated patch clamp considering the development of other screening technologies?

I think that automated patch clamp will likely take over more and more from manual.

THOMAS BINZER

I think that both automated patch clamp and manual patch clamp will live for a long time. And I think that automated patch clamp will likely take over more and more from manual. The key about patch clamping is that you measure directly on the ion channels, and you measure the primary signal, the true signal. Many of the alternative methods that are coming out do not measure the primary signal, the current or voltage, they measure derived parameters. And that’s why I believe that there will be a place for both manual and automated patch clamping for a long time.

OK. And so, my last question will be about the impact of robotic automation on the electrophysiologist job market. Will APC robots make electrophysiologists redundant?

In my opinion, the development of APC technologies can create more opportunities for electrophysiologists.

THOMAS BINZER

Absolutely not. I don’t think that a well-trained electrophysiologist will be made redundant anytime soon. In my opinion, the development of APC technologies can create more opportunities for electrophysiologists. I think that the adoption of new APC technology will actually just increase the focus on ion channels in the pharma industry, in CROs, and so they may need more people to do the work. But the electrophysiologists, they will then have to focus a lot more on designing the clever studies, developing the assays, and analyzing the results instead of moving glass electrodes around. Early-career scientists-electrophysiologists should pay more attention to experiment design, assay development, analytic skills, and learning about APC technologies because these are the key skills the companies will hire for in the future.

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I’m thankful to Thomas Binzer for taking the time to talk with me and sharing his insights.

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Photos provided by Thomas Binzer