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Research Papers

Size-Dependent Nanoparticle Margination and Adhesion Propensity in a Microchannel

[+] Author and Article Information
Patrick Jurney, Vikramjit Singh

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712

Rachit Agarwal, Krishnendu Roy

Department of Biomedical Engineering,
The University of Texas at Austin,
Austin, TX 78712

S. V. Sreenivasan

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712

Li Shi

Department of Mechanical Engineering,
The University of Texas at Austin,
Austin, TX 78712
e-mail: lishi@mail.utexas.edu

1Corresponding author.

Manuscript received May 31, 2013; final manuscript received September 24, 2013; published online November 19, 2013. Assoc. Editor: Henry Hess.

J. Nanotechnol. Eng. Med 4(3), 031002 (Nov 19, 2013) (7 pages) Paper No: NANO-13-1030; doi: 10.1115/1.4025609 History: Received May 31, 2013; Revised September 24, 2013

Intravenous injection of nanoparticles as drug delivery vehicles is a common practice in clinical trials of therapeutic agents to target specific cancerous or pathogenic sites. The vascular flow dynamics of nanocarriers (NCs) in human microcapillaries play an important role in the ultimate efficacy of this drug delivery method. This article reports an experimental study of the effect of nanoparticle size on their margination and adhesion propensity in microfluidic channels of a half-elliptical cross section. Spherical polystyrene particles ranging in diameter from 60 to 970 nm were flown in the microchannels and individual particles adhered to either the top or bottom wall of the channel were imaged using fluorescence microscopy. When the number concentration of particles in the flow was kept constant, the percentage of nanoparticles adhered to the top wall increased with decreasing diameter (d), with the number of particles adhered to the top wall following a d−3 trend. When the volume concentration of particles in solution was kept constant, no discernible trend was found. This experimental finding is explained by the competition between the Brownian force promoting margination and repulsive particle–particle electrostatic forces retarding adhesion to the wall. The 970 nm particles were found to adhere to the bottom wall much more than to the top wall for each of the three physiologically relevant shear rates tested, revealing the effect of gravitational force on the large particles. These findings on the flow behavior of spherical nanoparticles in artificial microcapillaries provide further insight for the rational design of NCs for targeted cancer therapeutics.

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Figures

Grahic Jump Location
Fig. 2

Number of 390 nm particles adhered to the imaged surface for a single run based on the manual counting method and the intensity quantification method, respectively

Grahic Jump Location
Fig. 1

(a) Cross-sectional scanning electron microscopy (SEM) image of 55 × 35 μm2 channel used in experiments. (b) Fluorescence images taken at the region of interest, designated by the yellow rectangle, on the top channel wall after 93 nm polystyrene spheres were flown in the channel for 20 s (left) and 360 s (right). (C) Time dependent intensity profiles across the top channel wall in the region of interest perpendicular to the flow direction. (D) Total number of particles adhered to the top channel wall in the region of interest at each 20 s intervals based on the measured intensity for a single experiment.

Grahic Jump Location
Fig. 3

(a) Representative fluorescence images of the top channel wall after 360 s of continuous particle flow in 55-μm-wide channels for each nanoparticle size tested at a shear stress of 7.5 Pa. (b) The number of adhered particles (ΔNsat) normalized by the number of particles in the margination volume as a function of time for a constant particle number concentration of n = (1.0 ± 0.2) × 109 ml−1. (c) The volume of adhered particles (ΔVsat) normalized by the volume of particles in the margination volume as a function of time for a constant particle volume concentration of ϕ = 3.1 ± 0.6 vol. %. (d) Percentage of particles adhered as a function of diameter for constant n = (1.0 ± 0.2) × 109 ml−1 (filled symbols) or constant ϕ = 3.1 ± 0.6 vol. % (unfilled symbols). The data for constant n = (1.0 ± 0.2) × 109 ml−1 can be fitted with a relation of Na/Nmar = 7 × 109 d−3 (line). (e) The volume of particles adhered to the 55 × 120 μm2 imaged section of the top wall as a function of diameter for constant n = (1.0 ± 0.2) × 109 ml−1 and constant ϕ = 3.1 ± 0.6 vol. %. For all plots, the error bars indicate the random uncertainty with a confidence interval of 95%.

Grahic Jump Location
Fig. 4

(a) Total particle adhesion for the top and bottom walls after 360 s of continuous flow. The bars above “T” are the data for the top wall while those above “B” are the data for the bottom wall. (b) Total particle adhesion of different sized nanoparticles to the top wall of the microchannel at different flow rates maintaining constant particle concentration of 1 × 109 particles/ml.

Grahic Jump Location
Fig. 5

(a) The hydrodynamic, Brownian, gravitational, van der Waals, and electrostatic forces as a function of diameter for submicron polystyrene spheres in DI water at a shear rate of 500 s−1 at a constant particle number concentration of 1 × 109 particles/ml. The electrostatic force shown is that between adjacent particles in the flow. (b) Electrostatic repulsive force between a marginating particle in the fluid and the adhered particles on the wall when the volume of the adhered particles is taken to be 3.46 × 10−4 m3 adhered per m2 channel wall area and zeta potential is taken to be −42 mV.

Grahic Jump Location
Fig. 6

Schematic of a particle approaching the channel wall saturated with adhered particles arranged in a square lattice. The nearest neighbor distance of the adhered particles is L. The smallest distance between the marginating particle and the channel wall is h. The distance between the marginating particle and an adhered particle is r.

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