title: Hypoxia-enhanced adhesion of red blood cells in microscale flow.
abstract: The advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro-gas exchanger integrated with microfluidics to study RBC adhesion under hypoxic flow conditions mimicking postcapillary venules.
  
  
  
  We simulated a range of physiological conditions and explored RBC adhesion to endothelial or subendothelial components (FN or LN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation of RBC adhesion was performed on 35 subjects with homozygous SCD.
  
  
  
  Significant heterogeneity in RBC adherence response to hypoxia was seen among SCD patients. RBCs from a HEA population showed a significantly greater increase in adhesion compared to RBCs from a HNA population, for both FN and LN.
  
  
  
  The approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification of RBC adhesion in a cost-efficient and patient-specific manner. We identified a unique patient population in which RBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup.
authors.affiliation: Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Myeongseop
authors.initials: M
authors.lastname: Kim
authors.affiliation: Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, USA.|Physical Intelligence Department, Max Planck Institute for Intelligent Systems, Stuttgart, Germany.
authors.forename: Yunus
authors.initials: Y
authors.lastname: Alapan
authors.affiliation: Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Anima
authors.initials: A
authors.lastname: Adhikari
authors.affiliation: Department of Hematology and Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.|Seidman Cancer Center at University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Little
authors.affiliation: Case Biomanufacturing and Microfabrication Laboratory, Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, USA.|Biomedical Engineering Department, Case Western Reserve University, Cleveland, OH, USA.|Department of Orthopaedics, Case Western Reserve University, Cleveland, OH, USA.|Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA.
authors.forename: Umut A
authors.identifier: 0000-0002-0331-9960
authors.initials: UA
authors.lastname: Gurkan
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000503:physiopathology; D001783:Blood Flow Velocity; D002448:Cell Adhesion; D004912:Erythrocytes / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008833:Microcirculation / Q000502:physiology*; D046210:Microfluidic Analytical Techniques / Q000379:methods
keywords: erythrocyte; lab on a chip; laminin; microfluidics; oxygen; sickle cell disease