title: A microfabricated deformability-based flow cytometer with application to malaria.
abstract: Malaria resulting from Plasmodium falciparum infection is a major cause of human suffering and mortality. Red blood cell (RBC) deformability plays a major role in the pathogenesis of malaria. Here we introduce an automated microfabricated "deformability cytometer" that measures dynamic mechanical responses of 10(3) to 10(4) individual RBCs in a cell population. Fluorescence measurements of each RBC are simultaneously acquired, resulting in a population-based correlation between biochemical properties, such as cell surface markers, and dynamic mechanical deformability. This device is especially applicable to heterogeneous cell populations. We demonstrate its ability to mechanically characterize a small number of P. falciparum-infected (ring stage) RBCs in a large population of uninfected RBCs. Furthermore, we are able to infer quantitative mechanical properties of individual RBCs from the observed dynamic behavior through a dissipative particle dynamics (DPD) model. These methods collectively provide a systematic approach to characterize the biomechanical properties of cells in a high-throughput manner.
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 36-841, Cambridge, MA 02139, USA.
authors.forename: Hansen
authors.initials: H
authors.lastname: Bow
authors.forename: Igor V
authors.initials: IV
authors.lastname: Pivkin
authors.forename: Monica
authors.initials: M
authors.lastname: Diez-Silva
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Goldfless
authors.forename: Ming
authors.initials: M
authors.lastname: Dao
authors.forename: Jacquin C
authors.initials: JC
authors.lastname: Niles
authors.forename: Subra
authors.initials: S
authors.lastname: Suresh
authors.forename: Jongyoon
authors.initials: J
authors.lastname: Han
mesh_terms: D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D055616:Microtechnology; D010963:Plasmodium falciparum / Q000254:growth & development*; D011312:Pressure