Microfluidic models of hemostasis and thrombosis​

Blood flow is a central regulator of blood clot formation; it transports blood cells and proteins to and from a clot and imposes forces that mediate cell adhesion and aggregation. We have developed a series of models for measuring and modeling different types clotting events including bleeding, deep vein thrombosis, and arterial thrombosis. We use microfluidic techniques in combination with optical microscopy to measure clot formation as as function of forces, geometry, and initiators and inhibitors of platelet function and coagulation. These models have been used to reveal fundamental mechanisms regulated by forces and flows and as tools to diagnose and measure the efficacy of therapies for bleeding and thrombotic disorders.

Related Publications

P. Mangin, K.B. Neeves, W.A. Lam, J.M.E.M Cosemans, N. Korin, S.W. Kerrigan, M. Panteleev. In vitro flow-based assay: from simple towards more sophisticated models for mimicking hemostasis and thrombosis. Journal of Thrombosis and Haemostasis, 19 (2021):582-587. DOI: 10.1111/jth.15143

M.G. Sorrells, K.B. Neeves. Adsorption and absorption of collagen peptides to polydimethylsiloxane and its influence on platelet adhesion flow assays. Micromachines, 11 (2020): 62. DOI: 10.3390/mi11010062 

M. Lehmann, R.M. Schoeman, P.J. Krohl, A.M. Wallbank, J.R. Samaniuk, M. Jandrot-Perrus, K.B. Neeves. Platelets drive thrombus growth in a hematocrit and glycoprotein VI dependent manner in an in vitro model of venous thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 38 (2018): 1052-1062. DOI: 10.1161/ATVBAHA.118.310731.

R.M. Schoeman, M. Lehmann, K.B. Neeves. Flow chamber and microfluidic approaches for measuring thrombus formation in genetic bleeding disorders. Platelets, 28 (2017): 463-471. DOI: 10.1080/09537104.2017.1306042.

R.M. Schoeman, K. Rana, N. Danes, M. Lehmann, J.A. Di Paola, A.L. Fogelson, K. Leiderman, K.B. Neeves. A microfluidic model of hemostasis sensitive to platelet function and coagulation. Cellular and Molecular Bioengineering, 10 (2017): 3-15. DOI: 10.1007/s12195-016-0469-0.
 
M. Lehmann, A.M. Wallbank, K.A. Dennis, A.R. Wufsus, K.M. Davis, K. Rana, K.B. Neeves. On-chip recalcification of citrated whole blood using a microfluidic herringbone mixer. Biomicrofluidics, 6 (2015): 064106. DOI: 10.1063/1.4935863.
 
 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. DOI: 10.1039/c5ib00108k.
 

O.J.T. McCarty, D. Ku, M. Sugimoto, M.R. King, J. Cosemans, K.B. Neeves. Dimensional analysis and scaling relevant to flow models of thrombus formation. Journal of Thrombosis and Haemostasis, 14 (2016): 619-622. DOI: 10.1111/jth.13241

S. Zhu, B.A. Herbig, R. Li, T.V. Colace, R.W. Muthard, K.B. Neeves, S.L. Diamond. In microfluidico: Recreating in vivo hemodynamics using miniaturized devices. Biorheology, 52 (2015): 303-318. DOI: 10.3233/BIR-15065.

B.R. Branchford, C.J. Ng, K.B. Neeves, J.A. Di Paola. Microfluidic technology as an emerging clinical tool to evaluate thrombosis and hemostasis. Thrombosis Research, 136 (2015): 13-19. DOI: 10.1016/j.thromres.2015.05.012.

K. Rana, B.J. Timmer, K.B. Neeves. A combined microfluidic-microstencil method for patterning molecules and cells. Biomicrofluidics, 8 (2014): 056502. DOI: 10.1063/1.4896231.
 
K.B. Neeves, O.J.T. McCarty, A.J. Reininger, M. Sugimoto, M.R. King. Flow-dependent thrombin and fibrin generation: Opportunities for standardization. Journal of Thrombosis and Haemostasis, 12 (2014): 418-420. DOI: 10.1111/jth.12482.
 
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. DOI: 10.1097/MOH.0b013e3283642186.

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.
 
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. DOI: 10.1007/s10439-012-0658-5

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. DOI: 10.1021/la2023727

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. DOI: 10.1039/B717824G.
 
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. DOI: 10.1111/j.1538-7836.2008.03188.x