U. ILLINOIS (US)—Instead of dyes or fluorescence, a new class of molecular probes for biomedical research requires only a light switch, similar to an ordinary house lamp, to illuminate the molecular world.

Researchers say the nanoLAMP (Nano-Layered Metal-dielectric Particles) solves a problem in biomedical research: the inability to measure multiple molecules simultaneously with a high degree of accuracy and reliability.

“This method, in principle, will allow us to image hundreds of molecular species quantitatively from a single molecule up to any limit,” says Rohit Bhargava, a researcher at the Beckman Institute at the University of Illinois.

“We have an almost unlimited ability with this design to put in any molecule and use it as a marker,” he says. “We don’t need it to be a dye or fluorescent molecule, but just need to change the molecular structure of the reporter.”

Details appear in Proceedings of the National Academy of Sciences.

The new method takes an existing spectroscopic technique called surface-enhanced Raman scattering (SERS) and uses nano-layered metal-dielectric particles that light up when exposed to laser light.

The breakthrough aspect of this method is that it is able to overcome deficiencies found in SERS through the design of the nanoscale structure of LAMPs using classical electromagnetic theory and advanced computing strategies.

The nanoLAMPS were created with a concentric, multi-shell structure that allows for fine tuning the electric field surrounding a molecule. Researchers applied fundamental electromagnetic theory to predict the electric field, then used algorithms and the computing power of the National Center for Supercomputing Applications (NCSA) at Illinois to optimize structures for Raman enhancement.

“It is smart design of nanostructures based on very fundamental physics,” Bhargava says.

The nanoLAMPS also have the advantage of eliminating the chemical effects seen with SERS enhancement techniques, allowing for more precise modeling.

“The unique part in this paper is we completely ignored the chemical enhancement by decoupling the molecule from the surface,” Bhargava says. “Instead, we embed the molecule in the dielectric layer between the metal layers.

“As a consequence, very, very few molecules are actually even close to the surface; they are all in the dielectric layer. That means we can completely eliminate the chemical effect and only rely on the electromagnetic effect for enhancement.”

The nanoLAMPs have a recognition link which connects the target molecule to the multi-shell, onion-like structure containing the reporter molecule. A laser light is used to excite the nanoparticles and acquire signals from the target molecule.

The nanoLAMPs can produce reliable, quantitative measurements from a single molecule or from hundreds of molecules, and from multiple species. The particles used are designed to be stable and won’t decay over time, and different metals or even dyes can be used in them.

“It’s an incredibly flexible platform,” Bhargava says. “It allows you to image any molecular species, presents many routes to fabrication, and you can put in any dye you like, any reporter, use most any metal you like.”

Bhargava says the acronym LAMPs is appropriate.

“Lamps light the way to ‘seeing’ molecules and the capability is always on, but you have to hit it with a beam of light to get a response back,” he said. “It is like flipping a switch when you shine a laser on it.”

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