NYU-Poly Nanoscientists Reach the Holy Grail in Label-Free Cancer Marker Detection: Single Molecules


Researchers at NYU-Poly used a nano-enhanced version of their patented microcavity biosensor to detect a single cancer marker protein, which is one-sixth the size of the smallest virus, and even smaller molecules below the mass of all known markers.


This achievement shatters the previous record, setting a new benchmark for the most sensitive limit of detection, and may significantly advance early disease diagnostics. Unlike current technology, which attaches a fluorescent molecule, or label, to the antigen to allow it to be seen, the new process detects the antigen without an interfering label.


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.


They believe the new limit of detection may be smaller than 0.01 attograms.
This latest milestone builds on a technique pioneered by Arnold and collaborators from NYU-Poly and Fordham University. In 2012, the researchers set the first sizing record by treating a novel biosensor with plasmonic gold nanoreceptors, enhancing the electric field of the sensor and allowing even the smallest shifts in resonant frequency to be detected. Their plan was to design a medical diagnostic device capable of identifying a single virus particle in a point-of-care setting, without the use of special assay preparations.


At the time, the notion of detecting a single protein—phenomenally smaller than a virus—was set forth as the ultimate goal. When the immune system encounters a virus, it generates 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.


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.


The research has been supported by a grant from the National Science Foundation.

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