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

无论是在发达国家(例如2020年英国的登月行动)，还是在世界上的贫困地区(例如世界卫生组织的全球疟疾计划)，医疗点快速检测设备，特别是纸质分析设备，都是强大的诊断工具。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，灵敏度有限，使其不适合诊断早期疾病。在不牺牲其优势的情况下大幅提高医疗点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，这项提议旨在引入一种新的范例，通过收集与咸水溶液相关的能量，在纸基分析设备中快速预浓缩生物标志物(即与特定疾病相关的分子)。这一全新的概念将在比色侧向流动装置中进行测试和验证，可能导致装置灵敏度提高数量级，而不依赖辅助电源，也不会影响装置的便携性、简单性和制造和使用的易用性。电动技术，即生物标记物被外部电场拖动，已成功地用于通过在装置的检测区域预浓缩生物标记物来提高纸基分析系统的灵敏度。然而，电子元件(例如电池、集成电路)的使用以及对电压供应和调节的要求严重影响了设备的简单性，并带来了围绕设备的可持续制造和处置的额外挑战，尤其是在低资源环境中。我们提出的策略将利用电解液之间界面上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，在检测区域快速引导和积累生物标志物。将进行实验和数值研究相结合的研究，以获得对所提议的预浓缩过程的质量传输机制的定量了解。将使用数学建模指导的方法来设计原理验证的横向流动装置，这些装置将被可行性测试和验证，用于模型分析物以及艾滋病毒和疟疾生物标记物的超灵敏检测。验证我们的生物标记物预浓缩的新范例将允许开发突破性的快速诊断技术，通过超灵敏且简单且低成本的横向流动试验、试纸和微流控纸基分析装置，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的非熟练用户操作，将支持NHS长期计划的交付，以实现更可持续的诊断主导和基于社区的医疗保健。这些技术还将有助于诊断学的全球民主化，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.