Solute-driven Online Preconcentration in Lateral Flow Assay (SOP-LFA) devices for ultrasensitive biochemical testing

在发达国家（例如，2020年英国登月行动）和世界上的贫困地区（例如，世界卫生组织的全球疟疾规划），即时快速检测设备，特别是基于纸张的分析设备都是强有力的诊断工具。这些设备可以实现快速、负担得起和广泛获得的诊断，但与基于实验室的分析技术相比，它们的灵敏度有限，不适合诊断早期疾病。在不牺牲其优点的情况下大幅度提高即时快速检测的灵敏度，是一项持续的技术挑战。为了应对这一挑战，本提案旨在引入一种新的范例，通过收集与盐水溶液相关的能量，在基于纸张的分析设备中快速富集生物标志物（即与特定疾病相关的分子）。这个全新的概念将在比色横向流动设备中进行测试和验证，可能会导致设备灵敏度的数量级提高，而不依赖于辅助电源，也不会影响设备的便携性，简单性，易于制造和使用。电动技术，生物标记物被外电场拖动，已经成功地用于通过在设备的检测区域预先浓缩生物标记物来提高基于纸张的分析系统的灵敏度。然而，电子元件（如电池、集成电路）的使用以及对电压供应和调节的要求严重损害了设备的简单性，并在设备的可持续制造和处置方面带来了额外的挑战，特别是在资源匮乏的环境中。我们提出的策略将利用电解质溶液界面产生的自发局部电场，在不使用任何电源或辅助设备的情况下快速引导和积累检测区域的生物标志物。将进行实验和数值研究相结合，以定量了解控制所提出的预富集过程的质量传递机制。数学建模指导方法将用于设计原理验证的横向流动装置，该装置将进行可行性测试和验证，用于模型分析物以及艾滋病毒和疟疾生物标志物的超灵敏检测。通过超灵敏、简单、低成本的横向流动测试、试纸和基于微流控纸的分析设备，验证我们的生物标志物预浓缩新范例将允许突破性快速诊断技术的发展，用于慢性和传染性疾病的早期和负担得起的诊断。这些创新、廉价、快速和高度敏感的诊断工具由社区中不熟练的用户操作，将支持NHS长期计划的实施，以实现更可持续的以诊断为主导和以社区为基础的医疗保健。这些技术还将有助于全球诊断民主化，这对于在发展中国家提供健康和经济可持续性至关重要。

Point-of-care rapid testing devices, particularly paper-based analytical devices, are powerful diagnostic tools both in developed countries (e.g., 2020 UK Operation Moonshot) and in deprived regions of the world (e.g., World Health Organisation's Global Malaria Programme). These devices can enable rapid, affordable, and widely accessible diagnosis, but compared to laboratory-based analytical techniques, have limited sensitivity, making them inappropriate for the diagnosis of early-stage diseases. Improving the sensitivity of point-of-care rapid tests substantially without sacrificing their advantages, is an ongoing technological challenge. To address this challenge, this proposal aims to introduce a new paradigm for the rapid preconcentration of biomarkers (i.e., the molecules associated with a specific disease) in paper-based analytical devices by harvesting the energy associated with salty water solutions. This radically new concept will be tested and validated in colorimetric lateral flow devices, potentially leading to orders of magnitude improvement in device sensitivity, without relying on auxiliary power sources, or compromising the device portability, simplicity, and ease of fabrication and use.Electrokinetic techniques, where the biomarkers are dragged by an external electric field, have been successfully used to improve the sensitivity of paper-based analytical systems by preconcentrating the biomarkers at the detection region of the devices. However, the use of electrical components (e.g., batteries, integrated circuits) and the requirement for voltage supply and regulation severely compromise device simplicity and introduce additional challenges around sustainable manufacturing and disposal of the devices, especially in low-resource settings. Our proposed strategy will exploit the spontaneous local electric field generated at the interface between electrolyte solutions to rapidly direct and accumulate the biomarkers at the detection region without using any power supply or auxiliary equipment. Combined experimental and numerical studies will be conducted to gain a quantitative understanding of the mass transport mechanisms governing the proposed preconcentration process. A mathematical modelling-guided approach will be used to design proof-of-principle lateral flow devices that will be feasibility tested and validated for ultrasensitive detection of model analytes and HIV and malaria biomarkers.Validating our novel paradigm for biomarker preconcentration will allow the development of breakthrough rapid diagnostics technologies, through ultrasensitive and yet simple and low-cost lateral flow tests, dipsticks, and microfluidic paper-based analytical devices, for early and affordable diagnosis of chronic and infectious diseases. These innovative, cheap, rapid and highly sensitive diagnostic tools, operated by unskilled users in the community, will support the delivery of the NHS Long Term Plan for a more sustainable diagnosis-led and community-based healthcare. These technologies will also contribute to the global democratisation of diagnostics, which is imperative in delivering health and economic sustainability in the developing world.