While PCR-, antigen-, and antibody-based technologies have been the backbone technologies in the development of COVID diagnostics tests, other methods not usually used in the life sciences are also being explored as strategies to improve the detection of the coronavirus.
In that vein, a team at Massachusetts Institute of Technology led by Alfredo Alexander-Katz, an associate professor of materials science and engineering at the school and cofounder of TriboSense Technologies, has adapted technology, typically used for physics applications, to create a rapid antigen COVID test that has been able to detect viral proteins in minutes with high accuracy.
Trained as a theoretical physicist, Alexander-Katz thought that the problems and bottlenecks that confronted COVID-19 testing early on in the pandemic would be solved by now, hence his late entry into the field – his team has only been working on the application of the TriboSense instrument for diagnostic use since early summer.
But with the number of coronavirus cases in the U.S. and Europe once again soaring to record numbers, the need for more testing has again moved to the forefront, with some pushing for more rapid antigen-based testing. Such tests, though, have been hampered by less than ideal accuracy. TriboSense's technology, Alexander-Katz thought, could offer a solution.
The value proposition of TriboSense's test, according to Alexander-Katz, is that it delivers high accuracy with fast time to results and at the point of care. The test, called TriboSense One, doesn't have an optical readout for detecting viruses like many current tests on the market, but instead provides a mechanical readout to assess the strength of biomolecular interactions, looking at friction to detect a sample's molecular interactions and confirm the presence of the virus in very small concentrations, Alexander-Katz said.
The instrument measures how molecules in saliva affect the motion of sensing beads with magnetic properties to determine whether SARS-CoV-2 viruses are present or not. The beads and the saliva are mixed together during sample prep. Currently, the firm's test detects the spike protein of the virus, but given the versatility of the test, the magnetic sensing particles can be customized to stick to different types of proteins, or example the nucleocapsid protein of SARS-CoV-2, which the firm is also pursuing.
The technology is based on increasing the binding strength of the sensing beads to a substrate via the molecules or viruses one is looking for. Alexander-Katz used an analogy of trying to rotate a big wheel on "a perfectly icy surface" to describe the technology. Normally it would slip. But now, "let's imagine, [you have] this little ball that has spikes on it, and these spikes could either penetrate or stick to the surface of the big wheel and the ice, so that would give you traction. The moment you get traction, you will start moving," he said. "You get more friction and you're able to translate a larger distance – that's what we're actually measuring." In this analogy, the virus is the ball with spikes and researchers are using microscopic magnetic spheres as the big wheels that are being rotated. By detecting how they move they're able to know if there's virus present in the sample.
According to the company, TriboSense One has a sample run time of less than a minute and prep time of five minutes or less, meaning up to 500 tests can be run per hour. That, said Heather Signorelli, VP and chief laboratory officer at HCA Healthcare, is one of the test's selling points and one reason her organization is looking into learning more about the instrument and test.
"The biggest issue [for COVID-19 testing] is that you need a varying degree of vendors in order to satisfy the capacity needs," she said. "At HCA we're using over 20 different cartridge types across the company. We have antigen, we have isothermal nucleic amplification, we have PCR, really a lot of different things." The TriboSense test could provide another highly sensitive option for testing at the point of care in these settings.
The test uses saliva samples. Once the sample is collected, the consumer only has to do "very simple work" on it, mostly pipetting the sample into the solution, Alexander-Katz said.
The team is developing its COVID test to run directly on the instrument, which costs about $2,000 per instrument to build, although Joe Donahue, the company's chairman of the board and a former managing director at Accenture Life Sciences, said that once the firm is able to scale up, that cost could drop to about $1,000. He added that the company isn't planning to make money on the instrument and instead will provide it free to organizations that sign up to use the test. The test itself would be between $5 and $6, he added.
Currently, the firm has hard data on spike samples using a model system, and Alexander-Katz said the limit of detection is between five and 10 viral copies per microliter, comparable to PCR tests on the market. He also said the team is considering submitting their eventual data as a manuscript for publication. The models have been performed repeatedly with high accuracy, but more field validation is needed to confirm its accuracy.
TriboSense hasn't compared its test side by side with other rapid antigen tests, Alexander-Katz said, because it doesn't have access to those samples.
While sensitivity is crucial for COVID-19 tests, especially at the point of care, Signorelli said there needs to be a bigger push for at-home testing, even if their sensitivity doesn't match the performance of PCR tests, the gold standard for SARS-CoV-2 testing. "Right now, we have antigen tests and they're okay, they aren't as sensitive, and we are seeing some both false positives … as well as false negatives."
Earlier this week, the Food and Drug Administration released a letter warning labs and healthcare providers about potential false positives when using rapid antigen tests.
TriboSense is talking with two unnamed large hospital systems, as well, to start surveillance testing for the eventual submission of the test and instrument to the FDA for emergency use authorization, Donahue added. The hospital systems are interested in using TriboSense's test in parallel with their current PCR tests, he said.
"We've actually already started some of the conversations with everything from schools, some businesses, an airline," Donahue said. The firm is looking for $500,000 to $1 million in funding to "ramp up, build more instruments, get the test ready," and once that funding goal is met the company will be ready to conduct studies in about three weeks, he continued. Depending on FDA EUA, the company said it would be ready to deploy platform testing within three months of receiving funding.
So far, the development has been all self-funded primarily by Alexander-Katz with no external funding in the few months the company has been around. The TriboSense Mechanically-Transduced Immunosorbent Assay technology, which unlike the TriboSense testing system, was patented in 2013 by Alexander-Katz and his partner and cofounder at TriboSense Joshua Steimel. According to Alexander-Katz, the idea to look at the technology for ways to adapt it as a diagnostics tool came at the end of May or beginning of June.
"I think everybody's desperate to go back to normal," he said, but with the current state of testing, "I don't think we're going to get there as it's going right now."
The technology was originally created to measure protein-protein, protein-DNA, DNA-DNA and other biomolecular interactions to detect and quantify how strong the interactions are. "We had to go from scratch," he continued. "We had never worked on viruses … and we adapted the technology to be able to do this."
Donahue said that the instrument would work particularly well for multiplex tests detecting SARS-CoV-2 and influenza because there's a lot of flexibility to test for different antigens in the SARS-CoV-2 virus and other viruses. Alexander-Katz said they eventually want to expand testing to other diseases, but the imminent focus is on COVID-19. "We think that this is an excellent avenue for immunoassays," he said.
Combination testing for influenza and SARS-CoV-2 that detects from one swab is another major need, Signorelli said, because patients don't want to have multiple "brain swabs" taken and a lot of POC equipment on the market today requires multiple swabs. In particular, she noted the strong desire for CLIA-waived tests that can be run by nursing staff and other healthcare providers.
Donahue said that the instrument would have the biggest impact in point-of-care settings due to its small footprint and portability – it's "a little bit smaller than a desktop computer," he said. "It's really small and just highly portable, and the reagents are really simple."
The team hasn't done work to adapt the platform and test for home use yet but said it would potentially be suitable for use in airports, restaurants, office buildings, and hospitals to provide rapid, accurate results. TriboSense is also having conversations with diagnostic and laboratory testing companies who could help scale up manufacturing of the test and instrument, although he declined to identify them.
In terms of reimbursement, although the test costs about $5 to $6 right now, at scale it could cost as little as $3, making it potentially attractive to payors, according to Donahue.
This story first appeared in our sister publication, 360Dx, which provides in-depth coverage of in vitro diagnostics and the clinical lab market.
