Novel gold nanoparticles can goose the signal from Raman reporters, or molecules whose jiggling atoms respond to a probe laser by scattering light at characteristic wavelengths. The discovery could lead to better-targeted drug delivery and deeper bioimaging within tissue. Called Brights – Bilayered Raman Intense Gold nanostructures with Hidden Tags – the probes developed at Washington University in St. Louis can bind to biomarkers of disease and shine 20 times brighter than their closest competitor for surface-enhanced Raman scattering. Nanostructures called Brights seek out biomarkers on cells and then beam brightly to reveal their locations. In the tiny gap between the gold skin and the gold core of the cleaved Bright (visible in the upper left), there is an electromagnetic hot spot that lights up the reporter molecules trapped there. The shell and core create an electromagnetic hot spot in the gap between them that boosts the reporters’ emission by a factor of nearly a trillion. These molecules intensely scatter light at characteristic wavelengths when probed with laser light. This phenomenon, called spontaneous Raman scattering, is by nature very weak. Thirty years ago, scientists accidentally discovered that it is much stronger if the molecules are adsorbed on roughened metallic surfaces; molecules attached to metallic nanoparticles were discovered to shine even brighter than those attached to rough surfaces. “It’s well-known that if you sandwich Raman reporters between two plasmonic materials, such as gold or silver, you are going to see dramatic Raman enhancement,” said Dr. Srikanth Singamaneni, assistant professor of mechanical engineering and materials science at the university’s School of Engineering & Applied Science. Singamaneni and postdoctoral research associate Dr. Naveen Gandra tried several different probe designs before settling on Brights. One method was creating intense electromagnetic hot spots by sticking smaller particles onto a larger central particle to create core-satellite assemblies; another was Click chemistry, which made stronger covalent bonds between the satellites and the core. “We had some success with those assemblies, but in the meantime we had started to wonder if we couldn’t make an electromagnetic hot spot within a single nanoparticle rather than among particles,” Singamaneni said. “It occurred to us that if we put Raman reporters between the core and shell of a single particle, we could create an internal hot spot.” This idea worked like a charm, creating Brights that shine about 1.7 x 1011 brighter than isolated Raman reporters. The researchers hope to test the Brights in vivo in the lab of Dr. Sam Achilefu, professor of radiology. Singamaneni has even more in mind for these probes. Since different Raman reporter molecules respond at different wavelengths, it should be possible to design Brights targeted to different biomolecules that also have different Raman reporters and then monitor them all simultaneously with the same light probe, he said. The Brights could even be combined with a drug container that would be released in the body when it has reached the target tissue, potentially eliminating side effects. The research appeared in Advanced Materials (doi: 10.1002/adma.201203415).