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Cell-­phoresis o fRed Blood Cells Revealing Biophysical Signatures in Falciparum Malaria

Santoso, Aline Teresa, Lee, Jeong-Hyun, Deng, Xiaoyan, Matthews, Kerryn, Islamzada, Emel, McFaul, Sarah, Myrand-Lapierre, Marie-Eve and MA, Hongshen (2015) Cell-­phoresis o fRed Blood Cells Revealing Biophysical Signatures in Falciparum Malaria. unknown.

Abstract

We describe the cell-phoresis mechanism for massively parallel analysis of red blood cell (RBC) deformability by transporting single cells through microstructures to measure their spatial dispersion. Analogous to gel electrophoresis, which transport molecules through nanostructures to measure their length, the spatial dispersion of RBCs within microstructures indicate their deformability. Similar to gel electrophoresis, cell-phoresis require minimal instrumentation, provide a simple image-based readout, and could be performed simultaneously on multiple samples as part of a biophysical assay. We applied the cell-phoresis mechanism to study the biophysical signatures of falciparum malaria where we demonstrate label-­‐free and calibration-­‐free detection of ring-­‐stage infection, as well as in vitro assessment of antimalarial drug efficacy. We show that all clinical antimalarial drugs rigidify RBCs infected P. falciparum and that recently discovered PfATP4 inhibitors show a distinct biophysical signature. We anticipate cell-phoresis to be a functional assay for screening new antimalarials and adjunctive agents, as well as for validating their mechanisms of action.

Item Type: Article
Date Deposited: 27 Apr 2016 23:45
Last Modified: 27 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/26110

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