Monday, May 12, 2014

High-Speed Scanning of τ (Tao)-Dots Enables Rapid Pathogen Detection

Researchers have developed a new approach for the rapid detection of multiple disease pathogens in a single test, with a method from the biomedical frontline: ‘decoding’ tunable photonic nanocrystals.
A demonstration successfully detected some of the world’s deadliest conditions –trace amounts of DNAs from HIV, Human Papillomavirus 16, Ebola virus, and Hepatitis B virus – simultaneously in a single test within minutes, requiring only a tiny sample.

The breakthrough follows the researchers’ earlier success in demonstrating the cutting-edge technology of tunable photonic nanocrystals, or “τ-Dots”, which can be coded in the time domain (‘Tunable lifetime multiplexing using luminescent nanocrystals’ Nature Photonics 2013).

The team has now found the other half of the puzzle – decoding the lifetime codes with high-speed scanning that can precisely determine the τ-Dots’ luminescent decay times to the microsecond.

“This method offers untapped biomedical potential in high-speed detection of pathogens, early-stage cancer diagnosis, and bioinformatic analysis towards personalised medicine,” said lead researcher Dr Yiqing Lu, Macquarie University.

“Our method recognises the difference in the lifetimes, just as people can check the colours of luminescent objects. We now are able to build a huge library of lifetime-colour coded microspheres, to perform multiple medical tasks or diagnoses at the same time.

“The time saved by omitting the need to grow or amplify a culture sample for testing, and eliminating the need to run multiple tests, will save future patients precious time so treatment can begin, which can be life-saving when managing aggressive disease states like meningococcal.”

ARC Future Fellow Associate Professor Dayong Jin said the method is also a significant step toward personalised medicine.

“Individuals’ genetic signatures are often behind the frequent failures of traditional symptom-diagnostics. The new toolkit will enable personalised diagnosis of individual’s genetic makeup, so that individually targeted therapies can be specifically tailored according to their decoded gene expression profile.”

Co-author, Professor J Paul Robinson from Purdue University said “This toolset is really a paradigm shift for identifying disease molecules in high-noise environments typical in biological systems such as cancer detection, high throughput screening and also in the bio detection domain.”

Although a working prototype has been developed, the project team are seeking commercial partners to assist with the verification of clinical efficacy followed by product development. This could see the new medical offering widely available in hospitals, pathology labs, and GP clinics.

The project has been the work of an international collaboration funded by an ARC Discovery Grant led by the former Macquarie Deputy Vice-Chancellor (Research) Professor Jim Piper, A/Prof. Jin at the Advanced Cytometry Labs, Dr. Robert Leif at Newport Instruments and Prof. J. Paul Robinson at Purdue University Cytometry Labs in USA.

TITLE: On-the-Fy Decoding Luminescence Lifetimes in the Microsecond Region for Lanthanide-Encoded Suspension Arrays

AUTHORS: Yiqing Lu, Jie Lu, Jiangbo Zhao, Janet Cusido, Françisco M Raymo, Jingli Yuan, Sean Yang, Robert C. Leif, Yujing Huo, James A. Piper, J Paul Robinson, Ewa M. Goldys & Dayong Jin



Significant multiplexing capacity of optical time-domain coding has been recently demonstrated by tuning luminescence lifetimes of the upconversion nanoparticles called ‘τ-Dots’. It provides a large dynamic range of lifetimes from microseconds to milliseconds, which allows creating large libraries of nanotags/microcarriers. However, a robust approach is required to rapidly and accurately measure the luminescence lifetimes from the relatively slow-decaying signals. Here we show a fast algorithm suitable for the microsecond region with precision closely approaching the theoretical limit and compatible with the rapid scanning cytometry technique. We exploit this approach to further extend optical time-domain multiplexing to the downconversion luminescence, using luminescence microspheres wherein lifetimes are tuned through luminescence resonance energy transfer. We demonstrate real-time discrimination of these microspheres in the rapid scanning cytometry, and apply them to the multiplexed probing of pathogen DNA strands. Our results indicate that tunable luminescence lifetimes have considerable potential in high-throughput analytical sciences.


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