Seeing Biomolecules with the Naked Eye

New Biosensor Could Enable Point-of-Care Disease Biomarker Detection

By Mark Dwortzan

Plasmonic resonance sensors enable label-free detection of (Y-shaped) antibodies with the naked eye. Different sensors, each consisting of square arrays of nanoholes, are immobilized with different
Plasmonic resonance sensors enable label-free detection of (Y-shaped) antibodies with the naked eye. Different sensors, each consisting of square arrays of nanoholes, are immobilized with different

Early diagnosis of illnesses such as cancer and Alzheimer’s disease has been shown to significantly improve patients’ survival rates, but today’s diagnostic tools typically require invasive biopsies or expensive and cumbersome optical detection devices. To screen large numbers of patients for such illnesses at the point of care will require low-cost, highly accurate, compact, fast, user-friendly tools.

Now a research team led by Assistant Professor Hatice Altug (ECE, MSE) has developed a prototype for a low-cost, portable diagnostic platform that could be used by untrained personnel to detect blood or saliva-based proteins that serve as biomarkers for selected cancers, Alzheimer’s disease, allergens and other illnesses. By eliminating the need for heavy and costly lab equipment, the new biosensing platform offers unique opportunities for point-of-care diagnostics in clinical and field settings.

The research team—Altug; members of her research group including postdoctoral fellow Ahmet Ali Yanik and three ECE graduate students; Boston University School of Medicine microbiologist John Connor; and University of Texas, Austin physicist Gennady Shvets—reported on this achievement in an early edition of the journal PNAS.

Consisting of a light source and a nanostructured surface, the biosensing platform enables users to detect the presence of specific antibodies—including those linked to deadly diseases—with the naked eye. To achieve that feat, the researchers fabricated a plasmonic (light-confining) surface patterned with segmented arrays of nanoscale holes, and coated each segment with single layer of proteins known to bind to specific antibodies.

The research team engineered the “nanohole arrays” on the biosensor surface to produce “Fano” resonances, which would appear in a spectrometer as an upside-down, asymmetric script “V.” Upon specific binding of antibodies on a nanohole array segment, this resonance undergoes a dramatic shift and the transmitted light drops significantly. When this process is observed by the naked eye, the sensor segment elements turn dark.

“When the biomolecules are captured by the proteins that recognize them, we can see with the naked eye antibody accumulation on the surface by looking at the intensity of the transmitted light,” says Altug. “This enables us to detect biomolecules without any labeling.”

Yanik, the first author of the PNAS article, observes, “It is really exciting to see a fundamental physical phenomenon such as Fano resonance behavior being directly applied to a real-world problem that can impact lives. We now have a very strong foundation upon which increasingly more complicated, lab-on-chip systems can be constructed.”  

The research team next aims to develop an integrated system that seamlessly combines a compact illumination source, nanostructured biosensor and visualization element. The ongoing effort is funded by the National Science Foundation (NSF) Smart Lighting Educational Research Center at Boston University as well as grants Altug has received from the NSF, Office of Naval Research and Massachusetts Life Sciences Center.

 

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