Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers. The future of public health is likely to become increasingly digital, and we review the need for the alignment of international strategies for the regulation, evaluation and use of digital technologies to strengthen pandemic management, and future preparedness for COVID-19 and other infectious diseases. Public-health need Digital tool or technology Example of use Refs. Digital epidemiological surveillance Machine learning Web-based epidemic intelligence tools and online syndromic surveillance Web-based epidemic intelligence tools: 20-23,25 Based on social media or online search data: 30-33 Survey apps and websites Symptom reporting 37,38,48,49 Data extraction and visualization Data dashboard 39-45 Rapid case identification Connected diagnostic device Point-of-care diagnosis 58 Sensors including wearables Febrile symptoms checking 51-53 Machine learning Medical image analysis 65,66
Sensitive, specific, rapid, inexpensive and easy-to-use nucleic acid tests for use at the point-of-need are critical for the emerging field of personalised medicine for which companion diagnostics are essential, as well as for application in low resource settings. Here we report on the development of a point-of-care nucleic acid lateral flow test for the direct detection of isothermally amplified DNA. The recombinase polymerase amplification method is modified slightly to use tailed primers, resulting in an amplicon with a duplex flanked by two single stranded DNA tails. This tailed amplicon facilitates detection via hybridisation to a surface immobilised oligonucleotide capture probe and a gold nanoparticle labelled reporter probe. A detection limit of 1 × 10−11 M (190 amol), equivalent to 8.67 × 105 copies of DNA was achieved, with the entire assay, both amplification and detection, being completed in less than 15 minutes at a constant temperature of 37 °C. The use of the tailed primers obviates the need for hapten labelling and consequent use of capture and reporter antibodies, whilst also avoiding the need for any post-amplification processing for the generation of single stranded DNA, thus presenting an assay that can facilely find application at the point of need.
Graphene application within electrochemical sensing has been widely reported, but mainly as a composite, which adds summative effects to an underlying electrode. In this work we report the use of laser-scribed graphene as a distinct electrode patterned on a non-conducting flexible substrate. The laser-scribed graphene electrode compared favourably to established carbon macroelectrodes when evaluating both inner sphere and outer sphere redox probes, providing promise of extensive utility as an electrochemical sensor. The laser-scribed graphene electrode demonstrated the fastest heterogeneous electron transfer rate of all the electrodes evaluated with a k(0) of 0.02373 cm s(-1) for potassium ferricyanide, which exceeds commercially available edge plane pyrolytic graphite at 0.00260 cm s(-1), basal plane pyrolytic graphite at 0.00033 cm s(-1) and the very slow and effectively irreversible electrochemistry observed using single layer graphene. Finally and most significantly, a proof of principle system was fabricated using the laser-scribed graphene as working electrode, counter electrode and underlying base for the Ag/AgCl reference electrode, all in situ on the same planar flexible substrate, removing the requirement of macroscale external electrodes. The planar three electrode format operated with the same optimal electrode characteristics. Furthermore, the fabrication is inexpensive, scalable and compatible with a disposable biosensor format, considerably widening the potential applications in electrochemical bio-sensing for laser-scribed graphene.
The acceptability and feasibility of large-scale testing with lateral flow tests (LFTs) for clinical and public health purposes has been demonstrated during the COVID-19 pandemic. LFTs can detect analytes in a variety of samples, providing a rapid read-out, which allows selftesting and decentralized diagnosis. In this Review, we examine the changing LFT landscape with a focus on lessons learned from COVID-19. We discuss the implications of LFTs for decentralized testing of infectious diseases, including diseases of epidemic potential, the 'silent pandemic' of antimicrobial resistance, and other acute and chronic infections. Bioengineering approaches will play a key part in increasing the sensitivity and specificity of LFTs, improving sample preparation, incorporating nucleic acid amplification and detection, and enabling multiplexing, digital connection and green manufacturing, with the aim of creating the next generation of high-accuracy, easy-to-use, affordable and digitally connected LFTs. We conclude with recommendations, including the building of a global network of LFT research and development hubs to facilitate and strengthen future diagnostic resilience. Sections• Bioengineering approaches, such as the use of nano-and quantum materials, nucleic-acid-based LFTs, CRISPR and machine learning, will improve the sensitivity, specificity, multiplexing and connectivity features of LFTs.• We recommend investing in an international LFT research and development hub network to spearhead the development of a pipeline of innovative bioengineering approaches to design next-generation LFTs.
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