NEW YORK (GenomeWeb News) – After years in development, a handheld point-of-care molecular diagnostic device from QuantuMDx is poised to hit the market next year with malaria and tuberculosis as its initial target markets, a company executive said last week on the sidelines of the 32nd Annual JP Morgan Healthcare Conference in San Francisco.
QuantuMDx has created a working prototype of the device, which is anticipated to be priced at around $500 and about the size of a cell phone. The company will be running trials internally through June and then it will beta test the device through the rest of 2014. If everything falls into place, the UK- based company will launch the instrument in 2015.
While other firms such as Akonni Biosystems, Seegene, and Quidel are either developing or have developed handheld or point-of-care molecular diagnostic instruments, QuantuMDx's device will offer advantages in speed, portability, and price, the firm's Co-founder and CSO Jonathan O'Halloran told GenomeWeb Daily News.
"We really wanted to reinvent the molecular diagnostic process … because we feel that if you are to do a real point-of-care molecular diagnostic device, it has to be portable," he said, adding that such a device must be able to provide results within 10 to 15 minutes, the amount of time a nurse or doctor spends with a patient, if it is to have use in a clinical setting.
QuantuMDx's device works with a patient sample that is placed into a cassette, which is then placed into the reader, which analyzes the sample and delivers the results.
The company had developed a benchtop instrument prior to the handheld device, but O'Hallaran said that the goal was always to develop an instrument that a clinician could carry around in a lab coat. The benchtop platform was never commercialized, he added, and instead was created "as a methodology to test different technologies to shrink to go into our handheld" device.
According to O'Halloran, in shrinking the benchtop technology into a point-of-care instrument, QuantuMDx reviewed each of the steps involved in getting results from a typical molecular diagnostic test — sample prep, PCR, and detection — to "reinvent" them and shorten the overall process.
First, the firm took the whole sample and did a mechanical lyse. O'Halloran said this is "nothing new," but then QuantuMDx further put the sample through a proprietary filter to separate it in a continuous flow format that combines affinity binding and chromatography, thus stripping the lysate of everything except the DNA.
"We've got this from whole sample in to PCR-able DNA coming out in under three minutes," O'Halloran said.
Next, to speed up the PCR process, the firm used a continuous flow method.
"When you look at the rate of incorporation of base pairs by polymerase, it's staggering, it's superfast," O'Halloran said. "The only limiting factor in terms of speed is the ramp rate … and that's why it takes so long."
But by using a macrofluidic approach, QuantuMDx's handheld device has been able to perform 30 cycles in less than seven minutes, and depending on the complexity of the sample, as fast as four minutes.
Continuous flow-based PCR, he acknowledged is "quite a dirty amplification methodology" that can result in artifacts. QuantuMDx circumvents this by using a silicon nanowire-based microarray technology the company licensed from Nanosys in 2009 for detection.
"Our specificity comes in the detection, so we don't necessarily worry too much about the fact we're amplifying artifacts," O'Halloran said.
The instrument then multiplexes the resulting amplicons "quite massively" within the tubes and in multiple channels. Probes are then spotted and a hybridization event occurs. The DNA is naturally negatively charged and through hybridization, a negative charge is built up on the surface of the nanowire, changing the resistance in the nanowire, allowing for measurement of changes in the current, and resulting in a diagnosis.
"Once we've hybridized it, we've got straight away a diagnosis, yes or no," O'Halloran said.
If more information is required, QuantuMDx has also created what it calls supercharged nucleotides to perform sequencing-by-synthesis steps. The target molecule hybridizes to the probe, and the first supercharged nucleotide is flowed in with polymerase. If the complement nucleotide or base is the next base on the template strand, the supercharged nucleotide is "incorporated into the nascent chain."
A large change in resistance in the nanowire is created if the supercharged nucleotide carries a large polyionic reporter. "This signal is stable as it is covalently tethered to the nucleotide," O'Halloran said.
The polyionic reporter is then cleaved, resetting the signal in the nanowire to the baseline resistance, and this is then repeated for the other three supercharged nucleotides and then repeated again, he said.
"Now, we're doing handheld DNA sequencing, and clinical grade sequencing, as well, which is really important," he said. While sequencing is not necessary for all applications, one market that the company plans to address, tuberculosis, does require targeted sequencing, O'Halloran said, because the TB genome has an H2 base pair hot spot that needs to be sequenced in order to understand drug resistance.
"There are well over 100 mutations within that hot spot alone," O'Halloran said.
QuantuMDx's technology will not compete with either benchtop or lower throughput sequencing platforms from Illumina, Life Technologies, or other sequencing firms, he said, adding that his firm's technology "fits in alongside clinical sequencing," but because it is targeted, "this allows [those firms] to expand their market. We're certainly not going to be competing with NGS technology."
The first application for the handheld instrument is anticipated to be drug-resistant malaria, a market that O'Halloran said is dominated by Cepheid with its GeneXpert technology.
Cepheid's model of placing fully integrated molecular diagnostic platforms for both diagnosis and drug resistance detection in "satellite" laboratories in locations with limited resources has done "great business," he said, but the model also has its limitations, including the need for a laboratory and electricity source.
"And so, the great things that they've done, we're trying to improve on [in order] to allow the rest of the rural communities that don't have access to this technology to have access to quality diagnostics," O'Halloran said. Globally about 700 million people are infected with malaria each year, and of that, about 35 percent are tested.
Initially, QuantuMDx will market its instrument as part of a soft launch in partnership with non-governmental organizations. It also is in discussions with potential industry partners.
While QuantuMDx has a pre-investigational device exemption meeting scheduled in March with the US Food and Drug Administration, O'Halloran said that the focus will be on the developing world and third-world countries. And as Cepheid has done, QuantuMDx expects to target high burden developing nations with its test.
In addition to malaria and TB, the firm has started investigating the HIV genome and is eyeing the sexually transmitted disease space as future opportunities.
As it continues building out its technology, QuantuMDx has started a financing round to raise between $8 million to $10 million, O'Halloran said, which would take the company to the point of commercializing the handheld device. Since its founding in 2008, the company has raised about £12 million ($19.7 million).
In addition to the POC MDx device, QuantuMDx is developing a benchtop sequencer that O'Halloran said will eventually compete with nanopore sequencing. Dubbed the 5 Percent Project — 5 percent of the company's time is devoted to the project — the effort aims at developing a DNA sequencing technology that arrays graphene wires in linear fashion. Single DNA molecules are fed through the wires, and as they go through each nucleotide is read.
The technology, he said, is "similar to having 1,000 nanopores stacked onto each other such that a single DNA molecule is read 1,000 times in one translocation."
The firm has just completed its proof-of-principle and the first chip has been developed. QuantuMDx is working with the Genome Institute of Singapore to analyze the generated data.