Educational Webinar: Microfluidic Immunofluorescence: A Role for High-Sensitivity Rapid Testing Today and Beyond

Hello and welcome. This is Mary Beth Din from mckesson Medical Surgical. Today's webinar microfluidic immunofluorescence, a role for high sensitivity rapid testing today and beyond is presented by Lumir. This presentation is being recorded to submit questions for our speaker. Please locate the Q and A panel in the lower left corner of your console. Our presenter today is Doctor Brian K Duo, a board certified Clinical Laboratory immunologist. He received his phd in immunology and medical microbiology from the University of Wisconsin Madison. He completed a postdoctoral residency in Clin Clinical Immunology at the Chicago Medical School. Doctor Duchateau has over 20 years of experience as a clinical laboratory director in 12 years of in vitro diagnostics experience. He currently serves as the Lumir DX Vice President of US Scientific and Clinical Affairs, Doctor Duchateau. I'll turn it over to you. So th thank you for that uh introduction. Uh um It makes me sound so old. Um Sometimes I feel old but I really appreciate the opportunity to be here today and, and speak with everyone. Uh Microfluidic is one of my favorite topics to speak on. Um I'll start with a disclaimer slide. Our Regulatory Affairs likes me to say that I may make some forward looking statements and anything that I do say shouldn't be misconstrued as an endorsement to utilize any lumer product in any uh off label way. All right. So with that out of the way, um you know, the program learning objectives for today are to describe what microfluidic technology is. And and most importantly how it works describe the clinical diagnostic utility of microfluidic technology because any technology without an application is not a great technology. And objective three is describe the analytic and clinical performance differences between some of the methods that you might be more familiar with like lateral flow and how they compare in contrast to this new technology called microfluidics. And the last objective of the presentation is to discuss the rapid microfluidic assays um as a resource in a variety of uh clinical diagnostic use cases. All right, let's just jump in here. So if you Google Microfluidics, what comes up is a definition that says microfluidics is the study of systems that can process small quantities of fluids by using tiny channels having dimensions at the micro scale. And like unlike a lot of things that you might put into Google, this is actually a really good uh concise definition. And you'll understand why I think this is a good um definition. Uh as we progress through the um the presentation today, you'll also notice that if you Google Microfluidics, you get about 7.8 million hits, which means this is a pretty hot topic right now. There's lots of uh studies and, and things going on in the field of microfluidics. Unfortunately, for um geeks like me, Kim Kardashian in comparison has 346 million hits compared to 7.8 million hits. So she's just slightly more popular than microfluidics. All right. Um So what are the, why are we talking about microfluidics? Why do um you know vendors like Lu Lumer DX want to incorporate microfluidics in their technology in their diagnostic systems. Well, the first uh advantage of microfluidic technologies is it uses minuscule amounts of specimen and reagent. And this is important especially for, you know, critically ill uh patients, pediatric patients. In fact, many institutions have uh initiatives to uh mitigate the amount of specimens that are collected from those types of individuals. And so microfluidics really plays into that miniscule amounts of reagents also allows you to keep the cost of these clinical diagnostic tests low because you know, one of the most expensive parts or pieces of any clinical diagnostic assay is the actual analytic uh um uh reagent or the um um a and and so you're only using small amounts that helps keep costs low microfluidics. By definition, micro is small tech which means reduced system footprint in a lab that is always important. Clinical diagnostic labs um are always seem to be fighting for space. And so microfluidics plays into that nicely, uh small reaction volumes equal shorter analysis times which equal faster results. And that's really what it's all about in this world is getting the uh clinical diagnostic testing closer to the patient and getting those results to the health care provider quicker. Um laminar flow within these tiny channels, equal equals greater control over the reaction laminar flow is what happens when you, if you look on the right hand side of the slide there, you'll see those microfluidic test channel channels. When you can engineer these channels so that they're really smooth and slick on the inside, then you create what's called laminar flow. And what that means is that the liquids move really smoothly through these micro fluidic channels. And when you do that, you can get really precise control over the reactions. And when you get nice precise control over the reactions, you can get high sensitivity and high specificity out of the clinical diagnostic assets that run on these microfluidic assays. Now, I will say that sensitivity and specificity is a little bit of a give and take because if you think about it, it's easier to move around very small volumes of liquid, much easier than, than moving around bit large quantities of liquid. But when you're looking for a rare analy, the more uh specimen you start with the better chance you have of finding that analy. So you wanna, it's a, it's a give and take. You wanna have enough uh specimens so that you can actually find what you're looking for, but not so much bestman that it's difficult to move around in these micro fluidic channels that you see pictured there on the right. So with that introduction, let me be the first to welcome you formally to the Age of Microfluidics. It is here. Um And why, why now, you know, why are we talking about this? And in the words of the enigmatic Bob Dylan these times, they are changing. And that's true today as it was when, when Bob Dylan uh wrote that song. And in order for there to be an opportunity for any new technology, there has to be a problem with the current dogma or the current um system that we're utilizing. And what that current system is, at least in the US is what we call the central lab process. And what that is is when a health care provider meets with a, with a patient and decides that that patient needs a clinical diagnostic test run, then they order that test in the his or lis system that uh patient shows up somewhere to get uh a drawn for that specimen, that specimen is somehow transported to the central lab where it is accessioned into the system. Um It all of its pre analytic uh stuff is done. It's tested that result then is somehow entered in back into the lis back into the his somehow the healthcare provider sees that result, interprets it and, and somehow communicates the result with the patient. Now, what's wrong with that is that is incredibly complex. There's lots of potential points for failure. And although it works for us, it really requires a delicate dance between lots of different people and lots of different departments and I won't go through it again. But that process is pretty much illustrated here on this slide. Um And what you can see is the the red axis here are, are points of potential failure. And you can see that there's many of them throughout that big complex process. And the blue clocks here, you can see that those represent extended waiting periods for the patient which is inconvenient. And also if the patient has to wait too long at any one of these spots, it's it becomes or can become a uh another potential failure point. So the allure of of point of care diagnostics is that you can eliminate all of those intermediary steps and really streamline um that the the process from when a uh a test gets ordered when the test is performed. And when the doctor sees that test and talks to the patient. And if you utilize the right point of care diagnostic, that utilizes the right methodology, you might even be able to deliver that result to the healthcare provider before the patient even leaves the uh physician's office. That's powerful. Now, I say allure here because I don't think that point of care diagnostics, whether it's microfluidic or any other type of point of care diagnostics has really lived up to their uh potential and all point of care diagnostic solutions at least to date have suffered from several major limitations. We're gonna talk about each one of them. So number one is limited test. Menu. Number two is these um point of care test. Either the, you know, testing cartridge itself or the testing strip itself or the instrument tend to be a high cost. And lastly even where we have implemented point of care where we need that result really quickly, we often tolerate poor performance because we need that uh result at the point of care so desperately. And in addition to these three major limitations that new point of care technologies like microfluidics should solve. There's other uh things that should that these technologies should also address. It should be easy to use, should be portable with connectivity. Uh All the reagents should be able to be stored at room temperature. Um You know, whatever technology you're using should be applicable for all common specimen types like serum plasma swabs, even urine. And most importantly, these results should be fast. Remember from the previous slide, one of the most important things here is to get that result back to the healthcare provider. Um and preferably even before the patient leaves the healthcare provider's office. So now what I want to do is switch gears a little bit and show you how the lumer DX microfluidic technology is addressing all of these major limitations. Let's talk about limited test menu first. So what you see here on the slide is an actual laboratory um outside of Seattle. And this laboratory has really embraced the concept of point of care diagnostics. And you can see that they do a lot of in the in the blue uh uh try uh blue uh rectangles here. You can see that they do a lot of point of care tests. A lot of different tests I should say. And because there is not one point of care platform that offers a comprehensive testing menu, they have to utilize lots of different uh point of care methods and platforms to accomplish all of those tests that they'd like to do. Now, that's very inconvenient for them because you'll notice behind um each of these testing platforms are, are cheat sheets on how these different essays need to be performed. So they have to keep their training current on lots of different platforms and they have to keep track of QC and proficiency testing on lots of different platforms. That's all a, a real challenge. So how does microfluidics address that? Well, if you see here listed above each of these test strips, these are the different types of um assays that can be used uh run currently on the uh Microfluidic Luera uh DX platform. So infectious disease assays will run on the platform, hematology and coag assays, chemistry assays like sodium and potassium. Um even molecular uh um assays which are are PC R like will run on that instrument and platform. And traditionally, the chemistries that are needed to uh perform an infectious disease assay versus a hematology coag versus a molecular assay were very, very different. And because those chemistries were so different, they couldn't be run on the same uh uh platform microfluidic changes that because this test strip can be um altered in lots of different ways. So the for instance, the reaction uh wells can be uh a change so that the depth and and dimensions can be changed, which changes the kinetics of the reaction. The instrument can be programmed to heat uh a stripped strip uh channel at one part of the reaction and not heat it at a second part. The timing of the of the reaction can all be changed. There's so many different parameters that can be changed on that test strip and within that test strip that it can accommodate lots of different assays. And in fact, if you look at these five different test strips that are on the slide here on the left, you can see that the architecture of each of these test strips is slightly different depending on the assay type that's gonna be run on them. So that's one way that microfluidics is addressing that historical limitation of limited test menu because ultimately all these different types of essays will be able to be run on the Lra Microfluidic uh test platform. All right. Secondly, high cost of total ownership. So what you see here over on the right is the actual strip production of um the Lra Microfluidic test strips uh being produced in in uh Scotland. And what you can see on the on the lower uh figure on the right is these are, these are uh test strips are produced um very quickly high throughput with very little labor input. You can see on the top slide here there is only one person running this big uh production line and these strips are being produced uh from large um large rolls of strips and uh uh films I should say, in fact, these films are kilometers in length and each of these lots that we produce are somewhere between 60 80,000 test strips is what a lot will produce. And so if you look back at the bullet points because this is such high speed manufacturing with very low labor input, we're able to, you know, literally produce hundreds of millions of strips per year. This was really important during the height of the uh uh the SARS Kobe two pandemic. You know, we were maybe one of the only vendors that never put any customer on allocation and never went on back order. And it was because of this manufacturing capability that we had low Anna analys specific reagent costs. We already talked about this because microfluidics require such as small volumes. The um you know, we're depositing really small um amounts of active ingredients onto these test strips which lowers cost last bullet point you see here too on the slide on the left, these manufacturing lines are incredibly um flexible. Um We can literally be producing SARS Kobe two and a gas in the morning, retool the line in about four hours and, and be producing a different um assay strip in the evening. That's unheard of um lateral flow. Uh and, and, and other products like that often take days to retool their lines. We're doing it in hours. And I really want to mention this last thing um over here on the right, you can see some of these high speed cameras. So there's multiple points during the manufacturing process where individual pictures of individual slides are taken and each one of these slides has a unique identification number so that we could go back into the archive and look at an individual slides pictures during the manufacturing process. And those high speed pictures are are saved. Um so that we can refer back to them over time and there's multiple pictures taken of each slide at various points in the manufacturing process. Now, I'll mention this because um early in the pandemic in 2020 we had a, a product recall and what we found out through the investigation is and it was on a lot that was about 80,000 test strips. And what we found out was through the investigation that it wasn't the whole lot of test strips that was affected by the problem. It was only about the last 3 to 500 test strips that were produced on this big long line and it was, um, a reagent deposition problem, you know, as we were, um, there wasn't quite enough reagent being deposited on the test on the last three or 400 test strips that were produced. And the reason we found that out is we looked back at the pictures of these test strips that were on the last 3 to 500. And you could tell that um the reagent deposition wasn't correct. The reason that was important is that data was compelling enough for the FDA to allow us not to recall 80,000 test strips on a single lot, but they let us recall just a few 100 test strips that were affected on the end of that lot. And that would not be possible without this uh sort of vis visual inspection process that we're utilizing very high tech stuff, you know, in the age of, of being green, um not only reducing uh medical weight, waste cost, but, but in the interest of being green, each one of these test strip weighs 0.75 g. If you look at a conventional lateral flow test on the second line, there it's 22 g. So you literally can perform 29 LRA DX tests on this microfluidic test strip and create the equivalent amount of waste of just one lateral flow device. All right. Last big historical limitation has been poor clinical performance. And what I'll do is uh to illustrate uh clinical and analytic performance. I'll talk about our SARS CO V two rapid antigen assay. And so what you can see here is um three very common um rapid antigen point of care tests that are on the market. Um They're listed here on the left and then on the right is the microfluidic um technology from, from lumer DX. So a lot of you probably already know this but there's nothing wrong with, with lateral flow technology. Um It's just that this technology really hasn't changed that much since the mid 19 fifties. You know, the early patents were filed by Becton Dickinson and Unilever. In the, in the eighties, the first clinical diagnostic test that was launched was beta HCG for pregnancy. Then in the nineties, there was lots of further improvement, refinement of lateral flow technology. Many more products were launched including many more infectious disease and even cardiac assays. And then by the two thousands, because this technology is cheap, it's easy to produce. There was over 200 companies that were producing lateral flow based tests with a broad portfolio with over a $2 billion market in diagnostics, just centric to lateral flow technology. So it's a technology that's been around a long time, hasn't changed very much since its inception. Uh And we know a lot about it and this is how it works. So all again, you know, lots of different tests over, you know, hundreds of different tests, but they all work basically the same. And if you look up in the left hand part of the slide here, what happens is you put a sample deposit a sample onto a sample pad, that sample is wicked through a nitrocellulose membrane by this wicking action. Um And along this nitro along this path, this nitrocellulose path, the sample will encounter uh conjugate. And if the Annaly that you're looking for is within that sample, the conjugate will bind and then at certain points in this nitrocellulose membrane, you have um molecules that capture the analy bound to the conjugate if it's present. And u usually those capture molecules are antibodies which are pictured here in the, in the second figure. And then in the bottom figure here, you'll see that their most lateral flow tests require uh uh the presence of two reactions. One to control that a reaction happened. It's a control line or a control band and then a second band will develop if the analy that you're specifically looking for is present will also develop. And that that's how uh most lateral flows work. Um What this slide represents is how the microfluidic technology from lumer DX works. And what you'll see is it's very, very different than the lateral flow technology that I just just just described. So we'll start here on the left hand part of the slide step one, a sample is added to a sample deposition port on the slide and through passive capillary action, that sample is um wicked up into the um the uh reaction channels here on the test strip, I will mention that this um part of the reaction is the only passive part. Once that sample by capillary action is taken up into these reaction chambers or the reaction channels, the sample is actively managed uh by the instrument and the computer program. So what happens specifically in SARS Kobe two is if you look in the middle part of this, the uh figure here where we have this magenta sphere that's supposed to represent SARS Kobe two antigen. And if that antigen is present, it will be bound by two different antibodies. Um one conjugated with a magnetic particle. And the second antibody conjugated with a uh fluorescent latex bead. There in step five, if that complex forms, there is an onboard magnet that will come up right underneath that test strip within the instrument, that complex will be bound by that magnet to the bottom of the test strip. In step six, there is a liquid less wash step that will remove anything from the reaction chamber that's not bound to the bottom of the test strip by the magnet. In test seven, step seven, I should say there is a onboard spectra photometer that will optically read um the amount of fluorescence that's present. And of course, the amount of fluorescence that's present is directly proportional to the amount of antigen that's present. And in step eight, the instrument will give you a qualitative result of either positive or negative. And this happens in just under 12 minutes. Now, what you'll see is there's a lot of descriptive words here like um you know, immunofluorescence magnetic particle separation spectra photometer. These are all things that you might find in a conventional lab analyzer sitting in a core uh laboratory and that's correct. Um a lot of um the chemistry that's utilized in this little uh point of care device, this little platform as we call it is really similar to the chemistries that are utilized in conventional core lab technology. And because those chemistries are are similar, you might expect that the clinical and analytic performance that we see out of assays run on this device would also be similar to performance of core lab uh tests and indeed they are. And in the second half of the presentation I'll discuss that. So in this slide, um I'm gonna show you a video. So under the under the uh red banner, there will be a video that's be about one minute in duration. Under the blue banner, there will be a second video that's about 20 seconds in duration. And these two videos are um two different types of essays that are run in the microfluidic uh uh that can be run on the microfluidic test strip and I'm gonna set them up before we uh show you the video because the video doesn't allow real time narration. So I'll tell you what you're gonna see, then we'll play the videos and then we can come back. So what you'll see on the right video is you will see a blood sample that's being aspirated up into the microfluidic test channels of the strip. You'll see some very active pronounced mixing. You'll see the lame or flow as we described earlier within that microfluidic test strip. You'll also see the sample being mixed with a proprietary substance that will take that blood sample and start to aggregate it into clumps. And what we're, what we're doing here is we are separating the plasma from the, from the red blood cells. And in the last part of the video, you'll see the instrument gently aspirating the the plasma away from the clumped uh red blood cells. And that uh plasma is being aspirated up into the reaction chambers where the actual reaction or clinical diagnostic test is gonna happen. This is really powerful technology because it takes it has the potential to take a finger stick blood sample for a test that will require either serum or plasma and do that pre analytic step on board the point of care device not having the laboratory or user uh required to separate plasma or serum, very powerful stuff on the right underneath the blue banner. This is about a 22nd video and this is um gonna show you how the immuno fluorescence of um this particular assay works. And this immunofluorescence is really similar to the immunofluorescence I just described for the SARS COVID two assay. And what you're gonna see is the fluorescently labeled latex beads being mixed um with the uh specimen using acoustic oscillation. Um And this again is all happening in these microfluidic test channels. So with that um Fidel, if you, if you don't mind, go ahead and start the first video on the right and let it play for about one minute and then start the second Fidel. Are you there? Yeah, I'm here. OK. Fidel. Are those videos complete? I I didn't see them play. Yes, they are complete. OK. All right. Moving along. So to give you some idea of uh how the microfluidic assay um by lumer compares to some of these conventional lateral flow assays. Here, here's a chart and you can see if you look at sensitivity for SARS CO V two, the microfluidic assay has the best sensitivity compared to the uh lateral flow point of care assays. Um It's analytic sensitivity here expressed in TC ID 50 is 32 compared to these other essays which are about 3 to 4 times less sensitive and also point out something uh important here that um the microfluidic assay from Lora DX is allowed to be used 12 days, post symptom onset, where the other uh assays are, are cleared for use. Only five or seven. We think that that's really important because if you look at this chart that on the left hand side is our ability to culture virus from individuals infected with SARS COVID two and on the uh X axis is days post symptom onset. And so what you can see is we lose the ability to culture virus from actively infected individuals somewhere around day 10 or day 12. So if you have an assay that is allowed to be used all the way up till 12 days. Post symptom onset, you have the ability to test an individual during their entire potential disease window. If you only have a test, that's allows you to test five or seven days, post symptom onset, there's many people that could still be actively infected and you wouldn't be able to utilize those tests at least in an unlabeled way. This slide um summarizes the clinical trial that, that we conducted uh on the microfluidic assay versus PC R. Uh Our predicate was, was Roch's PC R. It included 257 specimens uh from six different sites. Five in the US and one in the UK. All the subjects were symptomatic and presented within 12 days of a symptom onset. What we did is we use what's called a cross nostril uh collection. So we took one swab from one nostril, one swab from another nostril and then crossed those swabs into the other nostrils, took one swab and tested it with PC R and the other swab tested it with lumer DX. And in that, using that cross nostril method, those swabs were both equivalent and what we showed here in the, in the bottom um pain here is 97.6% sensitivity versus PC R. 96.6% specificity versus PC R. We did one other, one other thing is we looked at all 83 of our positive tests that were in our clinical trial and we did what's called B analysis. So we, we took all the samples that were zero days post symptom onset and put him in a bin and calculated a sensitivity. We took all the samples that were one day, post symptom onset, put them in a bin and calculated sensitivity so on and so forth all the way down to day 12. And if you look at this data, you'll see that Lu Luera Microfluidic acid didn't miss a sample versus PC R until day four. And then there wasn't another discrepant sample all the way until day 12. And this data was compelling enough for the FDA to allow a 12 day post symptom onset claim for the microfluidic um assay from, from L um there's been lots of studies that have done independent studies that are not our studies that have been done to look at the analytic and clinical performance of microfluidic versus lateral flow microfluidic versus PC R so on and so forth. And I'll show you some of those in the next few slides here. So what you see here on the left hand side of the slide is a study that came out last winter from the Mayo clinic. And it compared microfluidic versus lateral flow tests. And what you can see here in the second uh set of columns, there is all of these test types that are listed here on the right hand side of the square are are all performing about the same um wind viral loads are really high. If you look at the last set of of columns, great columns there, you can see that there are significant differences designated by the asterisk of the microfluidic test system versus the lateral flow test systems. And so those are those viral loads are things that you might encounter really early or really late in infection. Um And that's where you know, things that, that might matter during those points of infection in the right hand side of the slide, this is comparing microfluidic sensitivity versus viral culture. And again, you can see lumer DX is pictured there in the pink bars and you can see that the pink bars has the greatest sensitivity. Um of any viral culture method utilized, didn't matter how you looked at it, which viral culture method you utilized. Lumer DX was always more sensitive than the other test that was being compared to this is a test that came out of Boston Children's Hospital. And what this test, uh what this study did is you can see here on the left hand side where it says Quidel Sophia and BD Vor, what they were doing is they were trying to figure out what an analytic lod of these lateral flow type tests would be versus PC R. And what they determined is those tests had a sensitivity that was equivalent to about AC T of 27 or 28 versus PC R. We know from in-house testing and independent testing that the Lra microfluidic uh test system has a analytic sensitivity of about 3.2 picograms per ML or AC T of about 32 or 33. And I'll show you that data data here. This is independent data again out of the University of Washington. And um let me set this up because this is really important data. This is comparing microfluidic Lumme performance versus Roche um RT PC R. Every figure on this chart, whether it's a blue circle or a red square is positive by PC R and everything in red was also positive by Humera microfluidic technology. There was only two samples where that were positive by PC R and negative by lumer and they were both samples that had CTS greater than 33 which suggests these are really, really low viral load specimens. Now, if you infer how the other test systems might perform on this sample set, we know from the previous slide from Boston Children's Hospital that these other uh lateral flow methods have ac T of somewhere between 27 and 28. If you look at the package insert for quill and BD, they say don't use them past five days, post symptom onset. So for you were to utilize those within the package insert, you'd be missing all of these samples for Avid ID. Now it's a little bit better because their day's post symptom onset claim is seven days, not five, but you're still missing lots of different specimens. So these last two slides really illustrate what um sensitivity, how sensitivity can um increase the utility from which you can um um pick up different patients. Last couple of slides here. This is also really powerful data. So this is comparing uh lumer DX performance versus um three different methods. So uh other point of care devices, these are mostly lateral flow and versus PC R, this is a huge data set. It's almost 700,000 patients over two years. And what we did is we took um 50,000 lumer test results, almost a half a million PC R results and almost 200,000 lateral flow results over time. And we calculated out the percent positivity rate for each one of these methods using a, a five day rolling average and then grafted over two years. And if you look at the yellow panel, that's, that's that is labeled omicron, you can see that the percent positivity with patients tested with LRA was almost identical to patients tested with PCR. But the positivity rate picked up using other, using lateral flow devices was much, much lower than what was being picked up with lumer DX or with PC R. And this data really suggests that lumer DX has a sensitivity, at least a clinical sensitivity equivalent to the performance that you'd see at A PC R. Now, what I should point out here is if you look, you know, pre aic, you see that the lumer line is above PC R suggesting a higher positivity rate. The reason for that is this client that generated this data was only using lumer to, to test symptomatic patients where PC R was being utilized to test both asymptomatic and symptomatic patients. And so, if you were only utilizing a specific technology to test symptomatic patients, you'd expect the positivity rate to be higher. And indeed, it is or was up until this gray line. This customer utilized Loera devices at over 100 different sites. And what they did is at some point, they converted all of those sites over a small amount of time so that that they were using lumer to test the same cohort of specimens, both symptomatic and asymptomatic that they were utilizing PC R for. And when they did that, when these two methods were being utilized to test the same types of patients, the positivity rate became identical. There's also a, a large um study done out of Europe, uh a meta analysis that did a um systematic literature review of five different data banks. They looked at 9000 articles, did full reviews on 100 and 33 of them which represented 100 and 12,000 different specimens. And what this review concluded was that microfluidic technology showed the highest sensitivity of 88.2%. Now, this was 88.2% in studies that were blended. So some studies were asymptomatic patients. Some studies were symptomatic and some studies were both and even with blended technologies over 100 and 20 100 and 12,000 different specimen types, microfluidic had the highest sensitivity. And again, this was an independent study out of Europe. We took uh internally that study a a bit further um expanded it uh for several months, added more references to it and created this bubble graph. So this is internal data. And what this bubble graph is saying is we're looking at sensitivity of lumer DX, which is illustrated here in the on the far right, in the green bubbles and on the X axis is all different types of rapid antigen tests. Each bubble, whether it's big or small represents a sensitivity study that's in the published literature. And the size of the bubble is equivalent to how big the study was or how many participants were in the study. And what you can see here is um the blue bubbles are lateral flow. And you can see that there are some studies that show lateral flow has good sensitivity. But the vast majority of the studies show sensitivities below 80 for lateral flow. And in fact, some of the largest studies or most comprehensive studies show lateral flow sensitivity way way much lower than 80%. And the other thing that's interesting is if you look at where the green bubbles are versus some of these lab based technologies indicated here in in the rust color, you can see that the sensitivity of of the lra microfluidic assay is really equivalent to what you would get in a core lab uh analyzer. So last slide in summary, not all rapid antigen point of care devices are created equal. You know, if we look at lateral flow versus microfluidic technology, we get precise temperature and time control out of uh the microfluidic test strip that Loera uses but not out of lateral flow. There is active mixing and liquid list wash steps that happen in microfluidic, not in lateral flow. There is a magnetic particle separation which really um in increases uh or optimizes assay specificity that does not happen in lateral flow and lastly, a spectra photometric read really um gives you a uh objective reading, you know that there's no more of this uh you know pass this lateral flow device around all your friends and, and you know, have a group discussion on whether there's a band there or not. That doesn't happen with microfluidic technology because this spectra photometric reed is an objective result determination. And with that, I will open up for questions and discussion. Thank you, Doctor Duchateau. As a reminder, you can submit your questions about today's topic in the Q and A box and we do have some questions coming in. So I'll kick us off with the first one is the term micro fluidic scientifically defined. Um Yeah, I mean, the, the the rough definition I gave uh on one of my first slide and, and that's, you know, using uh moving around small amounts of liquid and microfluidic channels, but how that's done um differs from, you know, vendor to vendor. Um The strip design. Um The channel design, all of that is not standardized. Got it. Thanks. The next question here is why is the test specificity less than 100%? Well, I would say that any test that reports 100% specificity um just didn't have a big enough clinical trial because there's no test that is perfect. Um And there was some um tests especially early on in the uh pandemic that had really small uh clinical trial um numbers like 3040 specimens, 3040 patients and they were getting 100% sensitivity and 100% specificity. And, you know, that's, that's just not real world. That just means your trial wasn't big enough. Makes sense. All right. The next question, how does the test compared to molecular point of care test? Um So that's a great question. Um And you'll remember that I, I showed the, the graph um, where we had, you know, almost 700,000 specimens where we compared to about a half a million um molecular specimens. And you can see on that graph that the uh percent positivity that we were seeing out of the lumer test was almost identical to what the customer was seeing out of their molecular test. Um suggesting that at least the clinical sensitivity of the Loera test was almost identical to PC R. Now analytically, that might be a little bit different. But what we're seeing is that increased analytic sensitivity that is claimed by PC R really doesn't mean much clinically because patients are not at those really low viral loads for very long in their disease progression. Thank you. The next question beyond COVID. What other essays are under consideration for this platform? Yeah. Good, great question again. Um Yeah, we, we are not a COVID company. I mean, we, we have a COVID test but we, you know, we that was not um our desire was was not to be a a one test COVID company. Quite the contrary. Um I'll answer this question by, by saying that in Europe we have ce mark on Crpinr uh NT pro BNP Hemoglobin A one C um D dimer. So those are all tests that you uh might think that, you know, they're already launched in Europe. So that those would be the next logical tests that would probably come to the US market. I know that we're developing a, a TB test for the African continent. I think the first molecular test that you'll see on this microfluidic technology in the US market will be uh group a strap. Um I can tell you from an R and D perspective. We've looked at about uh 75 different essays and have uh good proof of principle data and probably about 35 different essays already that we know will work using the platform and the chemistries I've described. Thank you. Another question we had come in was how much cost? Um how much does it cost to determine a diagnosis compared to a PC R test? Yep. So that's a uh a really good question. Also, you know, our cost per reportable, we've done um really detailed analysis on this is much lower than the cost per reportable associated with, with PC R. Um There's much lower repeat rates with our essay than with PC R. Uh the medical waste is often lower. Um And I would encourage anybody that's really interested in the finances around this versus PC R or this versus lateral flow to get with uh, one of their sales reps and they can share some really um detailed, um, information with you. Got it. All right. Our last question here is, does the end of the public health emergency affect the emergency use authorization on this test? Yeah. So that's a great question too. We've had some confusion about that. So I'm glad someone asked that question. So the public health emergency is very different than the emergency use authorization. So the emergency use authorization that all uh SARS Kobe two tests came to market with initially is issued by the FDA. The that EU A is not linked to the public health emergency. So the public health emergency is scheduled by the Biden administration to end in May that we have not vendors have not been given, given any indication from the FDA of when they will end the EU A authorizations for diagnostic tests that are on the market. The FDA did say that when they do um end the eu A authorization vendors will be given um advanced notice and that vendors that are that have submitted or are actively generating data for a 5 10-K trial um will be allowed to will likely be allowed to leave their essays on market because the FDA knows you're working, the vendors working towards a a cleared version of that test. And I can tell you that um We are progressing uh very well through our, our 5 10-K clinical trial. Um and our intention is to have a um our device um 5 10-K cleared um and, and S substitute that 510 cleared device on the market for the EU A that's currently there. Great. Thank you so much for sharing your expertise with us today. Doctor Deuel. Um Please take, thank you. Yeah, please take a moment to review our disclaimers. And then we also invite you to view our upcoming webinars by visiting our website M ms.mckesson.com/educational dash webinars. In closing. I'd once again like to thank L Mia and all of you for attending today. Have a great day.