NEW YORK ─ Boston-based startup InnoTech Precision Medicine is collaborating with the Massachusetts Institute of Technology to develop a biosensor platform that multiplexes antigen and nucleic acid biomarkers to test for SARS-CoV-2 and other medical conditions.
The developers are leveraging the strengths of antigen and nucleic acid testing by "multiplexing up to eight biosensors for selective detection of their corresponding protein and nucleic acid targets," said Roya Khosravi-Far, InnoTech's CEO and cofounder.
By combining separate sensors that detect protein and nucleic acid biomarkers, they expect to overcome some of the challenges associated with current tests, she said.
Nucleic acid-amplification tests based on PCR technology and rapid antigen tests are the two most common types of tests being used to detect the SARS-CoV-2 virus, but each has its drawbacks. Though antigen tests enable rapid results, they lack the sensitivity required in some use cases. Meanwhile, PCR tests can be too sensitive, detecting trace amounts of the virus in an individual when the person is not infectious, and the time to results is slower than for antigen tests.
With an eye on improving performance and turnaround times over current tests, InnoTech has licensed technology from MIT that it believes can be further developed to provide results for protein targets in less than 15 minutes and molecular targets in less than 30 minutes.
The partners are collaborating to develop sensors, disposable test cartridges, and an instrument under a US National Institutes of Health Rapid Acceleration of Diagnostics initiative called RADx Radical — a program that supports the development of testing technologies that address current gaps in COVID-19 testing and support preparedness for future outbreaks.
Some of the work completed as part of the initiative was recently published in Analytical Chemistry, Khosravi-Far noted. In it, MIT developers reported the development of sensors "that enable rapid and antibody-free detection of SARS-CoV-2 viral proteins with high sensitivity."
"Such out-of-the-box approaches" could be "added to the existing toolkit we have to detect SARS-CoV-2," said César de la Fuente, a Penn Medicine presidential assistant professor in psychiatry, microbiology, chemical and biomolecular engineering, and bioengineering, commenting on the Analytical Chemistry publication.
"Particularly impressive was the stability of the nanosensors and functional demonstration of the technology in human saliva," said de la Fuente, who is not affiliated with InnoTech or MIT but is developing a biosensor based on printed electronic inks to detect SARS-CoV-2.
The biosensors at the core of the new platform can recognize respective biomarkers of interest in saliva, serum, or plasma as well as other biofluids, Khosravi-Far said, adding that the presence of target biomarkers in a sample results in a shift in infrared signals inherent to the sensors, which is read by an instrument.
The sensors consist of single-walled carbon nanotubes and specific polymers that can be combined for selective detection of protein or nucleic acid targets, and configured to detect emerging pathogens of interest, she said, adding that the developers can build sensors to detect new targets in 14 days or less.
As part of the testing platform, the disposable cartridge consists of channels for the sample as well as biomarker recognition and signal transmission sensors. For nucleic acid detection, RNA extraction and sample preparation are completed in the cartridge and an isothermal amplification cycle is being added, Khosravi-Far said.
Because the platform uses synthetic sensors, it circumvents problems such as lot-to-lot variation common with antigen tests that use antibody-based detection, she said.
Vikas Berry, head of the department of chemical engineering at the University of Illinois at Chicago, said, "This is an innovative carbon nanotube sensor technology in the area of antibody-free sensing. … Making [the platform] selective without an antibody is a step in the right direction." However, more development may be needed to enhance the selectivity of the platform's sensing element, he added.
Berry is developing biosensor-based diagnostic tests for SARS-CoV-2 active infections and other indications but is not affiliated with InnoTech or MIT.
Giuseppe Spoto, a professor of chemical sciences at the University of Catania, noted that the COVID-19 pandemic has shown that PCR-based testing is invaluable, but better tools are still needed, particularly for the detection of protein targets.
Though the InnoTech and MIT method will need to be validated on a broader scale, it directly addresses the need for better tools that have "the potential to be easily adaptable and improve on the performance of protein detection tests," said Spoto, who is not affiliated with InnoTech or MIT but is developing a biosensor-based testing platform for the plasmonic detection of nucleic acid and protein biomarkers.
InnoTech, founded in 2019, has a near-term aim to develop its platform for SARS-CoV-2 testing in urgent care centers, doctors' offices, and the home, but longer term it anticipates developing the technology to detect other medical conditions and for high-throughput testing in laboratories.
Furthest along in development is a test that detects multiple components of the SARS-CoV-2 protein in saliva, Khosravi-Far said.
Though levels of sensitivity and specificity are not yet available for its tests, the firm is seeing limits of detection down to 100 viral particles per milliliter of sample which, Khosravi-Far noted, compares favorably with lateral flow SARS-CoV-2 antigen tests in the market that show limits of detection of 10,000 viral particles per milliliter and higher.
The company believes that it can obtain US Food and Drug Administration Emergency Use Authorization early in 2023, or sooner, for the handheld instrument and first test, but it is not yet disclosing anticipated prices of tests or instruments. Validation studies for all tests in its pipeline are being designed to also enable future submissions for 510(k) clearances, Khosravi-Far noted.
Seeing an opportunity to improve on current SARS-CoV-2 tests, numerous companies are developing biosensor technologies.
In April, Greensboro, North Carolina-based Qorvo Biotechnologies may have paved the way for biosensor technologies seeking to enter the market for SARS-CoV-2 testing. It received FDA EUA for its bulk acoustic wave SARS-CoV-2 antigen test and in the same month, announced an award of $24.4 million in funding from the RADx initiative.
Harvard University's Wyss Institute is developing biosensor technology called eRapid that uses a proprietary nanocoating to reduce biofouling and nonspecific binding, increasing test accuracy.
And in Europe, Madrid-based startup Mecwins is developing biosensor technology that uses plasmonic resonance to enable multiplex testing of protein, RNA, and DNA biomarkers in a single platform to test for SARS-CoV-2 and other conditions.
Meanwhile, InnoTech has its eye on developing numerous tests. In the company's product pipeline are biosensor-based diagnostic tests to detect the onset of a cytokine storm, a severe immune reaction that can be an early indicator of sepsis and inflammatory conditions such as rheumatoid arthritis and can be used to monitor the health of patients on cancer immunotherapies.