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AMDI Developing 10-Minute Point-of-Care PCR System, Pursuing CLIA Waiver for Respiratory Panel

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NEW YORK – With the capacity to detect 32 targets from a single patient sample in 10 minutes, startup Autonomous Medical Devices Inc. (AMDI) hopes its sample-to-answer PCR system will make an impact at the point of care.

The Santa Ana, California-based company claims its novel sample prep and spinning disk microfluidics enable a low cost of goods, and it plans to position its Fast PCR System for infectious disease testing beginning with a CLIA-waived respiratory panel. Its core technology combines 15-second sample prep and ultra-fast PCR thermal cycling with spinning disk-based microfluidics.

AMDI was founded in 2019 as a spinoff of Sensor-Kinesis, a biosensor-based diagnostics maker that was itself a spinoff of medical device maker Pharmaco-Kinesis. Its CEO, David Okrongly — well versed in diagnostics having previously held the roles of senior VP of molecular diagnostics at Siemens Healthineers, chief operating officer at Exosome Diagnostics, president of diagnostics at Opko, and CEO of Quanterix — took the helm in 2021.

Okrongly said that the firm's high multiplexing is enabled by splitting a small volume of patient sample into multiple reactions. "We take the raw sample and put it into eight cuvettes that run eight individual PCR reactions," he said in a recent interview, adding that each of the eight chambers incorporates four-color detection.

The sample prep step briefly applies extreme heat and pressure, dubbed hyperbaric heating, to patient specimens placed in an iron metal component at the center of the cartridge. "It's a little mini pressure cooker," Okrongly said. Along with a few proprietary chemicals, this releases nucleic acids and removes inhibitors, he said.

In a poster presented at the 2023 annual conference of the Association for Diagnostics & Laboratory Medicine (ADLM, formerly known as AACC), AMDI said the method uses a cocktail of chemicals in its sample collection material to protect DNA and RNA from the high heat. It then applies a 15-second pulse of high pressure and 130-degree Celsius temperature using induction heating. "Material coming out of the hyperbaric heating is really clean," Okrongly noted, and it doesn't need any purification or beads.

Hyperbaric heating sample prep in turn allows the firm to drive its ultra-fast PCR — technically defined as PCR performed in less than 10 minutes — without the need for high concentrations of enzymes as might be required for other methods, he said.

Furthermore, "the big bugaboo about doing fast [PCR] has been solving the riddle of how to do heat transfer very quickly in the device," Okrongly said. "That's what we solved with our very thin profile."

The thin cuvettes can be heated and cooled very quickly, he said, "then we just rotate it, which can obviously happen in fractions of a second." The 40- to 45-cycle PCR step is completed in 7.5 minutes on the AMDI system, Okrongly said.

Thomas Lehnert, a microfluidics expert at École polytechnique fédérale de Lausanne in Switzerland and coauthor of a Lab Chip review published last month, said in an email that there are pros and cons to centrifugal microfluidics, such as that utilized by AMDI's system.

The key advantages include the easy automation of protocols — which is particularly important for POC systems — and no need for external pumps, Lehnert said. Disk-based systems are also suitable for multiplexing, Lehnert said, for example, in a Hahn-Schickard 19-target respiratory panel called RespiDisk described in Analyst in 2020.

However, powering microfluidics with centrifugal force can also cause complex fluid dynamics, Lehnert said, and the fluidic design can be more challenging than for conventional microfluidic chips. That said, "critical assay steps, such as mixing, may possibly be performed more easily and efficiently on a disk," he added.

AMDI's use of thin cuvettes for sample prep and PCR means "thermal transfer may be very fast, enabling fast reactions and fast thermal cycling," Lehnert said. In general, microchips require small volumes compared to conventional methods, and this tends to reduce the cost of reagents, he added.

The firm is developing a respiratory panel as its first application. As described in the recent announcement of a second round of funding from the Rapid Acceleration of Diagnostics Technology program (RADx Tech) at the National Institutes of Health's National Institute of Biomedical Imaging and Bioengineering, the first syndromic panel for the system will detect respiratory viruses such as influenza A and B, respiratory syncytial virus, and SARS-CoV-2.

Potential competition

The Fast PCR System could face competition on many fronts.

For example, other systems commercialized or in development using the ultra-fast approach include OnSiteGeneMolecular Biology SystemsThermal GradientGNA Biosolutions, and the Scope Fluidics PCR One acquired by Bio-Rad Laboratories in 2022 for $170 million along with subsidiary Curiosity Diagnostics.

This level of multiplexing puts the Fast PCR System on par with the legacy BioFire FilmArray, but with a significantly shorter turnaround time. The BioFire SpotFire reports results in 15 minutes, however, and its SpotFire R panel, cleared and CLIA-waived last year by the US Food and Drug Administration along with the instrument, detects 15 targets. BioMérieux also announced Thursday an investment in Norwegian diagnostics instrument maker SpinChip, and that firm's website describes development of an all-in-one system that can potentially perform immunoassay, clinical chemistry, hematology, coagulation, and molecular diagnostic tests using microfluidics and dual axle centrifugation.

Hahn-Schickard, a microsystems engineering firm based in Freiburg, Germany, developed its LabDisk test cartridges in collaboration with the University of Freiburg and developed the LabDisk player with researchers at Qiagen's Lake Constance center. The Hahn-Schickard team continues to develop the system, for example, publishing a method using LabDisk combined with nanobead extraction to capture cell-free DNA last year.

LabDisk was licensed to diagnostics maker SpinDiag, and that company's Rhonda system based on the tech claimed 36-plex capability and a 15-minute turnaround time. SpinDiag claimed to have performed 1 million COVID-19 tests during the pandemic, but last year it failed in a bid to find strategic investors and ceased operations due to insolvency, according to its website.

Hahn-Schickard is currently partnering with at least two other firms to commercialize LabDisk. Dermagnostix is developing tests to differentiate skin conditions like psoriasis and eczema, while Dialunox is a contract manufacturer offering test development on the Rhonda instrument.

Christian Fischer-Rasokat, associate director and head of business development at Dialunox, said in an email that Hahn-Schickard grants licenses for different fields of application, adding that when SpinDiag closed, the license likely went back to Hahn-Schickard.

Another similar system was developed by Branford, Connecticut-based Tangen Biosciences. That firm obtained Emergency Use Authorization from the FDA for its battery-operated spinning disk GeneSpark system and a loop-mediated isothermal amplification COVID-19 test in September last year. But in January, the RADx award recipient requested that the EUA be revoked, telling the FDA that it had ceased making the test and instrument, and there were no GeneSparks in distribution in the US.

DiaSorin acquired the Focus Diagnostics Liaison MDX spinning disk system from Quest Diagnostics in 2016 and has commercialized 12 assays, at least seven of which have obtained FDA clearance. At its 2023 Investor Day in December, the firm said it is developing a next-generation system called the Liaison MDx+, which will be finalized in 2024. The company plans to start converting its MDx panels to MDx+ formats and submitting to the FDA in waves over 2024 and 2025.

And, the SpinDx system from Sandia National Labs has also been offered for licensing and was most recently reported to be capable of performing both PCR and immunoassays. 

However, AMDI's Okrongly said that while there are many companies that have developed centrifugal systems, other platforms tend to move fluids around to different sections of the disk to do their thermal cycling. "We took a different approach," he said, with the system moving the disk between different heating zones.

The RADx support may ultimately also give AMDI a leg up. The company has a RADx-assigned adviser at the National Institutes of Health as well as access to regulatory consulting and the FDA's test evaluation program.

In addition to ADLM, the company last year brought the system to Association for Molecular Pathology and American Society for Microbiology Microbe meetings. "We've been very well received," Okrongly said, with potential customers particularly excited about the hyperbaric portion of the fast PCR disk.

With clinical lab staff and researchers, "we try to be as open as we can to make sure whatever product we come out with is what they need and what they would want to continue to work with," Okrongly said.

Through these conversations, the firm learned that connectivity at the point of care is a huge issue for users, and the firm is developing the system to use cloud-based computing and storage of patient data, with data also transmitted directly to the patient's health record. These qualities will be available to users "out of the box," Okrongly said. "Our goal is to make this a very seamless install," he said.

The company expects to offer the instrument primarily under reagent rental contracts, but should a user wish to purchase the system outright, Okrongly said it will cost under $10,000.

AMDI is not disclosing a timeline for launch of the Fast PCR System at this time, Okrongly said. Whether the future menu will include high-plex testing may depend on reimbursement considerations, but the real estate is available on the disk. After the respiratory panel clearance and CLIA waiver, the company plans to continue to expand the menu but is not ready yet to talk about that publicly. "Putting an instrument out with just one test on it isn't a sustainable strategy," he said.