How New COVID Testing Technology Can Improve Global Health with Sally McFall, PhD

• Northwestern University engineers have developed a new, highly sensitive COVID-19 test that provides PCR test results in just 15 minutes. 
• The DASH platform and has received Emergency Use Authorization status from the U.S. Food and Drug Administration, the FDA.
• DASH was originally designed to improve point-of-care testing for infectious diseases such as HIV, tuberculosis, and hepatitis, specifically for low- and middle-income countries where diagnosing infectious diseases can be challenging due to limited technology and slow results. 
• McFall worked with David Kelso, Clinical Professor of Biomedical Engineering at Northwestern, to develop DASH and a spinoff company, Molecular Minute Diagnostics, for this new technology. At the start of the COVID-19 pandemic, McFall and her team saw an opportunity to apply this technology to COVID-19 testing, and as a result, shifted their focus. 
• They received $21.3M from NIH’s Rapid Acceleration of Diagnostics (RADxSM) initiative to manufacture a COVID-19 test using DASH. This accelerated their progress dramatically. 
• With patients able to receive test results during their doctor’s appointments, the technology is expected to significantly reduce transmission rates for COVID-19, not only in higher resource countries but especially in low- and middle-income countries. 
• The technology is also expected to improve health outcomes for COVID patients who need immediate medical attention and who would benefit from early treatment plans deemed necessary by an early diagnosis. 
• Offering the benefits of a rapid test with the accuracy of a PCR test, the DASH test for COVID-19 offers 95 percent sensitivity and 98.5 percent specificity and uses both nasal swab and saliva specimens to produce diagnostics. 
• While the use of the DASH analyzer machine requires an authorized license, the technology is simple enough that those who operate the machine – which is the size of a large cereal box – need not be medical professionals or experts. 
• McFall and her team expect to begin distributing the DASH machines for COVID use by this summer. In the meantime, they are working on 26 different analytes or targets for future diagnostic testing that could potentially include testing for influenza, TB, sexually transmitted diseases such as chlamydia, gonorrhea, Trypanosoma, HIV, HCV, and HPV, as well as various kinds of genetic testing.

Rob Murphy, MD [00:00:05] Welcome to the Explore Global Health Podcast. I'm Rob Murphy, MD, executive director of the Harvey Institute for Global Health here at Northwestern University Feinberg School of Medicine. There are many hurdles to diagnosing infectious diseases in low- and middle-income countries. A major problem is the lack of laboratories with the proper equipment and trained staff who can get test results back to a patient quickly. Technology developed by Northwestern University engineers is about to change that reality. A new, highly sensitive, easy to use test for COVID-19 has received EUA or emergency use authorization status from the U.S. Food and Drug Administration, the FDA. This technology platform, called DASH, stands for Diagnostic Analyzer for Specific Hybridization (hence we call it DASH) requires just a nasal swab swipe, and fifteen minutes later, it delivers a result with the accuracy of PCR technology. The plan is to roll this technology out for COVID testing now, and soon, to diagnose other diseases and infections, such as sexually transmitted diseases and any other infectious disease in people anywhere in the world, but particularly in low- and middle-income countries. Sally McFall, co-developer of DASH, is here with details of this homegrown technology. Dr. McFall is a research professor of biomedical engineering at Northwestern Engineering and director of the Research Center for Innovation and Global Health Technologies, which is based partially at the Havey Institute for Global Health. She has extensive experience in technology development in low- and middle-income countries. Sally, welcome.

Sally McFall, PhD [00:01:47] Thank you, Rob.

Rob Murphy, MD [00:01:48] Back in 2017, you and Dave Kelso, clinical professor of biomedical engineering here at Northwestern, developed DASH and a spinoff company called Minute Molecular Diagnostics for this new technology. Let's go back to 2017 and tell us how this all began.

Sally McFall, PhD [00:02:06] Dave Kelso and I had some ideas about how to make a point-of-care PCR test be completed in the time that it takes for the patient to be at the doctor's office, for example. So we had read some different reports, particularly from Charlotte Gaydos's group, that people would wait for 15 minutes for a test result. But if it got longer than that, they just weren't able to wait. They had things they had to do and they had to move on. And so that was our goal is to make our tests 15 minutes or less. And so we started working on the technology together.

Rob Murphy, MD [00:02:42] And so Charlotte Gaydos, by the way, is a professor at Johns Hopkins University that you were collaborating with at the time correct?

Sally McFall, PhD [00:02:50] Right. So I received a grant to develop technology from the Johns Hopkins Center for Point of Care Technology Development for sexually transmitted diseases. And so that was one of the first tests that we were developing for DASH. Our model assay was for a chlamydia diagnosis, and we were also developing tests for other specimen types. So for a test to work, you need to be able to extract the DNA or RNA from the sample and then amplify it and detect it with PCR, different samples can be more challenging for different reasons, and we want our platform to be able to use all different types of specimens. So when we developed the test, we had to test it with a lot of different specimens. So we tested with vaginal swabs, nasopharyngeal swabs, and whole blood.

Rob Murphy, MD [00:03:38] Let's great. We're still working with Charlotte and colleagues at Hopkins in the POCTRN network, this point-of-care technologies research network, that's an NIH-sponsored entity that's really taken us all a long way. Do you want to tell us exactly how being in that network has helped the development process for DASH?

Sally McFall, PhD [00:04:03] Well, sure. So Rob and I are the co-PIs for one of the centers in this POCTRN network or point-of-care technology research network from NIH. So when COVID hit, NIH requested that POCTRN pivot to addressing COVID-19. So I happened to be kind of at the right place at the right time because, you know, I also had been thinking about pivoting to test COVID. Back then it was kind of funny. You know, I thought, "Oh, maybe it won't last that long, and I won't have time to develop a test and stuff like that." But I decided to develop a test for COVID. And I was able to work on that and develop both the sample prep and the amplification. And I had even thought, well, maybe I'll just use it to test the lab to see if we're all safe, you know, during this bad time. But anyway, so the POCTRN network was tasked by the NIH to lead the RADx program, the government's response to developing diagnostics for COVID-19. And so Dave and I applied to RADx and at the time our technology wasn't mature enough, and so they did what they called diverted us to another funding source. And so we were actually funded by the POCTRN network and a grant from our center, and that money enabled us to develop to the point where we were fundable by RADx. So we kind of, you know, we caught up.

Rob Murphy, MD [00:05:30] The NIH poured all this money into this RADx, Rapid Acceleration for Diagnostics for coronavirus. How fast did that speed up your development? Did it speed it up by one year, two years, five years?

Sally McFall, PhD [00:05:44] I'd say two years. The RADx award to Minute Molecular was 21.3 million dollars, and that was to allow us to scale up, to take our technology and be able to produce enough tests to make an impact in the pandemic. And that I don't actually remember exactly how much the award was for...

Rob Murphy, MD [00:06:09] 3.7 million.

Sally McFall, PhD [00:06:11] OK. 3.7 million through their partner network through CTHAN that allowed us to kind of catch up and get to the place where we could be eligible for that RADx award.

Rob Murphy, MD [00:06:24] Yeah, the only reason I bring it up is that you know, everyone always says, "Oh, the government is so slow," and you know everything. I mean, this started, I mean, day one was April 29th, 2020, and it really is amazing what has come out of that. And one of the star developments in that whole program is the DASH project. To get a 15-minute PCR developed at a spinoff from a university -- it's really been incredible. Let's go on and talk about some of the other issues related to that and find out a little bit more about you because you're just such a fascinating person who's developed this incredible 15-minute PCR device. What drew you to wanting to improve point-of-care testing for infectious diseases such as, let's go back to HIV, TB, and hepatitis, specifically for low- and middle-income countries?

Sally McFall, PhD [00:07:16] I've always wanted to have my work have an impact. You know, I'm a scientist, so I wanted to approach it through a scientific method. I'm not the kind of person that's going to go out and be like on a board for a charity and raise lots of money. I'm more introverted than that.

Rob Murphy, MD [00:07:34] You can always do that. You know,

Sally McFall, PhD [00:07:37] I decided I would just try to use what skills I have, you know, the talents I have to try to make an impact. When I found out about molecular diagnostics and started working with Dave Kelso on point-of-care technology, it just makes a lot of sense to me because, you know, the patient can receive the result in that same appointment. And if there's a medication that's required or even just the communication to the patient, this is what we're going to do. It makes so much sense. There's so much less loss to follow up. And if it's an infectious disease, you can cut down on transmission. So I just think that it makes a ton of sense for this kind of approach in our, you know, higher resource countries, but even more so in low- and middle-income countries.

Rob Murphy, MD [00:08:22] But it has applicability here too as well. I mean, imagine going into one of these urgent care centers and want to have a test for COVID or whatever it is and to have them take one of your cartridges and stick it in the machine after they get the specimen, whatever the specimen is, and get a PCR answer in 15 minutes. I mean, it is really very dramatic.

Sally McFall, PhD [00:08:47] Yeah, we're really excited about that because we think we can make a difference in things just like transmission, right? So you can help someone improve their health by, you know, especially with these medications now for COVID that, you know the antivirals, you can shorten their infection help prevent them from spreading it to someone.

Rob Murphy, MD [00:09:08] That's a good point because, you know, now it's all about test and treat. The two drugs that are approved right now are for early treatment. You got to start it within five days of your symptoms, and if you don't have any symptoms, five days of your test, and a lot of people, by the time they even get the results back and all that, you know, they're past the five days. So timing is really critical.

Sally McFall, PhD [00:09:29] Especially in our population where we have people who are vaccinated and when they become infected, their immune system is working. They get symptoms maybe even earlier than they would have if they hadn't been vaccinated. But they're not antigen test positive, they're not home test positive. And so if they can, if they have symptoms and they're able to get a PCR result, like with DASH, then they would be able to immediately be given the antivirals. So especially with, you know, in high-risk patients, I think that's really critical.

Rob Murphy, MD [00:09:58] Compared to the tests that are out there right now, the ones you go into Walgreens or CVS and you buy a test for COVID, let's just start there. But it could be for anything else. They sell a lot of different tests there now. Besides the speed, those tests are also about 15 minutes. Besides the speed, what's the difference?

Sally McFall, PhD [00:10:18] Well, that's exactly what we were addressing is that you can get a test, that kind of test that you can buy at the drugstore, and the result will be there in 15 minutes, but it is not as sensitive as PCR. A PCR test can be positive about two days earlier than an antigen test. So if you have symptoms, you go to the store, you get that test, you test yourself, it's negative. Then you're supposed to wait a couple of days and then test again. And that's great if you are able to do that if you're able to stay at home and isolate. And, you know, but if you are not able to, a test like ours, if you know that you're positive, then you can alert your employer. You can kind of activate those systems where people understand why you have to be at home rather than just saying, "I may or may not have COVID." So, yeah, the test is a lot more sensitive, and it's also easier actually to run because the swab just goes right into the cartridge, you break it open, you break this swab at this breakpoint, you cap the cartridge, put it into the instrument, and the result is in 15 minutes.

Rob Murphy, MD [00:11:22] Well, speaking from experience, just recovering from my three-week COVID experience, I can tell you, when it started, it was just a sore throat and laryngitis. I mean, and a little fever. Now you develop this technology thinking of low- and middle-income countries in mind. Why is this kind of technology needed in a low- and middle-income setting?

Sally McFall, PhD [00:11:44] So there are a number of things. One is kind of logistics. In our health care system, if you take a test at your doctor's office, they might send the sample to a testing company and then the result is returned to the doctor. You know, the nurse will let you know. Or maybe it's online where you log in and you can message your doctor and you might see your result there. But in a lot of low- and middle-income countries, they don't have all that infrastructure. Once they collect the sample, if they send it to a lab, it may take a few days for the sample to get there.

Rob Murphy, MD [00:12:22] We did one study, looking at doing sophisticated testing in a setting such as that and in a low-income country. And not only did it take days to get the results back, this was regarding infant HIV diagnosis, but the study that she presented it was, I think, 40 percent of the people never came back, and that that's true everywhere. Everyone doesn't always come back for their test results.

Sally McFall, PhD [00:12:49] Or if they come back and they don't get the result, then they feel disenfranchised right. And then they tell their friends, don't even bother.

Rob Murphy, MD [00:12:57] And plus, the lab has paid for that already. PCR typically is expensive, relatively expensive. So this could be a real backbone of some laboratories and particularly in a place where there's no access to big central labs or an emergency room or someplace like that. How effective is it? Can you put some numbers on this?

Sally McFall, PhD [00:13:20] So in our clinical study that we used to apply to the FDA for emergency use, our sensitivity against another emergency EUA-approved test was a little bit above ninety-five to 95.6 percent sensitive, and our specificity was, I think, 98.5 percent. So we're highly sensitive and specific to this other test that is more laboratory-based.

Rob Murphy, MD [00:13:47] That's great. You mentioned a couple of sample types. What sample types can you put in there? Can you use saliva? Can you use nasal swabs?

Sally McFall, PhD [00:13:55] Yeah, definitely. So we use nasal swabs. So a nasal swab is what we received our emergency use authorization as a specimen type. But we've also tested saliva and that works. We can use swabs that go into what's called viral transport medium, which is that pink liquid that a lot of hospitals like to use. So, you know, if they took a sample from a patient, they could either use DASH or, you know, if they had a different test they also want to use the sample for, they could use that.

Rob Murphy, MD [00:14:24] So it doesn't really make any difference. You can use kind of anything.

Sally McFall, PhD [00:14:28] Yeah, anything for COVID. We could use a throat swab. And then looking forward, our next test is going to be a test for flu and COVID. So that when a patient comes in and they have respiratory symptoms, that kind of an overlap, is it flu or is it COVID, we'll be able to distinguish that.

Rob Murphy, MD [00:14:47] And that would be in the same cartridge?

Sally McFall, PhD [00:14:49] Yes, in the same cartridge.

Rob Murphy, MD [00:14:50] In the same test. So you just put the one swab in and it'll come back both negative or positive or positive or negative.

Sally McFall, PhD [00:14:55] Either flu-type or SARS-CoV-2 COVID. And then we're also developing a test for strep throat because again, what we were thinking is if you have our analyzer, what else would you like to test for? So if you're testing for COVID, you probably want to test for other respiratory infections. And since especially Omicron starts with a sore throat we thought strep A would be a good thing to detect.

Rob Murphy, MD [00:15:19] Now it takes 15 minutes, but you can only do one of these at a time, right?

Sally McFall, PhD [00:15:23] That's right. If you need to have higher throughput than that, then you can have more than one DASH analyzer and they can be linked together. So you can have one kind of teacher and the other pupils or however you want to think about that. So that one administrator could kind of manage all of them.

Rob Murphy, MD [00:15:41] Tell us a little bit more about the equipment, the DASH. What does it look like? How big is it? Is it heavy? Can you carry it around?

Sally McFall, PhD [00:15:48] Yeah, it's about three to five pounds, I think, and it looks a bit like -- it's about the same sizes as a box of cereal. It's a really pretty blue. It has a clock in the front with lights that kind of go around in a circle and show you if the test is nearly done. So that kind of helps you, if say you put the swab in and now you're over talking to another patient, you can kind of look over and see if the result is going to come out soon.

Rob Murphy, MD [00:16:14] So there are definitely machines that you're using. You have 10 in your own lab. Where were those made?

Sally McFall, PhD [00:16:20] So those were made... We have a consulting firm. They've done a lot of hardware and software development. And we also have a mechanical engineer we've worked with for many years, Tom Westberg, and they built those analyzers.

Rob Murphy, MD [00:16:36] Are they here in Chicago or...?

Sally McFall, PhD [00:16:38] They are. It's the DiMonte Group. And then they taught our contract manufacturer how to build them.

Rob Murphy, MD [00:16:44] Oh, that's great. Well, so really, truly a local development project.

Sally McFall, PhD [00:16:50] It is, it's totally local. Yeah, we've all worked together for many years, so this has been really nice combination of all of our collaboration over the years.

Rob Murphy, MD [00:17:00] So when somebody purchases one of these and the cartridges, how do you go about training the user?

Sally McFall, PhD [00:17:07] So for our emergency use testing, that's a requirement from the FDA is that you just give them a pamphlet, you give the users a pamphlet and they're supposed to be able to run the test without any training and that was successful. But when we do supply the analyzer and the cartridges, you know, to a customer, I mean, I think we want to give them a little bit more than that. We'll come and make sure that they're comfortable.

Rob Murphy, MD [00:17:33] How sophisticated do you have to be to actually operate the machine?

Sally McFall, PhD [00:17:37] So, you know, our authorization is for a place that would have a CLIA license. But as far as being able to run the test, you don't need very much sophistication at all. You just need to be able to break the swab and put it into the analyzer.

Rob Murphy, MD [00:17:55] Like, like who could do it? Could a student do it? Could an administrator do it?

Sally McFall, PhD [00:18:00] Definitely. In our emergency use authorization clinical study, the people who did the tests were not laboratorians; they were study personnel nurses. I think there were some students.

Rob Murphy, MD [00:18:13] But you don't even have to have a medical background.

Sally McFall, PhD [00:18:15] You don't know, no. That's true.

Rob Murphy, MD [00:18:18] So now that you have this EUA approval, emergency use authorization from the FDA, what's happening right now? Are you selling any of these things or marketing them? Or what are the next steps?

Sally McFall, PhD [00:18:31] So our rollout plan is to begin to sell our analyzers and cartridges kind of mid-summer time. Right now, we're scaling up the production of the analyzers and the cartridges. So we are working with contract manufacturers, we're transferring the technology, and we're going through all the kinds of documentation that we need to have in place to sell a regulated product like this.

Rob Murphy, MD [00:18:54] The EUA is for COVID, right? Yes. OK, now originally this whole machine, this technology was developed for HIV viral load, other infectious diseases like influenza, hepatitis C, as well as sexually transmitted infections like chlamydia and gonorrhea. How soon are you going to expand beyond coronavirus testing?

Sally McFall, PhD [00:19:19] That's going to be as rapid as we can because we think that the real strength of DASH is it's a platform. It can be used in a number of different tests. And in fact, we have a plan to expand to a menu that has 26 different analytes or targets.

Rob Murphy, MD [00:19:36] Twenty-six targets?

Sally McFall, PhD [00:19:37] Yeah, not all at once. I mean, but 26 different tests that we'll be developing over time.

Rob Murphy, MD [00:19:44] You're going to actually have to have a catalog. Besides what you've mentioned, what other things are you looking at?

Sally McFall, PhD [00:19:51] So there's flu A, there's flu B, RSV, sexually transmitted diseases, you know, chlamydia, gonorrhea, TB, Trypanosoma, HIV, HCV, HPV. We could do other kinds of genetic testing. You know, anything that you want fast, I think, is something that we could do on DASH. So if you needed to test for relative drug sensitivity, you know, like warfarin kind of thing. And know it, what kind of drug to give to a patient, we could probably do something like that on DASH.

Rob Murphy, MD [00:20:24] Probably one of the most common questions I get is "I'm going to a wedding or destination event. One hundred and fifty people and we want some kind of test to do for everybody." Right now, a lot of those places are testing with the rapid tests, you know, the over-the-counter rapid tests. But like you said, you know, there's sensitivity in asymptomatics. First of all, most of them are not approved in asymptomatic people. But this sensitivity is not that good. Could DASH actually be used in some situation like that? I mean, I just picked that up because I get that question a lot. But I mean, it could be a workplace situation. It could be the Gridiron dinner in Washington, D.C. Maybe they would have done a little better if they had a DASH machine before that thing. But you know, being vaccinated obviously is not enough. Do you see anything like that?

Sally McFall, PhD [00:21:18] Oh, definitely. So first of all, DASH is also not authorized for asymptomatic patients. We didn't test for that.

Rob Murphy, MD [00:21:26] Do you think you'll apply for asymptomatic testing at some point?

Sally McFall, PhD [00:21:30] It's such a difficult category because FDA considers somebody who has been exposed as somebody who, say your next-door neighbor tells you that she has COVID and you had been having coffee with her the day before, and you just want to know, do I have COVID? You don't have any symptoms, but when you go to be tested, you're not considered asymptomatic and the FDA tests, you have to be not suspecting at all. So you have to test a lot of people to find those few that were exposed and weren't really even aware of it. A lot of companies and physicians use a test like ours or even the rapid tests with asymptomatic patients, and they're allowed to do that. And it might make sense to use DASH in that way, before a wedding or before travel. For me, you know, I like to know that I don't have COVID or I am not harboring the virus before I see my, you know, my mom, who's 90, and my dad, who's 92. So I could see that type of testing, you know, before you go to visit your relatives or before a wedding or, you know, a meeting?

Rob Murphy, MD [00:22:33] No, that's incredible. Sally, it really is just incredible what you and Dave, and Kara have done with Minute Molecular Diagnostics. I hope people appreciate that full-blown thermo cyclic PCR, which is like the best, is now available, is now available for COVID and is simple to use. I mean, it truly is amazing. My last question to you is what has it been like to be part of creating such an important technology, a real potential game-changer like this that has the potential to impact so many people around the world?

Sally McFall, PhD [00:23:14] I just feel really proud to belong to this team. Just the work that the members of our research team have done to combine their different skills, and their different experiences into something that really works. So when we first had the idea of a 15-minute test, we didn't know we would be able to do it or not, you know, it was kind of pushing the envelope. That's what some of the lab members said to me when we got the EUA, they were like, we really actually did it, you know, it's like, we're just kind of just realized it. But it's been incredible to have this opportunity. And also just with a POCTRN network, they've been so supportive. The POCTRN network is in their third cycle, and our lab has gotten funding from each of the cycles. So we're really kind of the baby. And we just kind of have developed and matured along with it. I'm really proud of all the hard work that our team has done to bring this all together. It was, you know, we've had software engineers, hardware engineers, biologists, chemists, all working together to create this, and within the cartridge, everything kind of flows from the sample to the answer. It's not like the chemist did this and the biologist did that. Everything has to fit together and that's how we work together as a team to do it. Also, just working with you, Rob, all the way through COVID, both of us on that RADx program. Your being on our advisory committee for the CTHAN award and kind of helped guide us through that period of time as we tried to catch up with the RADx. It's just been really rewarding.

Rob Murphy, MD [00:24:55] It truly has. I was just proud just to be part of it. I was really a very peripheral person in the whole thing, but it's amazing. And again, I already said it once, but I'm going to say it again. I mean, you know, everyone always is complaining the government can't do anything. And, you know, look at what's happened during COVID. We are in a pandemic. We develop vaccines to the market within 10 months, and we've revolutionized testing. I mean, there are billions of tests now available and now a 15-minute PCR test. I mean it really is incredible. It reminds me a little bit about PEPFAR. It was the president's emergency plan for AIDS relief when basically most people had just written off Africa and many low-income countries just saying, well, they're never going to be able to afford it. They're never going to be able to distribute it. They're never going to be able to monitor it. They're never going to -- never, never, all this. No, no, no. And PEPFAR was a huge success. And this is kind of in the same genre as that, you know, people said you couldn't do it, and then it gets done and it's great and it's a game-changer. And it's been so fun working with you. It's so fun talking to you today about your experiences over the last couple of years and getting this product out there and our homegrown Northwestern and Chicago product. And I'm sure everybody that's listening to this is going to be getting something tested one of these times. So and it's really, it's really quite amazing. So thanks for joining us and thanks for all the work. I'm so proud of you and this entire project. Thanks again.

Sally McFall, PhD [00:26:40] Oh, thank you so much, Rob. Thanks for having me on your podcast.

Rob Murphy, MD [00:26:50] Follow us on Apple Podcasts or wherever you listen to podcasts to hear the latest episodes, and join our community that is dedicated to making a lasting positive impact on global health.