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Singular perturbation theory for predicting extravasation of Brownian particles

机译:奇异摄动理论预测布朗粒子的外渗

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摘要

Motivated by recent studies on tumor treatments using the drug delivery of nanoparticles, we provide a singular perturbation theory and perform Brownian dynamics simulations to quantify the extravasation rate of Brownian particles in a shear flow over a circular pore with a lumped mass transfer resistance. The analytic theory we present is an expansion in the limit of a vanishing Péclet number (P), which is the ratio of convective fluxes to diffusive fluxes on the length scale of the pore. We state the concentration of particles near the pore and the extravasation rate (Sherwood number) to O(P1/2). This model improves upon previous studies because the results are valid for all values of the particle mass transfer coefficient across the pore, as modeled by the Damköhler number (κ), which is the ratio of the reaction rate to the diffusive mass transfer rate at the boundary. Previous studies focused on the adsorption-dominated regime (i.e., κ → ∞). Specifically, our work provides a theoretical basis and an interpolation-based approximate method for calculating the Sherwood number (a measure of the extravasation rate) for the case of finite resistance [κ ~ O(1)] at small Péclet numbers, which are physiologically important in the extravasation of nanoparticles. We compare the predictions of our theory and an approximate method to Brownian dynamics simulations with reflection–reaction boundary conditions as modeled by κ. They are found to agree well at small P and for the κ ≪ 1 and κ ≫ 1 asymptotic limits representing the diffusion-dominated and adsorption-dominated regimes, respectively. Although this model neglects the finite size effects of the particles, it provides an important first step toward understanding the physics of extravasation in the tumor vasculature.
机译:受近期使用纳米颗粒药物递送进行肿瘤治疗的研究的启发,我们提供了一种奇异的扰动理论,并进行了布朗动力学模拟,以量化布朗流体在圆孔内剪切流中具有集总传质阻力的渗透率。我们提出的分析理论是消失的佩克利数(P)极限的扩展,该极限是对流通量与扩散通量在孔隙长度范围内的比率。我们指出孔附近的颗粒浓度和渗透率(Sherwood数)为O(P 1/2 )。该模型对以前的研究进行了改进,因为该结果对于通过孔的颗粒传质系数的所有值都是有效的(如Damköhler数(κ)所模拟的那样),该系数是反应速率与扩散传质速率之比。边界。以前的研究集中在吸附为主的体系(即κ→∞)。具体来说,我们的工作为计算小佩克利特数时有限电阻[κ〜O(1)]情况下的舍伍德数(外渗率的度量)提供了理论基础和基于插值的近似方法。在纳米颗粒的渗出中很重要。我们将我们的理论预测和近似方法与以κ为模型的反射-反应边界条件的布朗动力学模拟进行了比较。发现它们在小P值和κdo 1和κ≫ 1渐近极限分别代表扩散支配和吸附支配状态时很好地吻合。尽管该模型忽略了颗粒的有限尺寸效应,但它为理解肿瘤脉管系统中渗出的物理学提供了重要的第一步。

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