Containing Ebola with Nanotechnology

in NEWS

Rapid, Point-of-Care Device Detects Virus in Complex Blood Samples

By Mark Dwortzan

 

NexGen Arrays prototype of SP-IRIS. (Image courtesy of NexGen Arrays)
NexGen Arrays prototype of SP-IRIS. (Image courtesy of NexGen Arrays)

By late January, 1.4 million people in Liberia and Sierra Leone could be infected with the Ebola virus. That’s the worst-case scenario of the Ebola epidemic in West Africa recently offered by scientists at the US Centers for Disease Control and Prevention. The CDC warns that those countries could now have 21,000 cases of the virus, which kills 70 percent of people infected.

One of the big problems hindering containment of Ebola is the cost and difficulty of diagnosing the disease when a patient is first seen. Conventional fluorescent label-based virus detection methods require expensive lab equipment, significant sample preparation, transport and processing times, and extensive training to use. One potential solution may come from researchers at the College of Engineering and the School of Medicine, who have spent the past five years advancing a rapid, label-free, chip-scale photonic device that can provide affordable, simple, and accurate on-site detection. The device could be used to diagnose Ebola and other hemorrhagic fever diseases in resource-limited countries.

In a multiplexed detection configuration, Ebola, Marburg and Lassa antibodies on the SP-IRIS surface capture corresponding viruses specifically. As shown in the images produced by the device, SP-IRIS then identifies and counts each virus particle and classifies it based on its size.
In a multiplexed detection configuration, Ebola, Marburg and Lassa antibodies on the SP-IRIS surface capture corresponding viruses specifically. As shown in the images produced by the device, SP-IRIS then identifies and counts each virus particle and classifies it based on its size.

The first demonstration of the concept, described in the American Chemical Society journal Nano Lettersin 2010 and developed by Professor Selim Ünlü’s (ECE, BME, MSE) research group in collaboration with Professor Bennett Goldberg (Physics, BME, ECE), showed the ability to pinpoint and size single H1N1 virus particles. Now, after four years of refining the instrumentation in collaboration with Associate Professor John Connor (MED) and other hemorrhagic fever disease researchers at the University of Texas Medical Branch, the team has demonstrated the simultaneous detection of multiple viruses in blood serum samples—including viruses genetically modified to mimic the behavior of Ebola and the Marburg virus.

Mentioned in Forbes magazine as a potentially game-changing technology for the containment of Ebola, the device identifies individual viruses based onsize variations due to distinct genome lengths and other factors. Funded by the National Institutes of Health, the research is showcased in ACS Nano.

Professor Selim Unlu (ECE, BME, MSE) (left) and Associate Professor John Connor (MED) have developed a rapid, chip-scale photonic device that can detect viruses, including Ebola, on site. (Photo by Steve Prue)
Professor Selim Unlu (ECE, BME, MSE) (left) and Associate Professor John Connor (MED) have developed a rapid, chip-scale photonic device that can detect viruses, including Ebola, on site. (Photo by Steve Prue)

“Others have developed different label-free systems, but none have been nearly as successful in detecting nanoscale viral particles in complex media,” said Ünlü, referring to typical biological samples in which a mix of viruses, bacteria and proteins may be present. “Leveraging expertise in optical biosensors and hemorrhagic fever diseases, our collaborative research effort has produced a highly sensitive device with the potential to perform rapid diagnostics in clinical settings.”

Whereas conventional methods can require up to an hour for sample preparation and two hours or more for processing, the current Boston University prototype requires little to no sample preparation time and delivers answers in about an hour.

“By minimizing sample preparation and handling, our system can reduce potential exposure to healthcare workers,” said Connor. “And by looking for multiple viruses at the same time, patients can be diagnosed much more effectively.”

The shoebox-sized prototype diagnostic device, known as the Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS), detects pathogens by shining light from multi-color LED sources on viral nanoparticles bound to the sensor surface by a coating of virus-specific antibodies. Interference of light reflected from the surface is modified by the presence of the particles, producing a distinct signal that reveals the size and shape of each particle. The sensor surface is very large and can capture the telltale responses of up to a million nanoparticles.

In collaboration with BD Technologies and NexGen Arrays, a BU Photonics Center-based startup run by longtime SP-IRIS developers David Freedman (EE10) and postdoctoral fellow George Daaboul (BME’13), the research team is now working on making IRIS more robust, field-ready and fast—ideally delivering answers within 30 minutes—through further technology development and preclinical trials.

SP-IRIS devices are now being tested in multiple labs, including a Biosafety Level-4 (BSL-4) lab at the University of Texas Medical Branch that’s equipped to work with hemorrhagic viruses. Other tests will be conducted at BU’s National Emerging Infectious Diseases Laboratories (NEIDL) once the facility is approved for BSL-4 research. Based on the team’s current rate of progress, a field-ready instrument could be ready to enter the medical marketplace in five years.

Find out more about SP-IRIS in this National Academy of Engineering radio clip.