Systematic Review: Microfluidics and Plasmodium

Abstract

Malaria affects 228 million people worldwide each year, causing severe disease and worsening the conditions of already vulnerable populations. In this review, we explore how malaria has been detected in the past and how it can be detected in the future. Our primary focus is on finding new directions for low-cost diagnostic methods that unspecialized personnel can apply in situ. Through this review, we show that microfluidic devices can help pre-concentrate samples of blood infected with malaria to facilitate the diagnosis. Importantly, these devices can be made cheaply and be readily deployed in remote locations.

Keywords: Peru; lab on a chip; microfluidics; plasmodium.

Figure 5

(A) The dielectric constant of muscular tissue as a function of frequency decreases in three major steps. The three steps are identified as a-, ß-, and 7-dispersion. Reprinted with permission from ref. [63] © 1957 ACADEMIC PRESS INC. Published by Elsevier Inc. (B) Electron scanning image of the channel and electrodes (Left). Magnitude and phase of the impedance values at different frequencies for PMN’s and RBC’s (Right). Reprinted with permission from ref. [66] © 1999 IEEE Journal of Microelectromechanical Systems. (C) Experimental MIFC system setup for Pf-iRBC detection using a microfluidic device (Left). EI transitions measured as uninfected RBCs and Pf-iRBCs crossed over the electrode probe. Measurement conditions: 2 MHz, 1 V, and 0.2% w/v BSA-PBS (Right). Reprinted with permission from ref. [69] © 2013 The Royal Society of Chemistry (D) Dielectric properties estimated using MMT modelling, during the parasite intraerythrocytic life cycle: (i) membrane capacitance, (ii) cytoplasm conductivity, and (iii) volume ratio occupied by parasites within the host cell. Mean values from the three TC experiments (symbols) and s.d. (error bars) are plotted for each time point. Smoothing splines (dashed lines) are plotted to represent the overall trend for each population. Statistical significance (Student’s t-test; * p, 0.05, ** p, 0.01, *** p, 0.001 and **** p, 0.0001) is represented for i-RBCs (N ¼ 3) versus c-RBCs and u-RBCs (N ¼ 6) at individual time points. Reprinted with permission from ref. [70] © 2018 Royal Society.

Figure 1

The life-cycle of Plasmodium spp. Reprinted, with permission, from the Centers for Disease Control and Prevention website, https://www.cdc.gov/malaria/about/biology/, accessed on 3 October 2021. Use of this material, does not imply endorsement or recommendation by CDC, ATSDR, HHS or the United States Government of this research. Copyright, 2020, Centers for Disease Control and Prevention.

Figure 2

Example of a lateral flow device from Reboud et al. (1) buffer chamber which acts as a pump when pressed. (2) Lateral flow detection strip. (3) Acetate films to cover the device. (4) Filter valves made from paper to prevent the reagents from mixing prematurely. (5) Filter paper for LAMP reaction. Reprinted with permission from. © 2018 National Academy of Sciences.

Figure 3

(A) RBCs and iRBCs in funnel shaped channels. The higher the deformability, the further the cells can travel downwards. Reprinted with permission from ref. [38] © 2009 Cellular Microbiology (B) Cell sorting by deformability using a matrix of funnel constrictions. Reprinted with permission from ref. [42] © 2016 The Royal Society of Chemistry (C) RBC traversing gaps in microchannels. Depending on the stage of the infection, the iRBC will become increasingly less deformable. Reprinted with permission from ref. [37] © 2003 National Academy of Sciences.

Figure 4

Results from inertial separation of unbound aptamers. Due to the dean drag forces, the unbound aptamers migrate towards the outer wall and into the water outlet. Bound aptamers and microfluidic beads experience a lift force which keeps them close to the inner wall. Reprinted with permission from ref. [51] © 2015 Scientific Reports.