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Sci Rep. 2018 Jun 19;8(1):9328. doi: 10.1038/s41598-018-27566-z.

Biomimetic post-capillary venule expansions for leukocyte adhesion studies.

Author information

1
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
2
Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
3
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
4
Mechanical and Aerospace Engineering Department, Case Western Reserve University, Cleveland, OH, 44106, USA.
5
Department of Biomedical Engineering, Case Western Reserve University School of Engineering, Cleveland, OH, 44106, USA.
6
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. alex.y.huang@case.edu.
7
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. alex.y.huang@case.edu.
8
Angie Fowler AYA Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA. alex.y.huang@case.edu.
9
Biogen, Cambridge, MA, 02142, USA.
10
Third Rock Ventures, Boston, MA, 02116, USA.

Abstract

Leukocyte adhesion and extravasation are maximal near the transition from capillary to post-capillary venule, and are strongly influenced by a confluence of scale-dependent physical effects. Mimicking the scale of physiological vessels using in vitro microfluidic systems allows the capture of these effects on leukocyte adhesion assays, but imposes practical limits on reproducibility and reliable quantification. Here we present a microfluidic platform that provides multiple (54-512) technical replicates within a 15-minute sample collection time, coupled with an automated computer vision analysis pipeline that captures leukocyte adhesion probabilities as a function of shear and extensional stresses. We report that in post-capillary channels of physiological scale, efficient leukocyte adhesion requires erythrocytes forcing leukocytes against the wall, a phenomenon that is promoted by the transitional flow in post-capillary venule expansions and dependent on the adhesion molecule ICAM-1.

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