Quantum nanodiamonds may help detect disease earlier

The quantum detection capabilities of nanodiamonds can be used to improve the sensitivity of paper-based diagnostic tests, potentially allowing for earlier detection of diseases such as HIV, according to a study by UCL researchers in the i-group. sense McKendry.

Lateral flow tests on paper work much like a pregnancy test in that a strip of paper is dipped in a sample of liquid and a change in color – or fluorescent signal – indicates a positive result and detection of viral proteins or DNA. They are widely used to detect viruses ranging from HIV to SARS-CoV-2 (lateral flow tests for Covid-19 are currently being tested across England) and can provide a rapid diagnosis, as the results have not been to be processed in a laboratory. .

The new research, published in Nature, discovered that inexpensive nanodiamonds could be used to signal the presence of a marker of HIV disease with a sensitivity several thousand times greater than that of gold nanoparticles widely used in these tests.

This greater sensitivity allows for lower viral loads to be detected, which means the test could detect lower levels of disease or detect disease at an early stage, which is crucial for reducing the risk of transmission from those infected and for effective treatment of diseases such as HIV.

The research team is working on adapting the new technology to test for COVID-19 and other diseases over the coming months. A key next step is to develop a hand-held device capable of “reading” the results, as the technique has been demonstrated using a microscope in a laboratory. Further clinical evaluation studies are also planned.

Lead author Prof Rachel McKendry, professor of biomedical nanotechnology at UCL and director of i-sense EPSRC IRC, said: “Our proof of concept study shows how quantum technologies can be used to detect levels. ultra-low levels of virus in a patient sample, allowing much earlier diagnosis.

“We have focused on detecting HIV, but our approach is very flexible and can be easily adapted to other diseases and types of biomarkers. We are working to adapt our approach to COVID-19. We believe that this new transformative technology will benefit patients and protect populations from infectious diseases. “

The researchers used the quantum properties of nanodiamonds made with a precise imperfection. This defect in the very regular structure of a diamond creates what is called a nitrogen vacuum center (NV). NV centers have many potential applications, from fluorescent biomarking for use in ultra-sensitive imaging to information processing qubits in quantum computing.

NV centers can signal the presence of an antigen or other target molecule by emitting bright fluorescent light. In the past, fluorescent markers have been limited by background fluorescence, either from the sample or from the test strip, making it more difficult to detect low concentrations of viral proteins or DNA that would indicate a positive test. However, the quantum properties of fluorescent nanodiamonds allow their emission to be selectively modulated, which means that the signal can be fixed at a defined frequency using a microwave field and can be efficiently separated from background fluorescence, addressing this limitation.

Optical results showed an improvement in sensitivity of up to five orders of magnitude (100,000 times) over gold nanoparticles (i.e., a much lower number of nanoparticles were required to generate a detectable signal). With the inclusion of a short 10-minute constant temperature amplification step, during which copies of the RNA were multiplied, the researchers were able to detect HIV RNA at the single molecule level. in a model sample.

The work has been demonstrated in the lab but the team hopes to develop the tests so that the results can be read with a smartphone or portable fluorescence reader. This means that the test could, in the future, be performed in low-resource environments, which would make it more accessible to users.

First author Dr Ben Miller (i-sense postdoctoral research associate at the London Center for Nanotechnology at UCL) said: “Lateral flow tests on paper with gold nanoparticles do not require laboratory analysis. , which makes them particularly useful in low-resource environments and where access to healthcare is limited, they are inexpensive, portable and easy to use.

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

Co-author Professor John Morton, Director of UCL’s Quantum Science and Technology Institute (UCLQ), said: “This interdisciplinary collaboration between UCLQ and the LCN i-sense team is a fantastic illustration of how fundamental work on quantum systems, such as the NV Center in Diamond, can evolve from the lab and play a crucial role in real-world applications in detection and diagnostics.UCLQ researchers explore and enable the impact of these and other quantum technologies by working with industry and other academic research groups. ”