Plasmonic Probes Help Quantify Breast Cancer Gene Segments

Hyperspectral imaging using plasmonic probes can ferret out a specific genetic telltale for breast cancer within individual cells, according to recent research from Purdue University.

That genetic telltale is BRCA1, a tumor suppressor gene. Measuring the number of BRCA1 messenger RNA (mRNA) splice variants in a cell can indicate if the gene is being under-expressed, a possible sign of breast cancer. Existing methods for detecting BRCA1 rely on samples made up of hundreds or thousands of cells, and cannot provide detailed information about how genes tied to cancer are being expressed.

A single gold nanoparticle, or monomer, appears green when illuminated (top left); a pair of gold nanoparticles, or dimer, bound to an mRNA splice variant, appear reddish (top right). Monomers and dimers also scatter light differently, as shown in the graph. Courtesy of Purdue University.

The new probes are made from gold nanoparticles, or monomers, tagged with oligonucleotides. Upon injection into a living cell, the monomers can hybridize to three selected BRCA1 mRNA splice variants, forming dimers that, when imaged hyperspectrally, exhibit distinct spectral shifts due to plasmonic coupling. The monomers reflect green light, whereas the dimers reflect red light. The number of dimers present corresponds to the cell’s number of BRCA1 mRNA splice variants. The technique can quantify mRNA splice variants in a single cell in about 30 minutes, the researchers said.

"With this method, we are basically able to spot a needle in a haystack, and we can determine if there are five needles in that haystack or if there are 50," said Dr. Joseph Irudayaraj, professor of agricultural and biological engineering and deputy director of the university’s Bindley Bioscience Center.

The technique also could increase our understanding of cell biology and paves the way for genetic profiling and diagnosis based on a single cell, Irudayaraj said.

The work was funded by the National Science Foundation, the Indiana Clinical Transitional Sciences Institute, Purdue Center for Cancer Research, Samsung and the Stanford National Institute of Health. It is published in Nature Nanotechnology (doi: 10.1038/nnano.2014.73).