Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network

Jevgenia Zilberman-Rudenko, Joanna L. Sylman, Hari H S Lakshmanan, Owen McCarty, Jeevan Maddala

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL. Red blood cells and platelets were assumed to be non-interacting spherical particles transported by the bulk fluid flow, and convection of the activated coagulation factor II, thrombin, was assumed to be governed by mass transfer. This model served as the basis for predicting formation of local shear rate gradients, stagnation points and recirculation zones as dictated by the bypass geometry. Based on the insights from these models, we were able to predict the patterns of blood clot formation at specific locations in the device. Our experimental data was then used to adjust the model to account for the dynamical presence of thrombus formation in the biorheology of blood flow. The model predictions were then compared to results from experiments using recalcified whole human blood. Microfluidic devices were coated with the extracellular matrix protein, fibrillar collagen, and the initiator of the extrinsic pathway of coagulation, tissue factor. Blood was perfused through the devices at a flow rate of 2 µL/min, translating to physiologically relevant initial shear rates of 300 and 700 s−1 for main channels and bypasses, respectively. Using fluorescent and light microscopy, we observed distinct flow and thrombus formation patterns near channel intersections at bypass points, within recirculation zones and at stagnation points. Findings from this proof-of-principle ladder network model suggest a specific correlation between microvascular geometry and thrombus formation dynamics under shear. This model holds potential for use as an integrative approach to identify regions susceptible to intravascular thrombus formation within the microvasculature as well as extravascular devices such as ECMO.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalCellular and Molecular Bioengineering
DOIs
StateAccepted/In press - Oct 20 2016

Fingerprint

Ladder networks
Microfluidics
Blood Flow
Blood
Thrombosis
Equipment and Supplies
Lab-On-A-Chip Devices
Stagnation Point
Microvessels
Platelets
Coagulation
Blood Platelets
Fibrillar Collagens
Convection
Blood Coagulation Factors
Venules
Shear deformation
Extracellular Matrix Proteins
Protein
Thromboplastin

Keywords

  • Mass transfer
  • Microfluidic network
  • Multi-bypass ladder
  • Platelets
  • Shear
  • Thrombin

ASJC Scopus subject areas

  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network. / Zilberman-Rudenko, Jevgenia; Sylman, Joanna L.; Lakshmanan, Hari H S; McCarty, Owen; Maddala, Jeevan.

In: Cellular and Molecular Bioengineering, 20.10.2016, p. 1-14.

Research output: Contribution to journalArticle

Zilberman-Rudenko, Jevgenia ; Sylman, Joanna L. ; Lakshmanan, Hari H S ; McCarty, Owen ; Maddala, Jeevan. / Dynamics of Blood Flow and Thrombus Formation in a Multi-Bypass Microfluidic Ladder Network. In: Cellular and Molecular Bioengineering. 2016 ; pp. 1-14.
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