Strategies for developing sensitive and specific nanoparticle-based lateral flow assays as point-of-care diagnostic device

Abstract From a home-based pregnancy self-testing kit, lateral flow assays (LFAs) have proliferated and gained widespread utilization as point-of-care (POC) test kits. Their prevalence is due to their portability, rapid time-to-result, simplicity, stability, and cost-effectiveness. LFAs are well-suited for early detection of infectious diseases, which threatens public health and the economy, enabling timely medical intervention, and management of disease and treatment. This is vital for rural and resource-limited settings where well-equipped laboratories with well-trained personnel are scarce. Nevertheless, LFAs have certain limitations, such as moderate sensitivity and target throughput, as compared to lab-based technologies. Also, the development of LFA, although well-defined, is not straightforward. In this review article, we will elucidate the iterative process of LFA development, and discuss strategies for generating sensitive and specific capture/detector agents, multiplexed detection and signal amplification. An important starting point in LFA development is the clear definition/identification of design inputs and predicate. Newly engineered capture/detector agents, such as nanobodies and aptamers, should possess high binding affinity and functionality in body fluid samples for practical field application. Also, chemical methods, combined with engineering, have enabled multiplexing and signal amplification capabilities for higher target throughput and detection sensitivity. Furthermore, LFAs can be augmented or adapted to other platforms, such as smartphone, spectroscopy and electrochemistry, for quantitative measurements that can engender wider applications and adoption. Through these advances, LFA will transform into a genuinely versatile platform, capable of delivering accurate results that are similar to lab-based technologies, while retaining its advantage as a simple, portable, inexpensive and rapid test.

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