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Breakthrough in Nanoresearch Detects Minuscule Cancer Marker

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A Fordham physics professor has used new nanotechnology he helped develop to detect a single marker for thyroid cancer, a breakthrough that may lead to practical early detection procedures for several other cancers.

Rendition of a BSA protein detected through hybrid whispering gallery sensor. The greater response to the nanotechnology was attributed to the proteins finding their way to the individual bumps of the nanoplasmonic particle, visible under a transmission electron microscope. Courtesy American Chemical Society

Last year, Stephen Holler, Ph.D., and Professor Stephen Arnold’s research team at the Polytechnic Institute of New York University and City University of New York, successfully detected the smallest RNA virus (MS2) through their newly developed and patented plasmonic hybrid whispering gallery mode sensor.

At that time the researchers predicted that the sensor might be successful in detecting particles even smaller than the RNA virus, which measured a mass of 6 attograms (1 attogram is a millionth of a billionth of a milligram).  Subsequent tests were done on a single thyroid cancer marker protein (Thyroglobulin) with a mass of 1 attogram, and an even smaller, standard assay protein (BSA) with a mass of 0.11 attogram.

The researchers’ whispering gallery mode sensor detected both proteins’ presence, smashing the detection limit previously reported for the virus and setting a new benchmark. The thyroid cancer protein is one-sixth the size of the smallest virus.

“Our limit of detection is now approaching a zeptogram—a sextillionth of a gram,” said Holler. “This is remarkable. What it means for cancer screening is that we have the sensitivity to easily detect the presence of a host of protein cancer markers. If someone undergoes a cancer treatment, this method can pinpoint following surgery whether some of the cells have been missed.”

The sensor works by drawing the bio-nano-particle to a nanoplasmonic “hot spot” and then measuring its presence through a shift in the wavelength of the resonance, i.e., light, of the whispering gallery’s sensor, a glass bead. Researchers said both the thyroid cancer and BSA proteins showed surprising sensitivity to the nanotechnology, which means that the whispering gallery mode sensor should easily be able to detect single-protein markers in breast, lung, liver, and ovarian cancers.

Holler has recently teamed up with Patricio Meneses, Ph.D., associate professor of biology at Fordham, to apply the whispering gallery sensor technology to look at HPV, or human papillomavirus, which is responsible for 99 percent of cervical cancers.

Single-protein (molecule) detection is fundamental to biochemical and biomedical research, Holler said, but is traditionally done through a more complex process using fluorescence microscopy and a dye-labeling process that can potentially alter the molecule’s function. The whispering gallery mode sensor uses “label-free” detection, which means that particles can be detected in their native state, with interactions potentially able to be followed in real time.

The research, “Label-Free Detection of Single Protein Using a Nanoplasmonic-Photonic Hybrid Microcavity,” appears in the June 18 online issue of the American Chemical Society’s NanoLetters and was supported by a grant from the National Science Foundation.

For more on Holler’s research visit Fordham’s Laboratory for Micro-optics and Biophotonics.

GRAPHIC: Rendition of a BSA protein detected through hybrid whispering gallery sensor. The greater response to the nanotechnology was attributed to the proteins finding their way to the individual bumps of the nanoplasmonic particle, which are visible under a transmission electron microscope.
Courtesy American Chemical Society

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