Harnessing Spin-Enhanced Nanodiamonds for Early Disease Diagnosis

COVID-19 highlights the enormous human and economic consequences of an emerging infectious disease. In this invited talk, I will discuss some of the recent breakthroughs by the i-sense EPSRC IRC programme in Agile Early Warning Sensing Systems for Infectious Diseases and Antimicrobial Resistance (www.i-sense.org.uk). We are a large UK-led interdisciplinary research consortium and aim to harness the power of advanced nanosensors, deep learning, genomics and data science to track, test and treat infections much earlier than ever before. Recent research highlights span from advanced materials to detect viruses¹, antimicrobial resistance² and deep learning to support field-based tests in low and middle income settings.³ We also led a recent review of digital technologies in the global public health response to COVID-19.⁴<br/>Herein, I will focus on our work on spin-enhanced nanodiamond biosensing for ultra-sensitive virus detection.¹ The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness, low cost and selective manipulation of their emission. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. We are investigating fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity and frequency-domain analysis to separate the signal from background autofluorescence, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10⁻¹⁹ molar for a biotin–avidin model, 10⁵ times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.<br/><b>References</b><br/>1. 'Spin-enhanced nanodiamond biosensing for ultra-sensitive diagnostics' Miller, Bezinge, Gliddon, Huang, Dold, Gray, Heaney, Dobson, Nastouli, Morton & McKendry <i>Nature</i> <b>587</b>, 588 (2020).<br/>2. 'Cantilever sensors for rapid optical antimicrobial sensitivity testing' Bennett, Pyne, McKendry <i>ACS Sensors</i> <b>5</b>, 3133 (2020).<br/>3. 'Deep learning of HIV field-based rapid tests' Turbe, Herbst, Mngomezulu, Meshkinfamfard, Dlamini, Mhlongo, Smit, Cherepanova, Shimada, Budd, Arsenov, Gray, Pillay, Herbst, Shahmanesh & McKendry <i>Nature Medicine</i> <b>27</b>, 1165 (2021).<br/>4. 'Digital technologies in the public health response to COVID-19' Budd, Miller, Manning, Lampos, Zhuang, Edelstein, Rees, Emery, Stevens, Keegan, Short, Pillay, Manley, Cox, Heymann, Johnson <i>Nature Medicine</i> <b>26</b>, 1183 (2020).<br/><b>Websites</b><br/>i-sense EPSRC IRC in Agile Early Warning Sensing Systems for Infectious Diseases and AMR: www.i-sense.org.uk<br/>McKendry group website: https://themckendrylab.com/<br/>McKendry UCL website: https://www.london-nano.com/our-people/our-people-bios/rachel-mckendry