NEW YORK – Austin, Texas-based startup Nuclein has developed a disposable handheld real-time PCR system and a prototype assay for SARS-CoV-2, the virus that causes coronavirus disease COVID-19.
The company is seeking partners to commercialize the system with hopes of making it available for at-home, physician-guided testing, among other potential use spaces.
Nuclein was founded in 2017 by Alan Blake and Richard Crockett. The two had previously co-founded Yorktown Technologies, a developer of genetically modified fluorescent fish, whose core GloFish IP was acquired by Spectrum Brands for $50 million. Prior to that, they had collaborated on a startup in the online learning space.
The company's core technology is a small, battery-operated real-time PCR system. Called the Nuclein Hand-Held PCR Test, it provides results in less than one hour.
"It is a technological leap," Blake said in an interview. "We believe it is critically needed to supplement the current testing tools that we have to combat the COVID-19 pandemic."
The firm overcame a host of challenges to port qPCR to a simple disposable device, Crockett said, specifically related to sample preparation, amplification, and detection.
For extraction, the firm has a few innovations in lysis and has adapted the process to move raw sample in one linear motion so it mixes with reagents and moves through chambers without complex fluidics, Crockett said. The firm has tested this extraction with a number of different types of cells, with good results.
Another of the innovations involves thermal cycling without use of pumps or other apparatuses, he said. Specifically, the firm's technology uses a magnetic displacer piston, whereby a simple electromagnetic coil drives a small magnet embedded in a plastic piston.
"As the piston moves to one end of the reaction chamber, it displaces the PCR reaction fluid to the other end of the reaction chamber," Crockett said. Since the two ends of the reaction chamber are kept at different temperatures, this effects the thermal cycling.
The device also uses standard fluorescence detection, overcoming the challenges of porting optical detection from the benchtop to a disposable unit. "The detector is right up against the reaction chamber and can, by use of a short light path and innovative filter design, use very low-cost components to do the same type of detection that would normally require dichroic lenses, mirrors, and other complex optical components," Crockett said.
The company developed this technology internally and has filed patent applications, Blake said. Â It originally started working on the device in 2017 with an eye toward an applied market application, namely to test mosquitoes for Zika virus. It had been in stealth mode, but the team saw an opportunity with the current crisis and need for COVID-19 diagnostics.
Blake emphasized that the device will require FDA evaluation, and it is intended for use in consultation with a medical professional, either in person or through telemedicine.
"We recognize that the FDA has not yet cleared any devices for at-home use, so we are hopeful that they would be interested in that type of application for our device," Blake noted.
That said, "The technology lends itself to a use in a variety of locations, and it would certainly be suitable from a technological perspective for at-home use in combination with telemedicine," Blake said, but he emphasized, "This is not intended for use outside of a consultation with a medical professional."
In the frequently asked question page of the FDA's Emergency Use webpage, the agency has said it "sees the public health value in expanding the availability of COVID-19 testing through safe and accurate tests that may include home collection." And, in a call with developers on Wednesday, the agency also suggested that point-of-care nucleic acid tests that have demonstrated safety and performance could potentially be overseen by a clinician through a telemedicine portal in order to enable home use.
Crockett reiterated that the Nuclein test is technologically simple enough that it could be operated in low-complexity settings, but the firm is not positioning it for direct-to-consumer testing. "Interpretation of the test we feel would be best suited in the space of a doctor-patient relationship," he added.
In addition, the technology could be used at "border crossings, airports, nursing homes, and rural settings – anywhere that you could imagine wanting to do a PCR test in under an hour with no technical expertise, and without having to mail in a sample," Blake said.
Nuclein is working to have the device and COVID-19 assay available by fall 2020. It has not yet run any live viral samples on the device, but has used viral RNA.
"Our goal is to have these devices widely available before the next cold and flu season, as there is potentially a second wave of COVID-19 around that time," Blake said.
Now, Nuclein is seeking partners to commercialize the device. The firm has a manufacturing partner in medical device manufacturer International Biophysics Corporation whose CEO, David Shockley, is on Nuclein's board of directors.
However, at some point Nuclein expects to scale production volume, so it is looking for potential strategic partners among assay developers, reagent producers, and large-scale manufacturers, Blake said.
Given the current COVID-19 doubling rate in the US outbreak, Crockett said that eliminating testing delays for qPCR results could help break the cycle of infection.Â
Nuclein has been privately funded to date. Blake said the team intends to approach the Biomedical Advanced Research and Development Authority (BARDA) for additional funding, but added that the main focus now is looking for partners "to help move forward as quickly as possible."