A Better, Faster, Cheaper Test for COVID-19

Since the outbreak of the COVID-19 pandemic, national and local governments have come to realize that although sheltering in place helps to flatten the curve" of new cases, economic and other considerations mean we can't stay home indefinitely. But if we are to regain some sense of normalcy, early detection of the novel coronavirus, SARS-CoV-2, will be essential to containing it-at least during the period between the easing of restrictions on gatherings and commercial activity and the development of a vaccine.

At this moment, the best diagnostic tests for SARS-CoV-2, based on real-time RT-PCR (rRT-PCR) assays, are sensitive, but they require expensive equipment and trained technicians. What's more, there's a relatively long turnaround time for getting an answer (at least 24 hours prep time after receipt of a sample, plus 6 hours to complete the actual test procedure).

Now a multidisciplinary group of researchers at the University of Minnesota, with expertise in magnetics, microbiology, and electrical engineering, says it has developed a test that is relatively cheap, easy to use, and quick to deliver results. The group, led by Professor Jian-Ping Wang, Distinguished McKnight University Professor and Robert F Hartmann Chair in the Department of Electrical and Computer Engineering, and Associate Professor Maxim C. Cheeran, from the department of veterinary population medicine, says it is looking to have a commercially viable version of its prototype system available soon enough to help speed up the pace of prevaccine testing. IEEE Spectrum interviewed Wang, an IEEE Fellow, about his group's portable testing system.

IEEE Spectrum: How would you describe your virus detection system in a sentence or two?

Wang: It's a portable platform based on magnetic particle spectroscopy (MPS) that allows for rapid, sensitive detection of SARS-CoV-2 at the point of care. Eventually, it will be used for routine diagnosis in households.

Spectrum: Give us a quick primer on the science underlying the MPS testing technique.

Wang: MPS is a versatile platform for different bioassays that uses artificially designed magnetic nanoparticles that act as magnetic tracers when their surfaces are functionalized with test reagents such as antibodies, aptamers, or peptides. Imagine them as tiny probes capturing target analytes from biofluid samples. For COVID-19 antigen detection, we functionalized our nanoparticles with polyclonal antibodies to two of the four structural proteins that are components of the coronavirus (nucleocapsid and spike proteins). The antibodies allow the nanoparticles to bind to epitopes, or receptor sites, on these particular proteins. The more binding that occurs, the greater the presence of the virus.

Spectrum: So, how does the MPS system answer the question Does this person have coronavirus?"

Wang: The MPS platform's job is to monitor and assess the real-time specific binding of the nanoparticles with these proteins. The quantity or concentration of the target analyte-in this case, the aforementioned proteins indicating the presence of coronavirus-directly affects the responses of the nanoparticles to the system's magnetic field. The magnitude of the difference in their behavior before and after the addition of the biofluid sample tells the tale. Because the biological tissues and fluids are nonmagnetic, there is negligible magnetic background noise from the biological samples. As a result, this volumetric-based immunoassay tool is not only uncomplicated, but also accurate and effective with minimal sample preparation.

Spectrum: Take us through the steps of a testing cycle using this device.

Wang: No problem. But let's back up a bit and note that our group has developed the MagiCoil Android app that processes information from the device's microcontroller in real time. And crucially, it also guides users on how to conduct a test from start to finish. The user interacts with the MPS handheld device using their smartphone, which communicates with the device via Bluetooth. Testing results are securely transmitted to cloud storage and could be readily shared between a patient and clinicians.

To run a test, the user begins by inserting a testing vial into the device and waiting as the system collects a baseline signal for 10 seconds. Then the user adds a biofluid sample into a vial and waits again as the antigen and antibody bind for 10 minutes. The system will automatically read the ending signal for 10 seconds, then display the results.

Spectrum: How did you know this would work?

Wang: This epitope binding of the nanoparticles and target analytes form viral protein clusters, similar to what occurred when we applied this technique to the detection of the H1N1 nucleoprotein reported in our previous work.

Spectrum: What makes your team sure there won't be a shortage of testing vials containing the functionalized nanoparticles (a situation comparable to the current shortage of reagents for COVID testing)?

Wang: For each test we use only a microgram of nanoparticles and a nanogram of reagents (antibodies, RNA fragments). We are already collaborating with nanoparticle companies, who supply us with high quality iron nitride nanoparticles for this application. Our group has also been seeking collaborations with biotechnology companies to secure sources of chemical reagents.

Spectrum: What challenges has your team faced and how did you overcome them?

Wang: Over the past decade, there was very little attention paid to filling the need in the market for a low-noise, easy-to-use, portable bioassay kit for the detection of viruses-not until we began working on detecting Influenza A Virus subtype H1N1 in the past year. We have steadily grown the team, accumulated experience in this research area, and optimized the MPS platform. In addition to full-time researchers, the MPS and MagiCoil team has benefited from the efforts of many talented graduate and undergraduate students from different areas. This work has resulted in the current version of the MPS device and the accompanying app.

I feel proud of my students for forging ahead on a project because they see it as an important bit of research and never giving up. Since the outbreak of the COVID-19 pandemic, we saw how critical it was for us to speed up work on our project so we could contribute to the fight against the virus by making our MPS device available as soon as possible.

Spectrum: Your team's aim has been to get this in doctors' offices so anyone could walk in, get tested, and walk out knowing whether they've contracted the coronavirus. But in places like New York City, people have been urged to stay away from hospitals and clinics unless they are experiencing acute symptoms. How important is it to go beyond the clinical setting to household use so even asymptomatic people know their status?

Wang: From the outset, we wanted to make it inexpensive and easy to use so untrained people could conduct tests at home or out in the field in remote areas that are the antithesis of clinical situations. It will let large portions of the population afford to get regular updates on whether they have contracted the virus. And because it is capable of transmitting test results collected from distant locations to centrally located data-analysis units, governments can have real-time epidemiological data at their fingertips. This would also significantly reduce the costs associated with tracking the spread of a disease and help health authorities more quickly evaluate and refine their disease control protocols.

Spectrum: How long before the system is commercially available?

Wang: We have just transformed the benchtop version of the system into a handheld version [which, at 212 by 84 by 72 millimeters, is about the size of an old-school brick cellphone]. We have carried out preliminary tests such as characterizing the minimum amount of magnetic nanoparticles detectable and the system's overall antigen sensitivity. And we're still homing in on the optimum concentration of antibody to be functionalized on the nanoparticles so they'll be most effective.

We anticipate that clinical trials will take an additional 3 to 5 months. At that point, we will work with local companies in Minnesota to mass-produce MPS devices. The University of Minnesota Office for Technology Commercialization has been helping us lay the groundwork for founding a startup company in order to accelerate the process of commercializing this handheld device the instant we receive the necessary government approvals.

Spectrum: You mentioned antigen sensitivity. How much virus must there be in a sample for the MPS system to detect it?

Wang: We are currently evaluating what is the lowest concentration of virus our test can detect. But based on our experience with the H1N1 flu virus, it will be less than 150 virus particles.

Spectrum: I know it's hard to say definitively, but give us a ballpark figure for the eventual price of the MPS testing system.

Wang: Based on our first prototype MSP device, we foresee the unit price starting at roughly US $100; the MagiCoil app, which is already completed and available for download from the Google Play store, is free. Testing vials containing the functionalized magnetic nanoparticles targeting the coronavirus will cost between $2 and $5 each.

Eventually, we plan to make a second-generation MPS device that's as small as today's smartphones. That step will require expertise in the areas of microfluid channel design, printed microcoils, high moment magnetic nanoparticles, automatic biofluid sample loading and filtering, optimized circuit layouts, etc. We are open to collaborations with other groups (including, but certainly not limited to, IEEE members) to make a better, lighter weight, sensitive, fully automatic MPS device.