Characterization of nanoparticle delivery in microcirculation using a microfluidic device.
This work focuses on the characterization of particle delivery in microcirculation through a microfluidic device. In microvasculature the vessel size is comparable to that of red blood cells (RBCs) and the existence of blood cells largely influences the dispersion and binding distribution of drug loaded particles. The geometry of the microvasculature leads to non-uniform particle distribution and affects the particle binding characteristics. We perform an in vitro study in a microfluidic chip with micro vessel mimicking channels having a rectangular cross section. Various factors that influence particle distribution and delivery such as the vessel geometry, shear rate, blood cells, particle size, particle antibody density are considered in this study. Around 10% higher particle binding density is observed at bifurcation regions of the mimetic microvasculature geometry compared to straight regions. Particle binding density is found to decrease with increased shear rates. RBCs enhance particle binding for both 210 nm and 2 μm particles for shear rates between 200-1600 s(-1) studied. The particle binding density increases about 2-3 times and 6-10 times when flowing in whole blood at 25% RBC concentration compared to the pure particle case, for 210 nm and 2 μm particles respectively. With RBCs, the binding enhancement is more significant for 2 μm particles than that for 210 nm particles, which indicates an enhanced size dependent exclusion of 2 μm particles from the channel centre to the cell free layer (CFL). Increased particle antibody coating density leads to higher particle binding density for both 210 nm and 2 μm particles.
Bioengineering program, Lehigh University, Bethlehem, PA 18015, USA. Electronic address: ant210@lehigh.edu.
Antony
A
Thomas
Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA 18015, USA. Electronic address: jit310@lehigh.edu.
Jifu
J
Tan
Bioengineering program, Lehigh University, Bethlehem, PA 18015, USA; Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA 18015, USA. Electronic address: yal310@lehigh.edu.
Yaling
Y
Liu
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004337:Drug Carriers; D004912:Erythrocytes / Q000166:cytology; D006041:Goats; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry; D051379:Mice; D008833:Microcirculation; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D044085:Microfluidics; D018613:Microscopy, Confocal; D055806:Microvessels / Q000502:physiology*; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011137:Polystyrenes / Q000737:chemistry*; D033081:Shear Strength
D000906:Antibodies; D004129:Dimethylpolysiloxanes; D004337:Drug Carriers; D011137:Polystyrenes; D018799:Intercellular Adhesion Molecule-1
Bifurcation region; Microcirculation; Microfluidic chip; Microvasculature; Nanoparticle; Particle distribution; Red blood cells; Shear rate