University Wins $5M Grant to Develop Point-of-Care Viral Diagnostic Chip


Technology Developed at BU to be Tested at Texas Lab
By Mark Dwortzan

Professor Selim Unlu (ECE, MSE) with IRIS, a pathogen detection platform
Professor Selim Unlu (ECE, MSE) with IRIS, a pathogen detection platform

The National Institutes of Health has awarded $4.8 million to a team of Boston University engineering and microbiology researchers to advance a chip-sized, low-cost, easy-to-use virus detection platform capable of rapidly detecting, at the point of care, the most lethal viral pathogens — particularly those, such as Ebola and Marburg, known to cause hemorrhagic fever. The technology developed at BU will be tested at a biosafety facility in Texas.

Led by BU School of Medicine Assistant Professor and principal investigator John Connor, BU College of Engineering Professor Selim Ünlü (ECE, MSE) and Assistant Professor Hatice Altug (ECE, MSE) will refine virus detection platforms they have developed independently. BU Engineering Associate Professor Catherine Klapperich (BME, MSE) and Research Assistant Professor Mario Cabodi (BME) will further advance microfluidics technology they’ve designed to integrate sample preparation in each of the two platforms. The BU researchers will partner with Becton Dickinson, a leading global medical technology company, to transform one of the virus diagnostic platforms into a working prototype, and enlist University of Texas Medical Branch Professor Thomas Geisbert, an internationally recognized expert on viral hemorrhagic fever diseases, to test it in his lab in Texas.

“We brought together this interdisciplinary team in order to develop a breakthrough detector system that will allow a simple test for the presence of viruses,” said Connor. “To do that we are trying to get rid of the need for enzymes or fluorescent labels and are building nanoscale platforms that can look for multiple viruses at the same time. The detectors that we are developing will be small and portable, making them easy to take to the site of an outbreak.”

Overcoming the extensive and costly training, sample preparation, refrigerated transportation and laboratory analysis that’s typical of conventional virus detection technology, these platforms promise to provide fast, point-of-care, fully-integrated diagnostics in clinical and field settings—dramatically improving our capability to confine viral outbreaks and pandemics.

Two Pathways to an Integrated Virus Detection Platform
In separate research collaborations with Connor, Ünlü’s and Altug’s streamlined biosensor platforms have already shown great promise in pathogen detection capability.

Developed by Ünlü’s research group, the Interferometric Reflectance Imaging Sensor (IRIS) can pinpoint single virus and other pathogen particles quickly, accurately and affordably. The shoebox-sized, battery-operated device is the first not only to provide rapid detection of single nanoparticles of interest, but also to measure their size—an important factor in confirming the identity of a suspected pathogen and rejecting dirt or other contaminants. To detect and size pathogens, IRIS shines light from multi-color LED sources on nanoparticles bound to the sensor surface. Light reflected from the sensor surface is altered by the presence of the particles, producing a distinct signal that reveals the size of each particle. Configured with a large surface area, the device can capture this telltale response for up to a million nanoparticles at a time.

Altug’s platform rapidly detects live viruses from biological media with little to no sample preparation. It’s the first to detect intact viruses by exploiting arrays of apertures of about 250 to 350 nanometers in diameter on metallic films that transmit light more strongly at certain wavelengths. When a live virus binds to the sensor surface, the effective refractive index in the close vicinity of the sensor changes, causing a detectable shift in the resonance frequency of the light transmitted through the nanoholes. The magnitude of that shift reveals the presence and concentration of the virus in the solution.

“Both of these techniques promise to overcome the limitations of conventional virus detection methods that require expensive equipment, relatively long process times, and extensive training to use,” said Ünlü. “Under the new NIH grant, our goal is to produce a highly sensitive, user-friendly, commercially-viable virus detection system that can be deployed at the point of care and detect viruses in about 30 minutes.”

To produce a fully integrated, point-of-care system, the researchers plan to incorporate a microfluidic sample preparation chip to work with Ünlü’s and Altug’s virus detection platforms. The goal for the microfluidics team is to improve the quality of the sample introduced to the sensing surface, by purifying, then concentrating, the starting sample solution.

“By leveraging Klapperich’s work in low-cost, disposable diagnostics and our collective expertise in microfluidic separation and purification techniques, we’ll seek to improve the overall performance of the diagnostic platforms, while retaining speed of analysis and a compact format,” said Cabodi.

Toward a Commercially Viable Prototype
Within five years, the researchers plan to validate multiple harmless test viruses on the two evolving microfluidics-enhanced diagnostic platforms, develop one of the platforms into a commercially viable prototype, and validate the prototype on pathogens in Geisbert’s Texas biosafety lab, which employs the highest degree of biocontainment precautions to isolate dangerous biological agents.

The final prototype should consist of a small “detector” chip containing integrated microfluidics that allows samples to be drawn over the active sensing components, and a working “reader” capable of rapidly reading the detector chips and providing diagnostic information. The system should be able to simultaneously assess multiple possible infectious agents with minimal sample handling, and be suitable for clinical use in resource-limited countries.