A team of researchers from University of Toronto Engineering has created a new type of dye-sensitized nanoparticle that can detect target chemicals at very low concentrations, while also distinguishing between molecules with very similar shapes.
When bound to their target molecules, the nanoparticles absorb light in the form of low-energy photons and use it to emit a high-energy photon. This chemical sensing ability could help pharmaceutical manufacturers detect impurities or enable researchers to find tiny traces of chemical pollutants in groundwater.
"Organic molecules called flurophores have been used for decades to absorb light and convert it into colorful emissions, but the process only works in one direction," says Professor Kai Huang, senior author on a paper published in Journal of the American Chemical Society that describes the new particles.
"With fluorophores, the excitation frequency has to be higher than the emission frequency, which means that they convert high-energy photons into low-energy photons. What makes our dye-sensitized nanoparticles special is that they are capable of upconversion, meaning that they can absorb light in the form of low-energy photons and emit higher-energy ones.
"For example, you could excite them with near-infrared light, which can easily be produced with low-cost lasers, and they would glow bright green in response."
Huang says that the difference between the excitation and emission frequencies makes it easier to sort the signal from the noise.
"It's like the difference between stargazing at night versus the daytime," he says.
"The stars shine the same brightness all the time, but during the day the sun is so powerful that it overwhelms them. Shifting the excitation frequency lower produces zero-autofluorescence background in the samples you are analyzing, while the luminescent nanoprobes keep shining; it is like turning off the sun, so you can see the stars better."
In the nanoparticles, the upconversion is made possible by ions of ytterbium and erbium, part of the chemical family of elements known lanthanides.
Previously, the typical approach to making these chemical-sensing agents resulted in nanoparticles shaped like flat hexagons. In these particles, ytterbium and erbium ions were embedded in a host matrix made of sodium, yttrium and fluorine, like chocolate chips in a cookie. The dyes are organic molecules coated on the outside, analogous to the icing.
When infrared light is shined on the particles, the dyes absorb the light energy and pass it on to the ytterbium ions, which act as an energy relay to pass it on to the erbium ions. The erbium ions do the upconversion, with the energy then getting re-emitted as green light.
"But there's a problem: if you pack the ytterbium atoms in too densely, they start to absorb not only the energy coming in, but also the energy coming out," says Jiaze Wu, a PhD student in Huang's lab and lead author on the new paper.
"This is called back-energy transfer: it means that the energy that would have been emitted by the erbium ions as green light instead gets bounced back to the ytterbium relay and never reaches the surface."
Wu, Huang and the team overcame this trade-off by changing the recipe. Instead of using sodium, yttrium and fluorine for the host matrix, they design a new matrix made of lithium, lutetium and fluorine.
They also altered the shape of the particles, from flat hexagons to a more diamond-shaped 3D structure, and gave them multiple layers: a dense core, surrounded by an inner shell, which in turn is surrounded by an outer shell.
"We were able to create nice gradient: the concentration of embedded ytterbium ions gets denser as you go through each layer, with the core being the most dense," says Wu.
"This arrangement enabled us to pack in much more ytterbium. In our particles, the light energy coming in flows almost entirely in one direction, inward toward the erbium ions."
These design changes were not simply lucky guesses; the team arrived at them after doing extensive computer simulations. In this way, they were able to virtually test out dozens of formulations and geometries before actually manufacturing the nanoparticles in the lab.
"We used Monte Carlo simulations and density functional theory to simulate how the energy would interact between different parts of the nanoparticle, right down to the atomic or even subatomic level," says undergraduate student Weixiang Ben, who led the computational work.
"That's how we showed that this core-shell-shell structure could actually function as a one-directional energy tunnel for incoming light."
Wu says that the new nanoparticles are much brighter than what came before; he estimates that the light being emitted is roughly 150 times brighter than upconversion nanoparticles that haven't been dye-sensitized, and about 50 times brighter than some of the most optimized conventional structures previously reported under same excitation condition.
This high sensitivity enables the nanoparticles to detect target molecules at very low concentrations — even a small number of bonded nanoparticles will glow brightly enough to be detected.
They are also able to easily distinguish between molecules that are structural isomers of each other, that is, that they are made of the exact same set of atoms, but arranged slightly differently.
"Let's say you're making a drug molecule, and your manufacturing process works fine, except that 10% of the batch is the wrong structural isomer," says Wu.
"That's a huge problem: it can make the drug less effective, or worse, lead to side effects that you definitely don't want. The current process for detecting this relies on very expensive analytical tests, but with these nanoparticles, you could do it using low-cost lasers and a very small sample."
Huang says that the next step toward commercial development will be work out a technique for mass-producing the nanoparticles.
"We're working on this already, in fact. We think it's feasible, but it requires a very long roadmap," says Huang.
"In the meantime, this model serves as proof-of-concept; with this technique, we can produce a very high-performance upconversion nanoparticle that could be customized to any molecule you might want to detect. That's something entirely new."
