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Duke interdisciplinary team develops new approach using nanoprobes to detect viruses
DURHAM, N.C.—Combining engineering and genomic research, a Duke University effort has developed a proof-of-principle approach that uses light to detect infections before patients show symptoms—marking the first time that scientists have demonstrated the use of nanoprobes to detect specific genetic materials taken from human samples.
The interdisciplinary Duke team, which has "generally been working to develop new ways to diagnose infectious disease," according to Geoffrey Ginsburg, director of genomic medicine at Duke's Institute for Genome Sciences & Policy, has now "found a number of molecular biomarkers based on host response to infection that can actually detect viral infection in hours or days of when a patient becomes symptomatic."
This discovery, described in a paper published recently in the online version of the journal Analytica Chimica Acta, was made possible by a surface-enhanced Raman scattering (SERS)-based detection approach, referred to as "molecular-sentinel" (MS) plasmonic nanoprobes, designed to detect an RNA target related to viral infection. The MS method, which was an achievement of Tuan Vo-Dinh, director of the Fitzpatrick Institute for Photonics at Duke, is described in the paper as "essentially a label-free technique incorporating the SERS effect modulation scheme associated with silver nanoparticles and Raman dye-labeled DNA hairpin probes."
Vo-Dinh and colleagues developed an MS nanoprobe to detect the human radical S-adenosyl methionine domain containing 2 (RSAD2) RNA target as a model system for method demonstration. Hybridization with target sequences opened the hairpin and spatially separated the Raman label from the silver surface, reducing the SERS signal of the label.
"The general idea that one could utilize these silver nanoparticles as a way to enhance and amplify the overall spectrum elicited in the context of introducing light is something that Vo-Dinh has pioneered and worked on for quite some time," Ginsburg explains. "This is the first time it has been down with an RNA probe, but he has published the same approach involving DNA technologies in the past."
That's where Ginsburg and his colleagues enter the picture, with their development of a method of measuring the host's response to infection through RNA profiling. The human RSAD2 gene has recently emerged as a novel host-response biomarker for diagnosis of respiratory infections.
The team's results showed that the RSAD2 MS nanoprobes exhibited high specificity and could detect as low as 1 nM target sequences.
"With the use of a portable Raman spectrometer and total RNA samples, we have also demonstrated for the first time the potential of the MS nanoprobe technology for detection of host-response RNA biomarkers for infectious disease diagnostics," they concluded.
"Our work has really demonstrated the strength of the RNA signal from the host response," says Ginsburg. "The fact that we can actually do this with an RNA molecule is an important step forward in detecting infections."
Next, the researchers will pursue the development of devices that measure multiple genome-derived markers and enable the more accurate and rapid diagnosis of infectious disease at the point of care, Ginsburg says.
"One can imagine having these tools in physicians' offices or even in a patient's home, and they may offer the fastest way to predict if people are going to have upper respiratory infections or viruses with that etiology," he says. "This would guide care decisions that will lead to more effective treatment and improved outcomes of antimicrobial therapy. Point-of-care diagnostics holds great promise to accelerate precision medicine, and more importantly, help patients in limited-resource settings gain access to molecular testing."
There are several scenarios that these devices may be able to address, Ginsburg says, such as "routine surveillance in high-risk areas if there is an outbreak."
"In the developing world, if this type of technology could be put in place at a low cost, then we really could have an impact on a major cause of mortality around the globe," he says. "We're motivated to help solve some of these problems, and that is the impetus for some of our work here."
Duke is currently in talks with "several groups" to bring such devices to market, Ginsburg says.
"We believe that a single molecule is not going to be significant enough to achieve success in clinical trials, and it's also going to be something that regulatory agencies will have a strong say over," he notes, "but I would say that in the next five to 10 years, point-of-care devices like this one will vastly improve the way we approach diagnostics."