Advances in Computational Fluid Mechanics in Cellular Flow Manipulation: a Review
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applied sciences Review Advances in Computational Fluid Mechanics in Cellular Flow Manipulation: A Review Masoud Arabghahestani 1,* , Sadegh Poozesh 2 and Nelson K. Akafuah 1 1 Institute of Research for Technology Development (IR4TD), University of Kentucky, Lexington, KY 40506, USA; [email protected] 2 Mechanical Engineering Department, Tuskegee University, Tuskegee, AL 36088, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-(859)-898-7700 Received: 28 August 2019; Accepted: 25 September 2019; Published: 27 September 2019 Abstract: Recently, remarkable developments have taken place, leading to significant improvements in microfluidic methods to capture subtle biological effects down to single cells. As microfluidic devices are getting sophisticated, design optimization through experimentations is becoming more challenging. As a result, numerical simulations have contributed to this trend by offering a better understanding of cellular microenvironments hydrodynamics and optimizing the functionality of the current/emerging designs. The need for new marketable designs with advantageous hydrodynamics invokes easier access to efficient as well as time-conservative numerical simulations to provide screening over cellular microenvironments, and to emulate physiological conditions with high accuracy. Therefore, an excerpt overview on how each numerical methodology and associated handling software works, and how they differ in handling underlying hydrodynamic of lab-on-chip microfluidic is crucial. These numerical means rely on molecular and continuum levels of numerical simulations. The current review aims to serve as a guideline for researchers in this area by presenting a comprehensive characterization of various relevant simulation techniques. Keywords: computational fluid mechanics; microfluidic devices; cellular flow; numerical simulations; molecular and continuum levels 1. Introduction 1.1. Microfluidic Systems for Cellular Flow Manipulation Most of the in vivo and in vitro studies have been carried out at a bulk-level. Although these techniques bring invaluable critical insights into various fields, including biology and medicine, they usually lack single-cell resolution features to recognize cell heterogeneities associated with diseases. For studying rare cell events and the intermediate extracellular signaling, through which cells communicate, analysis tools with the micro-level resolution are of significant importance. Microfluidics chips offer new approaches for cell assays and have also been used for studying of cell biology by providing platforms for manipulating, separating, sorting, filtering, trapping, and detecting tiny biological particles based on cellular heterogeneity. They can simulate small-scale fluid flow and chemical gradients and offer full manual control over the particles to study the desired details, e.g., for food market, clinical, pharmaceutical, and other applications [1–7]. Precise manipulations such as focusing, separation, and fractionation of cells is a vital capability of microfluidics which can be achieved by engineering hydrodynamics forces based on unique physical attributes of cells such as size [8,9], density [9,10], deformability [11–13], and morphology [14] using variety of methods such as crossflow filtration [15], electrode arrays [16], optical force switching [17] and other methods, some of Appl. Sci. 2019, 9, 4041; doi:10.3390/app9194041 www.mdpi.com/journal/applsci Appl. Sci. 2019, 9, 4041 2 of 24 Appl. Sci. 2019, 9, x FOR PEER REVIEW 2 of 23 whichand other can methods, be found some in detail of which in the reviewcan be found presented in detail in [18 in]. the In thisreview spirit, presented hydrodynamic in [18]. In phenomena, this spirit, whichhydrodynamic carry microenvironmental phenomena, which physicalcarry microenvironment impacts on cells,al arephysical critical impacts in almost on cells, all physiological are critical in functionsalmost all physiological and bodily systems. functions Generally, and bodily microfluidic systems. Generally, devices canmicrofluidic sort/isolate devices or partition can sort/isolate cells by activeor partition approaches cells by with active external approaches forces from with acoustics external [19forces,20], from magnetics acoustics [21,22 [19,20],], and electrokineticsmagnetics [21,22], [23], asand examples, electrokinetics as well [23], as as by examples, passive approachesas well as by such passive as cellularapproaches immobilization such as cellular [24 ],immobilization deterministic lateral[24], deterministic displacement lateral [25], anddisplacement hydrodynamic [25], filtrationand hydrodynamic [26]. 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