The quantum spin properties of nitrogen-vacancy defects in diamond have diverse applications including quantum computing and communications 1 , but nanodiamonds also have attractive properties for in vitro biosensing, including brightness 2 , low cost 3 , and selective manipulation of their emission 4 . Nanoparticle-based biosensors are vital for early disease detection, however, often lack the required sensitivity. Here we investigated fluorescent nanodiamonds as an ultra-sensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity 5 , and frequency-domain analysis 6 to separate the signal from background autofluorescence 7 , which typically limits sensitivity.We focused on the common, low-cost lateral flow format as an exemplar, achieving detection limits of 8.2 × 10 −19 M for a biotin-avidin model, 10 5 -fold more sensitive than gold nanoparticles; and a use-case demonstration of single-copy detection of HIV-1 RNA with a short 10-minute isothermal amplification step, including a pilot using a clinical plasma sample with an extraction step. This ultra-sensitive quantum-diagnostics platform is applicable to numerous diagnostic test formats and diseases with the potential to transform early diagnosis, benefiting patients and populations.Rapid point-of-care tests have transformed access to disease testing in a variety of community settings, including clinics, pharmacies and the home 30 . Among the most common tests worldwide are paper microfluidic lateral flow assays (LFAs), with 276 million sold in 2017 for malaria alone 31 . LFAs satisfy many of the REASSURED criteria 32 for diagnostics, however, despite widespread use they are still limited by inadequate sensitivity to detect the low levels of biomarkers necessary for early disease detection.Fluorescent markers can be highly sensitive, but are practically limited by background fluorescence from the sample, substrate, or readout technique. In the case of nitrocellulose substrates used in LFAs, there is a significant background autofluorescence 7 , which inherently limits sensitivity. Various methods have been reported to reduce this effect, such as membrane modification to reduce background fluorescence 33 , exciting in the nearinfrared range and using upconverting nanoparticles 34 , and time-gated detection using longpersistent phosphors 35 to separate background fluorescence, which has a shorter lifetime.These methods have shown ∼10-fold improvements in sensitivity over gold nanoparticles, limited by relatively low brightness.Here we show the use of FNDs as a fluorescent label in an LFA format as a demonstrator of their first use for in vitro diagnostics, taking advantage of their high brightness and selective modulation. The use of a narrowband resonator allows for the lowpower generation of microwave-frequency electromagnetic fields, suitable for a point-ofcare device, to efficiently separate the signal from the background in the frequency domain by lock-in 6 detection. We aimed, after characterisation, functionalisation,...

SummaryThe use of whole blood gene expression to derive diagnostic biomarkers capable of distinguishing between phenotypically similar diseases holds great promise but remains a challenge. Differential gene expression analysis is used to identify the key genes that undergo changes in expression relative to healthy individuals, as well as to patients with other diseases. These key genes can act as diagnostic, prognostic and predictive markers of disease. Gene expression ‘signatures’ in the blood hold the potential to be used for the diagnosis of infectious diseases, where current diagnostics are unreliable, ineffective or of limited potential. For diagnostic tests based on RNA signatures to be useful clinically, the first step is to identify the minimum set of gene transcripts that accurately identify the disease in question. The second requirement is rapid and cost‐effective detection of the gene expression levels. Signatures have been described for a number of infectious diseases, but ‘clinic‐ready’ technologies for RNA detection from clinical samples are limited, though existing methods such as RT‐PCR are likely to be superseded by a number of emerging technologies, which may form the basis of the translation of gene expression signatures into routine diagnostic tests for a range of disease states.

AbstrActbackground Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality. Objectives To systematically review, critically appraise and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use. Design Systematic review and meta-analysis.