Single Molecule Detection of a Cancer Biomarker
Using a nano-enhanced version of a device capable of detecting the smallest viruses in solution, researchers at the Polytechnic Institute of New York University (NYU-Poly) have demonstrated that they can detect a single cancer marker protein without the use of fluorescent labels. Stephen Arnold and his collaborators describe their new device in the journal Nano Letters.
In 2012, Dr. Arnold and his team were able to detect in solution the smallest known RNA virus, MS2, with a mass of 6 attograms. Now, the NYU-Poly team has detected: a human cancer marker protein called thyroglobulin, with a mass of just 1 attogram, and the bovine form of a common plasma protein, serum albumin, with a far smaller mass of 0.11 attogram. An attogram is 10-18 grams, or a millionth of a millionth of a millionth of a gram.
This latest milestone builds on a technique pioneered by Arnold and collaborators from NYU-Poly and Fordham University. In 2012, the researchers set a sizing record by treating a novel biosensor with plasmonic gold nano-receptors, 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.
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 a student in the Arnold laboratory and now 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.
Dr. Arnold and his collaborators 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 such as a cancer marker clings to a gold nanoshell attached to the microsphere, the microsphere’s resonant frequency shifts by a measureable amount.
This work is detailed in a paper titled, “Label-free detection of single protein using a nanoplasmonic-photonic hybrid microcavity.” An investigator from the New York City College of Technology also participated in this study. An abstract of this paper is available at the journal’s website.