New Matter: Inside the Minds of SLAS Scientists

Unlocking the Power of Hydrogel Beads in BLINK X PCR Diagnostics | New Product Award Winner with Hartmut Bocker, Ph.D.

June 19, 2023 Hartmut Bocker, Ph.D. (BLINK) Episode 153
New Matter: Inside the Minds of SLAS Scientists
Unlocking the Power of Hydrogel Beads in BLINK X PCR Diagnostics | New Product Award Winner with Hartmut Bocker, Ph.D.
Show Notes Transcript Chapter Markers

Our guest for this episode is BLINK Product Developer Hartmut Bocker, Ph.D., to talk to us about the BLINK X device that won the New Product Award at SLAS2023!  

Listen in to learn how BLINK X's lightning-fast cycling times and unique color-coded bead system are making cross-interference free multiplexing a reality. As we discuss the future of the BLINK X system, you'll learn about the development of a small device for consumer use and a high throughput platform for researchers.

Key Learning Points:

  • What makes the BLINK X new and innovative 
  • The inspiration behind the BLINK X device and its use cases
  • How and why BLINK uses hydrogel beads for the BLINK X
  • The advantages of using the speed system over traditional microfluidic PCR

Learn more about the BLINK X  by visiting: https://www.blink-dx.com/blinkx

Full transcript available on Buzzsprout.

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Hannah Rosen:

Hello everyone and welcome to New Matter, the SLAS podcast, where we interview life science luminaries. I'm your host, Hannah Rosen, and today we are joined by Hartmut Bocker, product developer at Blink. Blink won the SLAS 2023 New Product Award for their Blink X system. Welcome, Hartmut.

Hartmut Bocker:

Hi, Hannah, thanks for having me.

Hannah Rosen:

Our pleasure. So to start us off today, Hartmut, can you just tell us a little bit about your professional background and your expertise?

Hartmut Bocker:

Sure, my name is Hartmut Bocker and I've been doing actually the basic academia work for a career. So I did study biochemistry and also kept working on these molecular and biology fields, specialized in human genetics, especially in diagnosing inherited diseases and understanding the function there. From that I wanted to broaden my view again and went on to Blink, because here I really love to learn from all these different fields and especially have different engineering, software and laboratory intermingling. It's a fruitful collaboration for me to learn all these different areas together. That's my background and my expertise is actually bringing especially those fields together and try to keep them together and to as in each field there are lots of specialists, I just try to sometimes to translate the needs of the other field. All in this we can shape cool things together and that's what I'm drawing.

Hannah Rosen:

Fantastic. So how do you guys at Blink feel about winning the SLAS New Product Award?

Hartmut Bocker:

So actually we've been pretty humbled, we've been very surprised and honored because we didn't really had it on the map. I mean the SLAS is, I mean, it's a focus on screening and also a lab automation and, to be honest, our platform that we introduced over there is neither for real screening or not very automatized. So that's why it really speaks to for the SLAS community that it can see the actual impact of the technology which is underlying the Blink X is just the beginning, but the beads which are needed for this while working on this, these are the actual key feature. So that's why we've been really surprised and, yeah, it really shows that the SLAS community sees the perspectives of things.

Hannah Rosen:

Yeah Well, I definitely am excited to get into exactly what the Blink X does in a minute, but before we go into that, I just want to know what was Blink's overall experience at SLAS 2023? Was this your first time at an SLAS conference?

Hartmut Bocker:

Yes, indeed it was. I like the quality of the discussions we had. So we really had some interesting talks, especially about screening, of course, throughput and, in general, automation. It's just fantastic to see all these robots rotating and pipetting or handling stuff, and it's amazing, yeah, and it's great to be part of this crew, part of this community, as we also did learn quite a lot of these fields, but we additionally also discovered new ways or interesting use cases which we never had on the map, and this is very at the end. It was very eye-widening or like, yeah, broadening our knowledge of not just the field but also the applications, and so far, it was a fantastic experience, also during the whole fair itself, but also the discussions besides it. Yeah, it was great, and I think I really like the atmosphere because it's so fruitful or like empowering, so that's why I think it won't be our last SLAS For sure.

Hannah Rosen:

Wonderful. We love to hear that. As award winners, we love to have everybody back at our SLAS events, but especially our award winners. So let's get into the product itself. So can you just describe for us a little bit what is the Blink X system?

Hartmut Bocker:

Yeah, the Blink X is basically a PCR system which is based on tiny beads. So these tiny beads are picoliter-sized and we can use them already for sample prep. So beads are just thrown into a lysed sample. They catch and bind nucleic acids and as these beads are magnetic, we can simply retain them and the DNA is still stuck on these beads. So we can basically wash and load the PCR reagents on those and in the next step these beads are actually separated from each other. So we bring these aqueous beads, it's basically like a sponge, these beads. So we bring them into an oil, roughly shake them and then these beads individual from each other, separate from each other. With that we reach thousands of compartments where we can have independent reactions And the Blink X device is actually allowing at this to have a simple workflow, a simple handling, and it brings everything you need with it. And it's an R&D platform, so it's a laboratory device, so it still needs some, as I mentioned, manual handling, but it shows you the world of the beads and how to play around with them and it's actually working for generating or even transferring essays on this platform.

Hannah Rosen:

So what makes this Blink X system new and innovative?

Hartmut Bocker:

First of all, it's a really quick cycler. So we have these beads and we align them in the monodair, the XF sample in this monolayer, and with that we can really go quick, fast, So we can have cycling times of a few seconds, resulting in 10 minutes PCR for 45 cycles, including initial denaturation. We also have platforms around which can do the whole PCR in less than five minutes, And this is one of the key factors. And as we can really go quick. But more importantly, we can use these beads and apply color code to them. And this is a nice feature because you have not just one type of beads, you have certain types of beads, and with that you can code either samples, like patient A, or sample 1 has one color, next sample has another color, and you simply throw these beads together. At the end you can image them, you can scan them, and you can discriminate which bead belongs to which sample and what PCR results do they have. And with that you can. Actually it's this first system which can do truly cross-interference, free multiplexing by simply immobilizing primer probe sets to these beads. So you have your certain color beads. You immobilize primer probes on these beads, So, like, blue bead has HCV, green bead has EBV, so different types of targets. With that you can build huge panels and use this one panel to interrogate one sample for hundreds or plenty of targets. This is like a key feature because you can simply decode the beads later on and see which of the PCR has been just positive, but also to which extent they have been possible, because digital PCR results in absolute values, so in absolute concentrations. Yes, it's just answers so many questions you can interrogate your sample to. And it's also one of the first platforms, or maybe even the platform, allowing real-time PCR and melt curve analysis on compartments. So basically, as we have the beads and a monolayer and a camera on top, we can not just acquire an endpoint images, which is needed for digital PCR, but you can even take images out in each cycle, like for real-time, and analyze it. Or we can do even after the PCR melting process, again image by increasing temperatures and then analyze the melt dynamics of samples. And yes, it's just a fantastic tool and it's all about these beads, what it's working with.

Hannah Rosen:

Yeah, but it sounds like there's a lot of advantages to this system. First you mentioned the time, and then you mentioned all the ability to separate out the samples. So what is it about the beads that makes this PCR process so fast?

Hartmut Bocker:

It's actually as these beads are in a monolayer, the heat has to try to just It's pretty close to the heating source and cooling source. That's why heat has to travel only a short distance and with that we can really go quick. And as we know where the beads are, we can also model that we can not just hold temperatures but we shorted over swing temperatures, as we can predict already which temperature is right in the beats, their models for it. And this is something you can't do with bulk PCR or even with droplets in a larger tube, because then each of the compartments or just the volume switch at different temperatures and exposed to. This is one of the keys. And we also optimized course or system for good heat transfer. So our consumables we use are optimized for for heat transfer. They have a huge conductivity, so it's plastic, including lots of carbon and a graphite in there, and with that's not just the heat distribution is perfect, but also the heat transfer is pretty quick. That's the key for this one.

Hannah Rosen:

Wow, so you mentioned the you know the the speed of the PCR and then the ability to separate out your samples and run multiple assays. Are there any other advantages to using the speed system over traditional microfluidic PCR?

Hartmut Bocker:

Yeah, it's, it's pretty unconventional because you're not just use these beads for the analysis, but you can also use them already for the sample prep. So usually the sample prep is done in an additional step, right before the analysis actually happen. So it's, it's a workflow totally independent of the actual analysis, so usually done by spin columns or by trizol or other kinds of nucleic acid. And here you simply take your lysed sample so you can lyse sample either mechanically or chemically. And with that's the nucleic acids are available. You add a binding buffer to it and you add your beats to it and then it's basically the same chemistry as with silica matric columns, that the DNA or RNA is simply bound to the beats by sequence, unspecific interaction. So it's basically binds the backbone of the new click assets and with that you can really enrich new click assets to the beads. And when you process the beads further the nucleic acids still sticks to the bead. And then you simply add the loading rate. You load the PCR reagents in your reaction as the primar/probes might be already on the bead, and then you do the step into the oil to separate them and run the PCR. And this is, this is really key that we do not have to completely independent processes like sample prep and analysis, but we really keep it together and with that we have maximum sample utilization. And another cool thing about the beads is it's decoding, so we can introduce different codes to the beads, which are based, on one hand, on particles. So these are little fluorescent particles which are the color red and the beads and it's kind of a fingerprint of this bead. There are hundreds of beads with the same fingerprints, so they build a crew and we can, in theory, make more than 100 different codes for these beads In an example coding for different samples or coding for different targets when the beads are immobilized. This is also something completely new because once the beads are actually heated, as they are made of in hydro gel, they become liquid, but they have functionalization like a coating on the outside and this is the one that attracts or catches the nucleic acid. And as soon as the hydro gel is molten, this outer polymer is crosslinked and is contracting and thereby it's on one hand, pulling the nucleic acid into the reaction, into the what is now kind of drop it, and additionally it also traps the particles, so the particles which have been spread around. All these beads are then gathered and centralized to one subcompartment within the bead, and so basically all your coding particles are in one spot of the bead and the rest of the bead is still available for PCR, and with that you can easily have lots of different codes and still recognize the PCR signal in the beads, and this is something which does not exist in before. You can hear, it is really a nice system of beads and, yeah, I could tell you the hours of the nice parts of the beads.

Hannah Rosen:

Yeah, I mean, they sound really amazing and it's so funny because I feel like you're selling yourself a little short. You know, in the beginning you were talking about how you weren't really sure if it was, you know, automated enough for SLAS, but it sounds like you really cut out a lot of manual steps in the process by consolidating all these different parts of running an assay into essentially one system.

Hartmut Bocker:

Yes, exactly, we try to, and one thing we're still working on is, of course, the automatization. But as these beads also contain magnetic particles, it's actually an rather easy process to optimize them, the workflows, by simply using electromagnets, or I mean, you've seen them on the SLAS. There are lots of magnetic approaches, but still we haven't found the time yet because we've been busy on the other projects or like working on the beads or the X, yeah, or another platform.

Hannah Rosen:

Well, that's the exciting thing I think with this new product award is we get to see these products that already are, you know, innovative and revolutionary, and then there's still so much potential yet to come. So we get to see just kind of the start of this process and then we get to kind of just follow as the products become more efficient, improved and they can expand their applications out. I think that that's, in my opinion, one of the most exciting aspects of this new product award. So you know, you've gone on a lot about the advantages of these beads and it sounds like there are just tons. Are there any disadvantages to using this system?

Hartmut Bocker:

Yeah, of course it's still manual or includes some manual handling steps, but, as I mentioned, we're working on this. Second thing might be, as these beads are in and brought into an oil, this oil has an emulgator, so it's not a really drawback, it's just a thing where you have to take good care of that in your reaction mix. So your mix which you're using for the mastermixers, for doing the PCR, in this mix there might be some ingredients or reagents that are not easy transferable to our system, and I'm talking about detergents. So sometimes these mixes contain quite a lot of detergents, either from the enzymes or, for still a carryover, from the lysis. So where you open the samples you usually take some detergents to get the most of it. If there is a lot of detergents in the actual sample used together with the mastermix, then there might be that that it's incompatible to our system. Non-ionic detergents are much better and still there are things to replace them. So it's rather that your home brew reagent mix is maybe not working, but there are ways to compensate this. This is just one disadvantage I might think of. Through puts is still a point, I mean we have at the moment we have six wells, sounds little and when thinking of 96 well plates or even higher numbers, it is little, but it's not a real advantage because we are not limited by the amount of wells but rather by how many beads fit in there. So, as I mentioned, we can do this massive multiplexing you can still interrogate a sample for like tens or hundreds of targets only with these six wells, simply by putting differently coated beads into one well. But yeah, this is also another thing we're working on to increase throughputs, to have even more beads on another plate.

Hannah Rosen:

So are you looking to increase the number of wells, or are you just looking to increase the number of beads per well?

Hartmut Bocker:

Actually, we are thinking of reducing the number of wells, because in our system we're not depending on wells but rather on the pure number of beads. We have ideas, we have one big well and simply increase the surface of where beads are as they are in the monolayer. we can simply scale up the number of beads by increasing the surface area. By doing so, we don't need any wells anymore, because samples are anyway coated with a color code or, in case you do target, multiplexing the targets coated by their color code.

Hannah Rosen:

Wow. Do you foresee, do you think it's going to be difficult to convince researchers that eliminating the wells is going to increase the throughput? Because I feel like currently everybody thinks more wells, more samples, more throughput. Do you think that that's going to be an issue?

Hartmut Bocker:

We definitely see the resistance and it's only once you explain it they totally get it. So I mean, it's a complex system. It's not just that we have changed the workflow, but it's also the digital PCR which is also. It's more than 10 years now. We still have the impression that it's not fully understood by everyone. But additionally, these speeds and the ways of multiplexing as there are different ways of multiplexing are sometimes mind-blowing and overwhelming. So that's why we learned that this really needs good explanation to make this rather complex system I mean not complex to use but in the beginning maybe complex to understand what possibilities are available. We learned that we really have to take our time and explain how the system works and what possibilities result from this. And as we develop this Blink-X system, we really want to keep it open. So a thing is, we can't imagine of all the applications or all the things researchers or developers will do with it. So that's why we tried not to limit the possibilities, even though we can't imagine all of them. This resulted in a system which has a simple, wizard-like surface where you can have your workflow. But there's also another level, an expert level, where you can really dig yourself into software, change single parameters play around with blocks, and we tried to have it very graphic, so the software is also very graphic. Simply, you can take certain steps which the device is doing and put them in another place in a timeline and then the system can do different stuff, and this is something which we are aware of. This is sometimes overwhelming, but we already found that people which are really keen and interested and see the potential and they are playing in this expert level around. It's just great to see that this is also appreciated. As it's a research or developmental tool, we really wanted to have it open, but as we are also developing a diagnostic and in vitro diagnostic regulated device, this is then the total opposite, where everything is restricted so nothing can go wrong, and it's just fun to see these both different worlds.

Hannah Rosen:

Yeah, it seems like often there's that trade-off where you either have to narrow down the scope of what it can be used for and make it really simple and easy to use, or, if you want to keep it open, it maybe has a little bit more of a learning curve to it, so would you say that there's maybe a little bit of a steeper learning curve for the Blink X to learn how to use it?

Hartmut Bocker:

So I don't think that it's a learning curve for using it. So it's pretty straightforward. There might be a learning curve, but it's not very steep. It's a rather that it needs some time to understand the full potential it has because there are so many possibilities to it. So we do have collaboration partners and they have their device since a few months and they play around and out of the sudden they call you and say hey, I just realized I can also do this with that and this would be much easier, and I just didn't know about it And I just understood it. Right now. I wouldn't say it's a steep learning curve. It's just a learning curve which is not flattening very early.

Hannah Rosen:

Gosh, that's a good way of putting it. So what inspired you guys to pursue this whole bead system and create the Blink X?

Hartmut Bocker:

Yeah, so we were thinking of nanorectors or we were thinking of new ways of doing diagnostics and thought of little bodies that have everything they need for reaction. And, yeah, we've been playing around quite time. So Blink was actually founded eight years ago and it had not any founding idea. It was just the idea or the wish to do something with diagnostics again, because lots of people have been in this field already, and especially in devices or building devices for diagnostics and especially in rapid or point of care diagnostics. So what happened is all these people were just put together and then they've been given time and tools to play around And we followed different approaches. So we had certain ideas which we followed, which in the end, turned out to be like a nice story, but it didn't work out. And then at some point we just ended up with these beads. In the beginning they've been just hydrogel beads. Then we included the functionalization for catching nucleic acids and the incorporated all the particles for coding and, furthermore, also for magnetic handling. And it just grows step by step and there have been some path which were leading to different results, but with all these possibilities and all these tools necessary, we just created something and time by time system got more complex, yes, but sometimes it just needs this time to develop something new and not just kind of new. This is what happens in here, and, yeah, so it was just step by step in iteration and suddenly there was another idea. We followed up on it and then these beats have been getting better and better And at a certain time we actually wanted to show them to partners in industry or academia. We just sent them and then we realized, oh hey, they have nothing to handle those beads, they have nothing to analyze those beads. And with that we started thinking, because here we used customized devices for running the PCR, so we have really home-built PCR cyclers, and we also took commercial microscope and rework them so we can use them on our system. Even if we had supplied them or partners with it, it didn't work out because steps were still too peculiar And for this reason we just started to develop something where people can easily work with the beads, understand the potential, and that was where the idea of a small device with simple consumable was born, and this was basically the corner stone for the Blink X, and it took a year. Then we had some prototypes and then we already had all beta testers or the first devices until the beta testers and they were working on it, and with that we think we have found an easy and painless way to work with the beads and to get to know them. This was the first idea. It's basically just a tool to handle beads, to play around with these beads and to work with them. Then, step by step again it iterated, and as we have all these people, all these different peers in our rather small company, it's just wonderful to see how the software, development of hardware and also the lab people all play together to develop something. And had an idea to increase the functions even more of the Blink X, like the QRT, PCR we included, or a melting we included, which was not possible in the normal system, and all of this together led basically to this Blink X, to what it is now. It was a long journey, though, at least a long journey for the beads and a rather short but quite steep journey for the Blink X.

Hannah Rosen:

That's incredible to just hear the evolution of how you start with this broad idea and how it just keeps building and building, and building, and it's really, really cool. So you've alluded a little bit to your future plans with this product, but do you have anything specific that you're looking to accomplish in the next year with the Blink X system?

Hartmut Bocker:

Oh, yes, so the system I mentioned already, it has a QRT, pcr and melting. This is still on beta level, so we are we're developing even further, also together with our partners which are using it to understand their needs. So this will as these are pioneers, they say actually two sides of the medal. On one hand, they sometimes run into bugs or maybe sometimes trouble some time to get something starting, but on the other hand we can then help them and take very good care of them And with that they can be pioneers and even design the systems according to their needs And it turns out to be correct, fruitful collaboration with our partners And they can really understand the advantages of this early access program. So, especially in the QRT and melting, we're working on this. The PCR is pretty solid. But, talking about the beads, we also want to use another platform which is then a point of care device called BlinkOne. We also want to make a leap forward on the high throughput platform, which we haven't published yet.

Hannah Rosen:

Yeah, we'll call you back in a year and follow up. Perfect. So if there's any researchers out there who are listening and they're now interested in using the Blink X system, what would they need to know before they can get started?

Hartmut Bocker:

As we do everything in-house, also the production in-house, the access is still somewhat limited because we cannot fulfill the demand just out there for devices, but nevertheless, getting started is a thing you need to know. It's not an off-the-shelf product, I would say, or I mean the Blink X is, but the possibility is what to do with. It is far from being off-shelf because it comes with the beads and, depending on your needs, these beads are customized, so either for specific functions or the codes you exactly need, or even the primer/ probes directly bound so that the reagents that specify the PCR reaction, they can be already bound. So it's pretty customized then, and with that, users just need to know or interested researchers They still will be pioneers with the good and the bad things. And they should think often nice or in application with which really benefits from being digital on one hand, or, like this, multiplexing, and there are of course, plenty of essays or benefits for an assay. So at the end, interested people just should reach out to us and get in touch with us to learn more about it and to also understand at which points this Blink X system is now and all the other platforms and especially the beads. So I can just encourage people to just get in touch with us, and we are easy in communication and we also again want to have an open communication. So that's why we explain lots of things without being too secret about things.

Hannah Rosen:

Yeah, I think the biggest takeaway I'm getting from this is it's really it's all about the beads. It's really all about the beads.

Hartmut Bocker:

Indeed, and indeed, and the X is a platform to play around with those beads And once you have transferred an essay or developed an essay on this Blink X platform and then you can rather simply transfer an example to this point of care platform the Blink One I mentioned, because it has the same, the same system, same beads, it has a very similar optics, but it's fully integrated, automated, as a kind of point of care platform. And with that you can have your essays and basically, in lab quality without a lab. This is some approach researchers want to go, or partners in industry. Some of them only want to stick to research and work on the X for making progress or findings in their fields. But they are also quality control people around which are interested in it and work around with it. So lots of things I couldn't picture, lots of applications I wouldn't think of, but this is the fun part to learn a lot about the applications, about the different science.

Hannah Rosen:

Yeah, so exciting.

Hartmut Bocker:

Indeed.

Hannah Rosen:

Well, Hartmut, thank you so much for joining me today and telling me more about this system. I am just so excited I'm sure that you must just be really excited to see where this is going to go next, And I am too now. So I can't wait to be able to follow up with Blink and kind of see where these beads take you guys.

Hartmut Bocker:

Yeah, thank you, and indeed this is very interesting And I hope I could transfer some of my passion to the beads, because they're just wonderful.

Hannah Rosen:

Absolutely Well. we can't wait to see you guys at some more SLAS events so that we can continue to see all of the new applications that you discover for this product.

Introductions
Hartmut's Background
BLINK's Reaction to Winning the New Product Award
BLINK's SLAS2023 Experience
What is the BLINK X?
What Makes the BLINK X New and Innovative?
What Makes the Hydrogel Beads Fast?
Bead System Advantages Over Traditional Microfluidic PCR
Disadvantages of the Bead System
Learning How to Use the BLINK X Sytem
The Inspiration Behind the BLINK X
The Future Outlook for the BLINK X
What you Need to Know to use the BLINK X Sytem
Conclusion

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