title: Microfluidic cell-phoresis enabling high-throughput analysis of red blood cell deformability and biophysical screening of antimalarial drugs.
abstract: Changes in red blood cell (RBC) deformability are associated with the pathology of many diseases and could potentially be used to evaluate disease status and treatment efficacy. We developed a simple, sensitive, and multiplexed RBC deformability assay based on the spatial dispersion of single cells in structured microchannels. This mechanism is analogous to gel electrophoresis, but instead of transporting molecules through nano-structured material to measure their length, RBCs are transported through micro-structured material to measure their deformability. After transport, the spatial distribution of cells provides a readout similar to intensity bands in gel electrophoresis, enabling simultaneous measurement on multiple samples. We used this approach to study the biophysical signatures of falciparum malaria, for which 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 clinical antimalarial drugs universally reduce the deformability of RBCs infected by Plasmodium falciparum and that recently discovered PfATP4 inhibitors, known to induce host-mediated parasite clearance, display a distinct biophysical signature. Our process captures key advantages from gel electrophoresis, including image-based readout and multiplexing, to provide a functional screen for new antimalarials and adjunctive agents.
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Aline T
authors.initials: AT
authors.lastname: Santoso
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Kerryn
authors.initials: K
authors.lastname: Matthews
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Duffy
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Emel
authors.initials: E
authors.lastname: Islamzada
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: McFaul
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Myrand-Lapierre
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4 Canada. hongma@mech.ubc.ca and Department of Urologic Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Hongshen
authors.initials: H
authors.lastname: Ma
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D055592:Biophysical Phenomena; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D004586:Electrophoresis / Q000295:instrumentation*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000469:parasitology; D057166:High-Throughput Screening Assays / Q000295:instrumentation*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D010963:Plasmodium falciparum; D059010:Single-Cell Analysis
chemical_list: D000962:Antimalarials