Size and shape effects for the nano/micro particle dynamics in the microcirculation

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Lee, Sei Young

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The nano/micro particles have been widely used as a carrier of therapeutic and contrast imaging agents. The nano/micro particles have many advantages, such as, specificity, controlled release, multifunctionality and engineerability. By tuning the chemical, physical and geometrical properties, the efficacy of delivery of nano/micro particle can be improved. In this study, by analyzing the effect of physical and geometrical properties of particle, such as, size, shape, material property and flow condition, the optimal condition for particle delivery will be explored. The objectives of this study are (1) to develop predictive mathematical models and (2) experimental models for particle margination and adhesion, and (3) to find optimal particle geometry in terms of size and shape to enhance the efficiency of its delivery. The effect of particle size expressed in terms of Stokes number and shape, namely, spherical, ellipsoidal, hemispherical, discoidal and cylindrical particle on the particle trajectory is investigated. For discoidal and cylindrical particles, the effect of aspect ratio is also considered. To calculate particle trajectory in the linear shear flow near the substrate, Newton's law of motion is decomposed into hydrodynamic drag and resistance induced by particle motion. The drag and resistance is estimated through finite volume formulation using Fluent v6.3. Particle behavior in the linear shear flow does strongly depend on Stokes number. Spherical particle is transported following the streamline in the absence of external body force. However, non-spherical particles could across the streamline and marginate to the substrate. For non-spherical particles, the optimal [Stokes number] in terms of particle margination is observed; [Stokes number almost equal to] 20 for ellipsoidal, hemispherical and discoidal particle; [Stokes number almost equal to] 10 for cylindrical particle. For discoidal particle with [gamma subscript d]=0.2 shows fastest margination to the substrate. The effect of gravitational force is also considered with respect to the fluid direction. When the gravitational force is applied, mostly, gravitational force plays a dominant role for particle margination. However, using small particle aspect ratio ([gamma subscript d]=0.2 and 0.33), spontaneous drift induced by particle-fluid-substrate interaction could overcome gravitational effect in some cases ([Stokes number]=10, G=0.1). In addition the adhesion characteristic of spherical particle has been studied using in vitro micro fluidic chamber system with different particle size and flow condition. The experimental results are compared to the mathematical model developed by Decuzzi and Ferrari (Decuzzi and Ferrari, 2006) and in vivo test (Decuzzi et al., 2010). The optimal particle size for S=75 and 90 is found to be 4-5 [micrometer] through the in vitro non-specific interaction of spherical particle on the biological substrate. The suggested mathematical model has proven to be valid for current experimental condition. At the end, the mathematical model, in vitro flow chamber results and in vivo test have been compared and the scaling law for particle adhesion on the vessel wall has been confirmed.



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