NEW YORK – For many diagnostic firms, developing a portable immunoanalyzer has meant sacrificing sensitivity and specificity. Startup Proxim Diagnostics believes its Profile platform has solved the puzzle and is working to get its cartridge-based, handheld instrument ready for use during the SARS-CoV-2 pandemic.
The fully automated instrument performs enzyme-linked immunosorbent assays, much in the same way as larger immunoanalzyers used in central labs, such as Roche's Cobas or Abbott's Architect systems, said Proxim CEO Mikhail Briman.
Briman's goal when he started the company with cofounder Vikram Joshi was to create a point-of-care solution to run the same tests with the same sensitivity and precision as a central lab analyzer, which he said was "much easier said than done." He added that there has to be the right balance between the instrument and cartridge's complexity and the ease of manufacturing.
Proxim is developing a rapid antigen test for detecting SARS-CoV-2, but instead of using lateral flow technology, which he said can sometimes have issues with sensitivity, it is using a cartridge-based ELISA system, which provides increased sensitivity – especially for SARS-CoV-2, an area where there have been significant questions around rapid antigen tests' sensitivity and specificity.
The difference between Proxim's platform and other handheld systems, Briman said, is that "our sample handling process follows exactly the same biochemical steps as in the central lab equipment." He added that the firm chose electrochemistry as the detection method because "it's the most amenable method to the point-of-care environment, where you don't have to use expensive optics, that might require special maintenance, to detect biomolecules."
The platform is designed to run multiple kinds of tests, and a user can purchase the specific disposable cartridge preloaded with antibodies for the test needed, such as a test for interleukin-6 levels or troponin, scan the cartridge's QR code, which has information on what the test is and what the best procedure is, insert the cartridge, and let the instrument run. Briman said the firm made "certain detection chemistry tweaks" to make sure the detection method was particularly sensitive.
The cartridge will eventually cost about $1 to make, and one of the company's key plans is to use cheaper manufacturing methods to ensure the price of each cartridge and analyzer isn't too high, which would help its adoption in countries like China and India, Briman said. The low cost will also allow it to be used in rural areas that may not have access to centralized laboratory testing.
"That's one of the core ideas that we have … to make sure it's not just a Cadillac for the Western Hemisphere," he said.
Each cartridge comes with a three-plex immunoelectrochemical sensor with capture antibodies and fluid control sensors, as well as a lyophilized bead with reporter antibodies, according to a 2019 study published in Bioanalysis. It also has a blood-plasma separator and two blister pouches, one with wash buffer and one with signal generating substrate. Once results are determined, they can be transferred externally using WiFi, Ethernet, or a USB port. The data transfer options are up to the user, Briman said.
The laboratory industry has historically used batch processing testing, which provides a high volume of test results. Lately, though, that has changed because of the need for faster results, which central lab can't always accommodate, Briman said. The Profile instrument is not aiming for high-volume results, but is instead focused on quick results and portability, he added.
Customers can purchase the universal instrument and order a set of cartridges based on test menu preferences, with options to specify how many instruments and cartridges they want, as well as what kind of cartridges.
Proxim's antigen test for SARS-CoV-2 uses patients' nasal and saliva samples. The test is for detecting the nucleocapsid protein of SARS-CoV-2, which Proxim chose to focus on because "the N protein is thought to be stable … and is in abundance in the nasal/oral fluids," Briman said. He isn't sure yet how their antigen test performance compares to PCR-based testing, the gold standard for COVID-19 testing, but said that "analytically we are more sensitive than [other] rapid antigen tests" so he expects "very good agreement with PCR."
The firm will likely target point-of-care settings, such as urgent care clinics and physicians' offices, and because of the test's high sensitivity, it may have potential use in CLIA-waived settings, according to Briman. The antigen test has a limit of detection of 19 TCID50/milliliter. TCID50 represents the viral load at which 50 percent of cells are infected when a solution containing the virus is added to cell culture.
The firm has also developed antigen tests for influenza A/B and respiratory syncytial virus that could be multiplexed on a single cartridge.
In addition to its rapid antigen test for SARS-CoV-2, Proxim is developing an IL-6 blood and plasma test for the coronavirus, leveraging work it was doing even before the pandemic hit. Proxim had earlier contracted with Roche's Genentech to develop an IL-6 test to help with the diagnosis of sepsis and cytokine release syndrome, and so, Proxim was already well on its way in developing the technology when the pandemic arrived. Results can be achieved within 15 minutes, the Bioanalysis study found. The limit of detection for the IL-6 test was 0.6 pg per milliliter, and Proxim's platform had comparable results to larger immunoanalyzers typically used in centralized labs, including Roche's Cobas systems.
Some studies have shown that measuring IL-6 levels in SARS-CoV-2 patients can predict the severity of an infection and risk of respiratory failure, helping physicians and hospitals allocate resources to patients who will need mechanical ventilation and ICU beds more immediately. Roche and Beckman Coulter both have IL-6 tests that have received Emergency Use Authorization from the US Food and Drug Administration for use in SARS-CoV-2 patients.
Although Briman declined to specify exact commercialization timelines and regulatory plans, he said the company is actively discussing regulatory approvals, both internally and with the US Food and Drug Administration and plans to focus on the US market and obtaining Emergency Use Authorization from the FDA. The company has "nothing [left] to invent," he said, meaning the platform's development is complete, and is sending questions to the FDA as it plans its regulatory and commercial strategies.
It has also shored up its manufacturing plans – currently, Proxim is assembling the pilot cartridge lots, Briman said. But he added that the assembly process is straightforward and can be outsourced to contract manufacturers if needed.
During the pandemic, a major issue for test developers has been manufacturing capacity and supply chain limits. Briman declined to specifically comment how Proxim would navigate those bottlenecks, saying only that the firm is using similar manufacturing processes as other firms. He said the firm has "designed our cartridge in a way that will use the same manufacturing techniques/approaches as large companies with proven scale" of 10 million to 100 million cartridges per year.
In addition to tests for COVID-19, the Mountain View, California-based company has more than 10 other tests in development, including one for cardiovascular disease measuring troponin levels and procalcitonin tests for sepsis. The firm plans to pursue 510(k) clearance from the FDA for its other analytes, Briman added. Although he wouldn't specify exactly what stages of development those tests are in, he said they all "have a viable path to be cleared by the FDA."