Romana Schirhagl, co-founder, and Deepak Veeregowda, CEO of QT Sense are interviewed by Yuval Boger. QT Sense develops quantum sensing technology using NV center sensors in nanodiamonds for biomedical applications. Romana explains how their technology measures magnetic noise from free radicals inside cells, indicating cellular stress, similar to a small-scale MRI. Deepak discusses the company’s product, Quantum Nuova, which is available for research and diagnostic purposes, particularly in cancer and infectious disease detection. QT Sense describes their technology as having subcellular resolution and nanomolar sensitivity, sees a key advantage in applying NV sensors in living systems where the sensors move and rotate, and aim to impact millions of patients by 2030.
Transcript
Yuval Boger: Hello, Romana. Hello, Deepak. Thank you for joining me today.
Deepak Veeregowda: Good afternoon. Thanks, Yuval. It’s nice to be here.
Yuval: So, Romana, who are you and what do you do?
Romana Schirhagl: My name is Romana Schirhagl and I’m a professor at the University Medical Center in Groningen and also founder of QT Sense, which is a startup from my research group. And basically what we do there is that we have developed quantum sensing for biomedical applications. So for everything in living cells, in tissues, in patient samples. And what the company is doing is to make that into products that we can bring to the market, bring in the clinic, to make it small, user friendly, and the product.
Yuval: And Deepak, who are you and what do you do?
Deepak: So, yeah, this is Deepak and my background is in engineering and, and science, specifically in mechanical engineering. And then I was trained to apply this knowledge in biomedical science. So I spent almost 10, 15 years doing this. As well, in the past couple of years, I worked extensively on entrepreneurship and with this background, I co founded the company with Romana and I’m currently the CEO of the company, aiming at the growth and strategy for the business.
Yuval:I believe you’re using NV vacancy or NV center sensors, is that correct? Could you explain for the audience how NV sensors work?
Romana:Yes. So basically what we measure is similar to a clinical MRI, but on a much, much smaller scale. While clinical MRI uses giganticfield gradient tubes and coils for sensors, we use this tiny point defect in the diamond. We do our measurements by shining a laser at the defect. The laser makes the diamonds bright, and then we time how long it remains bright. That time is shortened in the presence of radicals or specific chemicals in the surrounding region. In our case, in the cell, those are free radicals. And the free radicals are an indicator that cells are under stress.
For example, if we treat cells with a drug, a cancer drug, the cancer drug is poisonous, they are stressed, which creates a lot of radicals, then this time that the NV center takes to go from bright to dark is shortened. And then we measure this time and this gives us an indication for the amount of magnetic signal that we have in that specific position. And since this sensor is very small and very local, we have very high spatial resolution and sensitivity. So we basically see everything that is within some nanometers from these small particles.
Yuval:So just to connect the dots for me, you mentioned radicals and then also you mentioned magnetic field. So how are they related?
Romana:So we measure magnetic noise. So a magnetic field is what you would have with a magnet, like your refrigerator magnet or something like that. We don’t measure magnetic field in that way, but we measure very tiny magnets that are flipping around. And this flipping around is done by the radicals. So we basically measure these very small flipping magnetic fields from the radicals in the surrounding region.
Yuval:You mentioned that you look at cells. So how close does the sensor need to be to the cells and how does it get there?
Romana:We use nano diamonds and we actually bring them inside the cells. So they are very small and the cells engulf them. So cells, almost all mammalian cells, more or less eat particles if they are a specific size. To some extent, they take them up and then they are inside the cells.
Yuval:So you essentially have sort of diamond dust, so to speak, that gets into the cells. Then you shine laser light on the cells and then you wait to see how long before the dust fluoresces. Is that about right?
Romana:Yeah, so. So it fluoresces and we make it bright and then we see how long it takes to get to the dark state.
Deepak:We shine the laser on the nano diamonds. So our target is the nano diamonds. So we basically excite those nano diamonds and that’s the fluorescence we monitor.
Yuval:So how does that work? Would one take a sample like a biopsy from a patient in the future, or is it done while the patient is there? How does it work clinically?
Romana:Yeah, so we have a few different applications, but how it usually goes is that we get samples from the clinic. Usually we work with rest material. So for instance, you can take a blood sample and then we put our diamonds in. So the patients gives the blood and then we take the sample and then we do our measurement. So it’s like an ex vivo measurement. So it’s not in the living patient, but in rest material. So when they do other diagnostics, they also usually take blood or as you mentioned, biopsies.
We can also work with tissues. Yeah, so. So they take the sample from the patient and then we get the rest material and then we do our trials with those.
Deepak:So the aim is to have some sort of an in vitro model that can capture some of the mechanisms in the body using the patient materials, as Romana explained. Yeah, so that’s, that’s clinically where we think we can add more value.
Yuval:And Deepak, NV sensors have been around for a while to do different things. How is your technology different than existing NV sensors?
Deepak:I’m not in depth with NV center nano diamonds. I think Romana can give some history about it, but some of the knowledge that I have gained in the past couple of months is that it’s not a mature technology yet. There has been a lot of work going on in this domain. Single NV centers are there, more stable, and have their own applications. But when you look at multiple NV centers, especially at nanoscale – nano diamond, there are more complexities associated with it and we are able to decipher that and apply it into a more complex biological systems. So about to be mature technology into a more complex biological systems is where we are applying. I think Romana, I think she can add a bit about the history of NV centers on this.
Romana:Technically, I would say the most striking difference is most people use bulk diamond and in a very clean environment. And what we are doing is using small particles that are in liquid in living samples and they are moving and turning and we have to track them. So most other people in the field don’t have to track, they just have to have a macroscopic diamond and then the NV centers are there and then they work with this. There’s different technology that people use. But for us, what is really the main difference is that it’s in a living system, swimming around, rotating.
Yuval:And Deepak, I understand you recently raised some money from an investor. Could you tell me about that please?
Deepak:Yeah, so we raised in equity and non dilutive as a team largely when you talk about the non dilutive, we have around 5.5 million at the moment. It’s consortium money all aimed at improving our product. So at QTSense we have transformed this technology into a product. The platform is Quantum Nuova. And this Quantum Nuova platform is better made fit to its pharma and academic research as well as for clinical research. So there’s this 5.5 million which would come across, it’s going to empower our Quantum Nuova discovery platform that’s going to aim at cancer research especially to add more value in medical oncology. And we also have the other half a million we have raised through equity. And that’s one of them is QDNL (QDNL Participations), that’s the VC firm in Amsterdam led by Tan Kris and others. We also have a business angel bringing in some money as well.
Yuval:Is the technology applicable to specific types of cells or specific types of materials? Or do you think it’s widely applicable in the biological sense?
Romana:Well, I would say it’s very versatile. So my research group has also looked at very many different applications. So we have looked at basically the whole zoo that you might want. So all kinds of patient samples, yeast cells, worms, cancer cells, lung cells. Yeah. So it’s quite versatile. There are some small adaptations depending on which exact application it is. But in principle, I would say the technology is very versatile.
Yuval:How were you able to validate it, to convince people that the results are real?
Romana:Yeah, this is a complicated question. Yeah. I mean, there are some things that you can do, for instance, if you have some expectations about what the biology should do, so you have some hypothesis, or you have, in biology, for example, there are these inhibitors. So you basically shut off a certain process or you turn on a certain process, and then you can see whether it actually does what you expect it to do. So that I would say is one thing. You can also make radicals in a somewhat controlled fashion in a tube and then measure it.
I’m not calling it calibration, but you can estimate what concentration you get. So if you make more of these radicals, you should also have a stronger signal so that you can do as well. The difficulties there lie in that our signal is very local. So this is something like other technologies that don’t have that resolution. So sometimes if we compare with standard techniques, they measure different molecules on a different length scale, on a different time scale, and then often it’s similar, but not necessarily always either, because we are so local. So sometimes this is a bit difficult to really have hard proof, like if you have a greater resolution than what was there before. We have a lot of data in a lot of cases that really make sense taken together. But if you have greater resolution, it depends on how critical people are. I think there are some people that would probably still say, are you really sure that’s real?
Deepak:If I may add to that, Yuval. If the question is in terms of applications, you’re trying to create value. Romana and her group have worked extensively on drug efficacy.
There is a publication on Piroxicam. It’s. It’s a drug consumed to reduce oxidative stress in cases of osteoarthritis or rheumatoid arthritic. There is clinical evidence that this drug has been prescribed for both the cases, but only in one case it works better. They picked up this topic and using the technology, the quantum sensing in these cells and the fluid, they were able to explain the mechanism of action of this drug. And that confirms existing clinical evidence why this drug works in one particular case far better than the other case between rheumatoid and arthritic arthritis. So basically we add value there. So the second element is the blood basics of the fundamentals of its technology itself. What we do is detect free radicals and also it is responsive to change in the concentration of the free radicals. It’s not only just detecting whether you have it or not inside the cell or around the cell, it’s also the concentration of it. There are also some existing techniques that give you some sort of an estimation as Romana said. For example, there are fluorescent dyes that you use to get if you have these free radicals related to oxidative stress or not, if you have what is a concentration change. And these dyes do show some changes and they have their own disadvantages. They can’t be real time, they’re not sequential, and so on and so forth. So if based on that information as well, we could see that our technique complements it or even gives better information. So all I want to say is in terms of if the technology works or not, to get that confirmation, there are two ways. One, whatever is the mechanism of action that is available in pharma, you know, we can back it up with our technology. There’s certain evidence towards that. And with respect to existing techniques, comparative techniques, we complement and supplement information.
Romana:Also, we have some data from applying that clinical trial. And that’s also very strong evidence. And if you can link your readout to some data from a blinded study. If you do a blinded study, you get samples, but you don’t know at the time what they are. So, in the end, after you have collected all your data for a year, then you unblind the study and then you find out. So you give your data and they give you the database of what the patients were, and then you basically combine the two. So at the time of measurement, nobody knows what actually what you’re measuring. So, so that is also, I think, a very, very powerful data and very cool moment. If you see like that you get something, then it really makes sense.
And still that that stands this rigorous test and still, still looks what you would expect if things work the way you think.
Yuval:You mentioned that you can measure the concentration of radicals. Can you also use this technology to identify which radical exists?
Romana:Not at this point. There are ways to do it. Like in principle, NV centers can measure anything that any magnetic resonance techniques can measure. So MRI, NMR, ESR. So there’s a bunch of methods available in principle, and they all have an optical equivalent. But the way we do it right now, we don’t do it. We do the very simplest pulsing sequence.
So we basically get the sum of what is there. So it’s equivalent to what you would do in a clinical MRI. So,the signal we get is like that. But with the clinical MRI, you also only get these gray images. You get a specific, like a concentration. But you could also do NMR spectroscopy, for instance. Then you get more, more chemical information or electron spin resonance.
Then you would get more chemical information. But we are not doing it at the moment. It’s more complicated.
Yuval:In your estimation, how long before this technology is available on the market beyond the research that you’re doing?
Deepak:It has taken around 10 to 15 years of work from Romana and her group to pick this technology, polish this technology and find the right applications for it. They have found a way to see how they could explain biological activity at subcellular level, at the cellular level, even in tissues and fluid samples. So the application is there. And what we have done at QTSense is we took this technology, which is in an advanced state compared to any other group I would say, from Romana’s group. And we have already productized it.
So one can buy this device from QTSense at the moment. So our markets are in two phases, in two segments. One market segment is in academic and pharma labs. If they want to understand the mechanism of action, they want to do some fundamental studies. If they want to develop a better in vitro model for their ADCs, the antibody drug conjugate interactions. Anything that they want to do at Phase 0 level. At the R&D level, we have a product segment called uantum Nuova discovery And we also have the second one that is uantum Nuova Diagnostics.
We are working extensively in terms of infectious disease. How can this technology solve some of these critical issues? Within the infectious disease, it could be early detection, it could be monitoring of those infections, especially in the sepsis area. So Quantum Nuova Diagnostics is the second product. So our technology has already been converted into these two products that one could buy off of our shelves.
Yuval:Give me a sense of numbers please, in terms of resolution or sensitivity or maybe and how this compares to existing methods.
Romana:So if you look at the sensitivity, we are somewhere in the nanomolar range. And if you look at spatial resolution. In principle, sensitivity decreases with distance to the power of six. So the further you are away, it goes very quickly that you don’t see anything if it’s too far away. It’s roughly a few tens of nanometers until you cannot see anything at all anymore. But basically you have this dependency with R to the sixth or the further away. So it’s not completely zero if you are further away, but it just goes very rapidly towards zero. And how does this compare to other methods? Well, in addition to that, we are looking at the particle and we have some kind of precision to where this particle is.
So for example, if we attach this particle to a mitochondrion, then we know they are together and then we know everything we see is really at this site. If we don’t attach it to something specific and it just swims around, then we are limited by the resolution of how precisely we can tell where the sensor is. So if we know it is some tens of nanometers from the sensor and then we have a bit less resolution depending on the movement as to determine where the sensor is. Exactly. So if we have some trick to determine the position, then we have higher precision on the location.
Deepak:Largely subcellular resolution and you know, a few nanomolars of concentration, we should be able to pick it up and draw some insights out of it.
Romana:In mitochondria we have a certain response and in cytosol we have a different response. Within the substructures of the cell, we can say what is happening where.
Yuval:Funding aside, in the past year, what was the most exciting moment that happened in your work?
Deepak:Romana has more to say, I guess. Romana, you want to start and then I will follow you after that.
Romana:My most exciting moment . One thing that we are seeing now. We are running this trial on sepsis detection and we have some cases where we see that our detection method seems to be better than what the clinicians can do. And you know, this is something that really motivates even more than the funding to see like hey, we can really, I mean this would be people in the future we could save. And if, if this is something we can really do. I mean this is like, yeah, this is like a huge motivation and super exciting for me if you, if something that we made can actually save somebody’s brother, mother, kid, whatever. I mean this is very, very exciting. So if we manage to do that and it seems now that we are going in that direction that it’s really starting to be useful in the clinic, then this is I think by far my most exciting thing I could say.
Deepak:Adding to that, Yuval, that we have an impact 2030 vision. So we think with the work that we are doing in terms of the excitement Romana just shared, we can touch more than a million patients, you know, by 2030. Especially our Quantum Nuova Diagnostics is being aimed at that level so that we have more to offer to the existing healthcare. So for me to your question about excitement, there are two things. One of the things I really got excited about is how a diverse team like ours worked so well. We have guys from optical engineering, we have guys from applications who come from totally different science backgrounds, they are more into spatial biology. And then you have guys from optics, a guy from software engineering who learned everything from scratch up. So how they bring all this knowledge and then they create this wonderful product. We were able to ship our first product, even though it’s still a prototype, to our first customer at the University Medical Center in Groningen.
That was a great moment where everything came together, all the work people put into it, to have that product in front of you, although it’s incomplete, but functionally it does everything. And that was good. Even better was when this device was installed at the University Medical Center. There were some of those who were earlier users of a similar device and they would come over and see the interface that we have built in with the device and they said wow, it’s so easy to use this device now. I could make a few clicks and I could get those kind of results. So that kind of excites and a cherry on the top is really that free radical is such an important biomarker in the medical biology field. And many of them have not even thought about the value you can get out of mapping it at subcellular resolution. And when we are talking, when we are knocking on doors and say, hey, is free-radical real time non-destructive to cell something that excites you guys? And I see that just their eyes go blink, all the stars. Can you do this actually? And when these guys come back with that feedback that yeah, well this is a wonderful technique they should have.
It can create more value for us. So the demand that we are able to create with this wonderful product like this is something that excites. Excites me particularly.
Yuval:Yeah. And last hypothetical question. If you could have dinner with one of the diagnostics or biology greats dead or alive, who would that person be?
Deepak:So if you could rephrase the question. So you’re talking about the experts in diagnostics or.
Yuval:It’s up to you. You’re getting a ticket to a dinner and you can invite whoever you want. Who would you invite to that dinner?
Deepak:Interesting question. I mean we’re looking at, looking at where quantum sensing should go, where we look at what we could aim at in the market and combination of technology and business-wise specifically in diagnostics. There are a couple of them and I think one of them I would really love to dine with are the guys who have developed a sepsis diagnostic tool. They’re a startup company, now 10 years old right, and they’re starting to have an impact. t’s a company in California working on sepsis diagnostics. So I would really like to have dinner with them. What it took them. They’re also saving lives, so sharing that experience would be great. That’s what I would aim at.
Yuval:And Romana?
Romana:Oh, I don’t know. I’m not, I, I don’t really have that. I don’t really think I have a wish to go to dinner with someone specific. I mean maybe you know, people from, from a big pharma company. I think there’s also a lot of very interesting people. So picking one is very difficult. I mean nowadays I really love to sit down with successful entrepreneurs and just quiz them forever.
Deepak:But if I may add on her behalf, I have to say that I think Romana would really love to go to dinner with one of those patients whose life has been saved because of our technology, because of our device so that you could diagnose the sepsis earlier. It saved them. I think she’s that kind of woman. She would go for dinner with those guys, happily sharing lunch or dinner with them.
Romana:They don’t have to go to dinner with me. As long as they are alive, I’m happy.
Deepak:Right.
Yuval:Very good. So, Deepak, Romana, thank you so much for joining me today.
Deepak:Thanks a lot, Yuval. Thanks for having us here. Appreciate that.