Rapid point-of-care testing solutions to meet clinical needs

Abstract

There is increasing demand for point-of-care testing solutions for both the diagnosis and monitoring of diseases. As has been demonstrated during the pandemic, paper-based lateral flow devices are an excellent candidate for rapid and large population testing providing a binary yes or no answer for the presence of a single covid-specific biomarker. For these devices to be most effective and more widely applicable they instead require to be quantitative and deliver multiplexing capabilities, i.e., be able to measure simultaneously more than one disease biomarker. In this thesis the focus is on the inclusion of the above capabilities into create the next generation of lateral flow devices (LFDs) for wider clinical applications. Using the laser-based direct-write (LDW) technique that implements polymerisation of a photopolymer to produce impermeable barriers within the porous membranes inside a LFD I have demonstrated the use of multiple parallel channels for multiplexed detection whilst removing issues such as cross reactivity and the requirement for tests with larger footprints that ensue a higher cost. This multiple channel flow architecture was also utilised to add semi-quantitative measurement capabilities to the LFD. Further the thesis also explored the use of passive flow control within the LFDs enabled via precise laser-patterning of flow constrictions. The constrictions generate a delay in the flow at given points along the LFD and assist in enhancing their detection capabilities, i.e., their sensitivity. These techniques were applied to demonstrate a multiplexed screening test for Tuberculosis that meets real world requirements. This thesis presents a rapid detection of blood-based biomarkers: CRP, SAA1, LBP and CFHR5 with a multiplexed lateral flow test that has the capability to distinguish those patients with TB from healthy controls with significant accuracy. The diagnostic competence expressed in the form of area under the curve (AUC) was 0.92 for the best two biomarkers and its sensitivity and specificity meets the WHO guidelines for a TB rule-out screening test. Tuberculosis was responsible for 10 million cases globally in 2019 and despite huge efforts the numbers are still increasing.

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Identifiers

ORCID for Robert Eason: orcid.org/0000-0001-9704-2204

ORCID for Paul Elkington: orcid.org/0000-0003-0390-0613

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