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

用于超灵敏生化测试的侧流分析 (SOP-LFA) 装置中溶质驱动的在线富集

• 批准号: EP/X01813X/1
• 负责人: Guido Bolognesi
• 金额: $ 25.77万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX01813X%2F1
• 关键词: Solute; driven; Online; Preconcentration; Lateral

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.

床旁快速检测设备，特别是纸基分析设备，在发达国家（例如，2020年英国登月行动）和世界贫困地区（例如，世界卫生组织的全球疟疾规划。这些设备可以实现快速、经济实惠且广泛使用的诊断，但与基于实验室的分析技术相比，灵敏度有限，不适合早期疾病的诊断。在不牺牲其优势的情况下大幅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，该提案旨在引入一种用于生物标志物快速预浓缩的新范例（即，与特定疾病相关的分子），通过收集与盐水溶液相关的能量。这种全新的概念将在比色侧流装置中进行测试和验证，可能导致装置灵敏度的数量级改进，而不依赖于辅助电源，或损害装置的便携性、简单性以及制造和使用的容易性。已经成功地用于通过在装置的检测区域预浓缩生物标志物来提高纸基分析系统的灵敏度。然而，电气部件（例如，电池、集成电路）以及对电压供应和调节的要求严重损害了装置的简单性，并围绕装置的可持续制造和处置引入了额外的挑战，特别是在低资源环境中。我们提出的策略将利用在电解质溶液之间的界面处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处的生物标志物。将进行实验和数值研究相结合，以获得一个定量的了解的质量传输机制，建议的预浓缩过程。一个数学建模指导的方法将被用来设计验证的原则侧流设备，将进行可行性测试和验证模型分析物和艾滋病毒和疟疾生物标志物的超灵敏检测。验证我们的生物标志物预浓缩的新范例将允许突破性的快速诊断技术的发展，通过超灵敏，但简单和低成本的侧流测试，试纸，和微流体纸基分析设备，用于慢性病和传染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，以实现更可持续的诊断主导和基于社区的医疗保健。这些技术还将有助于全球诊断民主化，这对于发展中国家的健康和经济可持续性至关重要。