Advances in Computational Fluid Mechanics in Cellular Flow Manipulation: a Review

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Advances in Computational Fluid Mechanics in Cellular Flow Manipulation: a Review 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]. These filtration devices have [26]. also These been devices extensively have usedalso been and extensively proposed to used study and mechanical proposed shearto study stress, mechanical and cell shear deformability stress, and and cell the deformability recent advances and ofthe these recent applications advances of can these be found applications in [27–30 can]. This be found is extremely in [27–30]. helpful This since is extremely deformability helpful of RBCssince (reddeformability blood cells) of canRBCs represent (red blood a potential cells) can sign represent of several a potential sicknesses sign [28 of]. Moreover,several sicknesses microfluidic [28]. devicesMoreover, have microfluidic been proposed devices to have study been the proposed possible etoff ectsstudy of the microbubbles possible effects in microvessels of microbubbles [28] toin representmicrovessels the [28] effects to ofrepresent these bubbles, the effects which of canthese form bubbles, in the which blood vesselscan form occasionally in the blood and vessels cause possibleoccasionally pathological and cause events, possible such pathological as preventing events, the food such to as reach preventing to the cellsthe food in specific to reach regions. to the Also,cells targetedin specific drug regions. delivery Also, via targeted nanomaterials, drug delivery such asvia carbon nanomaterials, nanotubes, such was as introduced carbon nanotubes, recently was and significantlyintroduced recently increased and the significantl efficacy ofy theincreased drugs [the31– 34efficacy]. As evaluationof the drugs of [31–34]. these particles As evaluation are highly of dependentthese particles on their are highly microenvironments, dependent on finding their microenvironments, the optimum design finding point is facingthe optimum some di designfficulties point [35] andis facing microfluidic some difficulties systems can[35] oandffer microfluidic exceptional abilitiessystems tocan screen offer theexceptional nanoparticles abilities to resolveto screen these the dinanoparticlesfficulties [1]. toZhu resolve et al. [36these] presented difficulties an in-dept[1]. Zhu review et al. of [36] nanoparticle presented delivery an in-dept steps inreview cellular of flowsnanoparticle and summarized delivery steps several in cellular microfluidic flows and models summarized specialized several in nanoparticle microfluidic evaluations models specialized related to suchin nanoparticle investigations. evaluations Particle related sorting to mechanisms such invest areigations. required Particle to direct sorting the drugsmechanisms to the targeted are required cells, andto direct numerical the drugs methods to the have targeted proved themselvescells, and numerical to be efficient methods in conducting have proved such simulations themselves [ 37to, 38be]. Microfluidicefficient in conducting devices, generally, such simulations implement [37,38]. any one Microfluidic of the two didevices,fferent generally, approaches; implement active approaches any one andof the passive two different approaches. approaches; In the latter, active as approaches opposed to and former passive which approaches. relies on fluorescent In the latter, labels as opposed or beads, ato variety former of which techniques relies basedon fluorescent on inherent labels differences or beads, in cellular a variety morphology of techniques among based cell groupson inherent (e.g., size,differences shape, in compressibility, cellular morphology and density) among are cell employed groups to(e.g., sort size, cells. shape, In active compressibility, manipulation and approaches, density) basedare employed on specified to sort field, cells. the In cellactive array manipulation is immersed approaches, in a space whereinbased on energy specified distribution field, the resultscell array in controlledis immersed forces in a space that move wherein cells energy along desireddistribution paths. results On the in controlled other hand, forces in passive that move techniques, cells along the twodesired predominant paths. On the opposite other hand, forces, in known passive as tec wallhniques, lift force, the two which predominant tends to repel opposite cells from forces, wall, known and shearas wall gradient lift force, lift which force, whichtends to is repel due to cells the curvaturefrom wall, of and the shear fluid parcelgradient velocities lift force, and which tends is to due repel to cellsthe curvature from center, of determinethe fluid parcel cell equilibrium velocities and positions tends in to the repel cross cells section from of center, microchannel determine [39 ].cell A summaryequilibrium of forcespositions exerted in the on cellscross/particles section isof shownmicrochannel in Figure [39].1 for A passive summary separation of forces technique. exerted It on is noteworthycells/particles to is mention shown thatin Figure complex
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