In modern cancer treatment, there is significant interest in studying the use of drug molecules either directly injected into the bloodstream or delivered by nanoparticle (NP) carriers of various shapes and sizes. During treatment, these carriers may extravasate through pores in the tumor vasculature that form during angiogenesis. We provide an analytical, computational, and experimental examination of the extravasation of point particles (e.g., drug molecules) and finite-sized spheroidal particles. We study the advection-diffusion process in a model microvasculature, consisting of a shear flow over and a pressure-driven suction flow into a circular pore in a flat surface. For point particles, we provide an analytical formula [Formula: see text] for the dimensionless Sherwood number S, i.e., the extravasation rate, in terms of the pore entry resistance (Damköhler number κ), the shear rate (Péclet number P), and the suction flow rate (suction strength Q). Brownian dynamics (BD) simulations verify this result, and our simulations are then extended to include finite-sized NPs, in which no analytical solutions are available. BD simulations indicate that particles of different geometries have drastically different extravasation rates in different flow conditions. In general, extreme aspect ratio particles provide a greater flux through the pore because of favorable alignment with streamlines entering the pore and less hindered interaction with the pore. We validate the BD simulations by measuring the in vitro transport of both bacteriophage MS2 (a spherical NP) and free dye (a model drug molecule) across a porous membrane. Despite their vastly different sizes, BD predicts S = 8.53 E-4 and S = 27.6 E-4, and our experiments agree favorably, with S=10.6 E-4± 1.75 E-4 and S=16.3 E-4 ± 3.09 E-4, for MS2 and free dye, respectively, thus demonstrating the practical utility of our simulation framework.

Surfaces that include heterogeneous mass transfer at the microscale are ubiquitous in nature and engineering. Many such media are modelled via an effective surface reaction rate or mass transfer coefficient employing the conventional ansatz of kinetically limited transport at the microscale. However, this assumption is not always valid, particularly when there is strong flow. We are interested in modelling reactive and/or porous surfaces that occur in systems where the effective Damköhler number at the microscale can be O(1) and the local Péclet number may be large. In order to expand the range of the effective mass transfer surface coefficient, we study transport from a uniform bath of species in an unbounded shear flow over a flat surface. This surface has a heterogeneous distribution of first-order surface-reactive circular patches (or pores). To understand the physics at the length scale of the patch size, we first analyse the flux to a single reactive patch. We use both analytic and boundary element simulations for this purpose. The shear flow induces a 3-D concentration wake structure downstream of the patch. When two patches are aligned in the shear direction, the wakes interact to reduce the per patch flux compared with the single-patch case. Having determined the length scale of the interaction between two patches, we study the transport to a periodic and disordered distribution of patches again using analytic and boundary integral techniques. We obtain, up to non-dilute patch area fraction, an effective boundary condition for the transport to the patches that depends on the local mass transfer coefficient (or reaction rate) and shear rate. We demonstrate that this boundary condition replaces the details of the heterogeneous surfaces at a wall-normal effective slip distance also determined for non-dilute patch area fractions. The slip distance again depends on the shear rate, and weakly on the reaction rate, and scales with the patch size. These effective boundary conditions can be used directly in large-scale physics simulations as long as the local shear rate, reaction rate and patch area fraction are known.

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.

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We study the problem of mass transport to surfaces with heterogeneous reaction rates in the presence of shear flow over these surfaces. The reactions are first order and the heterogeneity is due to the existence of inert regions on the surfaces. Such problems are ubiquitous in the field of heterogeneous catalysis, electrochemistry and even biological mass transport. In these problems, the microscale reaction rate is characterized by a Damköhler number $\unicode[STIX]{x1D705}$, while the Péclet number $P$ is the dimensionless ratio of the bulk shear rate to the inverse diffusion time scale. The area fraction of the reactive region is denoted by $\unicode[STIX]{x1D719}$. The objective is to calculate the yield of reaction, which is directly related to the mass flux to the reactive region, denoted by the dimensionless Sherwood number $S$. Previously, we used boundary element simulations and examined the case of first-order reactive disks embedded in an inert surface (Shah & Shaqfeh J. Fluid Mech., vol. 782, 2015, pp. 260–299). Various correlations for the Sherwood number as a function of $(\unicode[STIX]{x1D705},P,\unicode[STIX]{x1D719})$ were obtained. In particular, we demonstrated that the ‘method of additive resistances’ provides a good approximation for the Sherwood number for a wide range of values of $(\unicode[STIX]{x1D705},P)$ for $0<\unicode[STIX]{x1D719}<0.78$. When $\unicode[STIX]{x1D719}\approx 0.78$, the reactive disks are in a close packed configuration where the inert regions are essentially disconnected from each other. In this work, we develop an understanding of the physics when $\unicode[STIX]{x1D719}>0.78$, by examining the inverse problem of inert disks on a reactive surface. We show that the method of resistances approach to obtain the Sherwood number fails in the limit as $\unicode[STIX]{x1D719}\rightarrow 1$, i.e. in the dilute limit of periodic inert disks, due to the existence of a surface concentration boundary layer around each disk that scales with ($1/\unicode[STIX]{x1D705}$). This boundary layer controls the screening length between inert disks and allows us to introduce a new theory, thus providing new correlations for the Sherwood number that are highly accurate in the limit of $\unicode[STIX]{x1D719}\rightarrow 1$.