Cool. Awesome. Thank you, James, for the introduction.

Yep. So my name is Chris. I’m a senior FAS over at Omega Bio-tek and I have the pleasure of introducing some pretty cool innovation in regards to optimizing high-volume preps on nucleic acid extractions. And actually, I have these two props with me and one of these is actually the kind of the conception of all this. This came from this plate which is pretty cool. It was extra tall. I’ll talk about it a little bit more in detail about it. I’ll leave it right here for now, but you can obviously check these out before and after.

So as a brief introduction and agenda to what we’re doing:

I’ll introduce to you about some green boxes. If they have not infiltrated the lab then hopefully they will in the future. We’ll talk about cfDNA just to kind of brief overview but kind of a little bit more detail about that only in the sense that this was kind of like the initial project that begetted the onset of exploring this high volume technology. And of course, being that once we have that kind of up and running and prove that proof of concept it’s time to expand that into another realm of nucleic acid replication. So we looked at plasmid as well, 50 and 100 mL preps. Last but not least I’ll have some conclusions where we can even expand this further. Some sprinkles on a Sunday I’ll mention maybe the possibility of doing high volume blood.

So first things first, our advantage as a company we like to pride ourselves on our products. We have some pretty good performance and kind of going into that equality and the value is pretty great too. But one of the things that I think sets us apart is that the team that I work with we provide exceptional support and through that process basically becomes a little bit more, kind of that small company feel but you still have the big company support of having a good product and label behind it.

Our typical kind of how to of how we approach things is through this four step process: we like to consult with the client first and see what they really need and we go from there to an evaluation process in which we are able to actually take in samples if they want run them on a theoretical system that they would actually run and then we can implement that same system so they can be pretty much almost guaranteed because we all know at the end of the day you still have to run your own due diligence when you get to the lab.

Last but not least we do provide customization in terms of reagents because when you get the box that you go through your runs you can customize it so that maybe you get huge jugs or you do one-per-day kind of deal, but that’s kind of the benefit of the customization.

So going into cell free DNA (cfDNA) I know Sarabeth had the pleasure at least kind of explaining this in further detail– I think that screen she had was a better slide than this admittedly so I will give her points on that. The thing is, with cfDNA, it’s a pretty good system now in terms of what you see in the market in terms of a biomarker and a tool to give you a snapshot of what’s going on in the body. So, the two biggest kind of systems that we see that in is in pregnancy and also in the oncology sphere. Right now, that’s a pretty big thing that’s going on. So, you know, the onset of this plate was actually as a result of what I’ll get into in a second, which is why cfDNA is so hard to kind of get. And because in its nature it is a small fragment, in some people in some cases you know I mentioned 170 to 180 base pairs (bp), but it can actually be smaller than that as well.

We want to maximize that amount that we’re getting in the beginning. Most typically when I first was installing systems out there and people were asking me about hey you guys have a cfDNA kit they’re like oh you know I’m looking like 500 microliters 1 mL, then like six months later then everyone’s like never mind, we’ll do two. Never mind, and now it sounds like the typical average it looks like to be 4 mL. However, there’s still certain instances where you might need to have a little bit better of that snapshot I was talking about, and then now we’re going to maximize that input. Going back on the kind of the impact of everything, ultimately it is easier to draw blood than it is to do an invasive biopsy. So that’s kind of like the ultimate why behind everything right, so 10 mL does sound like quite a lot of material indeed, but you know two draws of blood is probably better than going under. So that’s kind of the larger impact behind everything which is pretty great.

So let’s see if I can get…

This is the green box I was talking about earlier. Just a quick overview of the kit itself, it’s been around for probably another seven years at this point, so a lot of our customers like to use it for that oncology sphere and non-invasive prenatal testing (NIPT) sector that I mentioned previously. It is a bead-based format, and as a result we can now have a variable volume up in the front. So we have that 1 to 10 mL variability. The processing time right here, I had listed 65 minutes for our proof of concept that we were about to show you in terms of the data. However, once you expand this out to a bigger system, for instance the LM1800 with two heads, then the idea is to expand this to a 96 sample set which you could be done in, theoretically, around two hours. So that’s a significant improvement versus the current systems that we have in place for a 10 mL solution. And of course, the solution volume can get pretty low. In reality, I said 50, you’re looking at really a 60 to 70 microliter solution you’ll lose a little bit from adhesion to the tip comb as well as the absorbance of the beads. If you want to get really fancy though, there’s a way probably to utilize the dual system in the sense that, you know, you could do your last wash as a magnetized standard liquid hander wash and then go into a liquid handling process for elution. That is the only downside of a magnetic bead-based approach or magnetic processor is that that tip comb kind of limits you in terms of the volume that you can use. But by having a hybridized machine like the Lynx, you can actually have some pretty good flexibility and to kind of go a little bit further.

So pretty sure you guys have seen enough of this machine right so far. We’ll have a little clip of the tall plate in action. This is a completely un-resuspended plate right over here. It has beads at the bottom. A little quick video. You can see, even with the full binding volume with what’s a 20 mL, what we can do is variablize the type of mixing that we do, and then we can actually get some pretty good mixing and resuspend samples even at a completely dead state. So that’s the motors doing some really good work. I will say, the displacement at full makes it so that you’re looking at around 18ish mL of like actual capacity with that 25 mL plate. Yes, it can handle 25, but we don’t want to get too sketchy by getting up too far.

In terms of the system components that we are working with, we worked with the very basic system, ultimately. At the end of the day, you know, admittedly the VVP is very cool, but you know, we get to use this the standard ST tool. And we get to do the differential factor here is the MagRod XL. So this was kind of the conception that came about as a result of that plate, was that people were looking for 10 mL solutions, but it was the fact that they were either doing something very fancy or kind of elaborate with splitting the sample up front or there wasn’t necessarily anything out there in the magnetic processing sphere to actually just get the full sample into one well.

Magnetic processing overall is a significant advantage over liquid handling, because as Sarabeth mentioned earlier, it’s flipped by moving beads around it is significantly better than just moving all that liquid at full binding volume around 20.02 mL. So that’s going to be a lot of aspirations if you had to actually deal with that. The accessories are pretty simple, I had only noted one heater shaker. For the workflow that we’re about to get into, you’ll see kind of like the process being in a staggered format as opposed to something in a parallel process, I’ll get to that in a second.

And then of course the accessories and the consumables will scale based on a number of samples that you wish to run. For today’s sake, I will be over going over our proof of concept data that we have shown to make it so that we have realized that this is a feasible step to go and expand this into further completion.

So in terms of the workflow itself, pretty simple because we get to use a magnetic processor, but that’s actually the reason why it’s its strength is in that simplicity. But as a result, we can find ways to save time throughout the method, and that’s really one of the huge factors here in terms of the end result of what we could kind of picture in the future for this. So we have our pipetting tool that we get, and then we’re going to transfer our initial lysis reagents into that well that has the samples. We’re going to assume that the sample’s already plated into that 24-well. From then, we move that and then mix it a little bit before going on to shake it and it can incubate. But that incubation step now allows us to have free time to then fill out the plates that we have on the back end. So now the head is free, the plate is just shaking on its own, and it’s an independent unit, and then we can now just dispense out all the reagents. You save tips.

Admittedly, there’s a lot of plates. But that’s, you know, you’re using plates instead of tips in this situation. And then you’re going to save a little time because you can actually do two processes from this point on.

So, we’re going to grab that plate once it’s done, move it to the recessed position. Because that 20 mL is very high, what we can do is have that recessed IMAG-Z magnetize some beads, and we can pull away a little bit of material so that we can now safely go in with the tip comb and we don’t have to worry about cross-contamination.

Once that binding buffer and everything is added, we can go ahead and just simply mix it around, have a good job doing that, and then completion is the bind wash-elute with the MagRods. But what’s pretty great about this is the concept of that staggered approach is what I was mentioning earlier. Is that normally, when I was doing this approach, it was in parallel. So, if you go back, basically all the plates got that treatment at the same time. But the idea behind this is that, while that binding is taking place, a secondary plate can actually go in and start the incubation process. And then while that’s happening, the binding is already going on at the same time. So in theory, you can get two plates for the price of one. And if you had that mimicked on the right side of an LM1800, then you can reduce your time significantly on a 96-set of samples.

Overall, we’re seeing, let me click through these. The conclusion as a result of seeing everything is these are the major advantages that we get to see from a hybridized system that has magnetic processing and liquid handling very much accessible in one.

By using this plate and their technology, we’re able to get a no sample split option, pretty low elution volume, and a streamlined workflow that is pretty easy to see as it happens.

As far as the yields that came through the proof-of-concept samples, this is a data set that we had conglomerated over a set of three different sample types that we get from QC lots that we use internally in-house. So, we compare these against home cooking to make sure that you’re doing pretty well. And as a result, we have found that the yields that we’re getting from the various sample types were pretty good. And just to make sure, we had to make sure that the inhibition was pretty good. So overall, you’re actually seeing a little bit cleaner results coming out of the Dynamic Devices. You can blame a little bit of me getting too used to robots in terms of inhibition on the manuals. But overall, we’re seeing some pretty clean stuff that’s coming out of this. So really happy with how all the initial experiments went. Abbie just came for a week and we just got it done. So that was really cool to get that up and running as quick as we can.

But of course, this is somewhat as a result of this crazy plate that we made that’s a little bit safe on the side by the way. Of course, we had that large capacity I had mentioned, and of course it is the open-ended SPS format thing. I like the little knobs on the side if you want to take a look at it. It makes it a little bit safer than a standard naked plate, if you will, because if the machine were to actually shut down, then it has something to rest on as if you were to shut down in the middle of the transport movement.

So, we’re going to go on to how we expanded this now into a sphere of plasmid, which is another high-volume opportunity that we can use. The plasmid matrix is a little bit more complex than using something like plasma. First of all, just the complexity of the biological sample itself has the potential of all sorts of other things getting in there. Plasma, you know, you go into a spin process, you’re starting out with a relatively clean set of samples. But the other hard part about plasmid, of course, is the integration of multiple steps. And what I mean by that is the necessity to kind of get rid of that flocculent that appears after the alkaline lysis takes place. So our approach to this, and to utilize the advantage of having a large bore 24 head that’s dedicated, we’re able to use that to our advantage and use the lysate clearance beads that we offer and take away that flocculent without having to centrifuge the samples. Thereby eliminating a huge kind of hurdle in the sense that you don’t have to get an offline centrifuge or something wild to kind of make that process smooth.

The processing throughput, I will say, these two points over here are actually quite… it’s one of those things in the field that’s like, there’s a system out there that can get rid of your spin and their centrifugation. But unfortunately, their process throughput is a little bit lacking. So the Lynx is pretty advantageous in the sense that, in our theoretical build, you could eliminate both the processing throughput problem by processing over four plates of material as well as the integration of not having to do the centrifugation. Last but not least, the liquid handling portion is pretty important, and getting that those four hurdles done and complete for plasmid prep is of course what we’re trying to accomplish here. So, it’s actually even less complicated than the plasma because you don’t even need an iMagZ. Because at max volume like I said before it was at the 18ish. At our max capacity in this particular workflow, we’re looking at around 16 and a half mL, so we can go straight in without having to take away any of the liquid. So this is a full-on magnetic processor kind of situation where it’s very simple and easy to use. So in that sense, we are going through almost the exact same steps. It’s even easier because there is no kind of incubation, if you will, that we had to kind of muscle through. The alkaline lysis reagents are added, and once you tip mix and you clear this flocking out with beads, then you have created a clean lysate which goes through a really basic bind wash-elute protocol that will just kind of do its own thing.

And of course, that switch can happen seamlessly if you had those two sides as I was saying before. Our preliminary data that we can show is pretty nice. It’s nicely shown that our bands are showing where we need to be. We compared it against home cooking of course.

And we have a 50 mL pellet that we tested against and a 100 mL pellet. Our hope is to expand this data set out to even more samples and to kind of expand this into that LM1800 kind of situation where we do that dual plate and kind of pull it through the whole process. But from a preliminary standpoint it looks very, very promising. It looks like a very good system in terms of what we are able to offer in conjunction with Dynamic Devices by combining those two technologies.

Overall, it’s been really cool to see the culmination of kind of more innovation in the sphere where it feels like innovation is hard to come by nowadays in terms of nucleic acid purification. The bead-based format has been around for a long time, but the market will adapt accordingly to what we need in terms of the biological sphere. The impacts of what the science is doing in terms of diagnostics, and even if you look at companies like BillionToOne, it’s really cool stuff and it impacts our day-to-day lives.

So to be able to kind of utilize these tools to our advantage in the future is why we are all here. Anyway, thank you so much for letting me talk a little bit more about what Omega has to offer. Thank you, James, for this time and yeah, it’s been great.