Lateral flow test engineering and lessons learned from COVID-19

Abstract

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.

Anti-N SARS-CoV-2 assays for evaluation of natural viral infection

“…In the context of a health emergency, SARS-CoV-2 screening and diagnosis can be improved by introducing lateral flow tests ( Budd et al, 2023 ; Afzal, 2020 ).…”

“…Reverse transcription-polymerase chain reaction (RT-PCR) remains the gold standard for diagnosing COVID-19, and genomic sequencing has become vital for tracking variants. However, lateral flow tests (LFTs), albeit less sensitive than PCR, have enabled an unprecedented scale of global testing in clinical and public health, owing to their simplicity, low cost, accessibility, rapid results and ability to detect infectiousness ( Budd et al, 2023 ). Serological tests are elective methods to assay seroconversion and epidemiology of SARS-CoV-2 and will represent an important instrument to track immune response promoted by future vaccine against this virus.…”

An update on lateral flow immunoassay for the rapid detection of SARS-CoV-2 antibodies

“…Although the production on large scale of assays using new technologies is challenging, mainly for the availability of new sophisticated label materials, for many of these results are encouraging, showing a significantly greater performance compared with gold nanoparticle-based commercial kits [47] , [50] , [53] , [54] . Another method to improve sensitivity is the use of an external reader to amplify the signal [20] , [46] .…”

Direct immunoassay on a polyester microwell plate for colorimetric detection of the spike protein in swab and saliva samples

“…However, one barrier to accepting LFTs during the pandemic was their limited accuracy. 18 Furthermore, the LFT response is qualitative, making it impossible, for example, to provide a relationship between the quantity of the target and the contagion time.…”