Towards the Use of a Smartphone Imaging-Based Tool for Point-of-Care Detection of Asymptomatic Low-Density Malaria Parasitemia

Abstract

Background: Globally, there are over 200 million cases of malaria annually and over 400,000 deaths. Early and accurate detection of low density parasitemia and asymptomatic individuals is key to achieving the WHO’s 2030 sustainable development goals of reducing malaria-related deaths by 90% and eradication in 35 countries. Current rapid diagnostic tests are neither sensitive nor specific enough to detect the low parasite concentrations in the blood of some asymptomatic individuals. Methods: Here, we combine an imaging-based sensing technique, particle diffusometry (PD), with loop mediated isothermal amplification (LAMP) on a smartphone-enabled device to detect low levels of parasitemia often associated with asymptomatic malaria. After amplification, PD quantifies the Brownian motion of fluorescent nanoparticles in the solution during a 30 second video taken on the phone. The resulting diffusion coefficient is used to detect the presence of Plasmodium DNA amplicons by comparing to coefficients of negative samples using a one-way ANOVA test.Results: As few as 1 parasite/µL of blood was detectable in 45 minutes without DNA extraction. We detected Plasmodium falciparum (P. falciparum) parasites from asymptomatic individuals’ whole blood samples with 89% sensitivity and 100% specificity when compared to quantitative polymerase chain reaction (qPCR). Conclusions: PD-LAMP is of value for the detection of low density parasitemia especially in areas where trained personnel may be scarce. The demonstration of this smartphone biosensor paired with the sensitivity of LAMP provides a proof of concept to achieve widespread asymptomatic malaria testing at the point of care.

Quantifying Brownian motion in the presence of simple shear flow with particle diffusometry

“…The first assumption is that the experiment is performed within a quiescent solution. Previously, we constructed enclosed microfluidic chips to minimize fluid flow in PD measurements to avoid evaporation-driven flows and temperature gradients (Clayton et al 2019 ; Colbert et al 2021 ). However, small amounts of potential flow may be present due to imperfections in constructing the microfluidic chip.…”

“…PD has also taken this approach by expanding its use to a more portable application, measuring amplified DNA presence to detect pathogens. Recently, a smartphone-adapted mobile imaging device has been used to detect the presence of V. cholerae in environmental water, malaria in 10% blood, and SARS-CoV-2 in 10% saliva (Moehling et al 2020;Colbert et al 2021Colbert et al , 2022. These previous works involving PD on a portable device laid out the foundation for the technology to be used at the point of use.…”

Quantifying Brownian Motion in the Presence of Simple Shear Flow with Particle Diffusometry

“…PD has also taken this approach by expanding its use to a more portable application, measuring ampli ed DNA presence to detect pathogens. Recently, a smartphone-adapted mobile imaging device has been used to detect the presence of V. cholerae in environmental water, malaria in 10% blood, and SARS-CoV-2 in 10% saliva (Moehling et al 2020;Colbert et al 2021Colbert et al , 2022. The portable smartphone-enabled device can record the sample and compute the diffusion coe cient at the point of use.…”