Recent malaria control efforts have yielded significant progress toward reducing the burden of this disease. A 25% reduction in malaria-related deaths was reported between 2010 ? 2016. Despite this success, malaria still represents a staggering global burden with more than 200 million people infected in 2018, resulting in more than 400,000 deaths. Moreover, recent data collected by the World Health Organization suggest that no additional, significant progress has been made in reducing global malaria cases over the past few years. A key challenge to eradicating malaria is diagnosing asymptomatic malaria patients who are unlikely to receive anti-malaria drugs despite being able to cause transmission of the malaria parasite to others. At the same time, quantification of malaria parasites in people expressing malaria symptoms is also of critical importance to finding patients who are at high risk for cerebral malaria, which is often fatal, especially in children. Hence, compounded by increasing insecticide and drug resistance, there is a critical need to develop new approaches for widely deployable malaria rapid diagnostic tests (RDTs) that are accurate over a large dynamic range, identifying both asymptomatic patients and those at risk for cerebral malaria. Current RDTs cannot meet this need. This proposal seeks to achieve important milestones towards the development of a porous silicon optical diagnostic for malaria that can meet the aforementioned critical need in an easy-to-use and affordable platform. We will first demonstrate highly sensitive and quantitative malaria biomarker (PfHRP2) detection using optical readout of porous silicon films in a model system (Aim 1) and then demonstrate robust detection of the malaria biomarker in blood (Aim 2). This work leverages the simplicity in measuring changes in the optical properties of porous silicon that directly correlate to the quantity of protein captured in the pores, and the large internal surface area of porous silicon within a small areal footprint that enables the efficient capture of significantly more malaria biomarkers per finger-prick of blood than current RDTs. Key scientific innovations include grafting a bifunctional polymeric brush from porous silicon to realize both a high density of capture probes for malaria biomarkers and antifouling properties to ensure negligible non-specific binding when testing blood samples. We have assembled a research team with expertise in optics and nanoscale porous biosensors (Weiss), surface chemistry and antifouling coatings (Laibinis), and low resource diagnostic tools for infectious diseases (Adams) to address the need for improved RDTs for malaria control and elimination. We expect our porous silicon optical diagnostic to enable more informed treatment of malaria patients across a wide spectrum. Expected long-term impacts include improved global surveillance for malaria resource allocation and elimination of malaria.
Widely available malaria diagnostics cannot accurately identify asymptomatic malaria patients or individuals at high risk for cerebral malaria, preventing dissemination of the most appropriate therapeutic treatments and making malaria eradication an unattainable goal. We propose a simple, highly sensitive, cost-effective porous silicon optical diagnostic capable of quantitatively detecting malaria proteins over a 5 order of magnitude dynamic range. Our surface functionalization approach using a bifunctional polymer that can both selectively capture target molecules from blood and prevent biofouling makes the porous silicon optical diagnostic a potentially viable choice not only for malaria but also for several other diseases of global concern with known biomarkers.