[00:00:05] >> Welcome to form 2029 of fans who have been our series and in this series we've been focusing on point of character knowledge in health care and today we are seminar would be a 4th one this month in the series and we have Dr Carlos Moreno from Emory University's School of Medicine who will speak on the resonance of the x. bollock acoustic resonance sensing platform the Nano finance vibe in our series has sponsored by the Southeastern nanotechnology infrastructure corridor in short scenic which is one among the 16 sites under n.s.f. funded program called national nanotechnology quantitative infrastructure in shock we call it an n.c.i. the goal for this program has to support extra long researchers both working in there in academia as well as industries or rocking in various research topics in micro nanotechnology to go to one of these sites and use the facilities for the research activities and scenic is an academic collaboration between 2 centers in the Institute for electronics and nanotechnology at Georgia Tech that's asked and our partner joint school of nanoscience and an engineering and this is our nano scale fabrication and categorization resource and any extra users may be able to go to one of our sites scenic sites and access our facility for their research and alongside research resources we also offer our staff expertise. [00:01:51] Which would be a great help for the researchers there looking new devices. In Charge scenic as a one stop shop for your nanotechnology research needs and more information is available at the site that is in the slide there on the left side scenic dock at a dock e.b.u. With that said we do have one last where they've been are in the series which will be next Thursday at 11 by Professor laid on a mile from the University of Georgia he'll be speaking on federal hydrodynamic isolation of subjugating Demoiselles a nexus on's and with that said is a pleasure to invite Dr Carlos Moreno from. [00:02:37] Emory University School of Medicine I'd like to briefly interviews him and. Dr Moore in no pain as b. s. and m. as in aeronautics and astronautics from mit and worked for NASA before he understood b.s.d. in general takes and molecule biology from Emory University in 1988 is currently on Associate Professor of pathologic and lab medicine and biomedical informatics at the Marina City where he is a member of the Winship Cancer Cancer Institute as well is specializes in cancer by informatics and cancer genomics and his lab has used whole genome expression Alice's And next generation sequencing to identify biomarkers of Agnes of disease and prostrate cancer is a section editor in chief of the cancer biomarkers section of the journal Cancer she is a corn mentor on a patent application for a system to detect biomarkers using peers or electric resonators in 2017 he co-founded resonance the x. developed rapid point of care diagnostics and wrote for the delay It's my pleasure on behalf of nano fans are in store in white. [00:03:51] Dr Carlos Marlowe to speak on this topic resonance d.x. bug acoustic resonance sensing platform Dr Murray. Well thank you very much Paul for this invitation to speak for the Nana fans within our series It's my pleasure to be here to talk about resonance d.x. and our book acoustic resident sensing platform. [00:04:19] So 1st my disclosures I'm a co-founder of residence d.x. and I do have equity in the company and and so that is. Part of the reason why we're I'm giving this seminar. So today I'm going to talk to you today about about our. Work on the 19 and this pandemic is everyone knows has as crippled the world there have been over 41000000 cases and over 1100000 deaths worldwide and in the u.s. over a 1000000 cases and over 220000 dead Americans this year. [00:05:03] Over 80 countries have closed their borders and it's infected a pretty a worldwide everywhere in every almost every country in the world is as has been touched by this pandemic. And. Worldwide we are working on I'm trying to reopen our economies safely and trying to to understand the disease to develop vaccines to develop therapies I am going to be talking about diagnostic testing which is another key component if I having rapid diagnostics to allow for contact tracing and safe. [00:05:48] Social interactions and work interactions so that we don't have to give a seminar virtually we can be in the same room of fully one day soon. So we are working on developing a rapid point of care SARS could be to test to diagnose active infection by the tech thing. [00:06:09] Presence of covert 900 proteins using antibodies. The technology that we have is a is a novel flexible platform technology that's not limited to detecting Kovi 2 or $1000.00 is it can be used to detect virtually any antigen to which you have an aspecific and a body. So it can use any and a body and it can also use any 5 fluid in in our case what we're we're studying is to detect. [00:06:46] Protein from the 1000 virus in in saliva. One advantage Another advantage of this platform is that it allows us to multiplex multiple antibodies in a single test and that is useful for a variety of reasons which I'll get into shortly. So this is shows here one of our ships and this is a sensor array so it's called bulk acoustic resonance sensing because we excite the the chip with. [00:07:23] Electro magnetic energy and it gets reflected off of a brac reflector in the chip and and what we're exciting is a layer of ph electric crystals on the top that are functional oddities with electrodes and antibodies that are bound to those electrodes as you can see we have multiple resonators on one chip so in this case 6 resonators and and 8 we this allows us to have a positive control. [00:08:01] Device resonator and a negative control that we can use for self calibration to make sure the test is working and to. Measure our background. And because this is done using silicon wafer electronics fabrication technologies it's massively scalable and so this can hopefully allow us to produce millions and millions of tests in fairly short amount of time. [00:08:34] The way that this bars for short block acoustic resonance sensing works is that we have these gold electrodes or functionalized with a layer of antibody in this case to Kofi 1900 and it is excited by and and measured by the instrument electronics so we have a saliva sample that's applied to it and this this this excitation. [00:09:02] Through the Bragg reflector we're able to detect. The amplification of these natural resonant frequencies that the antibodies have that there's a fundamental harmonic that is the thickness extension which is simply an up and down kind of motion and that's subject to dampening by by liquids but the secondary harmonic mode is the thickness assure mode which is more resistant to effects by liquids and is amenable to this type of detection and fluid. [00:09:39] Once a the energy in binds to the antibodies. It is it causes a change in mass of the antibody layer and this changes the resonant frequency that they vibrate at naturally and and so we can measure that change in resonant frequency and this is sort of the basis upon which we can measure the presence or absence of. [00:10:10] That adage of interest in this case we're looking at the Spike protein which are shown in red here around the virus and this is obviously not to scale but but it's a conceptual idea. So one of the great things about this is that it's a very rapid type of detection we don't have to amplify d.n.a. over multiple cycles and and so. [00:10:41] The electronic detection is almost instant Tasing is that the main. Factor. That requires any time is sort of an incubation of the sample with the Ana body to allow the antigen to bind to the Ana body but we can do this in under 5 minutes and that's very important for this type of a test because if you're going to be testing many people all the time you want to be able to do it rapidly and that makes it makes a big difference in the usability of the test and another important thing about it is its accuracy its It is it's very sensitive and it's very accurate and that is and that is. [00:11:26] An advantage of this technology another very significant advantages ease of use. And there's not really any. Skill technician. Needs 2 to operate the device and all that need to do is essentially apply the sample and then insert it into the instrument and then get a reading and so it's alternately something that we're hoping could be over the counter. [00:11:58] And one part of the reason for that is that it doesn't require any religions or or lasers or substrates or anything like that and so the lack of regions makes it easy to use and it also is helpful with supply chain issues when a lot of Regents now are difficult to obtain for many of the manufacturers of diagnostic tests. [00:12:23] And there's no sample preparation or processing So essentially the saliva goes into the test and it goes straight into onto the detector and then is measured very rapidly there's no processing involved and because of the fact that it's so simple to use we are hoping that we're going to be able to get a clear waved type of approval which would then allow this to be not used in a in a central laboratory with trained technicians but more you know in an over the counter type of a scenario out in society where that these tests were needed. [00:13:09] There's a lot of situations that a test like this could be really very useful the initial type of application would likely be at a place like c.v.s. or Walgreens or something like that where you could just go in there in that case you might have someone who is. [00:13:25] Trained you know someone who's a pharmacist or a nurse. You know running the test but ultimately we want to move I've been out of that setting into a place like an airport where you could test everyone who's arriving at the airport before they go inside or before they board a plane at the gate. [00:13:45] Stadiums so that people could go to n.f.l. games and baseball games and soccer games. Colleges and Universities like you know here you know we could have a seminar in person as opposed to virtually. Large office buildings where you have a lot of people going to work you know that would be tension you know something where people wouldn't necessarily have to work from home all the time dentist office where you know you you know you you're really getting into high risk activity and you know getting into some of your cleaning someone's teeth if they've got code that's a very high risk situation so that would be a great application theaters you know the theaters right now more centrally shutdown than in so you know actors musicians what have you all you know concerts these things are you know things that are critical for really for our life in our culture and getting things back to normal. [00:14:44] So that's where Lee what we're hoping to be able to do with this is to help accelerate return to a semi normal life. And you know vaccines are hopefully coming soon. But even if there are approved you know in the next few months it could be you know one to 2 years before there's it's a. [00:15:08] Fission immunity you know in vaccination where it gets deployed and everyone gets vaccinated in who knows there could be people who are resistant to vaccines and don't want to take them so I'm not so convinced necessarily that code 900 going to go away as soon as soon as we have a vaccine. [00:15:28] Our technology is based on. Some patents that came out of Georgia Tech actually from built that residence d.x. is licensed on the fundamental technology of using bulk acoustic residence and detection as well as a pending patent application which I'm one of the co-inventors. That is for an entire system that would integrate this type of technology into detection of antigens in via fluids for biomarker measurements. [00:16:08] And so that the original. Technology was developed as I mentioned here in Georgia Tech in Bill Hans lab and this is from a number of years ago when they were look doing experiments to to demonstrate the to the fundamental technology and showed a couple of things that were poor and one is that there is a linear dose response of an engine 2 to the frequency shift so these are frequency shifts here and this is a dilution. [00:16:43] Of. In this case. Culture super name of head neck cancers that. Have some secretion of a k t v In this case phosphorylation Katie and that's the Anna body that is used for to discriminate head neck cancers that are positive and negative for h.p.v. and. One of the key things that came out of this is that this technology is actually $4.00 to $8.00 times more sensitive than allies a so essentially the Eliza detection dropped out you know at a $1.00 to $10.00 dilution whereas the. [00:17:29] Bar's detection was able to detect it wonder $41.00 to $80.00 and so this shows that we were actually quite a bit almost an order of magnitude more sensitive than allies which is kind of the standard gold standard for detecting proteins and so so so this is something that where you know is important when you want to be able to detect over 1000 you don't want to have false negatives you don't want to miss an infection you want to be sensitive enough to detect everyone who's infected because you don't want to let the person who's infected into that concert or that that airplane right. [00:18:12] So given the fact that we're about $48.00 times more sensitive than a standard allies and. Then we can we can extrapolate knowing that there are allies is that have a detection level in the $44.00 peak a gram permille range. And and so our theoretical that actually will be somewhere. [00:18:41] Around 18th of this right which. If your grammar was about a little over 5 or something like that and that a quick that. Is equivalent to $23.00 viral particles per microbe leader now. For a standard p.c.r. test the detection is about 6 viral particles from Mark we are fixed you know McWilliams So you know we may not get quite to the level of sensitivity of p.c.r. but we potentially we could get very close and you know that you know given the fact that it's a bright their point of care a 5 minute test you know getting closer to the sensitivity of p.c. ours is going to be. [00:19:29] Probably what we need to achieve to make it a useful test. So these are these chips basically they have to get integrated into a printed circuit board p.c.b. and and then packaged into. A test device that includes essentially a sample reservoir that someone who'd be spitting into and and then a preloaded wash buffer and there sensor array would be in here and you would a and then whatever fluid goes through has to go into some sort of waste reservoir. [00:20:11] And so course this presents some challenges because we have to keep the electronics dry and separate from the the fluids and so that and have to banish how the fluids flow and we actually have a team from Georgia Tech capstone teams seniors that are working on this fluidics aspect of it and they've come up with some interesting designs with an inlet and outlet and we have our chip underneath here. [00:20:44] And this is kind of showing the whole. Piece to put in circuit board with the inlet in the outlet and the sensor in there and they've done some work on determining what kind of valves to use the most possibility here as a as a sort of a ball and spring type valve that would allow for unidirectional flow and prevent back flow and they've done some some analyses showing that the pressure is are not unreasonable and that this is something that can be dealt with so this is one possibility way of that we may end up using but you know we haven't really finalized our designs yet but but this is certainly you know an interesting approach that could it could could work. [00:21:29] So here and there schematic we have our test test device but we also have to have something. To site it to read the data and this is a just storing sort of a possible desktop sort of reader instrument something like this you know which which actually provides the stimulation signals and detects the frequencies that are coming out of could potentially read multiple test devices at one time or you could be you know essentially you know if you had a lot of people to process then you could you could have multiple test devices being read by an instrument like this. [00:22:09] But. The way the way that that would essentially work is you'd have the patient with would spit into the sample put it into the into the device and stick the device into the reader and essentially what they read or instrument does is it 1st pulls in the wash buffer to read the baseline resonant frequency and confirms that everything's working Ok then it would pull in the sample and flow the sample onto the resonators and bait for a few minutes. [00:22:41] And then after you know it's bound for 3 or 4 minutes you know then the energies of bound then it would pull in the wash buffer and remove anything any sort of unbound proteins that were back into the same buffer that it started in so the same ph in temperature and salt concentration everything's the same from before and after the only difference is what's stuck to the antibodies and and then the instrument reads the resonance after being what the samples washed and provides a positive or negative result would be it would actually give you a very simple type of readout you know just a positive or negative kind of thing and so besides a sort of desktop instrument another way that we're looking to potentially do this would be a handheld instrument that would. [00:23:35] To be able to basically handle a single test device at a time but it would be more portable On have rechargeable battery and could be used in a you know place like you know many of the you know use cases such as the you know where the entrance to a stadium or a theater or something like that. [00:23:55] So this is kind of. You know the concept it's not the fine these are these are concepts they're not photographs these are so we are we're still in the design phase to certain extent but we're hoping to have all our designs finalized very shortly. So today we've done a fair amount of testing we tested about $95.00 devices and. [00:24:21] That includes over to around $263.00 individual resonators on those $95.00 devices and we tested 6 different antibodies. We've just had negative control and body and I'm positive control for us live approaching 4 different covered 1900 bodies. And and we're pretty excited about the data so this is just our negative control our body the blue line is the baseline before incubation with the sample and then the red line is after incubation with saliva containing Spike protein that's spiked in there somewhere spiking in Spike protein and. [00:25:06] That is. And then it's washed with P.B.'s tea again which is sort of our buffer and read a 2nd time and so we're saying that you know it's fairly fairly low background and there's some background but it's fairly low and it was showing here the frequency along the x. axis and this is the power on the right so this is where we get our resident frequency. [00:25:30] And when we incubate do this with a resonator that's functionalized with an anti coded 19 and a body to spike protein. Then we do see a nice shift so afterwards when you see it's a very relatively easy to detect shift in resonant frequency and so this is sort of what the data looks like the raw data looks like when we when we perform on the test. [00:25:59] We also have tested. Positive controls of saliva protein and here you can see that we have before we have the p.b.s. t.v. and then the saliva without any spike protein is. Only in red and then testing it again the same resonator with saliva protein that spiked in with with coated proteins there's not really a subsequent shift or maybe a slight shift because it's incubated a little bit longer with saliva and so it's possible there's a little bit more of the saliva protein that's but dividing to the to the resonator so but by and large the positive control is working as expected the negative controls working as expected in an r. and r. Spike protein antibodies are working as expected so this is exciting and we're really you know. [00:26:50] I working very hard to try and get this. Translated into commercialization and we have very good signal to noise as well so this is just showing another example of the testing of the spike protein m n a shift and so we're getting shifts in that in the $1.00 to $2.00 megahertz range at a variety of different concentrations of. [00:27:20] Spike protein and actually this is showing sort of our. Respond dose response curve and this is actually of this shouldn't say peak Negron should say pictogram my mistake. So we were getting measurements down in the in the peak a gram per milliliter just like $25.00 if you're grams and going. [00:27:49] On up so we're you know there is there is some background which we're working on methods to minimize that and actually I think we've we made some some good strides in that direction actually as far as reducing not nonspecific binding to the resonators so so we're we're excited about about how this is as panning out. [00:28:14] And then there are other applications potentially for this. For it's a platform technology so so one way that you could potentially. Flip this paradigm on its head is to functionalize the resonators with Spike covered 106 by proteins and then apply. A blood sample from the patient or saliva sample potentially and determine whether or not that antibodies from the patient actually find to the proteins that are that are crossing point there and so so that's that's a one other application if you if you were able to do this in the same test because we can function as multiple resonators and you could determine in the same single test whether or not someone is infected or if they've been previously infected and whether that they have you know have antibodies to to the virus so that could be a you know really useful application of this technology. [00:29:20] Another one would be like we're starting to get into flu season so if you could at the same time in a single test determine whether someone distinguishing coded $1000.00 in the flu or r.s.v. then then you know that suits common type of viruses if you very useful to be able to know if someone had serious similar symptoms and you're not sure with a single test I could be very very hopeful as well. [00:29:49] Down the road another thing that we could potentially do is discriminate bacterial from viral infections using. Receptors or in the bodies or things like that that might. Be able to tell us whether or not these are viral indigents or bacterial and engines and because there's a huge over use of an overprescription of antibiotics when sometimes people have viral infections and and antibiotic resistance is a major health problem so being able to reduce the overprescription of antibiotics. [00:30:24] Would potentially be another useful application in the future. And then also you know for as far as you know just in general there are a lot of situations where there are biomarkers that might inform how a clinician might treat a patient what type of drug they might give them and also potentially to to determine whether or not they're responding to the treatment you know and being able to do this in real time you know in in an i.c.u. or an emergency room or you know or even for a cancer patient there's there's a lot of potential ways that we could you know get very useful data very quickly to. [00:31:08] Clinicians as they're as they're treating their patients and in helping them decide of the best course of therapy for them. Ok. So where are we now and where he's been so we started the company founded about 3 years ago long before code came along and we've been working on developing our initial prototypes and raising grant funding and stuff like that and then. [00:31:40] And then. When Cove it hit this spring we started working furiously to generate you know to sort of pivot to detection of the source code too and. We are in the process now of generating developing full working prototypes and generating the clinical data that we're going to need in order to attain hopefully f.d.a. emergency use authorization in the early part of next year and once that's done then hopefully we will be able to launch and scale such that we can be churning out millions of tests a month a year from now. [00:32:29] So so that's the plan that's that's what we're hoping to do. It's want to acknowledge there's a lot of people that have been involved in this of course. John Ashley is the c.e.o. of residence d.x. and has been with me every step of the way in this journey and there's a we have an amazing team of people at residence d.x. who are working this problem from every angle and we have a number of collaborators at Emory and at Georgia Tech we've had great support from the I and. [00:33:05] We're even fabricating our our wafers. And we've had tremendous funding support from Emory from the Georgia Research Alliance and from there and I hoping that very shortly I'll be able to add n.s.f.. To this list we'll see we're working on it and. And we have a great team of advisors as well so yeah this is this is a team effort and we are. [00:33:36] Hot in pursuit of getting these tests into the hands of the people who need them. But before. We can do that we have to we have to do all of the final design testing that's necessary to get f.d.a. approval. So with that I'd. Like to just thank everyone for attending for listening and I'm happy to take any questions Thank you Carlos for your. [00:34:06] Presentation and if you do have. Questions just came in I want to read it for you. Because your time. First question is from Fox I'll check he's asking great standing great talk maybe possible improve sense duty by enhancing transport of fire particle to census of race law midterm showed that wider transport can be enhanced by limiting the seeming of the fluid into lation to sensor how dollars you're sitting in your chip and can it be reduced. [00:34:41] Well that's a great question and that is actually something that we are investigating that has not been finalized at this point so you know in theory we could probably go. As low as you know 10 microns but you know we haven't really evaluate I think that there are there are pros and cons right now you know a lot of our testing the testing that we've done to date doesn't have a ceiling we've basically been doing it in open wells. [00:35:19] But shortly from now very soon we will have the flow chamber you know complete and built and we'll be doing additional testing in that scenario. You know there's a trade off when you have a larger chamber and you've got more energy in there that can bond and of bodies at any given time. [00:35:39] But you know if you have a smaller ceiling then there's a smaller distance for the images to diffuse so I am not sure that you know is. I suspect that that what we would probably need to do to to have confidence in how that ceiling affects our sensitivities actually do the experiment and manufacture multiple chambers at different heights and see if and how that affects our sensitivity I know that we would be able to flow less volume over over the chamber if the ceiling was lower but whether or not that would be negatively or positively impact our sensitivity we can't say without actually doing the experiment. [00:36:28] Thank you next comment is from David got fried and his question is he said thanks Carlos' What is the advantage compared to Q c m r Sufis last month resonance techniques Well that's a totally different technology and to be to be completely honest I'm not an expert in surface plasma resonance so I don't know that I could really. [00:36:55] Answer that question and in a way that is appropriate for the confident of what I was saying so I think I'm going to have to pass on that one sorry but on the physical size wise it's straightforward what you are now looking is free deployable it's a you know that So all in all. [00:37:15] I'm bound to reach Well certainly I mean this is I mean it's going to the idea here is to make a very inexpensive simple test surface plasma resonance I do know that that would be a much more complex and expensive if that's right it's very cost effective in your case yes. [00:37:35] And I need the questions let me see. If not I have a question that. You know what is the frequency difference between I mean just approximately just want to see the sensitivity between the blank as well as once you add it to your specific antigen you know there is a shift in the resonant frequency towards your left and glad to note that it's in megahertz So what would be the difference technically approximately between the blank as well as the actual the control as well as the actual underage and that you're trying to dodge and try to do you know analysis Well the differences in the frequency differences yet have have been generally and the one to. [00:38:25] We have high concentrations we sometimes see as high as 10 megahertz. But but in probably the more typical type of application I think we're going to be still looking at $1.00 to $2.00 megahertz is going to be. What we're going to be detecting most of the time the great thing is that your detection isn't likely to us which is the which is a huge huge advantage which will get it done in our early detection stages as well. [00:38:54] And it's a huge advantage still well there are no questions I would like to conquer. Dr Carlos Moreno one more time on behalf of not a fans are DNS and we all have a great.