Simulation of malaria-infected red blood cells in microfluidic channels: Passage and blockage

Abstract

Malaria-infected red blood cells (iRBCs) become less deformable with the progression of infection and tend to occlude microcapillaries. This process has been investigated in vitro using microfluidic channels. The objective of this paper is to provide a quantitative basis for interpreting the experimental observations of iRBC occlusion of microfluidic channels. Using a particle-based model for the iRBC, we simulate the traverse of iRBCs through a converging microfluidic channel and explore the progressive loss of cell deformability due to three factors: the stiffening of the membrane, the reduction of the cell's surface-volume ratio, and the growing solid parasites inside the cell. When examined individually, each factor tends to hinder the passage of the iRBC and lengthen the transit time. Moreover, at sufficient magnitude, each may lead to obstruction of narrow microfluidic channels. We then integrate the three factors into a series of simulations that mimic the development of malaria infection through the ring, trophozoite, and schizont stages. These simulations successfully reproduce the experimental observation that with progression of infection, the iRBC transitions from passage to blockage in larger and larger channels. The numerical results suggest a scheme for quantifying iRBC rigidification through microfluidic measurements of the critical pressure required for passage.

Microfluidic-based measurement of erythrocyte sedimentation rate for biophysical assessment of blood in an in vivo malaria-infected mouse

“…RBCs loss their deformability, which leads to block microcirculation of vital organs. 48,49 To determine the biomechanical properties of malaria-infected RBCs, several methods including mechanicalbased approaches [48][49][50][51][52][53] and electrical impedance-based approaches 54,55 have been employed by using a microfluidic device. As a clinical demonstration using the proposed method, blood sample was collected from an in vivo malaria-infected mouse at indicated times.…”

Constriction Channel Based Single-Cell Mechanical Property Characterization

“…Initially, the constriction channel design was used to quantify the mechanical properties of RBCs [23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40]. In 2003, Chiu et al, characterized complex behaviors of Plasmodium falciparum infected RBCs using the constriction channels with sizes at 8, 6, 4, and 2 µm in width [23] (see Figure 1a).…”

“…[47] Meanwhile, the microfluidic constriction channel is used to quantify the cellular entry and transition process through a micro channel with a cross-sectional area smaller than the dimensions of a single cell, enabling high-throughput single-cell mechanical property characterization [23][24][25][26] (see Table 1). This technique was first used to evaluate the mechanical properties of RBCs [23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40], which was then expanded to study the deformability of WBCs [24,41,42] and tumor cells [25,[43][44][45]. Leveraging mechanical modeling of the cellular entry process into the constriction channel, the microfluidic constriction channel design can collect size-independent intrinsic biomechanical markers such as cortical tension or Young's modulus [35,[46][47][48].…”

Biomechanical properties of red blood cells in health and disease towards microfluidics

“…[1][2][3][4] Pathological alterations in RBC deformability have been associated with various diseases 5 such as malaria, 6,7 sickle cell anemia, 8 diabetes, 9 hereditary disorders, 10 myocardial infarction, 11 and paroxysmal nocturnal hemoglobinuria (PNH). 12 Because of its pathophysiological importance, measurement of RBC deformability has been the focus of numerous studies over the past decades.…”