Direct numerical simulations of heavy particles suspended in a turbulent fluid are performed to study the rate of inter-particle collisions as a function of the turbulence parameters and particle properties. The particle volume fractions are kept small (∼10−4) so that the system is well within the dilute limit. The fluid velocities are updated using a pseudo-spectral algorithm while the particle forces are approximated by Stokes drag. One unique aspect of the present simulations is that the particles have finite volumes (as opposed to point masses) and therefore particle collisions must be accounted for. The collision frequency is monitored over several eddy turnover times. It is found that particles with small Stokes numbers behave similarly to the prediction of Saffman & Turner (1956). On the other hand, particles with very large Stokes numbers have collision frequencies similar to kinetic theory (Abrahamson 1975). For intermediate Stokes numbers, the behaviour is complicated by two effects: (i) particles tend to collect in regions of low vorticity (high strain) due to a centrifugal effect (preferential concentration); (ii) particle pairs are less strongly correlated with each other, resulting in an increase in their relative velocity. Both effects tend to increase collision rates, however the scalings of the two effects are different, leading to the observed complex behaviour. An explanation for the entire range of Stokes numbers can be found by considering the relationship between the collision frequency and two statistical properties of the particle phase: the radial distribution function and the relative velocity probability density function. Statistical analysis of the data, in the context of this relationship, confirms the relationship and provides a quantitative description of how preferential concentration and particle decorrelation ultimately affect the collision frequency.

Development of novel carriers and optimization of their design parameters has led to significant advances in the field of targeted drug delivery. Since carrier shape has recently been recognized as an important design parameter for drug delivery, we sought to investigate how carrier shape influences their flow in the vasculature and their ability to target the diseased site. Idealized synthetic microvascular networks (SMNs) were used for this purpose since they closely mimic key physical aspects of real vasculature and at the same time offer practical advantages in terms of ease of use and direct observation of particle flow. The attachment propensities of surface functionalized spheres, elliptical/circular disks and rods with dimensions ranging from 1 µm to 20 µm were compared by flowing them through bifurcating SMNs. Particles of different geometries exhibited remarkably different adhesion propensities. Moreover, introduction of a bifurcation as opposed to the commonly used linear channel resulted in significantly different flow and adhesion behavior, which may have important implications in correlating these results to in vivo behavior. This study provides valuable information for design of carriers for targeted drug delivery.

Direct numerical simulations of a turbulent fluid laden with finite-sized particles are performed. The computations, on a 1283 grid along with a maximum of 262 144 particles, incorporated both direct particle interactions via hard-sphere collisions and particle feedback. The ‘reverse’ coupling is accomplished in a manner ensuring correct discrete energy conservation (Sundaram & Collins 1996). A novel two-field formalism (Sundaram & Collins 1994a) is employed to calculate two-point correlations and equivalent spectral densities. An important consideration in these simulations is the initial state of fluid and particles. That is, the initial conditions must be chosen so as to allow a meaningful comparison of the different runs. Using such a carefully initialized set of runs, particle inertia was observed to increase both the viscous and drag dissipations; however, simultaneously, it also caused particle velocities to correlate for longer distances. The combination of effects suggests a mechanism for turbulence enhancement or suppression that depends on the parameter values. Like previous investigators, ‘pivoting’ or crossover of the fluid energy spectra was observed. A possible new scaling for this phenomenon is suggested. Furthermore, investigations of the influence of particle mass and number densities on turbulence modulation are also carried out.

In this work, we describe the fabrication and working of a modular microsystem that recapitulates the functions of the "Neurovascular Unit". The microdevice comprised a vertical stack of a poly(dimethylsiloxane) (PDMS) neural parenchymal chamber separated by a vascular channel via a microporous polycarbonate (PC) membrane. The neural chamber housed a mixture of neurons (~4%), astrocytes (~95%), and microglia (~1%). The vascular channel was lined with a layer of rat brain microvascular endothelial cell line (RBE4). Cellular components in the neural chamber and vascular channel showed viability (>90%). The neural cells fired inhibitory as well as excitatory potentials following 10 days of culture. The endothelial cells showed diluted-acetylated low density lipoprotein (dil-a-LDL) uptake, expressed von Willebrand factor (vWF) and zonula occludens (ZO-1) tight junctions, and showed decreased Alexafluor™-conjugated dextran leakage across their barriers significantly compared with controls (p < 0.05). When the vascular layer was stimulated with TNF-α for 6 h, about 75% of resident microglia and astrocytes on the neural side were activated significantly (p < 0.05 compared to controls) recapitulating tissue-mimetic responses resembling neuroinflammation. The impact of this microsystem lies in the fact that this biomimetic neurovascular platform might not only be harnessed for obtaining mechanistic insights for neurodegenerative disorders, but could also serve as a potential screening tool for central nervous system (CNS) therapeutics in toxicology and neuroinfectious diseases.

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We have developed a methodology to study particle adhesion in the microvascular environment using microfluidic, image-derived microvascular networks on a chip accompanied by Computational Fluid Dynamics (CFD) analysis of fluid flow and particle adhesion. Microfluidic networks, obtained from digitization of in vivo microvascular topology were prototyped using soft-lithography techniques to obtain semicircular cross sectional microvascular networks in polydimethylsiloxane (PDMS). Dye perfusion studies indicated the presence of well-perfused as well as stagnant regions in a given network. Furthermore, microparticle adhesion to antibody coated networks was found to be spatially non-uniform as well. These findings were broadly corroborated in the CFD analyses. Detailed information on shear rates and particle fluxes in the entire network, obtained from the CFD models, were used to show global adhesion trends to be qualitatively consistent with current knowledge obtained using flow chambers. However, in comparison with a flow chamber, this method represents and incorporates elements of size and complex morphology of the microvasculature. Particle adhesion was found to be significantly localized near the bifurcations in comparison with the straight sections over the entire network, an effect not observable with flow chambers. In addition, the microvascular network chips are resource effective by providing data on particle adhesion over physiologically relevant shear range from even a single experiment. The microfluidic microvascular networks developed in this study can be readily used to gain fundamental insights into the processes leading to particle adhesion in the microvasculature.

Existing microfluidic devices, e.g. parallel plate flow chambers, do not accurately depict the geometry of microvascular networks in vivo. We have developed a synthetic microvascular network (SMN) on a polydimethalsiloxane (PDMS) chip that can serve as an in vitro model of the bifurcations, tortuosities, and cross-sectional changes found in microvascular networks in vivo.Microvascular networks from a cremaster muscle were mapped using a modified Geographical Information System, and then used to manufacture the SMNs on a PDMS chip. The networks were cultured with bovine aortic endothelial cells (BAEC), which reached confluency 3-4 days after seeding. Propidium Iodide staining indicated viable and healthy cells showing normal behavior in these networks. Anti-ICAM-1 conjugated 2-μm microspheres adhered to BAEC cells activated with TNF-α in significantly larger numbers compared to control IgG conjugated microspheres. This preferential adherence suggests that cultured cells retain an intact cytokine response in the SMN. This microfluidic system can provide novel insight into characterization of drug delivery particles and dynamic flow conditions in microvascular networks.