“Researchers first proposed quantum-dot technologies for medical applications back in the late 1990s, but there were concerns that quantum dots could be toxic inside the human body,” explains team leader Warren Chan. “However, toxicity is not an issue for quantum dots when they are used for patients outside of the body. Our group has now demonstrated, for the first time, that quantum dots can identify the hepatitis B virus in blood samples taken from infected patients.”

In their study, the researchers performed a blind experiment by analysing patient samples using both traditional PCR techniques and the quantum-dot barcodes. They then compared the results from the two analyses to see if they matched, which was indeed the case. “We also found that if we use multiple QD barcodes, we can enhance the accuracy of the diagnoses,” explains team member Jisung Kim. Indeed sensitivity can be increased from 54.9−66.7% for single QD barcodes to 80.4−90.5% for multiple ones.

Barcoding diagnostic technologies

Barcoding diagnostic technologies such as this have been around for more than 15 years, and most of these work using “Luminex” or similar types of barcodes doped with organic fluorophores. Here, colour codes microbeads into as many as 100 distinct sets by dying them with fluorescent molecules and each set of signature beads carries specific detection reagents – such as an oligonucleotide probes, antigens or proteins – on its surface. Molecules to be analysed in a sample bind to these detection reagents and a “reporter” molecule coupled with another fluorophore measures the reaction on the bead surface. These interactions are then measured by exciting with laser beams and the signal measured with a detector.

While efficient in such an application, the fluorophore molecules themselves do suffer from inherent limitations because they have very broad fluorescence spectra, which makes it difficult to differentiate between similar emission colours. And, microbeads doped with multiple organic fluorophores usually require multiple lasers to excite them, which makes for bulky and costly instruments.

QDs are alternative to fluorophores

As an alternative to fluorophores, Chan’s team has been developing quantum dots (QDs) for over a decade now. These QDs contain biorecognition molecules on their surface to detect genetic biomarkers of pathogens like HIV, malaria, hepatitis B and C, and syphilis, all of which are carried in blood. QDs have many advantages over organic fluorophores for making unique optical barcodes, including the fact that they have a narrower spectral line width. What is more, different light emissions from the dots can be excited with a single wavelength of light.

The team, reporting its results in ACS Nano DOI: 10.1021/acsnano.6b01254, says that it will now be trying to figure out how best to commercialize its technology so that quantum dots can be used in hospital for diagnosing diseases. “This could be the first medical use of quantum-dot technology,” Chan tells nanotechweb.org.