Doped Nanocrystals Developed for Bioimaging

A synthesis of lanthanide-doped core-shell nanocrystals has resulted in advanced light-control properties for bioimaging applications including cancer diagnostics, medical imaging and therapeutic delivery.

A research team from the National University of Singapore (NUS) along with colleagues from Saudi Arabia and China found a chemical structure that can exhibit efficient upconversion in nanoparticles through a special arrangement of energy levels.

Upconversion emission materials are ideal for bioimaging because of their effectiveness as contrast agents for the detection of cancer cells, more so when the background emission of noncancerous tissues can be minimized. Opaque tissues can be turned into glassy, transparent substances by using these biomarkers, which rely on near-infrared excitation.

For sensing applications, separating optical signals from the background can be tricky when the signal and noise occur at the same wavelength. This problem can be solved with upconversion — a nonlinear optical process — where two low-energy photons of an incident beam can be converted into a single photon of higher energy, which can then be easily distinguished from the background.

The ability to convert light using these nanomaterials for heating also offers promising applications in photodynamic therapy and drug delivery.

The researchers focused on controlling the optical properties of nanomaterials by doping rare-earth metals in confined layer-by-layer structures. The nanoparticle shell can be doped with various rare-earth metals, resulting in a broad tunability of the upconverted emission.

By producing nanoparticles with tunable emission that should also have a low toxicity, the researchers have made a great leap in the development of upconverting materials.

They designed core-shell nanoparticles that separate the upconversion process from that of light emission. Photons are absorbed in the core of the nanoparticles and turned into excited electrons, after which they cascade from the core of the nanoparticles into the excited state of rare-earth dopants in the shell. While there, these electrons relax and emit light.

Although such sequential energy transfer has been investigated for certain semiconductor nanoparticles and nanowires for solar energy applications, it has not been done so before for rare earth-doped nanoparticles.

Xiaogang Liu, associate professor at NSU, said that finding upconverting ions that emit in a wide-ranging spectral region had been unsuccessful previously because an efficient photon upconversion had been restricted to a small number of lanthanide ions with emitted light signals detectable by the naked eye.

“We perform photon upconversion on an array of rare-earth metals,” Liu said. “Photon upconversion turns low energy near-infrared light into higher energy made visible with the rational design and chemical synthesis of a core-shell nanostructure.”

His team prepared nanoparticles that could demonstrate an upconversion emission ranging from violet, blue, green to red yellow, with significantly longer infrared excitation wavelengths of up to 980 nm. An important aspect of using light with a 980-nm wavelength is that the transparency of living tissue is high in infrared, enhancing the opportunity to use these nanoparticles for cancer detection. The multiple emission colors demonstrated in this research also could potentially be used for a more reliable biological diagnostics application, such as multiple cell markers.

Opportunities for other applications

The ability to convert low energy near-infrared light into higher-energy visible emission, along with low levels of toxicity to cells and ease of processing, will turn nanometer-size lanthanide-doped crystals into ideal materials for numerous applications.

“This work made me confident that we will see exciting new applications for these particles soon,” said Thomas Nann, a research professor from the University of South Australia, whose research is in this same field. “Upconverting nanoparticles are materials with a tremendous potential for application. However, due to the need for a rigorous selection of usable upconverting ions, science appeared not to have made any headway for some time prior to this discovery.”

Liu’s team noted the uniqueness of its design, which is the use of core-shell nanostructures and gadolinium ions for energy migration that enhances the ability to produce a wide range of lanthanide-doped nanocrystals to yield upconverted luminescence.

“Benefiting from the sublattice of gadolinium ions as a network for energy migration, these judiciously designed nanoparticles light up those less commonly used lanthanide ions like terbium, europium and samarium under near-infrared excitation,” said Chun-Hua Yan, a chemistry professor at Peking University in China. “I do believe that this model, with its uniqueness and versatility, will vastly enrich the currently available upconversion materials and will have impact on relevant fields such as luminescent biolabeling, multiplexed data storage and displays.”

The NUS team has filed a related patent for its discovery and is working with clinicians to develop diagnostic models for practical use.

The research was published in Nature Materials.

For more information, visit: www.nus.edu.sg