Researcher develops nanoparticle-based tags to detect viruses and cancer with high sensitivity

Updated: Jul 10, 2018

Brookhaven National Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time.

How can we detect cancer and viruses with high sensitivity? Physical chemist Laura Fabris-;an associate professor in the Materials Science and Engineering Department at Rutgers, the State University of New Jersey, and principal investigator of the Fabris NanoBio Group-;is addressing this very question. Her research focuses on the synthesis, functionalization, characterization, and application of tiny metallic nanoparticles. These "plasmonic" nanoparticles greatly enhance the intensity of the signals produced by a surface-sensitive technique for detecting molecules. Fabris and her research group use the transmission electron microscopes at the Center for Functional Nanomaterials (CFN)-;a U.S. Department of Energy Office of Science User Facility at Brookhaven National Laboratory-;to visualize the nanoparticles and understand how to improve their morphology to improve clinical diagnoses.

Plasmonics is the study of how free electrons at the surface of a material are excited by light to have collective charge oscillations. What are plasmonic nanoparticles, and why are they of interest in biomedicine?

Traditionally, plasmonic nanoparticles are small metal particles that absorb light at different wavelengths depending on their properties-;for example, gold absorbs light at 520 nanometers and silver at 400 nanometers-;and amplify this light like a lens or concentrator does. Their strong interaction with light occurs because the electrons on the surface oscillate coherently with the light hitting them, in response generating an electric field that is locally much more intense than the original. This intense field can be taken advantage of downstream to increase the detection limit in a chemical analysis technique called Raman spectroscopy, which is used to identify the presence of biomolecules.

My group focuses on understanding how the light-matter interactions change with the composition, shape, and size of the nanoparticles. For example, when electromagnetic fields interact with these metal nanoparticles, there is a high localization of the electric field in places with lots of curvature (corners, edges, tips). So if you can generate particles with lots of spiky regions, then there will be many areas-;"hot spots"-;where the electric field is enhanced. The electric field can be amplified anywhere from 1000 to 10,000 times, and this amplification is reflected downstream when we measure the intensity of the Raman signals. When molecules of interest are placed near the surface of these hot spots, the Raman signals can be enhanced by 10 or 11 orders of magnitude. This enhancement is sufficient for detecting single molecules.

My group has synthesized gold nanostars-;spherical cores with many spiky tips like a sea urchin-;for this very reason. A lot of discovery science in the growth of nanoparticles is often done with gold because it is much more stable as compared to some other metals. Silver and aluminum oxidize very readily, and copper does not absorb light as intensely and its shape is harder to tune. In terms of applications, gold is of interest because it is not cytotoxic-;we can use it in cells without killing them.

How does Raman spectroscopy work? What information does it provide, and why does the detection limit need to be increased?

Raman spectroscopy is a technique used to measure molecular vibrations, providing a fingerprint of chemical bonds that are present in molecules. In this technique, light from a laser beam is directed at a sample. After molecules absorb this radiation, they are excited to a very short-lived, highly excited state. When the molecules relax to a lower energy level, they emit (scatter) light, which is collected by a detector that records the intensity. Any change in energy between the incident and scattered light is associated with specific molecular vibrations.

Because each molecule has a unique vibration frequency, Raman scattering can be used to determine a material's chemical composition and crystal structure. This technique, which has been around for more than 100 years, works great for high concentrations of materials but it does not have the sensitivity to detect materials at low concentrations. For example, the concentration of proteins and other biomarkers in our body are too low for detection by regular Raman scattering.

But in 1977, scientists understood that if a molecule of interest happens to be in close proximity to plasmonic nanoparticles, then the intensity of the Raman signal gets amplified. This phenomenon is due to the enhanced scattered electric field that results when the nanoparticles interact with the electromagnetic radiation from the laser. Molecules adsorbed onto the surfaces of plasmonic structures experience this strongly enhanced field, and the end effect is that the Raman scattering signal obtained from these adsorbed molecules is a lot more intense. This technique is called surface-enhanced Raman scattering, or SERS