Robust and easy-to-use platforms are bringing PCR diagnostic tests into homes, pharmacies, and high-stakes environments such as airports
Credit: Sadik Demiroz/Getty Images
Nearly 40 years ago, American biochemist Kary Mullis developed the polymerase chain reaction (PCR). This technique impacted research in the life sciences so fundamentally that in 1993, less than a decade after he developed PCR, Mullis received the Nobel Prize in Chemistry. In academia and industry, scientists quickly made broad use of PCR, and to this day, applications keep expanding.
When Mullis accepted his Nobel Prize, he recounted what he had been thinking during his struggle to realize his vision: “Would it work at all was important. The next most important thing was, would it be easy to do?”
Today, PCR is extremely easy to use because of lots of hard work by scientists around the world. As the examples described here reveal, anyone can use PCR today, sometimes even in their homes.
PCR is usually used by scientists in laboratories. But what about the rest of us? To broaden access to PCR technology, Salt Lake City, UT-based Co-Diagnostics (Co-Dx) is developing the Co-Dx PCR home platform. According to Dwight H. Egan, the company’s CEO, “The Co-Dx PCR is an at-home and point-of-care rapid test.” The first assay created for this device, he says, “is designed to detect SARS-CoV-2 RNA with high accuracy using real-time PCR in around 30 minutes.”
The platform, which incorporates a reusable compact hub and a single-use cartridge, is being designed to support single and multiple pathogen assays. “Raw data is analyzed by a secure cloud-connected software, and results are displayed on the user’s mobile device, allowing optional transmission to the user’s electronic health records,” Egan explains. “The anonymized cumulative data can be shared for epidemiology and scientific studies, and for real-time geographical monitoring.”
To make such a system possible, Co-Dx uses cost-effective optics and components. Egan says, “The company has brought the manufacturing of several critical components in-house—including device manufacturing, engineering, software, dye synthesis, and oligonucleotide synthesis—and that allows process know-how to be kept as trade secrets.”
As a result, the Co-Dx platform is economical and has a small footprint. It is being developed for use almost anywhere. Although this platform is not on the market yet, Egan says that a single sample instrument will cost about $300, and each test will run about $20.
The company has plans for the platform beyond the COVID-19 test. Indeed, Egan says that assays can also be developed for several other respiratory diseases and sexually transmitted infections. Testing for COVID-19 and other diseases with this platform promises to go to consumer applications beyond home use. Egan notes, “We are also leveraging relationships with national pharmacy chains with the intention of offering the platform in retail pharmacy locations across the country.”
In Belgium, scientists at Imec analyze a person’s breath for indicators of infectious disease. This nonprofit R&D organization applies nano- and digital technology to a range of world problems, including healthcare. During the pandemic driven by SARS-CoV-2, Imec developed its COVID-19 breathalyzer.
As Peter Peumans, PhD, CTO for health technologies at Imec, explains, “We decided early on during the COVID-19 pandemic to focus on breath, because it was clear that exhaled particles were the way that the virus spreads.” The level of virus in exhaled particles also correlates to a person’s level of contagion. “So, we wanted to look for the virus inside exhaled particles,” Peumans notes.
Imec scientists planned to use real-time PCR (RT-PCR) to detect and quantify mRNA transcribed from DNA in SARS-CoV-2. To do that, Peumans and his colleagues first needed a way to gather the exhaled particles. “We needed to develop something that could collect particles efficiently and was easy to breathe through,” he details. “At the same time, it had to collect these particles in a very small volume so that the downstream workflow could be very sensitive.”
To do that, the Imec scientists made a two-layer silicon device. Breath enters holes in the top plate and exits through slightly offset holes in the bottom plate. “It’s a labyrinth for air essentially,” Peumans says. The device is perforated by a large number of holes, so a person can easily exhale through it, but exhaled particles can’t make the turn between the silicon layers. Like a Formula One race car coming into a turn too fast, the exhaled particles go off the “track” and hit the barrier. That captures the particles in a concentrated volume. Then, the particles are analyzed with a real-time PCR technology that Imec developed earlier for another application.
The scientists moved very quickly from an idea to a device. “It took us only about four months to go from sort of a paper-napkin drawing to hardware that we could test clinically,” Peumans recalls. “In a number of clinical studies, we compared this approach to the oral-pharyngeal swabs, saliva, and also the rapid antigen test, and we see that breath actually is the most sensitive of all the test approaches.” Peumans points out that the breath-based test is especially sensitive in the first few days of infection, “and that’s important because those are also the days where you’re most infectious.”
The current version of this detector could be used in what Peumans calls “high-stakes environments,” such as airports. In just 15 minutes, the device can analyze a traveler for SARS-CoV-2.
The COVID-19 pandemic, though, is not the only use of this technology. “We’re taking a hard look now at other indications beyond COVID,” Peumans declares. One of those indications is tuberculosis. Here, too, Peumans notes that “there are good signs that breath is a better sample.”
Beyond making calls and taking selfies, a smartphone can also contribute to PCR applications. For example, a smartphone can control Philadelphia, PA-based Biomeme’s Franklin PCR platform and display the results. “Our platform essentially transforms your smartphone into a mobile lab for advanced DNA/RNA detection and real-time disease surveillance,” asserts Max Perelman, co-founder, president, and CEO of Biomeme. “Each battery-powered thermocycler enables multiplex real-time detection of up to 27 targets with results in an hour or less, depending on the assay and test method.”
Including the battery, the Franklin weighs just four pounds. Biomeme’s next-generation Franklin ISP (Integrated Sample Prep) provides automated sample preparation for a wide range of sample types, and prototype versions can detect up to 45 targets. “To identify host-response signatures, we apply machine learning to enormous amounts of biological data obtained from human subjects to ascertain the human immune response to infection,” says Chris Woods, MD, MPH, chief medical officer at Biomeme. “Simply put, it is the art of reading the genetically encoded and highly specific response to illness to more accurately determine the root cause, the degree of risk, and/or the response to therapeutic intervention.”
Biomeme developed this technology for environmental, animal, and human-health applications in low-resource settings. “Over the years, our team has developed a diverse portfolio of PCR and isothermal tests including everything from biowarfare agent panels to food safety, water quality, industrial QC, vector surveillance, environmental DNA, animal health, and most recently human diagnostics with our EUA SARS-CoV-2 tests,” explains Jesse vanWestrienen, co-founder and biology lead at Biomeme. “Moving forward, we have plans to introduce host-response applications that cover a wide range of disease conditions from infectious diseases to autoimmune diseases and even drug response.” As an example, the first host-response test detects viral infection as soon as three days before symptoms develop.
So, yes, PCR is now very easy to do, probably easier than Mullis could have possibly imagined when he developed the technique in the 1980s. Now, it’s so simple to use PCR that the number of at-home platforms is surely just getting started.
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