BU lab-on-chip wins NIH funding

October 5, 2011 — The National Institutes of Health (NIH) awarded Boston University (BU) engineering and microbiology researchers $4.8 million to develop a chip-sized, low-cost and easily deployed virus detection platform for point-of-care viral pathogen detection, targeting Ebola and Marburg, among others. BU’s technology 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. In separate research collaborations with Connor, Ünlü and Altug have brought their streamlined biosensor platforms into pathogen detection roles.

BU Engineering Associate Professor Catherine Klapperich (BME, MSE) and Research Assistant Professor Mario Cabodi (BME) will further advance microfluidics technology they’ve designed, integrating 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.

A "simple test" for viruses will "get rid of the need for enzymes or fluorescent labels," noted Connor. Nanoscale platforms that can look for multiple viruses at the same time, in a small and portable form factor, will be beneficial on the front lines 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.

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.

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.

Courtesy of Mark Dwortzan, Boston University. Learn more at www.bu.edu.

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