Mass transport limitations and surface interactions are important phenomena in microfluidic devices. The flow of water is laminar at small scales and the absence of turbulent mixing can lead to transport limitations, especially for reactions that take place at surfaces. Microscale devices have a high ratio of surface area to volume, and proteins are known to adsorb preferentially at interfaces. Protein adsorption plays a significant role in biology by mediating critical processes such as the attachment of cells to surfaces, the immune response and the coagulation of blood. Simulation tools that can quantitatively predict transport and protein adsorption will enable the rational design of microfluidic devices for biomedical applications. Two-dimensional random sequential adsorption (RSA) models are widely used to model the adsorption of proteins on surfaces. As Brownian dynamics simulations have become popular for modeling protein adsorption, the interface model has changed from two-dimensional to three-dimensional. Brownian dynamics simulations were used to model the diffusive transport of hard-sphere particles in a liquid and the adsorption of the particles onto a uniform surface. The configuration of the adsorbed particles was analyzed to quantify the chemical potential near the surface, which was used to derive a continuum model of adsorption that incorporates the results from the Brownian dynamics simulations. The equations of the continuum model were discretized and coupled to a conventional computational fluid dynamics (CFD) simulation of diffusive transport to the surface. The kinetics of adsorption iii predicted by the continuum model closely matched the results from the Brownian dynamics simulation. This new model allows the results from mesoscale simulations to be used as a boundary condition for micro- or macro-scale CFD simulations of transport and protein adsorption in practical devices. Continuum models were used to interpret experimental measurements of the kinetics of protein adsorption. A Whispering Gallery Mode (WGM) biosensor was constructed and used to measure the adsorption of fibronectin (FN) and glucose oxidase (GO) onto several types alkysilane self-assembled monolayers (SAMs). Computational fluid dynamics was used to model the transport of protein in the flow cell of the biosensor. Various models were fitted to the experimental data, taking into account the transport limitations predicted by the CFD simulations. The fitted parameter values and the quality of fit of the various models were analyzed to test hypotheses about the mechanisms of adsorption. Cells were cultured on silane surfaces coated with FN to assess its biological activity, and a colorimetric assay was used to determine the enzymatic activity of the adsorbed glucose oxidase. The results of the GO activity assay were compared to the activity predicted by the models. The WGM biosensor, transport simulation and kinetic model fitting enabled new insights into the adsorption of proteins on functionalized surfaces at solution concentrations that were previously unattainable. The process of CFD simulation and experimental validation was applied to the design of microfluidic bioreactors for an in vitro tissue engineered model of an alveolus. The objective was to optimize the design of the microreactors so they operate more like plug flow reactors. Microreactors experience significant deviations from plug flow due to the high ratio of surface area to volume and the no-slip boundary condition at the walls of the chamber. iv Iterative CFD simulations were performed to optimize microfluidic structures to minimize the width of the residence time distributions of two types of chambers. Qualitative and quantitative visualization experiments with a dye indicator demonstrated that the CFD simulations accurately predicted the residence time distributions of the chambers. The use of CFD simulations greatly reduced the time and cost required to optimize the performance of the microreactors.


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Graduation Date





Hickman, James


Doctor of Philosophy (Ph.D.)


College of Sciences



Degree Program

Modeling and Simulation









Release Date

June 2012

Length of Campus-only Access


Access Status

Doctoral Dissertation (Open Access)


Dissertations, Academic -- Sciences, Sciences -- Dissertations, Academic

Included in

Psychology Commons