Researchers Use ‘New Physics’ to Create Imaging Contrast Agent

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SYDNEY, June 24, 2019 — Scientists at the University of Technology Sydney (UTS) and Fudan University in China have breached a limitation in physics to create a new biomedical imaging contrast agent that will allow for significant improvement in optical imaging technology.

To optimize the brightness of a contrast agent and to efficiently illuminate single cells and biomolecules, the challenge lies in overcoming “concentration quenching.” This limitation is caused by cross relaxation of energy between emitters when they’re too close to each other. Having too many emitters leads to a quenching of the overall brightness.

“The new approach in this research was to unlock the concentration quenching effect by using the pure rare-earth element ytterbium that only has a single excited state to avoid intersystem cross relaxation,” explained professor Dayong Jin, a senior author on the study and director of the UTS Institute for Biomedical Materials and Devices (IBMD). “A network of over 5000 pure ytterbium emitters can be tightly condensed within a space of 10 nm in diameter, a thousand times smaller than a cell.”

At this emitter density, all possible atomic doping sites are occupied by ytterbium within the crystal lattice structure, and once properly passivated (made unreactive) by a thin layer of biocompatible calcium fluoride, the material is free of concentration quenching.

“This enables the efficiency of photonics conversion to approach the theoretical limit of 100%. This not only benchmarks a new record in photonics and materials sciences, but also opens a lot of potential applications,” Jin said.

Lead author Yuyang Gu, a doctoral student at Fudan, said, “Using this new contrast agent in a mouse model allowed us to see through the whole mouse.”

The fundamental physics of fluorescent probes used in optical imaging dictates a narrowly defined NIR optical transparency window, beyond which visible light cannot penetrate tissue. Designing a contrast agent able to absorb and emit in the NIR without losing the energy is difficult.

“Although ytterbium has a ‘pure energy’ level that helps protect photons absorbed in the NIR band before being emitted," Jin said, "with negligible loss of energy,the simple excited state only permits emissions in the very similar band of NIR, which makes it impractical to use the conventional color filters to discriminate the emissions from the highly scattering environment of laser excitation.”  

“The research needed ‘new physics.’ We really had to think outside the box,” he said. 

Rather than spectrally filtering the signal emissions, the researchers employed a time-resolved technique that paused the excitation light and took advantage of the “photon storage” property of ytterbium emitters, slowing down the emission of light long enough to allow a clearer separation between the excitation and emission of light in the time domain. Jin likened this phenomena to the scenario when, after powering off the TV, the long-lived fluorescence of the “ghost” image is seen as an afterglow in the darkness.

Professor Fuyou Li, chief investigator at Fudan, said he hoped to find more applications based on fine-tuning of the decay process.

The research was published in Nature Photonics (

Published: June 2019
Biophotonicscontrast agentoptical imaginglaser excitationNIR

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