Malaria diagnosis and prognosis with an electrokinetic-driven aptamer-based lateral flow assay.

ongoing

Malaria remains a public health concern, with 247 million cases and 619,000 deaths reported globally in 2021. Despite the increasing prevention and control measures driven by the World Health Organization (WHO), nearly half of the population is still at risk of malaria, with a reported increase in the incidence of imported malaria in European countries. To this end, implementing large-scale, high-coverage, early diagnosis, and accurate prognosis of severe malaria is critical to reducing the impact of malaria in Europe. Due to its high sensitivity, parasite counting by microscopy observation is the current gold standard method. However, it is inappropriate for its application at the point of care (PoC). The rapid diagnostic tests (RDTs) based on lateral flow assay are the best option for PoC testing since they accomplish the REASSURED criteria WHO recommends. However, this method doesn't provide quantitative prognostic information and has proved low clinical sensitivity with low parasitemia samples (asymptomatic parasite carriers). With this aim, I propose for the first time the development of a smartphone-powered electrophoretic-driven aptamer paper-based LFA capable of providing a quantitative measurement of 2 parasite (PfHRP2, pan-pLDH) and 2 host (ang-2 and CRP) malaria biomarkers within minutes. Compared to capillarity-driven LFA, the flow control by electrophoresis enables the application of different synergic strategies to increase assay sensitivity, such as integrated incubation steps and purification of interfering biomolecules. Highly specific aptamers will be developed by a fast and cost-effective microfluidic selection approach, used as bioreceptors with stability for electrokinetics. This will enable an early diagnosis and an accurate prognosis of malaria, reducing the risk of developing severe symptoms. Upon successfully validating the device in non-endemic areas (host institution), I expect its use in low-resource, malaria-endemic areas.