Nanoprobes beam brightly on biomarkers

Ashley N. Rice, ashley.rice@photonics.com

Step aside, surface-enhanced Raman scattering probes. There’s a new nanoprobe in town, and it can shine 20 times brighter than a conventional probe when swept with an infrared laser. The discovery could lead to better-targeted drug delivery and deeper bioimaging within tissue.

The design, developed at Washington University in St. Louis, is based on a novel gold nanoparticle arrangement and Raman reporters – molecules whose jiggling atoms respond to a probe laser by scattering light at characteristic wavelengths. Called Brights – Bilayered Raman-Intense Gold nanostructures with Hidden Tags – the probes seek out biomarkers on cells, then beam brightly to reveal their locations.

“Trapping the Raman reporter molecules between two nanostructured gold layers forms the key design element in attaining such remarkably bright individual nanostructures,” Dr. Srikanth Singamaneni, assistant professor of mechanical engineering and materials science at the university’s School of Engineering & Applied Science, told BioPhotonics. “Brights, as we call them, overcome the deficiencies of existing SERS [surface-enhanced Raman scattering] probes and lay a path forward for this powerful bioimaging modality into routine in vivo applications and clinical settings.”

Researchers at Washington University in St. Louis have developed nanostructures called Brights, which seek out biomarkers on cells and 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), an electromagnetic hot spot lights up the reporter molecules trapped there. Courtesy of Naveen Gandra.

The shell and core create an electromagnetic hot spot in the gap between them, boosting the reporters’ emission by a factor of nearly a trillion.

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.

“Most of the previous attempts were pertained to sandwiching the Raman reporters between two or more metal nanostructures,” Singamaneni said. “While this approach results in large SERS enhancement, these assemblies are not stable and are prone to loss of structural integrity in physiological environments. Furthermore, the size of the nanoparticle assemblies is significantly larger than the individual nanostructures, which is unwanted.”

Singamaneni and postdoctoral research associate Dr. Naveen Gandra tried several probe designs before settling on Brights. One method created intense electromagnetic hot spots by sticking smaller particles onto a larger central particle to make core-satellite assemblies; another, click chemistry, made stronger covalent bonds between the satellites and the core.

In vitro studies with the Brights – which shine about 1.7 x 10¹¹ brighter than isolated Raman reporters – performed significantly better for imaging breast tumor cells compared with the individual nanostructures, Singamaneni said.

“Brights still need to be tested in vivo,” he said. “In vivo studies using tumor-bearing mouse models will be our next step to verify the SERS-based bioimaging efficacy of these nanostructures.”

The first practical application, Singamaneni said, “would be to use SERS probes for in vitro biosensing applications. Previously, such applications relied on weak SERS tags, which significantly affect sensitivity of these assays.”

The research appeared in Advanced Materials (doi: 10.1002/adma.201203415).