Researchers at UMass Medical School (UMMS) have successfully developed light-emitting nanocrystals that could help advance non-invasive bioimaging technologies. These nanocrystals would enable utilization of persistent luminescence nanoparticles for bioimaging applications in the clinic, and in research laboratories. This would allow functional and structural biological processes in patients and in living animals to be evaluated.
The new nanocrystals demonstrate an exceptional signal-to-noise-ratio when compared to other in vivo optical imaging probes that are currently being used.
During imaging they do not require any excitation resource, such as light, and existing imaging systems can be used to directly detect these nanoparticles.
Materials that have the ability to emit light for a time period which could last from minutes, hours or even a day even after the excitation source has been turned off are considered to have persistent luminescence. Humans have been utilizing materials with persistent luminescence for over 1,000 years. They are commonly used in luminous paints, watches and clocks, electronic displays, traffic signs, textile printing and emergency signage.
Ultra-small luminescent phosphors are playing an increasingly vital role in medicine and science. Our straightforward method for producing these tiny near-infrared persistent luminescence nanoparticles, coupled with their superior performance and luminescence renewability, is groundbreaking. It opens up opportunities for developing a new generation of technologies to use in medical imaging diagnosis and therapy, as well as other applications in photonics and biophotonics.
Gang Han, PhD, assistant professor of biochemistry & molecular pharmacology and principal investigator of the study
Similar persistent luminescence nanoparticles that can be used for safe imaging, by injecting the particles into live biological tissues, are being sought by biomedical researchers. When existing imaging technologies including X-ray imaging, ultrasonic imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), electron tomography (ET), optical coherence tomography (OCT), and micro-computed tomography (micro CT) could be used along with a persistent luminescence material it would greatly enhance the capabilities available for physicians and biomedical researchers to perform diagnosis.
Current methods for producing these light-emitting particles are complex. They require synthesis with extremely high temperature annealing (>1,000°C) and a complicated physical process to transform large, bulk crystals into nanoparticles. This often creates heterogeneous particles that quickly agglomerate in solution and are too large for use in biological tissues, as their size could potentially disrupt cellular systems and cause harm.
Dr. Han and his team utilized a new methodology for production and they dubbed the resulting nanocrystals as “luminous pearls.” Han named these nanocrystals after the Chinese tale of the seven fairies. In this tale, daytime sunlight was stored in luminous pearls and they were than released “to weave the rose clouds of the dawn.”
“This image is particularly apt, because the methods described in the paper produce near-infrared luminescence nanoparticles that in effect have renewable luminescence,” said Han.
The new aqueous production method utilized in this study, involves a suitable chemical approach for generating uniform, ultra small nanoparticles that are of the size of a protein. Hydrothermal synthesis was used and the chemical reactions between substances took place in a sealed heated aqueous solution. This led to production of zinc-gallium-chromium nanoparticles. The secret for creating near-infrared persistent luminescence nanoparticles that are uniformly ultrasmall was the zinc to gallium molar ratio.
The “luminous pearls” provided vivid images even when a brief LED light irradiation was given before being injected into a live mouse. The images were even through deep tissue. However, after 30 minutes the signal decreased in a gradual manner. This could be reactivated at any desired time, and repeatedly. Furthermore, the nanoparticles that were produced hydrothermally, demonstrated good stability. After these nanoparticles were inserted, they remained viable for a period lasting a month.
It’s likely these hydrothermally produced nanocrystals are smaller but brighter than similar materials due to the fact that they have fewer defects, with more regular shapes and complete crystal facets. They can also be repeatedly recharged within deep tissues and have the potential to be directly adapted for use in commercially available imaging systems.
This study has been published in the Journal of the American Chemical Society. It was a spotlight article and also an editor’s choice.