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Nanodiamonds enhance paper-based diagnostic testing

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A University College London (UCL) study has demonstrated that the quantum properties of nanodiamonds can be harnessed to heighten the sensitivity of paper-based diagnostic tests, potentially allowing for the earlier detection of viruses such as HIV and SARS-CoV-2.

Paper-based lateral flow tests work in a similar way to pregnancy tests; a strip of paper soaked in a fluid sample changes colour (or produces a fluorescent signal) to indicate a positive result and the detection of virus proteins or DNA. This type of test is widely used to detect viruses – with lateral flow tests for SARS-CoV-2 being piloted in England – and can provide a rapid diagnosis as the results do not need to be sent to a lab for processing.

Now, UCL researchers have shown that low-cost nanodiamonds could be used to signal the presence of an HIV disease marker with a sensitivity thousands of times greater than the gold nanoparticles widely used in these tests. This allows lower viral loads to be detected, meaning that the test could detect lower levels of disease or allow for an earlier diagnosis; this can be crucial for reducing transmission risk.

“Our proof-of-concept study shows how quantum technologies can be used to detect ultralow levels of virus in a patient sample, enabling much earlier diagnosis,” said Professor Rachel McKendry, lead author of the Nature study. “We have focused on the detection of HIV, but our approach is very flexible and can be easily adapted to other diseases and biomarker types.

“We are working on adapting our approach to Covid-19. We believe that this transformative new technology will benefit patients and protect populations from infectious diseases.”

The study made use of the quantum properties of nanodiamonds manufactured with a precise imperfection; this defect creates a nitrogen-vacancy (NV) centre. NV centres have many potential applications, ranging from fluorescent biomarking for ultra-sensitive imaging to information processing in quantum computing.

The NV centres can signal the presence of a target molecule by emitting a bright fluorescent light. While in the past, fluorescent markers have been limited by background fluorescence – either from the sample or test strip – the quantum properties of nanodiamonds allow their emission to be selectively modulated. This means that the signal can be set to a certain frequency distinct from background fluorescence.

The UCL researchers’ results shows up to 100,000 times improvements in sensitivity compared with gold nanoparticles. By including a 10-minute constant-temperature amplification step, in which copies of the RNA were multiplied, they were able to detect HIV RNA at the level of a single molecule in a sample.

Dr Ben Miller, first author of the study, commented: “Paper-based lateral flow tests with gold nanoparticles do not require laboratory analysis, making them particularly useful in low-resource settings and where access to healthcare is limited. They are low cost, portable, and user friendly.

“However, these tests currently lack the sensitivity to detect very low levels of biomarkers. By replacing commonly used gold nanoparticles with fluorescent nanodiamonds in this new design, and selectively modulating their (already bright) emission of light, we have been able to separate their signal from the unwanted background fluorescence of the test strip, dramatically improving sensitivity.”

The researchers are now working on adapting the technology to produce a rapid test for Covid-19 and other diseases. A key next step will be developing a hand-held device with which anyone can “read” the results (including in low-resource settings), as the technique was demonstrated using a microscope.

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