Microfluidic analysis of red blood cell deformability as a means to assess hemin-induced oxidative stress resulting fromPlasmodium falciparumintraerythrocytic parasitism

Abstract

Hemolytic anemia is one of the hallmarks of malaria and leads to an increase in oxidized heme (hemin) within the plasma of infected individuals. While scavenger proteins sequester much of the circulating heme, it has been hypothesized that extracellular heme may play a central role in malaria pathogenesis. We have previously developed the multiplex fluidic plunger (MFP) device for the measurement of red blood cell (RBC) deformability. Here, we demonstrate that the measurement of changes in RBC deformability is a sensitive method for inferring heme-induced oxidative stress. We further show that extracellular hemin concentration correlates closely with changes in RBC deformability and we confirm that this biophysical change correlates with other indicators of cell stress. Finally, we show that reduced erythrocyte deformability corresponds with both erythrophagocytosis and RBC osmotic fragility. The MFP microfluidic device presents a simple and potentially inexpensive alternative to existing methods for measuring hemolytic cell stress that could ultimately be used to perform clinical assessment of disease progression in severe malaria.

Within‐host modeling of blood‐stage malaria

“…Alternatively, it has been suggested that debris released from rupture of infected pRBCs leads to destruction of bystander RBCs, which would lead to a fixed ratio of bystander death to pRBC rupture. There are a number of experimental studies that have looked at the role of different host immune responses, such as complement and phagocytes, in mediating accelerated pRBC removal, a number of which may provide some evidence of host responses being involved in the destruction of uninfected RBCs . Exploring these different mechanisms of bystander destruction using modeling could help make sense of the experimental literature on mechanisms and host risk factors associated with severe anemia.…”

Assessing the Vascular Deformability of Erythrocytes and Leukocytes: From Micropipettes to Microfluidics

“…Deformability measurement using microfluidics uses minute amounts of a whole blood or purified RBC/WBC in suspension flowing through a funnel-shaped micro-constriction(s) in a disposable plate. As demonstrated in our previous publications, and discussed in the following section, microfluidics devices are capable of providing reproducible intra-and inter-individual data, detecting oxidatively damaged RBC, identifying changes in RBC deformability consequent to storage, and identifying leukocytes [20][21][22][23][24][25][26][27][28].…”

“…As evidenced by the number of publications and patents being generated annually, the promise of microfluidic devices in medicine is seemingly unbounded. One area of particular interest to our laboratories has been in the field of transfusion medicine [20][21][22][23][24][25][26][27][28]. Annually over 100,000,000 units of blood are collected worldwide for transfusion purposes.…”

“…Importantly, this design also incorporates collection outlets allowing for recovery, and further testing, of cell populations with differential deformability profiles. Our research to date has demonstrated that this microfluidic microfiltration device is capable of isolating circulating tumor cells Assessing the Vascular Deformability of Erythrocytes and Leukocytes: From Micropipettes… DOI: http://dx.doi.org/10.5772/intechopen.90131 from leukocytes, malaria-infected and oxidized RBC from normal cells, granulocytes and lymphocytes from whole blood, and detecting early immune cell activation consequent to degranulation [26][27][28]81].…”

“…In evidence of this, both biological conditions and pharmacologic agents that affect hemoglobin content and/or viscosity or the RBC cytoskeleton alter cellular deformability and have profound in vivo and in vitro effects on RBC function and survival [5][6][7][8][9][10][11][12][13][14][15][16]. Indeed, RBC deformability can be a diagnostic indicator of RBC abnormalities and the quality of stored RBC prior to transfusion [17][18][19][20][21][22][23][24][25][26][27][28].…”