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.
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