U.K.-based DnaNudge expects its lab-on-chip-based system to complete validation tests and win clearance for field deployment within days...
The race to produce systems to test for Covid-19 with quick turnaround results has been a priority for many biomedical companies. One of these companies, U.K.-based DnaNudge, expects its lab-on-chip-based system to complete validation tests and win clearance for field deployment within days, according to its founder, Chris Toumazou.
The professor from Imperial College founded DnaNudge. The firm had earlier this year showcased a portable lab on a chip to carry out in-store DNA testing to help consumers to shop for food items which match their specific nutrition needs based on genetic profile. Now the system has been adapted to enable a rapid lab-free PCR (polymerase chain reaction) test that can detect Covid-19 and deliver results in just over an hour.
DnaNudge’s solution uses its patented and miniaturized NudgeBox analyzer and cartridges to provide a substantial improvement on current lab-based PCR testing times – which take at least 1-2 days before a patient can receive the results. The system combines a genomic DNA extraction protocol and multiplex real-time PCR amplification using the simple-to-use instrument and low-cost single-use cartridge. The swab is placed directly into the cartridge and then straight into the box for analysis.
The process requires accurate control of a number of key factors to help ensure a high-quality result. The core lysis and solid phase DNA extraction protocol is integrated in the core of the cartridge and purified material passed to an array where 72 independent DNA amplification reactions are very carefully controlled and monitored to determine particular genetic variants. The system was developed in conjunction with Cambridge, UK-based technology consultancy TTP, utilizing expertise in cloud communication expertise and biological assay development, as well as system engineering, thermal control and optics and design, through to manufacturing.
It’s like a ‘printer’
Speaking to EE Times, Toumazou said the concept is similar to the printer world, where you have the box (printer) with all the firmware and processing, and the cartridge, which extracts and amplifies DNA from a swab from the patient’s cheek. “The heart of the system is the firmware and processor. There is sophisticated electronics in the box employing lots of processors, and it controls the servo system which turns the cartridge too.” He said the key differentiator its solution offers is ‘multiplexabilty’ on one optical chip, a small miniaturized optical array. “The fact that we have 72 well plates means we can put on one chip all the primers for the Covid-19 virus.”
The UK’s Department of Health and Social Care has procured 10,000 DnaNudge Covid-19 RNA testing cartridges to roll out to clinical sites. Toumazou said, “Early validation results for our technology in the Covid-19 patient study have been excellent. The DnaNudge test was developed as a lab-free, on-the-spot consumer service that can be delivered at scale, so we clearly believe it offers very significant potential in terms of mass population testing during the Covid-19 pandemic.”
He added, “We are hoping to get clearance to deploy within the next few days, and for Medicines & Healthcare products Regulatory Agency clearance to use it in the filed without the full CE mark certification.” If this happens, Toumazou gave us some indication of how many tests could be carried out. “With 40 boxes we can do 14,000 tests in a week, while with 2,000 boxes we can do one million tests in a week. We are hoping by end of May 2020 we will have around 300,000 cartridges and around July August one million cartridges.” We asked whether as a startup they could cope with that capacity. The response was assuring: they have contract manufacturers lined up, with Benchmark to produce the boxes and Jabil the cartridges.
Replacing the optics with semiconductors
We also asked Toumazou what was next. He said the next generation of boxes would replace the optical chip with semiconductor DNA sequencing technology, as developed by one of his other companies, DNAe. Last week, this company announced that the US Food and Drug Administration (FDA) had granted its LiDia-SEQ technology and first assay with “Breakthrough Device” designation.
LiDia-SEQ is a semiconductor sequencing-based diagnostic platform, where analysis and read-out take place on a single silicon chip, and run direct from specimen in a rapid, easy to use format. Ion sensitive field effect transistors (ISFETs) are used to detect nucleotides as a simple electrical signal. As nucleotides are incorporated during the step-by-step construction of nucleic acids, they release hydrogen ions, which can be detected as an electrical signal. If there is no match, no hydrogen ions are released, and no signal is detected. This method is universally applicable to sequencing of any DNA or RNA on a standard CMOS semiconductor chip. There is no need for fluorescent dyes or labels, or precision optics, which make current DNA analysis equipment bulky and expensive.
This eliminates the need to measure optical signals or use lasers and microscopes. The system can perform a range of genomic analyses, to deliver fast, accurate and insightful diagnoses. The entire process is automated, from raw sample through to actionable report, in a cartridge-contained, hands-free format.
The DNAe device will support a pipeline of rapid and cost-effective tests, including for infectious disease diagnostics, cancer, infection control, and preparedness and response for pandemics. The first assay for which the device was granted the FDA breakthrough device status is in infectious disease, a direct-from-specimen test for bloodstream infections and antimicrobial resistance to detect and identify infections that can lead to sepsis.