Numerical simulations of cell flow and trapping within microfluidic channels for stiffness based cell isolation

Aljaghtham, Mutabe; Liu, Zixiang; Guo, Jing; He, Jin; Çelik, Emrah

doi:10.1016/j.jbiomech.2019.01.010

Cited by 5 publications

(11 citation statements)

References 41 publications

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“…The simulated shear stress experienced by the cells at flow rates of 0.5 and 1 μL/min are 1.3 and 3 dynes/cm, respectively, values which are comparable with other methods such as microwells (0.1–5 dynes/cm 2 ). , Flow rates equal or greater than 2 μL/min cause higher shear stresses (>6 dynes/cm 2 ) on the cells, which could interfere with cellular function. Overall, our results agree with other studies where authors have employed similar flow rates to capture single cells in hydrodynamic traps. , …”

Section: Resultssupporting

confidence: 92%

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On-Chip Analysis of Protein Secretion from Single Cells Using Microbead Biosensors

et al. 2023

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The profiling of the effector functions of single immune cellsincluding cytokine secretioncan lead to a deeper understanding of how the immune system operates and to potential diagnostics and therapeutical applications. Here, we report a microfluidic device that pairs single cells and antibody-functionalized microbeads in hydrodynamic traps to quantitate cytokine secretion. The device contains 1008 microchambers, each with a volume of ∼500 pL, divided into six different sections individually addressed to deliver an equal number of chemical stimuli. Integrating microvalves allowed us to isolate cell/bead pairs, preventing cross-contamination with factors secreted by adjacent cells. We implemented a fluorescence sandwich immunoassay on the biosensing microbeads with a limit of detection of 9 pg/mL and were able to detect interleukin-8 (IL-8) secreted by single blood-derived human monocytes in response to different concentrations of LPS. Finally, our platform allowed us to observe a significant decrease in the number of IL-8-secreting monocytes when paracrine signaling becomes disrupted. Overall, our platform could have a variety of applications for which the analysis of cellular function heterogeneity is necessary, such as cancer research, antibody discovery, or rare cell screening.

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Section: Resultssupporting

confidence: 92%

“…Overall, our results agree with other studies where authors have employed similar flow rates to capture single cells in hydrodynamic traps. 45,52 Next, we assessed the effects of flow rate on cell viability. Monocytes isolated from peripheral blood were stained with Hoechst and introduced into the device.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

On-Chip Analysis of Protein Secretion from Single Cells Using Microbead Biosensors

et al. 2023

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“…Since the particle dynamics is essentially resolved in a sub-grid fashion, the LB-LD approach can be easily coupled with direct-numerical-simulation (DNS) suspension solvers to tackle multiscale, multicomponent particulate suspension flows. One example of such flows is blood flow suspended with numerous, interacting nanoscale biomolecules and microscale blood cells through microfluidic systems [27,28,29] or biological structures [30,31].…”

Section: Introductionmentioning

confidence: 99%

Multiscale method based on coupled lattice‐Boltzmann and Langevin‐dynamics for direct simulation of nanoscale particle/polymer suspensions in complex flows

Liu

Zhu

Clausen

et al. 2019

Numerical Methods in Fluids

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Summary A hybrid computational method coupling the lattice‐Boltzmann (LB) method and a Langevin‐dynamics (LD) method is developed to simulate nanoscale particle and polymer (NPP) suspensions in the presence of both thermal fluctuation and long‐range many‐body hydrodynamic interactions (HIs). Brownian motion of the NPP is explicitly captured by a stochastic forcing term in the LD method. The LD method is two‐way coupled to the nonfluctuating LB fluid through a discrete LB forcing source distribution to capture the long‐range HI. To ensure intrinsically linear scalability with respect to the number of particles, a Eulerian‐host algorithm for short‐distance particle neighbor search and interaction is developed and embedded to LB‐LD framework. The validity and accuracy of the LB‐LD approach are demonstrated through several sample problems. The simulation results show good agreements with theory and experiment. The LB‐LD approach can be favorably incorporated into complex multiscale computational frameworks for efficiently simulating multiscale multicomponent particulate suspension systems such as complex blood suspensions.

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“…Decoupling the interaction by solving for the flow-induced stresses in a fluid solver and deformations in a structural solver separately can be used to circumvent these complexities. Aljaghtham et al [45] decoupled the interaction by modelling a cell as a non-moving, rigid body in a computational fluid dynamics (CFD) program.…”

Section: Numerical Methods For Fluid-structure Interactionmentioning

confidence: 99%

“…Cell deformability has been recognized as a critical factor in the cancer metastasis as deformation of cells leads to changes in mechanical properties, thus mutating the cells [43]. Mechanical properties such as stiffness of cells is therefore used as markers to identify healthy and unhealthy cells [45,86]. Microfluidics technology has been adopted in the studies of cell deformability and estimation of cell mechanical properties through precise control of the flow-induced deformation in microto nano-scale [86,87].…”

Section: Deformation In Microchannelmentioning

confidence: 99%

A particle-based numerical method for modelling of fluid-structure interactions in biomanufacturing processes

Lee¹

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The study of human physiology and target medicine has made a great leap with the discovery of cell culture, an operation under the more general topic of biomanufacturing. One key biomanufacturing technique for the creation of in-vitro threedimensional tissue models and even diseases is the extrusion-based bioprinting, but the associated mechanical stresses can become so high that the cell viability significantly decreases. Therefore, methods that can characterize stresses induced in cell-laden bioinks during the printing process are critical to the advancement of bioprinting, ensuring high efficacy in the biomanufacturing technique. In this dissertation, a particle-based numerical method, commonly known as smoothed particle hydrodynamics (SPH), is developed to emulate the fluid-structure interactions between bioink and cells. To represent the cell deformations and motions, the SPH solver is coupled with an element bending group (EBG) model, which treats the cell as a solid membrane with liquid filling. The method is validated through comparison with experimental data on deformations and transport of a MCF7 cancerous cell through a microchannel. Upon validation, the method was applied on a model extrusion-based bioprinting configuration, considering in addition the use of cytoprotective gel particles to encapsulate the cells in the bioink, thereby maintaining a high cell viability. Using the deformations of the gel particles as boundary conditions, flow-induced stresses on the protective encapsulation can be computed by a separate finite element analysis. Stress analysis suggests the presence of a high stress region near the converging section before the bioprinter nozzle outlet, which is the likely cause of low cell viability in extrusion-based bioprinting. The results also indicate that the protective property from the encapsulating gel particles is due to the substitution of flow-induced stresses with internal stresses on the cells, which can be up to 90% less than the former. The findings from this research demonstrate that the two-dimensional SPH-EBG methodology developed here is a promising tool to predict stresses on cells within bioinks. Such a capability will not only facilitate the design of extrusion-based bioprinters, but also be applicable to other biomanufacturing techniques that involve cell-laden flows.

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Numerical simulations of cell flow and trapping within microfluidic channels for stiffness based cell isolation

Cited by 5 publications

References 41 publications

On-Chip Analysis of Protein Secretion from Single Cells Using Microbead Biosensors

On-Chip Analysis of Protein Secretion from Single Cells Using Microbead Biosensors

Multiscale method based on coupled lattice‐Boltzmann and Langevin‐dynamics for direct simulation of nanoscale particle/polymer suspensions in complex flows

A particle-based numerical method for modelling of fluid-structure interactions in biomanufacturing processes

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