The ability to control the motion of particles and cells in microchannels has been a center of fascination since the advent of microfluidics. Entire fields have been created in order to accomplish separation, volume reduction and overall positioning of particles and cells within microfluidic devices in the fastest and most accurate manner possible. While most of these technologies rely on low Reynolds number operation, one technique entitled inertial focusing takes advantage of the inertia of the surrounding fluid and the interaction between a particle and the channel itself which cause the lateral migration of particles across streamlines to equilibrium positions within a flow. The major advantage of inertial microfluidics in biomedical and microfluidic applications is that it is inherently high throughput being dependent on inertia whereas most microfluidic concepts are dependent on low Reynolds number operation. / Engineering and Applied Sciences

Consumer demand for fresher foods has necessitated the use of non-thermal technologies in processing milk. Two Dean Flow UV reactors (1/16" ID × 1/32" Thick & 1/8" ID × 1/32" Thick) were designed in the laboratory. The objective of this study was to examine the efficacy of designed UV reactors at four levels of Reynolds numbers (Re) on inactivation of Escherichia coli W 1485 cells and Bacillus cereus spores in raw cow milk (RCM), commercially processed skimmed cow milk (SCM) and raw soymilk (RSM). RCM, SCM and RSM were inoculated separately with E. coli W 1485 and B. cereus spores and were treated through the designed reactors for a residence time of 11.3 ± 0.1 s, equivalent to an UV dose of 0.05 J/ml in 1/16" ID reactor and 0.02 J/ml in 1/8" ID reactor. Four levels of Re were tested in the range of 181-1372. The influence of tube diameter (thickness of milk exposed to UV) and Re (indicator of turbulence) at constant residence time (11.3 ± 0.1 s) on inactivation of both the bacteria in both the UV reactors was analyzed using two-way ANOVA with proc GLM in SAS software. E. coli was inactivated to non-detectable levels (≥7.8 log10 CFU/ml) in SCM from the second level of Re (532.2) in 1/16" ID reactor. E. coli was also inactivated significantly (> 5logs) in RSM at the highest Re (1372) but this was not achieved in the case of RCM (712.7). Increasing the residence time to 14.2 s or greater (17 s) (equal to UV dose of 0.06 and 0.08 J/ml) inactivated E. coli cells to non-detectable levels in RCM using 1/16" ID reactor at the highest level of Re (712.7). Reduction of E. coli cells were in the range of 0.45-7.78 logs whereas B. cereus spores were in range of 1.06- 3.29 logs in all types of milk used in this study. The interaction effect of tube diameter and Re was statistically significant for E. coli cells in RCM, and SCM; B. cereus spores in SCM, and RSM (p < 0.05) whereas this was statistically non significant for E. coli cells in RSM and B. cereus spores in RCM (p > 0.05). Main effects of Reynolds number, and tube diameter were statistically significant (p < 0.05) on inactivation of B. cereus spores in RCM and E. coli cells in RSM. Inactivation efficiencies for both bacteria were higher in 1/16" ID reactor than 1/8" ID reactor. Using the 1/16" ID reactor at highest level of Re (RCM Re = 712.7, RSM Re = 1372), inactivation of standard plate count (SPC) present in RSM and RCM, and lipid oxidation during storage period (0, 1, 3 and 7 days) were measured. Inactivation of SPC in UV-treated RSM (3 logs) was lower than thermal pasteurization at 72°C for 20 s (7 logs). In case of RCM, the SPC was inactivated to 1.9 logs from 4.2 logs. Sensory evaluation (olfactory) of UV treated, untreated (milk passed through the 1/16" ID reactor while the UV lights turned off), and fresh RCM (control) suggested no change in flavor after treatment and upto 1 day after storage in refrigerated condition, but a perceivable change in the quality of UV treated and untreated cow milk were observed during the 3rd and 7th days when compared with fresh RCM (milked same day). RCM was treated with different UV dose levels (0.04, 0.05, 0.08, 0.12 and 0.16 J/ml) to examine the effect of UV light on malondialdehyde and other reactive substances using TBARS test kit. Reactive substances such as malondialdehyde content increased as the UV dose increased. The presence of malondialdehyde and other reactive substances were not significantly different (p < 0.05) in both thermal and UV-pasteurized soymilk; whereas these substances were found to be higher in UV-treated RCM after 7 days of storage than the untreated milk stored for 7 days at 4 °C and the fresh RCM. The designed reactors 1/16" ID and 1/8" ID reactors were useful to inactivate bacteria present in milk. But, the inactivation efficiency was more in 1/16" ID reactor than 1/8" ID reactor.

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This thesis focuses on fundamental aspects of microfluidic systems and applies relevant findings to innovative designs for advanced particle manipulation applications. Computational Fluid Dynamics (CFD) is adopted for fluid modeling, based on the Finite Volume method. The accuracy of the solutions obtained is confirmed by grid sensitivity analysis and by comparisons with experimental work. Curved microchannel features and the induced Dean flow are studied through a parametric space exploration and simulations. The Lagrange-Euler coupling method – Surface Marker Point methodology – is applied to simulate large-size particles (of comparable size to the channel). Through this simulation approach, all the forces on such particles are directly derived through solving the governing equations and the influence of these particles on the flow is considered in a fully coupled manner. A new approach – the Frozen Flow & Flow Correction Coefficient method – is developed, making trans-relaxation-time simulations possible and improving computational efficiency significantly, for 3D simulations of arbitrary shape and size microparticles in complicated microfluidic channels. Detailed comparisons between simulation results and experiments involving particle sedimentation and particle equilibrium position have been conducted for methodology validation. Mechanisms of hydrodynamic particle manipulation are then studied, including hydrodynamic focusing and separation. It is found that the Tubular Pinch effect, Dean flow and the Radial Pressure Gradient effect interact to yield two distinct particle separation mechanisms. For advanced applications, particle focusing, non-magnetic and magnetic separation for neutrally buoyant particles are proposed, based on newly gained insight on the above-mentioned mechanisms. Appropriate channel designs have been proposed both for particle focusing and size-based particle separation, while the vertical-magnetic-Dean separation scheme is highlighted for magnetic separation. Finally, a new integrated system is proposed, that combines the above novel designs into a device-like ensemble. It promises to offer functionality for biomaterial separation and detection, including different types of cells, antigens and biomarkers.

Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.