Microfluidic models of vascular injury

HTMFA

Multishear microfluidic flow assay for high-content evaluation of shear dependent platelet function. (A) A six channel device reversibly bonded to a glass slide containing micropatterned collagen. The average wall shear rate in the channels from bottom to top is 50, 90, 170, 320 470, and 920 1/s. (B) Immunofluorescence of 50 µm CTF spots within two of the channels. The dotted white line indicates the position of the walls of the channel. Scale bar = 50 µm. (C) Platelet aggregates on spots following a 5 min. flow assay of human whole blood. Platelets are labeled with an anti-CD41 antibody (blue). Scale bar = 50 µm.

We have developed a number of microfluidic models that simulate intravascular injury for the purpose of studying biophysical mechanisms of blood clot formation and diagnosis of bleeding and thrombotic disorders. The approach of theses models is to recreate certain features of an injured vessel within microfluidic channels and measure clot formation using an variety of microscopy techniques. An example is shown above, where blood is perfused through a network of channels over micropatterned collagen and platelet accumulation is measured in real-time. These devices capture the dynamics of flowing blood with the throughput of a static well-plate assay. We have used this approach to study platelet adhesion and aggregation, platelet-endothelial cell interactions, the effect of blood flow on coagulation and fibrin formation, and to characterize the clotting potential of patients with bleeding disorders and their response to therapies.

Related Publications

J.L. Sylman, D.T. Artzer, K. Rana, K.B. Neeves. A vascular injury model using focal heat-induced activation of endothelial cells. Integrative Biology, 15 (2015): 801-814. PMID:26087748

A.A. Onasoga-Jarvis, K. Leiderman, A.L. Fogelson, M. Wang, M.J. Manco-Johnson, J.A. Di Paola, K.B. Neeves. The effect of factor VIII deficiencies and replacement and bypass therapies on thrombus formation under venous flow conditions in microfluidic and computational models. PLoS One, 8 (2013): e78732. PMID: 24236042

K.B. Neeves, A.A. Onasoga, A.R. Wufsus. The use of microfluidics in hemostasis: Clinical diagnostics and biomimetic models of vascular injury. Current Opinion in Hematology, 20 (2013):417-423. PMID: 23872531

K.B. Neeves, A.A. Onasoga, R.R. Hansen, J.J. Lilly, D. Venckunaite, M.B. Sumner, A.T. Irish, G. Brodsky, M.J. Manco-Johnson, J.A. Di Paola. Sources of variability in platelet accumulation on type I fibrillar collagen in microfluidic flow assays. PLoS One, 8 (2013): e54680, doi:10.1371/journal.pone.0054680. PMID: 23355889

R.R. Hansen, A.R. Wufsus, S.T. Barton, A.A. Onasoga, R.M. Johnson-Paben, K.B. Neeves. High content analysis of shear dependent platelet function in a microfluidic flow assay. Annals of Biomedical Engineering, 14 (2013): 250-262. PMID: 23301359

R.R. Hansen, A.A. Tipnis, T.C. White-Adams, J.A. Di Paola, K.B. Neeves.  Characterization of collagen thin films for von Willebrand factor binding and platelet adhesion.  Langmuir, 27 (2011), 13648-13658. PMID: 21967679

K.B. Neeves, S.F. Maloney, K.P. Fong, A.A. Schmaier, M.L. Kahn, L.F. Brass, and S. L. Diamond.  Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregates.  Journal of Thrombosis and Haemostasis, 6 (2008), 2193-2201. PMID: 18983510

K.B. Neeves and S.L. Diamond.  A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood.  Lab on a Chip, 8 (2008), 701-709. PMID: 18432339