title: A biomimetic microfluidic chip to study the circulation and mechanical retention of red blood cells in the spleen.
abstract: Red blood cells (RBCs) are deformable and flow through vessels narrower than their own size. Their deformability is most stringently challenged when they cross micrometer-wide slits in the spleen. In several inherited or acquired RBC disorders, blockade of small vessels by stiff RBCs can trigger organ damage, but a functional spleen is expected to clear these abnormal RBCs from the circulation before they induce such complications. We analyzed flow behavior of RBCs in a microfluidic chip that replicates the mechanical constraints imposed on RBCs as they cross the human spleen. Polymer microchannels obtained by soft lithography with a hydraulic diameter of 25 μm drove flow into mechanical filtering units where RBCs flew either slowly through 5- to 2-μm-wide slits or rapidly along 10-μm-wide channels, these parallel paths mimicking the splenic microcirculation. Stiff heated RBCs accumulated in narrow slits seven times more frequently than normal RBCs infused simultaneously. Stage-dependent retention of Plasmodium falciparum-infected RBCs was also observed in these slits. We also analyzed RBCs from patients with hereditary spherocytosis and observed retention for those having the most altered mechanical properties as determined by ektacytometry. Thus, in keeping with previous observations in vivo and ex vivo, the chip successfully discriminated poorly deformable RBCs based on their distinct mechanical properties and on the intensity of the cell alteration. Applications to the exploration of the pathogenesis of malaria, hereditary spherocytosis, sickle cell disease and other RBC disorders are envisioned.
authors: Institut National De La Transfusion Sanguine, Paris, F-75739, France; Inserm, UMR_S1134, Paris, France, F-75739; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratory of Excellence GR-Ex, Paris, France.
authors: Julien
authors: J
authors: Picot
authors: Papa Alioune
authors: PA
authors: Ndour
authors: Sophie D
authors: SD
authors: Lefevre
authors: Wassim
authors: W
authors: El Nemer
authors: Harvey
authors: H
authors: Tawfik
authors: Julie
authors: J
authors: Galimand
authors: Lydie
authors: L
authors: Da Costa
authors: Jean-Antoine
authors: JA
authors: Ribeil
authors: Mariane
authors: M
authors: de Montalembert
authors: Valentine
authors: V
authors: Brousse
authors: Bruno
authors: B
authors: Le Pioufle
authors: Pierre
authors: P
authors: Buffet
authors: Caroline
authors: C
authors: Le Van Kim
authors: Olivier
authors: O
authors: Français
mesh_terms: D032701:Biomimetics / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D004912:Erythrocytes / Q000166:cytology* / Q000469:parasitology / Q000648:ultrastructure; D018056:Hemorheology; D006801:Humans; D008833:Microcirculation; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D010963:Plasmodium falciparum / Q000302:isolation & purification; D013103:Spherocytosis, Hereditary / Q000473:pathology* / Q000503:physiopathology; D013154:Spleen / Q000098:blood supply* / Q000648:ultrastructure