title: Density-based separation in multiphase systems provides a simple method to identify sickle cell disease.
abstract: Although effective low-cost interventions exist, child mortality attributable to sickle cell disease (SCD) remains high in low-resource areas due, in large part, to the lack of accessible diagnostic methods. The presence of dense (ρ > 1.120 g/cm(3)) cells is characteristic of SCD. The fluid, self-assembling step-gradients in density created by aqueous multiphase systems (AMPSs) identifies SCD by detecting dense cells. AMPSs separate different forms of red blood cells by density in a microhematocrit centrifuge and provide a visual means to distinguish individuals with SCD from those with normal hemoglobin or with nondisease, sickle-cell trait in under 12 min. Visual evaluation of a simple two-phase system identified the two main subclasses of SCD [homozygous (Hb SS) and heterozygous (Hb SC)] with a sensitivity of 90% (73-98%) and a specificity of 97% (86-100%). A three-phase system identified these two types of SCD with a sensitivity of 91% (78-98%) and a specificity of 88% (74-98%). This system could also distinguish between Hb SS and Hb SC. To the authors' knowledge, this test demonstrates the first separation of cells by density with AMPSs, and the usefulness of AMPSs in point-of-care diagnostic hematology.
authors.affiliation: School of Engineering and Applied Sciences.
authors.forename: Ashok A
authors.initials: AA
authors.lastname: Kumar
authors.affiliation: Department of Chemistry and Chemical Biology, and.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Patton
authors.affiliation: Department of Chemistry and Chemical Biology, and.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Hennek
authors.affiliation: Department of Chemistry and Chemical Biology, and.
authors.forename: Si Yi Ryan
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Chemical Biology, and.
authors.forename: Gaetana
authors.initials: G
authors.lastname: D'Alesio-Spina
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118;
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425; and.
authors.forename: Julie
authors.initials: J
authors.lastname: Kanter
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118;
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Shevkoplyas
authors.affiliation: Department of Laboratory Medicine, Children's Hospital Boston, Boston, MA 02115.
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
authors.affiliation: Department of Chemistry and Chemical Biology, and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138; gwhitesides@gmwgroup.harvard.edu.
authors.forename: George M
authors.initials: GM
authors.lastname: Whitesides
mesh_terms: D000755:Anemia, Sickle Cell / Q000175:diagnosis* / Q000235:genetics; D002452:Cell Count; D002469:Cell Separation / Q000191:economics / Q000379:methods*; D002498:Centrifugation; D014644:Genetic Variation; D006801:Humans; D019095:Point-of-Care Systems / Q000191:economics; D012372:ROC Curve; D013997:Time Factors
keywords: cell sorting; density gradient centrifugation; erythrocytes; polymers; sickle cell anemia