NEW YORK ─ A molecular test being developed by Scanogen could speed up bloodstream infection diagnostics by detecting microorganisms directly from whole blood, eliminating the need for culturing and potentially reducing time to result to 90 minutes from days.
The firm's approach, which detects the binding of single-molecule biosensors to nucleic acid targets from microorganisms, was shown in a recently published Nature Communications study to be as sensitive as PCR in simulated clinical samples. However, unlike PCR the method doesn't need target amplification or sample purification, which require time and training to implement, said Alfredo Celedon, the firm's founder and CEO.
Scanogen's technology, called single-molecule tethering (SMOLT), generates a signal when micron-sized beads tethered by double-stranded DNA probes inside a capillary are displaced in the presence of a target pathogen.
Beads tethered by a probe can be differentiated from beads that are not specific to the target of interest because the long-probe tethered beads are displaced by a greater distance. The displacement is determined by processing images obtained with a low-magnification lens and a low-cost digital camera.
"PCR is a very powerful technique but requires complicated chemistry and synthesis to generate new molecules so that a signal can be detected," Celedon said. "We can develop more powerful assays by detecting the hybridization of probes to a target."
The high sensitivity of Scanogen's detection technology means that other steps are also simplified, he said. For instance, centrifugation or filtration to remove components that may inhibit a PCR reaction are not needed. Sample preparation in SMOLT involves lysis using a detergent and heat.
In the recent study, which involved the collection of data from 200 tests run on normal samples spiked with known concentrations of pathogen, Scanogen showed that its technology can detect RNA molecules in whole blood, urine, and sputum. The technology also detected Candida species and two bacterial species, Staphylococcus aureus and Pseudomonas aeruginosa, in whole blood at limits of detection of between 1 and 3 CFU per ml, comparable to current PCR tests on the market, Caledon said. The technology also readily lends itself to multiplexing that would enable identification of up to 20 targets per test run.
The SMOLT technology could become important for the treatment of patients suspected of sepsis if its performance in clinical samples compare favorably with its performance in spiked-in samples, Philip Verhoef, an infectious disease doctor and researcher at Kaiser Permanente in Honolulu, Hawaii, said in an interview. Verhoef is not affiliated with Scanogen but contributed to a peer review of the Nature Communications study.
"The way to find out whether the [Scanogen] test is going to be a game changer is to validate it further using animal models or clinical samples from patients with sepsis," he said.
All molecular tests with US Food and Drug Administration clearance that seek to identify bloodstream pathogens, with the exception of tests developed by T2 Biosystems, require microorganisms to be grown in culture media before a pathogen can be identified, Verhoef noted.
According to T2 Biosystems, its T2Bacteria Panel and T2Candida panels identify sepsis-causing pathogens directly from whole blood in three to five hours. The firm said the limit of detection of the T2MR instrument on which the tests run is 1 CFU per ml.
"Traditionally, when a patient is suspected of sepsis, in order to confirm the presence of a bloodstream infection and the causative pathogen, clinicians must rely on blood cultures and sub- or post-culture technologies," said Roger Smith, vice president of science, research, and development at T2 Biosystems.
"Blood cultures can take days to return results and then subsequent molecular and susceptibility testing is required to determine the exact drugs that can effectively treat the particular pathogen, during which time a patient's health can continue to decline," Smith added. "With sepsis, early detection and early effective therapy saves lives."
Smith declined to comment specifically on Scanogen's test.
The single-molecule tethering platform being developed by Scanogen would most directly compete with T2Bio's systems, but also with other molecular tests for bloodstream infections that operate after a positive blood culture, including tests produced by BioMérieux, Luminex, GenMark, and Accelerate Diagnostics. Scanogen expects that its first assay will be a sample-to-answer test called Sepsis-ID.
A commercial test would require further automation, clinical studies, and obtaining regulatory clearances, Celedon said.
Scanogen has thus far received $9.5 million in grants from the National Institutes of Health to develop its technologies. The company said it is initiating a financing round for an undisclosed amount to support further development of its technology and to conduct clinical studies.
To move the platform closer to commercialization, some manual steps need to be automated to enable a fully integrated disposable cartridge and instrument, Celedon said.
From there the company expects it will engage in US-based multicenter clinical studies and plans to enroll about 2,000 patients. Scanogen plans to leverage the results to apply for 510(k) clearance with the US Food and Drug Administration and launch a commercial test in about two and half years.
The firm has additional products in its development pipeline that it plans to launch after the sepsis test. For example, Scanogen is conducting validation studies of a test for active tuberculosis running on its single-molecule tethering platform, using patient samples supplied by Geneva-based Foundation for Innovative New Diagnostics.
It is also developing a portable, battery-operated point-of-care instrument that will be suitable for use outside the laboratory including in rural and low-resource settings, and it is developing a rapid respiratory panel to detect SARS-CoV-2, influenza A/B, and other seasonal respiratory viruses to run on its laboratory and point-of-care instruments.
Scanogen plans to manufacturer its tests internally and hire a sales team to target US markets. To commercialize and market its tests outside the US, it plans to engage with diagnostic industry partners, Celedon said.
For clinical testing in a laboratory, the company envisions that its future customers will be able to stack testing modules on top of each other. An eight-module stack, with each module running tests for up to 20 pathogens, will cost about $50,000, Celedon said, adding that the price is significantly lower than the instruments with which it intends to complete.
The firm anticipates offering pricing to laboratories at between $20 and $50 per test, while competing multiplexed tests are priced at $200 or more per test, he added.