By Greg Cima
NEW YORK – Backed by a mix of governmental contracts and VC funding, Irish startup Altratech is laying out a bold vision that its home-use microfluidic tests could replace PCR as the standard for molecular diagnostics.
Unlike PCR's approach of amplifying a target genetic sequence, Altratech's UbiHealth testing system incorporates peptide nucleic acid (PNA) technology developed with the US National Institutes of Health to attach molecular targets to beads with far greater mass. The test uses capacitance to identify the type and number of beads in a multiplex test, allowing what CEO Tara Dalton calls "molecular detection by proxy." The Cork-based firm's 20-person team is starting its foray into the molecular testing space with syndromic respiratory and fever assays, with chronic disease monitoring tests to follow.
The fist-sized battery-operated reader and credit card-size test cartridges deliver quantitative results to a user's smartphone within 15 minutes. Dalton said the components are shelf stable by virtue of using synthetic peptides. By incorporating simple, yet sensitive, complementary metal-oxide-semiconductor (CMOS) technology to measure capacitance into a design with no moving parts other than the beads used to move and detect the sample, the firm is aiming for prices below $30 for the reader and below $5 per test.
Dalton said the company has not yet started clinical trials, so its accuracy data are limited, but in internal testing with SARS-CoV-2 RNA in contrived samples, Altratech's test had 100 percent detection compared to RT-PCR in concentrations ranging from 500,000 copies to 1,000 copies of RNA. The tests returned positive results for three of six samples with 100 copies of the viral RNA, and the company aims in coming weeks to achieve detection between 50 and 100 copies with high sensitivity and specificity using contrived human saliva samples.
The company has also found that off-target RNA segments were detected about 1 percent as often as the target RNA segment, suggesting good specificity.
Dalton said during a presentation earlier this month at the Molecular and Precision Med Tri-Conference that in those internal tests, the assays were capturing upward of 80 percent to 90 percent of their targets. However, she acknowledged that Altratech's technology has lower dynamic range than PCR, with sensors that are limited to about four orders of magnitude.
Altratech's readers are several years away from being suitable for home use, though. The firm is currently raising money for clinical trials ahead of an expected launch in late 2025, and Dalton said the firm will try to gain traction first by selling to institutional buyers such as NGOs, governmental public health authorities, hospitals, and nursing homes as it forms the partnerships needed to later break into the direct-to-consumer market.
Adding mass to amplify signal
The test works in the following manner - once a blood or saliva sample is added to one of Altratech's test cartridges, biorthogonal PNAs latch onto specific sequences from each target molecule and then form a bridge between the target and a magnetic bead. Magnets in the reader pull those beads out of the sample fluid and through the stationary fluid in the microfluidic channels, where non-magnetic reporter beads attach to another sequence of the target molecule. As the magnetic beads are pulled further through the microfluidic cartridge, they drag the molecular targets and the 200 nanometer-diameter reporter beads to the cartridge's CMOS sensors.
During a heating step, the reporter beads release and fall onto the sensors, where PNAs bind the reporter beads to specific sensors and changes in capacitance identify the types and quantities of each type of target in the multiplex test.
Dalton said the quantification provided through Altratech's tests can provide important information such as whether an HIV patient's retroviral drugs are working well, or whether someone who is getting over an influenza infection is likely still contagious.
"It isn't enough for us to just say 'yes' or 'no,'" she said. "We want to be more nuanced about how we think about managing our illnesses at home."
The design and test procedure are simple enough for use outside clinical practices yet able to handle the shortfalls of many molecular diagnostic tests developed during the pandemic, she said.
"To me, they need to be multiplex, they need to be multi-analyte, they need to have wireless upload, they need to seamlessly interact with smart technology, and the most important thing is they need to be cheap," she said. "During the pandemic, you could justify $100 for a test when people were kind of desperate – you really wanted to know."
Post-pandemic, though, tests need to sell for under $10 each, she said. She predicts that home-based diagnostic testing will continue to become more powerful for guiding people's healthcare and improving access to health information, reducing the need to bring people into clinics for test results.
After Tri-Con, which was held in San Diego, Dalton said she came down with flu-like symptoms following her travels back to Ireland. She stayed out of the lab to avoid getting her coworkers sick but found herself wishing she had access to a test that could tell what was making her sick, whether she was getting better, and when she could return to work. But she added "I wouldn't have paid $100 for it."
Standing out from the pack
Altratech first began to take shape a decade ago, founded in 2013 by Tim Cummins, who has spent about 30 years in leadership roles of companies developing semiconductor and sensor technologies, and Brian O'Farrell, a genetics and biotechnology researcher who assembled Altratech's science and nanotechnology team. Dalton came on board as CEO in 2017, bringing her experience as a cofounder of the University of Limerick spinout Stokes Bio, a high-throughput microfluidic PCR instrument developer that was bought by Life Technologies, now part of Thermo Fisher Science, in April 2010.
Before the pandemic, Altratech secured €3 million in funding through the European Union's Horizon 2020 program for a project starting in late 2017 to develop a blood-based, point-of-care test that could help shift HIV viral load testing out of laboratories and into clinics. That project ended in November 2021, and according to a document posted on the EU's Horizon 2020 website, the firm said in its last reporting period that it had proven its target-enrichment bead and PNA probe system could capture HIV RNA from plasma samples without enzymatic reactions, centrifugation, sample preparation, or reverse transcriptase steps. The firm said at the time it was working with clinicians on trials to detect SARS-CoV-2 virus in samples from COVID-19-positive patients.
As it developed its technology, the firm has taken steps toward potential product commercialization. In December 2021 Venture capital and private equity firm Kernel Capital announced that Altratech had completed a €5 million investment round led by the Bank of Ireland Kernel Capital Growth Fund and Infinity Capital, each of which invested €1.5 million. Enterprise Ireland also invested €500,00 and Claret Capital provided €1.5 million venture debt facility.
Also, in September 2021, Altratech and the US Department of Health and Human Services jointly filed a US patent application related to methods of capturing target molecules using PNAs. And, in March 2022, Altratech received US Patent No. 11,274,291, titled "Sample preparation method and apparatus," for its methods of preparing a nucleic acid sample for use with PNA probes to bind and capture identifiable quantities of a target molecule. The firm said the latter is also patented in Europe and China.
In September 2022, the firm secured a $749,000 contract with the US Health and Human Services Biomedical Advanced Research and Development Authority (BARDA) to develop its handheld at-home SARS-CoV-2 detection test prototype and validate its performance in a pre-clinical study.
Altratech plans to enter the market with a respiratory panel that identifies not only the usual suspects of COVID-19, influenza, and RSV but also IgE antibodies indicative of an allergic reaction such as hay fever, Dalton said.
The next assay in the queue is a multiplex syndromic test for use in the developing world to distinguish among typhoid fever, dengue fever, and hantavirus infection. After those tests, Dalton said she looks forward to getting into diagnostics that can help monitor patient response to cancer therapies and HIV viral loads, to name a few examples.
Dalton said that, as a Europe-based company, it would be easier to debut the firm's products in Europe with plans to later enter the US market, although that launch could shift toward the US, depending on the sources of seed funding. Though it's certain the firm will seek CE marking for its products, the regulatory pathway in the US is less clear. Dalton said Altratech is working with consultants toward deciding which path to pursue with the US Food and Drug Administration.
The pandemic created a gold rush among diagnostic firms to fill the need for testing, especially at-home testing. Altratech's plans for a 2025 debut puts the company in the wake of that eruption of molecular and antigen tests.
Dalton sees potential competition from the likes of molecular test developers Cue Health, Sherlock Biosciences, and Mammoth Biosciences as Altratech heads toward the launch pad, but she predicts the firm will stand out in the crowd by offering lower cost multiplex tests.
Cue and Mammoth declined to comment for this article. Sherlock provided a statement in response that it is focused on delivering affordable, accurate molecular tests that will be available over the counter and accessible in decentralized global markets.
"Our novel chemistries enable very simple, low-cost devices that can be easily used by consumers around the world," the firm said.
Dalton noted the widespread availability of blood sugar tests as a life-changing development made possible through at-home diagnostics. Along with home-use pregnancy tests and COVID-19 assays, people have become accustomed to getting answers about their health on their own, and she thinks the future is in nuanced, high-content results.
While competitors are adapting and repurposing PCR technologies, Dalton said Altratech hopes to deliver next-generation molecular tests capable of delivering results on not only why people are sick but also whether they are getting better. Such a test, she said, could replace many uses of PCR, especially outside of healthcare facilities.