Vincent J Vezzaa, Adrian Butterwortha, Perrine Lasserrea, Ewen O Blaira, Alexander MacDonalda, Stuart Hannaha, Christopher Rinaldib, Paul A Hoskissonc, Andrew C Wardd, Alistair Longmuire, Steven Setforde, Eoghan CW Farmerf, Michael...
SARS-CoV-2 diagnostic
practices broadly involve either quantitative
polymerase chain reaction (qPCR)-based nucleic amplification of viral
sequences or antigen-based tests such as lateral flow assays (LFAs).
Reverse transcriptase-qPCR can detect viral RNA and is the gold standard
for sensitivity. However, the technique is time-consuming and requires
expensive laboratory infrastructure and trained staff. LFAs are lower
in cost and near real time, and because they are antigen-based, they
have the potential to provide a more accurate indication of a disease
state. However, LFAs are reported to have low real-world sensitivity
and in most cases are only qualitative. Here, an antigen-based electrochemical
aptamer sensor is presented, which has the potential to address some
of these shortfalls. An aptamer, raised to the SARS-CoV-2 spike protein,
was immobilized on a low-cost gold-coated polyester substrate adapted
from the blood glucose testing industry. Clinically relevant detection
levels for SARS-CoV-2 are achieved in a simple, label-free measurement
format using sample incubation times as short as 15 min on nasopharyngeal
swab samples. This assay can readily be optimized for mass manufacture
and is compatible with a low-cost meter.
Antibiotic resistance has been cited by the World Health Organisation (WHO) as one of the greatest threats to public health. Mitigating the spread of antibiotic resistance requires a multipronged approach with possible interventions including faster diagnostic testing and enhanced antibiotic stewardship. This study employs a low-cost diagnostic sensor test to rapidly pinpoint the correct antibiotic for treatment of infection. The sensor comprises a screen-printed gold electrode, modified with an antibiotic-seeded hydrogel to monitor bacterial growth. Electrochemical growth profiles of the common microorganism, Escherichia coli (E. coli) (ATCC 25922) were measured in the presence and absence of the antibiotic streptomycin. Results show a clear distinction between the E. coli growth profiles depending on whether streptomycin is present, in a timeframe of ≈2.5 h (p < 0.05), significantly quicker than the current gold standard of culture-based antimicrobial susceptibility testing. These results demonstrate a clear pathway to a low cost, phenotypic and reproducible antibiotic susceptibility testing technology for the rapid detection of E. coli within clinically relevant concentration ranges for conditions such as urinary tract infections.
Using both multi-informative molecular network and score-based approaches as prioritization strategies, the Northeastern Atlantic marine terebellid Eupolymnia nebulosa was selected for in-depth chemical investigation. A family of 16 new metabolites named nebulosins was isolated and structurally characterized from extensive analyses of HRMS/MS and NMR spectroscopic data. Nebulosins feature an unprecedented highly substituted thiolane ring leading to up to four contiguous chiral centers. The relative configurations were assigned through a combination of NOESY analysis, spin−spin coupling constant analysis, and NMR chemical shifts measurements, while the absolute configurations were determined by comparison between experimental and theoretical ECD spectra. This family of natural product exhibits promising antioxidant activities in both ORAC and ROS assays.
SARS-CoV-2 diagnostic practices broadly involve either qPCR based nucleic amplification or lateral flow assays (LFAs). qPCR based techniques suffer from the disadvantage of requiring thermal cycling (difficult to implement for low-cost field use) leading to limitation on sample to answer time, the potential to amplify viral RNA sequences after a person is no longer infectious and being reagent intense. LFA performance is restricted by qualitative or semi-quantitative readouts, limits on sensitivity and poor reproducibility. Electrochemical biosensors, and particularly glucose test strips, present an appealing platform for development of biosensing solutions for SARS-CoV-2 as they can be multiplexed and implemented at very low cost at point of use with high sensitivity and quantitative digital readout. This work reports the successful raising of an Opti-mer sequence for the spike protein of SARS-CoV-2 and then development of an impedimetric biosensor which utilises thin film gold sensors on low-cost laminate substrates from home blood glucose monitoring. Clinically relevant detection levels for SARS-CoV-2 are achieved in a simple, label-free measurement format using sample incubation times of 15 minutes. The biosensor developed here is compatible with mass manufacture, is sensitive and low-cost CE marked readout instruments already exist. These findings pave the way to a low cost and mass manufacturable test with the potential to overcome the limitations associated with current technologies.
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