Investigation of bioparticle separation in microfluidics using micropillar arrays

Investigation of the factors causing disease is the primary aim of basic researches in the field of bioparticle separation and clinical diagnostics. In this respect, isolation of cells or biomolecules from more complex samples such as blood, sputum, saliva, etc. is required. Unfortunately, there are some limitations for these studies when the target bioparticles in the samples exist in very small quantities. Also, most of the current methods for bioparticle separation that are used in research and clinical laboratories, have been available for several decades. The majority of these methods need a large amount of sample, several manual steps, and could take hours to be done. They can be categorized into two groups: methods that are mainly based on differences in physical properties between particles, and methods that include specific biomolecular recognition. Application of microfluidics as an essential tool in analysis and research in biological fields is increasing due to the advantages that it offers in bioparticle separation. The advantages such as lower cost, smaller sample amount, shorter separation duration, understandable fluid dynamics, and disposable devices. Currently, there are various types of microfluidic systems; however, they can be classified into two main groups: 1) Physical properties based platforms in microfluidic separation and 2) Specific biomolecular recognition based platforms in microfluidic separation. One of the microfluidic devices that is used for isolation of bioparticles, consists of a rectangular microchannel in which micro-pillars' (or micro posts) array are located in the vertical direction with the height equal to the channel height. The used materials for fabrication of this bioseparation device can be either solid or porous materials. For many applications in the field of bioparticle separation, efficient isolation of bioparticles is crucial. Isolation efficiency depends on two factors including the interception efficiency, and the binding efficiency. To clarify, the interception efficiency is the fraction of particles in a flow that are intercepted by a collector, and the binding efficiency is the possibility of binding of the intercepted particles to the surface of a collector. Because of the fact that there is no evidence to suggest the measurement of the binding efficiency value, this thesis focuses on interception efficiency. Interception of particles is studied in various realms of science such as biological particle capturing, air filtration, marine ecology, etc. The four principal mechanisms that are known as classical mechanisms contribute in particle interception including the direct interception, diffusion, inertial impaction, and gravitational sedimentation. In addition to the four mechanisms of particle interception, there are other important physical effects imposed by the post surface on a particle when it approaches the solid surface. The direct interception is a result of streamline kinematics. To explain, when a moving particle in a flow locates on a streamline that finally approaches the post with a distance less than the radius of the particle, it collides to the post and the direct interception occurs. Meanwhile, the most important factor in interception efficiency is the direct interception, and other factors have a negligible effect on interception efficiency. Solid materials such as polymers, glass or silicon are used for constructing most of the microfluidic devices that are designed for particle separation. However, there are some restrictions for this type of devices. For example, low efficiency of particle capturing, limited function in isolation of sub-micron particles, and limitations in the application for various particle types. While, for suspended particles in a liquid, the isolation efficiency of a solid post is very low. The two reasons causing this are: 1) a bulk flow effect 2) a near-surface effect. Utilization of porous materials could resolve the stated restrictions. A porous medium can be defined as a material consisting of a solid matrix with an interconnected void. There are two factors involved in the improvement of interception efficiency of a porous post in comparison with a solid one. The first factor is related to the changes in the flow field due to the use of the porous structure. In other words, by penetrating many more streamlines to the porous structure, a higher interception occurs. The other factor is the reduced hydrodynamic resistance of a porous post, which is assumed to have a negligible value for it. The comparison between interception efficiency of a solid and porous post is investigated by developing a model of a single circular post inside a rectangular channel. Analysis showed that higher interception efficiency is achieved by using a porous material for the post. For further investigations, models are developed based on the parameters that would improve interception efficiency. Parameters such as the materials of porous structure, shape of the post, different configuration for post arrays, and geometrical parameters between post arrays. Models are simulated by COMSOL Multiphysics (v5.2) software, which utilizes the finite element method (FEM). The governing equations for free media region are the continuity equation for the conservation of mass, and the 2-D Navier-Stokes equations for the conservation of momentum. Meanwhile, for flow regimes that completely are inside a porous structure, Darcy's law can be applied. However, for flow regimes that are a combination of free and porous media, Darcy's law is not so accurate. For analyzing such problems, modification of Darcy's law which was proposed by Brinkman commonly is used. Stated equations are solved for various models and different particles for two fluid types, which are water and blood. The flow is low Reynolds number laminar flow, and the solutions obtained for the steady state condition. Results indicated that interception efficiency is significantly improved by selecting porous material for the post. Additionally, by choosing a hexagonal cross section, and a square configuration of the posts higher interception efficiency is achieved. Furthermore, the results revealed that using blood as the working fluid results in greater interception efficiency in comparison with water.