NEW YORK – Following CLIA waiver for its 15-minute qPCR system and combination COVID/influenza assay earlier this year, diagnostics developer Nuclein is further expanding into the point-of-care testing space with plans to begin clinical trials later this year for two new tests.
Nuclein obtained 510(k) and CLIA waiver from the US Food and Drug Administration in January for its DASH system and a multiplex test to detect COVID-19, influenza A, and influenza B infections.
At first blush, this all may seem unusual for a small startup. "It's very rare for such a new entrance to the space to get not only 510(k) but also CLIA waiver on a PCR system," said Nuclein CEO Alan Blake.
However, the DASH system has a formidable pedigree.
Developed over a decade by researchers David Kelso and Sally McFall, along with their colleagues at Northwestern University's Center for Innovation in Global Health Technologies (CIGHT), the system was initially commercialized by their startup, Minute Molecular Diagnostics, with $21.3 million in support from the National Institutes of Health's Rapid Acceleration of Diagnostics (RADx).
Minute Molecular obtained FDA Emergency Use Authorization for the DASH in 2022 along with a test for COVID-19, and subsequently merged with Nuclein in 2023.
Nuclein placed DASH units in the market under the EUA, Blake said, but its larger focus has been commercializing its COVID/flu test through the FDA 510(k) and CLIA waiver process. Now, the firm no longer has EUA systems on the market but has instead transitioned exclusively to the 510(k)-cleared DASH systems.
With its initial regulatory goal achieved, "we're working to expand our respiratory menu," Blake said, specifically aiming to enter trials this year for a combination COVID, flu, and respiratory syncytial virus assay and a test to detect strep A infection.
Longer term, Nuclein is also eyeing assays for sexually transmitted infections, Blake said, as the STI space is a particularly great fit for a rapid molecular approach.
The CIGHT team described the DASH system in an evaluation of the COVID test published last year.
The cartridge consists of six sample preparation chambers in the main cartridge body and a PCR chamber in the microfluidic extension, according to the study. The analyzer elutes viral RNA from the swab, and targets of interest are bound to paramagnetic particles through sequence-specific capture, while amplification uses a one-step RT-qPCR reaction.
In an evaluation of 313 outpatients described in the study, the DASH SARS-CoV-2 test demonstrated 95.5 percent positive percent agreement and 98.7 percent negative percent agreement with the Cepheid Xpert Xpress SARS-CoV-2 PCR test, with a low invalid rate of 0.3 percent.
Speed's the key to POC
At the point of care, clinicians frequently race the clock to accurately diagnose and treat patients within a single visit. For infectious diseases, this is particularly critical, as once patients leave the likelihood they will return for their test results gets slimmer.
The speed and ease of use of the DASH system may give it an advantage in a point-of-care space increasingly focused on test-to-treat care model, which overall targets testing times of 20 minutes or less. There were at least 17 CLIA-waived molecular diagnostic tests for infectious diseases on the market as of March 2024, according to one review of point-of-care MDx, and DASH's 15-minute turnaround time appears to be the most rapid of them all.
The DASH performs such rapid qPCR by integrating 10-minute sequence-specific magnetic capture for sample preparation and five-minute thermal cycling reactions enabled by rapid heat exchange.
"This is a very unique technology," Blake said.
And although there are currently at least three other companies developing systems that are as fast as the DASH, "this is out there now," Blake said. "It is actually FDA-cleared and CLIA-waived, we have an in-house manufacturing facility, and we're producing and shipping product," he added.
The DASH system is compact — about the size of a cereal box — and can operate from battery power, and it doesn't need to vent heat, "so, it can sit basically anywhere," Blake said. It was also designed with connectivity in mind, with WiFi and Bluetooth enabling it to sync up with electronic health records.
The workflow is also quite simple. For the combo test, providers swab a patient's nose, break the tip of the swab into the test cartridge, insert the cartridge, and then wait for the results. The test requires no liquid handling steps or training to use, and cartridges are also shelf stable for one year.
So far, "we've received a very positive response in the marketplace," Blake said.
Building out
The system currently multiplexes four targets, Blake said, but Nuclein expects to be able to expand that in the future.
"We also believe we can target a variety of different sample types," Blake said.
Nuclein is distributing DASH through Henry Schein and Cardinal Health, and is currently growing its internal sales team, Blake said. It is also making instruments available under a reagent rental strategy and is "competitive on cost," he said.
Although Nuclein was originally founded with core technology for at-home, handheld PCR testing, Blake said the firm is not focused on that right now. "We're still interested in the home market in the long term, but our focus is very much in the point-of-care space right now with the DASH system and expanded menu," he said.
Recent changes in federal funding, however, have impacted Nuclein. The firm received a Phase II award from Smart4TB, a US Agency for International Development (USAID) program administered out of Johns Hopkins University, but recently learned that funding was cut.
Blake noted that the current uncertainty can be quite challenging, particularly for companies that spend tens of millions of dollars and many years developing diagnostic products and ramping up manufacturing and sales.
"It's a very long process, very capital intensive — a lot of the companies start the process, but unfortunately not very many are able to get to the other side," he said.
Nuclein will keep moving ahead, however, and the firm expects to attend conferences and get the word out about its system.
"There is not a lot of awareness that now there is a 15-minute test for COVID and flu," he said, but, "finally, we have the best of both worlds — the speed of an antigen test and the performance of PCR."