title: Femtogram Resolution of Iron Content on a Per Cell Basis: Ex Vivo Storage of Human Red Blood Cells Leads to Loss of Hemoglobin.
abstract: The magnetic characteristics of hemoglobin (Hb) changes with the binding of dioxygen (O2) to the heme prosthetic groups of the globin chains: from paramagnetic ferrous Hb to diamagnetic ferrous oxyhemoglobin (oxyHb) with reversibly bound O2, or paramagnetic ferric methemoglobin (metHb). When multiplied over the number of Hb molecules in a red blood cell (RBC), the effect is detectable through motion analysis of RBCs in a high magnetic field and gradient. This motion is referred to as magnetophoretic mobility, which can be conveniently expressed as a fraction of the cell sedimentation velocity. In this Article, using a previously developed and reported instrument, cell tracking velocimetry (CTV), we are able to detect difference in Hb concentration in two RBC populations to a resolution of 1 × 107Hb molecules per cell (4 × 107atoms of Fe per cell or 4-5 femtograms of Fe). Similar resolution achieved with inductively coupled plasma-mass spectrometry requires on the order of 105-106cells and provides an average, whereas CTV provides a measurement for each cell. CTV analysis revealed that RBCs lose, on average, 17% of their Hb after 42 days of storage, the maximum FDA-approved length of time for the cold storage of RBCs in additive solution. This difference in Hb concentration was the result of routine RBC storage; clinical implications are discussed.
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University , 320 Koffolt Laboratories, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
authors.forename: J J
authors.identifier: 0000-0003-1723-9774
authors.initials: JJ
authors.lastname: Chalmers
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University , 320 Koffolt Laboratories, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.|Department of Biomedical Engineering, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University , 320 Koffolt Laboratories, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
authors.forename: A F
authors.initials: AF
authors.lastname: Palmer
authors.affiliation: Department of Pathology, University of Pittsburgh , 3636 Boulevard of the Allies, Pittsburgh, Pennsylvania 15213, United States.|The Institute for Transfusion Medicine, University of Pittsburgh , 3636 Boulevard of the Allies, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: M H
authors.initials: MH
authors.lastname: Yazer
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: L
authors.initials: L
authors.lastname: Moore
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University , 320 Koffolt Laboratories, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
authors.forename: P
authors.initials: P
authors.lastname: Amaya
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University , 320 Koffolt Laboratories, 151 West Woodruff Avenue, Columbus, Ohio 43210, United States.
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.affiliation: Center for Biostatics, The Ohio State University , 310 H Lincoln Tower, 1800 Cannon Drive, Columbus, Ohio 43210, United States.
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: M
authors.initials: M
authors.lastname: Zborowski
mesh_terms: D058948:Cell Tracking; D004912:Erythrocytes / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000032:analysis* / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D012212:Rheology
chemical_list: D006454:Hemoglobins; D007501:Iron; D010100:Oxygen