Subscribe
Share
Share
Embed
Science in Real Time (ScienceIRT) podcast serves as a digital lab notebook—an open-access, conversational platform that brings the stories behind cutting-edge life science tools and techniques into focus. From biologics to predictive analytics and AI-powered innovation, our guests are shaping the future of therapeutic discovery in real time.
Carli: Welcome back to Science in Real-Time, the show where we dive deep into the discoveries, technologies, and the people shaping the future of therapeutic research. I am your host Carli Reyes and in today's episode we're joined by Tarun Vemulkar, CTO and co-founder of Semarion, a company that's redefining how we handle and study cells with their innovative SemaCyte platform. We'll explore how their technologies bridges biology and material science to accelerate drug discovery and how it's opening up new possibilities for scientists working with complex cell models. Let's jump right into the conversation.
Carli: It is amazing to be able to have you here and be able to talk a little bit about Semarion and your journey as well and I thought that it would be very fitting to start a little bit with your background. So can you share with our audience a little bit about yourself?
Tarun: Hi Carli, absolute pleasure to be here, thank you for letting me join. My background is a slightly interesting one, I guess, given that I currently work in the world of cell biology in which I'm a little bit of a black sheep because actually I'm a material scientist slash physicist by trade. So I began my career basically researching and developing the next generation of field effect transistors. They're things that go into microchips that power computers.
Tarun: I then worked in the semiconductor industry at scale seeing how these microchips were manufactured in an absolutely massive way. But then what I really was interested in doing is taking some of the precision engineering and advanced materials from the semiconductor industry and deploying them in more biological applications. So I then went to do a PhD at the University of Cambridge and that was focused really on developing a novel type of magnetic nanoparticle where we actually borrowed things from the magnetic memory industry, so hard drives basically, and that nanoparticle we used as a novel way to treat glioblastoma brain cancer basically.
Tarun: And I guess, long story short, a lot of the learnings about interfacing that advanced material system with the cell biology then turned into the foundation behind Semarion's platform today.
Carli: For those new to Semarion, how would you describe the company's mission?
Tarun: Yeah, so Semarion fundamentally what we're trying to do is really empower drug discovery teams and massively increase the throughput of their cell-based assaying workflows essentially. And that's by delivering them cells, specifically adherence cells, as standardized multi-flexible reagents that can slot into their existing research infrastructure.
Carli: I believe that you have also, you're also the co-founder of Semarion and I couldn't help myself but ask, what was the original spark that led to Semarion? And we'll definitely go more into detail in a little bit, but I couldn't hold myself, I'm wondering what was that initial spark?
Tarun: I think over the course of my PhD, I really always wanted to commercialize the science I was doing and I really wanted to see sort of short-term impactful results from some of the more complex deep technology that I was interested in building. So that was always sort of a ground motivation for me fundamentally, I guess. And then I founded Semarion together with my co-founder, Jerone, and we were both good friends over the course of our PhDs.
Tarun: Jerone is a clinical neuroscientist and I guess at some point we just got to talking about the challenges in the world of clinical neuroscience that I as a physicist, material scientist, maybe didn't quite have much of a handle on. And what he described to me was basically that he was trying to do a lot of these really, really cool, I guess, sRNA-based drug treatments on these complex cell models. It sounded really amazing, but then he ended up saying, well, I do spend a lot of my time just managing and culturing and babysitting my cells and what that tends to lead through is just basically issues in reproducibility and throughput and really a lot of weekends spent going in and feeding my cells.
Tarun: And I guess over the course of us talking about it, we tried to unpack maybe what was the fundamental root cause of this. And we had a bit of an 'aha' moment where we realized, you know, a lot of this stems from the fact that these adherence cells just fundamentally really like to be stuck to a surface, right? Their biological phenotype relies on them being stuck to a surface. And a lot of the inefficiency comes in when you've got to somewhat aggressively take them from one surface, like a growth flask, and then put them into a different vessel, like a well plate in which you're doing an experiment, for example.
Tarun: And that just sort of breeds a bunch of inefficiencies in the workflow. And so we were just wondering, just as a simple concept, well, what if you could leave the cells attached to the surface, but then move the surface itself into suspension? And that sort of became the birth of the kernel of the idea behind Semarion, I guess.
Carli: That sounds wonderful. And as somebody who has experienced the pains of cell culture, I resonate with that a lot. And it definitely sounds like such an amazing technology that we'll definitely go into more detail in a bit. Semarion's innovation really is centered around this SemaCyte cell multiplexing platform. I'm wondering if you can give us a little bit of a high level sense of what is it and why it matters, now informed by that spark that led to Semarion.
Tarun: At a very high level, and maybe the simplest and somewhat most fun way of describing what a SemaCyte is, is basically a microscopic micron scale flying carpet for cells. It's basically a mobile surface that carries a small clusters of cells on it, and it can be released into suspension and then handled by pipettes and robotic automation tools and dispensed really conveniently and easily, basically.
Tarun: I guess the why it matters is we had sort of looked at this process of going from, I guess, culture flask or growth flask to well plate. And over the course of quite a few years of this process being deployed in the pharmaceutical industry, we really felt that this sort of fundamental aspect of adherent cells being stripped and replated really hadn't seen a lot of innovation. And we thought there was potentially room here for an end-to-end solution that could deal with some of the embedded inefficiencies in adherent cell workflows.
Carli: Yeah, that sounds like it makes a lot of sense. And I cannot help but think now about the science of the SemaCyte deep behind it. And I'm wondering, how does it work in the scientific and engineering level?
Tarun: If you can imagine a single SemaCyte, it's a little carrier for a cell. Think of a really little box into which cells are able to fit and attach and remain happily, basically. That individual little box is made of a highly engineered thermoplastic, and it contains within it a very fancy little magnetic actuator, basically, as well as an optical barcode. So these are sort of all of the features that go into a semicide.
Tarun: For show and tell, what I brought with you is a little Petri dish. So essentially, what we give end users are Petri dishes that have SemaCyte embedded in them. I'm not sure if you can see the little pattern there.
Tarun: Yeah, that little shiny pattern is basically an array of 50,000 SemaCytes that have been micropatterned onto the bottom of that Petri dish. So if you imagine that surface has just been broken up into a bunch of little tiles, each tile is a SemaCyte. And for when an end user wants to actually run their culturing workflows, basically, or run a cell assay, they take their cell suspension, simply seat it onto the SemaCyte.
Tarun: The cells drop on. Once they sort of hit the SemaCyte, they fall in and attach. Once they're attached, you just gently agitate the dish, and it releases the SemaCyte into suspension, because the SemaCyte are attached to the dish with a smart glue or a smart release polymer, basically.
Tarun: And at this stage, what you have is you basically have a suspension of little carriers for cells, or little flying carpets with cells attached. And the cells are in their happy adherent morphology. You haven't used any harsh treatments to get them off the surface, because they've taken the surface with them.
Tarun: And they can now basically go directly into something like a drug library for an assay. Or if you're interested in making large batches of these cells, what you can do is you can actually take that cell suspension and freeze it down in cryovials, which is typically how cells are stored in industry. So now what you have is basically cells adhered to a surface, frozen in a vial, that the next time you want to run the same experiment, you just pop over to the freezer, grab them, and you can go, because you don't have to wait for them to recover and reattach.
Carli: What kind of cell types or application could benefit most from this platform? Just considering that there's different cells that require different conditions. And I'm wondering about those cell types and what applications could benefit more.
Tarun: I mean, in terms of applications, we're really focused on, I guess, the end-to-end, in vitro discovery cascade, I would say. So we look at everything from target ID, all the way to optimizing leads. Although I'd say our sweet spot in terms of the way people run assays is usually screening to lead optimization.
Tarun: In terms of the types of cells that could work with the platform, it's really built to work with, of course, specifically adherent cells. So suspension cells or blood-based cells, not really our focus. It's really focused on adherent cells.
Tarun: So that's most typically the things you would think of are maybe immortalized cell lines from a variety of different indications. People are generally very familiar with cancer cell lines because a lot of research work gets done on them. But also I think more and more in this day and age, we're seeing more complex cells being used.
Tarun: So adherent cells that are basically derived directly from patient samples, perhaps, as well as things like IPS-derived stem cells or sort of cells that are derived from IPSCs, basically. And I think there's a lot of value added using a system like ours with some of these more complex scarce cell types, because inherently, SemaCytes make a lot of those screening processes more efficient, and it can also miniaturize those assays fundamentally.
Carli: That sounds magnificent. And I couldn't help but start thinking also about other applications and impacts that I've read a little bit about the SemaCytes, more specifically, its multiplexing capacity. And I was wondering if you can describe what that would enable for researchers.
Tarun: Yeah, absolutely, Carli. I think the multiplexing sort of capacity or cell multiplexing as a concept is what we think of as probably the most valuable and most interesting part of the SemaCyte platform. And really, I think we're trying to address what we saw as a pretty fundamental limitation of wellplate-based workflows, right? So microwells in which your drugs are contained for a drug library, for example, when you're doing a screening experiment. You can typically only add one cell type per well, because it's pretty hard to tell apart the identity of cells under a microscope.
Tarun: But often, you have workflows where researchers are looking at screening panels of cells, tens, in some cases, up to hundreds of different types of cells for essentially the same drug library. And that means they've got to do this in series for every single type of cell. That can be, I mean, A, just painful, but B, it takes a lot of time and it costs a lot, both in terms of reagent, but also in terms of the sort of personnel time spent on it.
Tarun: All SemaCytes within one Petri dish have the same barcode, but you can have multiple different Petri dishes with SemaCytes containing different barcodes. So if you had a panel of cells that you want to screen against a drug library, for example, you would take cell type 1 into Petri dish 1 containing barcode 1, cell type 2 into Petri dish 2, so on and so forth. Once the cells have attached, you just release them all into suspension and you pool all of those suspensions together.
Tarun: What you now have is basically a mixed cell population in liquid, but you can uniquely tell the identity of the cell on every single SemaCyte just by looking at the barcode that that SemaCyte contains. And that's basically a barcode that you can look at in a bright field image of an optical microscope. Yeah, so now what you have is basically this pooled cell population and depending on, I guess, the sensitivity of the specific assay you're running, we can look at up to 8 to 10 different cell types in the single well of a 384 plate at the same time. So you've now condensed your entire set of panel and dropped it all into one well simultaneously.
Carli: This is such a wonderful technology and I cannot help but think also about the folks who make it possible because we always see all these amazing technologies and you really are in awe with them because they're allowing us to really move the needle forward. But I'm really also interested in the humans that make that possible. So I was wondering, you know, developing something like this cannot be easy, especially with all the nuances and all the applications that it potentially has. So I'm wondering what were some of the toughest challenges that you you and your team faced when you were getting SEMASites off the ground?
Tarun: I think certainly in the early days of building Semarion and building the SemaCyte technology, what we were doing is we were borrowing all of these advanced materials and fabrication methods from the semiconductor industry, right? And we were trying to deploy them in the cell biology applications. So all of a sudden we had to really validate and double check and make sure that any, say, variations in our manufacturing processes or design changes that we were implementing to make our product seamlessly integrate to end users was not affecting our biological outputs in any way because we're trying to marry a system of materials that cells typically haven't been used together with, essentially.
Tarun: And cells can be finicky little things and tend to be sensitive to the environments around them. So a lot of work and a lot of the challenges for us were really in trying to understand exactly how we could build this platform, a, to be deployed seamlessly into end users workflows, and b, to give them the biological outputs and endpoints that they were used to seeing, but significantly more efficiently.
Carli: I think that that challenge perfectly exemplifies how Semarion is such a great example of physics meets biology as well. And I was wondering, how did your team's interdisciplinary background shape this technology? I have already some ideas, but I would love to hear from you.
Tarun: I mean, it's absolutely fundamental to it. I think across our team we have people who identify as scientists, physicists, biologists, engineers. So it's basically people speaking a whole number of different scientific languages, right? And that makes, I think, for really interesting discussions and really interesting approaches to problem solving. So it means that we can sit in a room and you get scientific perspectives on the exact same topic from a whole bunch of different angles. And you really get to sort of explore that journey together.
Tarun: So it's been a really interesting and rewarding, I guess, experience building this common knowledge and sort of foundational understanding, and then being able to have all the different insights slot into that. And I think overall, that means that we're able to tackle problems in a much more dynamic and creative way than we would have been able to, were we not such a mixed group of scientists, basically.
Carli: Yeah, it sounds like it definitely would be. And not only for the scientific community, but also for all the scientists that partake in this. And going back to the interdisciplinary nature of Semarion, this highlights even more how much of a robust technology it is. And I was also pondering, you know, as I am talking with the CTO and co-founder of Semarion, I was wondering if there was any, what was the biggest learning curve for you personally, in taking Semarion from this idea that is incredibly groundbreaking. And if we would have even mentioned it a few years ago, I can hear already people saying, you know, that sounds like a great idea. It would be amazing if we could materialize it. And you folks actually did that. And I'm wondering, what was that learning curve for you?
Tarun: I think there's maybe, there's two points I'd like to touch on here. I think the first one is from the perspective of, I guess, being a scientist transitioning into turning your technology into a product, right? Scientists, I think, tend to take a science-first or maybe even a technology-first approach to their work. And what I had to mentally transition into was taking a product and application-centric approach to our work.
Tarun: And that meant we really had to, we had the proof of concept built, but in the early days, we had to do the legwork and go out there and speak to end users and pharma companies and biotech companies and really, really deeply understand what a lot of the challenges were that they were working with. And then how we would adapt the technology to address those challenges now that we knew that it could actually do what we needed it to do. So taking this sort of, yeah, this product and applications-first approach and making sure that we gave the end users what they needed, as opposed to just being technologists who could geek out on inevitably and infinitely optimizing and building their technology.
Tarun: There was a balance to be struck there, but yeah, changing it into the product-centric approach was a big learning curve for me. And I think the other part was what we touched on a little bit earlier, is when you have this diverse team of people approaching deep technical problems from a variety of different perspectives, getting them all to speak the same language and pull in the same direction is honestly, it's a really interesting but super rewarding sort of experience to grow through. And I think just going through that has led all of our team to grow a lot and it's been a really enjoyable and rewarding process.
Carli: Absolutely. And I cannot help but start thinking about what is ahead for you folks, the future of SemaCytes and the future of Semarion. And I'm wondering, where do you see then the SemaCyte cell multiplexing platform evolving in the new few years? Are there any new features or expansions that you folks are working on? It sounds like with such an interdisciplinary team, you folks are never short of ideas. So I'm wondering what has come up, if you can share.
Tarun: Yeah, ideas is certainly one thing we're never short of that I can attest to. But this is where I guess, refer to my previous answer, taking a product and application-centric approach really, really does matter.
Tarun: And so I think something that we're really excited about in the next couple of years is expanding into some of these more complex cell types and more complex assay types as well. So I think something that we've seen a lot of interest in the end user community for is things like being able to work with patient-derived cell material. Patient-derived cell material is scarce and it is hard to screen.
Tarun: And so if you can have a technology where you can do something like say, combine cell material from multiple different patients into one experimental condition, you can miniaturize and multiplex your assay and increase the breadth and depth of data that you can get from it. And something like that in the area of something like biomarker identification is an area that we're pretty interested in. Something else that we've seen a lot of interest in is in the area of neuronal cell cultures.
Tarun: So we've had a lot of people talk to us about the challenges associated with working with neurons as a cell type, but in general, the complex co-cultures that are needed to really be able to get a good modeling of disease-relevant phenotypes in a dish. And that usually means that you've got to do something like combine neurons with astrocytes, with microglia, and the ratio of those actually matters as well. And so these complex cell co-cultures are, I think, an area in which SemaCyte multiplexing could actually be pretty impactful in the future.
Carli: Absolutely. And for folks who are curious about learning more about the SemaCyte platform and specifically how they can address these bottlenecks that I'm sure many folks are experiencing in their labs, especially with applications like multiplexing, I'm wondering where should they go to get in contact with Semarion?
Tarun: Yeah, I mean, they can definitely drop by our website. We have a bunch of resources and application notes on there. You can also follow our LinkedIn for more updates from us. If people are based in Europe or the UK and they're going to be at the ELRIG Drug Discovery Conference in October, we'll be there. Come find us.We'll also be at SLAS in Boston in January. So yeah, do come find us there as well if you're interested in saying hi.
Carli: Yes, absolutely. And finally, to wrap up, I'm curious if you have any piece of advice that you'd shared with scientists or even entrepreneurs like yourself who want to bring new technologies into this world. You already have shared a lot of your process, but I'm wondering if there's one main piece of advice you would give our listeners.
Tarun: There's probably a lot of pieces of advice I could give about starting a technology company. I'll try to boil it down to one. The first thing I'll say is if that's something that you're interested in, it takes perseverance, but it is incredibly satisfying and rewarding to see the science that you've built go out into the hands of other people and being used with real impact. So as a scientist, if that's something that drives you, then I definitely encourage you to look at entrepreneurship as a potential route towards that, I guess.
Tarun: In terms of advice, the one thing I would say is in a small company where you have a foundation in sort of deep tech or deep science, there's often a lot of uncertainty. There's things like funding uncertainty. There's things like technical uncertainty. There's things like customer adoption uncertainty. So you kind of have to get really, really comfortable with uncertainty. You've got to get used to making decisions on limited information and not let yourself get stuck in a quagmire trying to find the perfect answer.
Carli: Absolutely. And I think that that would apply to so many folks. We should all be listening, even if we're not doing like actively science on the bench. That is something that we should all definitely take with us. And that pretty much wraps up our time together.
Thank you so much, Tarun. It's been incredibly inspiring to see and hear more about how Semarion is really pushing the boundary of what's possible in cell biology. And it's incredibly inspiring in so many different ways. I personally cannot wait to see how the SemaCytes are going to keep evolving. I am especially interested in those applications like multiplexing. So I'm definitely going to keep an eye out there. And I would definitely encourage all of our listeners to also do the same and continue seeing how the SemaCytes and Semarion are going to continue transforming research and discovery.
Tarun: Brilliant. Thank you very much, Carli. Cheers for having me. This has been a lot of fun. It's been great discussing Semarion with you and our SemaCyte technology.
Carli: And that was it for today's episode. That was a truly inspiring look at how smart materials are transforming cell-based research. If you'd like to learn more about Semarion and their work, check out the link to their website in the description box below. And if you enjoyed this conversation, don't forget to subscribe to Science In Real Time, share it with a friend or a colleague, and leave us a review or a comment.It really helps others discover the show.
Carli: Thanks for tuning in and we'll catch you next time on Science In Real Time.