Engineers at the University of Toronto have developed a new type of dye-sensitized nanoparticle that can detect chemicals at extremely low concentrations while also telling apart molecules that are nearly identical in shape.
The tiny particles produce a light signal after attaching to the chemical they are designed to detect. They absorb low-energy photons and convert that energy into higher-energy photons, creating a bright optical signal that researchers can measure.
That unusual ability could have practical uses in several fields. Pharmaceutical manufacturers, for example, could use the particles to identify unwanted impurities in drugs. Environmental researchers could potentially use them to search for very small amounts of chemical pollutants in groundwater.
Turning Infrared Light Into a Bright Green Signal
“Organic molecules called fluorophores 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 the 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.”
This process, known as upconversion, gives the nanoparticles an important advantage. Because the light used to activate them has a different frequency from the light they emit, researchers can separate the desired signal more easily from background light generated by the sample itself.
Huang compares the effect to looking at the night sky.
“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.”
The Challenge of Making Nanoparticles Brighter
The particles rely on ions of ytterbium and erbium, which belong to the lanthanide family of chemical elements, to carry out the upconversion process.
Earlier versions of these sensing nanoparticles were typically made as flat hexagonal structures. Ytterbium and erbium ions were distributed through a host material made from sodium, yttrium and fluorine. The researchers compare this arrangement to chocolate chips embedded in a cookie, while organic dye molecules covering the outside resemble icing.
When infrared light hits the nanoparticles, the dyes first capture the incoming energy. That energy is transferred to ytterbium ions, which serve as a relay, and then passed to erbium ions. The erbium ions perform the upconversion step, allowing the stored energy to emerge as green light.
Making this system brighter, however, has historically created another problem.
“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.”
A Layered Design Creates a One-Way Energy Path
To overcome that limitation, Wu, Huang and their colleagues redesigned both the composition and structure of the nanoparticles.
Instead of building the host matrix from sodium, yttrium and fluorine, the researchers created a new matrix using lithium, lutetium and fluorine.
They also changed the particles from flat hexagons into more three-dimensional, diamond-shaped structures. Each particle contains several distinct regions: a dense core surrounded by an inner shell and then 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.”
Rather than arriving at this design through trial and error alone, the team relied heavily on computer modeling. Researchers simulated dozens of possible chemical formulations and particle shapes before manufacturing the most promising versions in the laboratory.
“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.”
Nanoparticles Up to 150 Times Brighter
The resulting nanoparticles produce a much stronger signal than earlier designs.
According to Wu, their emitted light is roughly 150 times brighter than that of upconversion nanoparticles that have not been dye-sensitized. Under the same excitation conditions, they are also about 50 times brighter than some of the most highly optimized conventional structures previously reported.
That brightness translates directly into greater sensitivity. Because each nanoparticle generates such a strong optical signal, even a very small number of particles attached to their target molecules can produce enough light to be detected.
The sensors can also distinguish between structural isomers. These molecules contain exactly the same types and numbers of atoms, but those atoms are arranged differently. Such subtle structural differences can matter enormously in chemistry, particularly in drug manufacturing.
Spotting the Wrong Molecule in a Drug Batch
“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.”
That combination of high sensitivity and molecular selectivity could make the technology valuable for detecting impurities that are difficult or expensive to identify using conventional methods.
The same basic approach could also be adapted for environmental monitoring, where researchers often need to detect extremely small concentrations of contaminants mixed into much larger volumes of water.
The Next Step Toward Commercial Use
The technology is still at the proof-of-concept stage. Before the nanoparticles could be widely adopted, researchers would need to develop a practical way to manufacture them in large quantities.
Huang says that work is already underway.
“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.”
