Scientists from the Polytechnic Institute of Brooklyn, New York — Just months after setting a record for detecting the smallest single
Stephen Arnold, university professor of applied physics and member of the Othmer-Jacobs Department of Chemical and Biomolecular Engineering, published details of the achievement in Nano Letters, a publication of the American Chemical Society.
In 2012, Arnold and his team were able to detect in solution the smallest known
At the time, the notion of detecting a single protein—phenomenally smaller than a virus—was set forth as the ultimate goal.
“Proteins run the body,” explained Arnold. “When the immune system encounters virus, it pumps out huge quantities of antibody proteins, and all cancers generate protein markers. A test capable of detecting a single protein would be the most sensitive diagnostic test imaginable.”
To the surprise of the researchers, examination of their nanoreceptor under a transmission electron microscope revealed that its gold shell surface was covered with random bumps roughly the size of a protein. Computer mapping and simulations created by Stephen Holler, once Arnold’s student and now assistant professor of physics at Fordham University, showed that these irregularities generate their own highly reactive local sensitivity field extending out several nanometers, amplifying the capabilities of the sensor far beyond original predictions. “A virus is far too large to be aided in detection by this field,” Arnold said. “Proteins are just a few nanometers across—exactly the right size to register in this space.”
The implications of single protein detection are significant and may lay the foundation for improved medical therapeutics. Among other advances, Arnold and his colleagues posit that the ability to follow a signal in real time—to actually witness the detection of a single disease marker protein and track its movement—may yield new understanding of how proteins attach to antibodies.
Arnold named the novel method of label-free detection “whispering gallery-mode biosensing” because light waves in the system reminded him of the way that voices bounce around the whispering gallery under the dome of St. Paul’s Cathedral in London. A laser sends light through a glass fiber to a detector. When a microsphere is placed against the fiber, certain wavelengths of light detour into the sphere and bounce around inside, creating a dip in the light that the detector receives. When a molecule like a cancer marker clings to a gold nanoshell attached to the microsphere, the microsphere’s resonant frequency shifts by a measureable amount.
The research has been supported by a grant from the National Science Foundation (NSF). This summer, Arnold will begin the next stage of expanding the capacity for these biosensors. The NSF has awarded a new $200,000 grant to him in collaboration with University of Michigan professor Xudong Fan. The grant will support the construction of a multiplexed array of plasmonically enhanced resonators, which should allow a variety of protein to be identified in blood serum within minutes.
The publication in Nano Letters marks the 100th journal-paper published since the 1978 founding of NYU-Poly’s Microparticle Photophysics Laboratory for BioPhotonics, directed by Arnold.
Publication: Venkata R. Dantham, et al., “Label-Free Detection of Single Protein Using a Nanoplasmonic-Photonic Hybrid Microcavity,” Nano Letters, 2013, 13 (7), pp 3347–3351; DOI: 10.1021/nl401633y
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