Inside the Diagnostics Industry: MDx Emerging on Mobile Platforms

Most of the conversation regarding shifting test volumes of advanced molecular testing toward decentralized locations has focused on whether this type of testing, including next-generation sequencing-based testing, will be housed in large, reference laboratories or whether the testing will be performed in smaller, local laboratories as the price of instruments declines. But emerging technology companies are making the case that advanced testing can be accurately performed even closer to the patient as a point-of-care (POC) test performed in a clinic, doctor’s office, or even in field environments. “There is a push to explore what one can do with a smart phone and consumer electronic devices, but that is not 100 percent aligned with diagnostic market requirements,” says Arjang Hassibi, Ph.D., founder and CEO of InSilixia (Sunnyvale, Calif.), which is developing a POC, highly-multiplexed nucleic acid detection  platform. “The hardware in smart phones is more applicable to measure easy physiological signals, like EKG, but the toolbox is very limited. But there is a need to bring in vitro diagnostic tests, both basic metabolites and more complex, to the POC or near patient settings.” InSilixia was a Distinguished Award winner in the Nokia Sensing XChallenge, in which microdiagnostic systems were highlighted.  The goal, Hassibi says, should be an automated, portable molecular diagnostic (MDx) instrument costing less than $1,000 (per-test price of less than $50) that can target up to 1,000 nucleic acid (DNA or RNA) targets with high accuracy in an hour. With award money and venture capital investments in tow, many companies will be launching commercialization efforts within the next year. The technology behind these systems could make “bedside” genomics a reality, but company executives are focusing their efforts on finding the ideal markets for these emerging platforms, recognizing that POC success will be biomarker dependent. “A prostate cancer gene might not need to be known immediately, whereas with an actionable, critical care marker you would want to know sooner rather than later,” says Jared Bauer, CEO of ApolloDx, a Salt Lake City-based company developing a multitest, mobile diagnostic platform. Bringing testing to the site of patient care holds the promise of lowering costs, increasing workflow efficiency, and providing a more personalized care experience. “The infrastructure needs and cost of sending out a test can be substantial. If you can get the same result at the POC within 10 minutes, you can discuss the results right there and then, and can cut out some of the massive infrastructure requirements,” Bauer tells DTET. “Physicians have been reduced to clerks. A pediatrician told me he spends a portion of his time everyday making multiple calls to laboratories.” Aside from the potential gains in workflow efficiency, such technology can impact patient care. Generating actionable MDx results takes too long and is too costly. As an example, Hassibi cites testing options for urinary tract infections, which he says generate 7 million visits annually. A dipstick test ($30) is approximately 70 percent accurate in identifying infection, but it generates results in half an hour. By contrast, a urine culture may take days ($40 to $100) but can detect E. coli infections with near perfect accuracy. MDx can determine not only E. coli infections but also the resistance profile of strains, with similarly superior accuracy, but DNA analysis (more than $500) could take weeks. “The positive economic argument for these mobile platforms is more than just unit and test costs,” says Jo-Ann Stanton, Ph.D., the lead of a University of Otago (New Zealand) team developing a portable polymerase chain reaction (PCR)-based DNA sequencing instrument. “Real-time access to diagnostic information means a response can be made at the time and place it is needed.” Implications of Mobile Platforms for Laboratories “Small, portable, low cost DNA sequencers certainly have the potential to bring genomic medicine out of large centralized pathology laboratories and closer to the patient,” writes science program lead Leila Luheshi, Ph.D., on the blog of the health policy think tank, PHG Foundation (United Kingdom). “The availability of mobile sequencing might also become particularly important for rapid genomic testing outside large-scale health care facilities, in community medical centers or as parts of mobile screening units.” Luheshi cautions, though, that demonstrating both the analytical validity and clinical utility of these devices is “likely to be long and far from straightforward . . . , [but] caveats aside, it is important to remember that the world’s first DNA sequencer in a USB stick is now up and running, and the future of ‘mobile genomics’ looks bright.” Additionally, experts believe that mobile genomics can improve access in resource-limited markets as well as improve the timeliness of care in developed nations, particularly in the area of infectious disease testing. While the technology is expected to be disruptive, it will not be the demise of traditional laboratories. “It is not a doomsday for the laboratory,” Bauer says. “We are going to market working with the laboratories. Laboratories need to be involved.” DTET conducted a survey of the emerging marketplace to identify mobile platforms that have entered or will enter the commercial realm within the next year. The Freedom4 platform utilizes quantitative PCR to identify DNA sequences in real time. The platform was developed over six years at the University of Otago and is being spun out of the university’s commercialization office in partnership with the New Zealand company Ubiquitome. Stanton, lead of the Freedom4 device development team, tells DTET via e-mail that the device is poised to become a commonly used tool both in and out of the classic health care environment for rapidly detecting suspected viruses or bacteria. The device weighs the same as a typical laptop but is palm-sized. The Freedom4 has a six-hour battery life and can be tethered to a laptop or connect wirelessly via smart phones or tablets, running custom software, for results analysis and interpretation. The Freedom4 device is currently commercially available for research use only with early access pricing of $10,000 for the remainder of 2014. Per-test pricing and regulatory strategy will depend on the diagnostic development partner, Stanton says. The open platform has demonstrated analytical equivalence to commercial lab-based platforms and assays for a range of gastrointestinal and respiratory viruses. InSilixia’s Hydra-1K platform utilizes a complementary metal-oxide-semiconductor-based DNA analysis technology. The platform uses conventional reagents including polymerases and synthesized DNA oligonucleotides. DNA sequence identification is enabled by a highly-multiplexed amplification and pixel-level DNA capturing and optical detection, all in the same reaction chamber. Hassibi tells DTET that the company’s initial focus will be in high-volume infectious disease detection in clinics and other near-patient settings. The company expects its first commercial product to be available after approval through the 510(k) process in late 2015. Hassibi says InSilixia’s strategy is to aggregate test volume through a combination of pursuing larger, clinically relevant markets in-house and partnering (through licensing agreements). The Hydra-1K could drastically undercut current diagnostic methods. The company says it can run highly accurate DNA tests in an hour for less than $50 per test on a small reader which costs about $250. ApolloDx unveiled in September its mobile ApolloDx Diagnostic Platform. The simple, 7 ounce analyzer, disposable cartridge, and proprietary smartphone app can generate laboratory-quality, GPS-tagged results, the company says. Bauer says the device is capable of advanced agent detection in human, veterinary, agriculture, and biothreat applications. Within 10 minutes of test strip insertion, quantitative and qualitative results are displayed and securely transmitted and integrated into “almost any” medical or laboratory software system. The CLIA-waived platform will be capable of in vitro and companion diagnostics but will launch initially in the veterinarian and agriculture markets sometime next year. The experts DTET spoke to see a further evolution, down the road, toward direct patient testing, with results linked electronically to providers. Many of the profiled companies are already planning for this as is Atomo Diagnostics (Australia), which is adapting its AtomoRapid platform for self-testing applications in the second quarter of 2015. The AtomoRapid, which integrates blood collection, blood delivery, and lancing mechanism directly into the test cassette, can accommodate test strips for a wide variety of conditions from celiac disease and allergy to infectious diseases. The device, half the size of an iPhone, has been deployed in South Africa for HIV and malaria testing and will expand to Southeast Asia by the end of the year and East and West Africa in 2015. CE Mark submissions have been made for AtomoRapid HIV, which will be submitted to the U.S. Food and Drug Administration for approval in the second half of 2015, Byron Darroch, Atomo Diagnostics’ business development director, says. “AtomoRapid revolutionizes the way the rapid testing is done in the field, through the engineering out of human errors commonly seen in the use of traditional ‘bits in a box test kits,’” Darroch tells DTET via e-mail. “Current test kits are made up of up to six components that the user has to then use in the right sequence of steps—something that is not always easily accomplished.” Takeaway: There is a definite trend toward advanced, mobile diagnostics. In the coming year, mobile platforms capable of DNA sequencing, primarily for the detection of infectious diseases, will emerge commercially.