Constricted Channel Research Articles

Long-Term Stable and Multifeature Microfluidic Impedance Flow Cytometry Based on a Constricted Channel for Single-Cell Mechanical Phenotyping.

The microfluidic impedance flow cytometer (m-IFC) using constricted microchannels is an appealing choice for the high-throughput measurement of single-cell mechanical properties. However, channels smaller than the cells are susceptible to irreversible blockage, extremely affecting the stability of the system and the throughput. Meanwhile, the common practice of extracting a single quantitative index, i.e., total cell passage time, through the constricted part is inadequate to decipher the complex mechanical properties of individual cells. Herein, this study presents a long-term stable and multifeature m-IFC based on a constricted channel for single-cell mechanical phenotyping. The blockage problem is effectively overcome by adding tiny xanthan gum (XG) polymers. The cells can pass through the constricted channel at a flow rate of 500 μL/h without clogging, exhibiting high throughput (∼240 samples per second) and long-term stability (∼2 h). Moreover, six detection regions were implemented to capture the multiple features related to the whole process of a single cell passing through the long-constricted channel, e.g., creep, friction, and relaxation stages. To verify the performance of the multifeature m-IFC, cells treated with perturbations of microtubules and microfilaments within the cytoskeleton were detected, respectively. It suggests that the extracted features provide more comprehensive clues for single-cell analysis in structural and mechanical transformation. Overall, our proposed multifeature m-IFC exhibits the advantages of nonclogging and high throughput, which can be extended to other cell types for nondestructive and real-time mechanical phenotyping in cost-effective applications.

Pressure-driven formation of sub-femtoliter droplets in constricted T-shaped nanofluidic channel and application to isolation and counting of single nanoparticles

Nanofluidics has developed, enabling the analysis of single nanoparticles such as viruses and macromolecules using nanochannels. However, since nanoparticles migrate randomly by Brownian motion with displacements comparable to the nanochannel size, it is difficult to array and process nanoparticles individually in continuous phase flows with biological analyte concentrations of pM–nM. The present study developed a method to generate aqueous droplets of 102 aL–100 fL volumes in an organic phase in a nanochannel by pressure-driven flow control, and applied the method to the isolation of single nanoparticles with 101−102 pM concentrations. A T-shaped nanochannel with a narrow constriction section was proposed to locally enhance the shear force to form smaller droplets by 102 kPa external pressure, without increasing the pressure loss by downscaling the channel. The proposed channel design was validated, droplets with 0.8–1.0 fL volumes were formed with pL/min flow rates at Ca = 0.5–1.4 × 10−3, and the dynamics of droplet generation was well characterized by the linear scaling law. Using the developed device, encapsulation and counting of single fluorescent nanoparticles and single fluorescently-labeled DNA molecules in droplets were successfully demonstrated. This work will contribute to the development of droplet nanofluidics and ultrasmall analytical applications.

Modulation of Water Vapor Sorption by Pore Engineering in Isostructural Square Lattice Topology Coordination Networks.

We report a crystal-engineering study conducted upon a platform of three mixed-linker square lattice (sql) coordination networks of general formula [Zn(Ria)(bphy)] [bphy = 1,2-bis(pyridin-4-yl)hydrazine, H2Ria = 5-position-substituted isophthalic acid, and R = -Br, -NO2, and -OH; compounds 1-3]. Analysis of single-crystal X-ray diffraction data of 1-2 and the simulated crystal structure of 3 revealed that 1-3 are isomorphous and sustained by bilayers of sql networks linked by hydrogen bonds. Although similar pore shapes and sizes exist in 1-3, distinct isotherm shapes (linear and S shape) and uptakes (2.4, 11.6, and 13.3 wt %, respectively) were observed. Ab initio calculations indicated that the distinct water sorption properties can be attributed to the R groups, which offer a range of hydrophilicity. Calculations indicated that the significantly lower experimental uptake in compound 1 can be attributed to a constricted channel. The calculated water-binding sites provide insights into how adsorbed water molecules bond to the pore walls, with the strongest interactions, water-hydroxyl hydrogen bonding, observed for 3. Overall, this study reveals how pore engineering can result in large variations in water sorption properties in an isomorphous family of rigid porous coordination networks.

Experimental measurement and numerical modeling of deformation behavior of breast cancer cells passing through constricted microfluidic channels

During the multistep process of metastasis, cancer cells encounter various mechanical forces which make them deform drastically. Developing accurate in-silico models, capable of simulating the interactions between the mechanical forces and highly deformable cancer cells, can pave the way for the development of novel diagnostic and predictive methods for metastatic progression. Spring-network models of cancer cell, empowered by our recently proposed identification approach, promises a versatile numerical tool for developing experimentally validated models that can simulate complex interactions at cellular scale. Using this numerical tool, we presented spring-network models of breast cancer cells that can accurately replicate the experimental data of deformation behavior of the cells flowing in a fluidic domain and passing narrow constrictions comparable to microcapillary. First, using high-speed imaging, we experimentally studied the deformability of breast cancer cell lines with varying metastatic potential (MCF-7 (less invasive), SKBR-3 (medium-high invasive), and MDA-MB-231 (highly invasive)) in terms of their entry time to a constricted microfluidic channel. We observed that MDA-MB-231, that has the highest metastatic potential, is the most deformable cell among the three. Then, by focusing on this cell line, experimental measurements were expanded to two more constricted microchannel dimensions. The experimental deformability data in three constricted microchannel sizes for various cell sizes, enabled accurate identification of the unknown parameters of the spring-network model of the breast cancer cell line (MDA-MB-231). Our results show that the identified parameters depend on the cell size, suggesting the need for a systematic procedure for identifying the size-dependent parameters of spring-network models of cells. As the numerical results show, the presented cell models can simulate the entry process of the cell into constricted channels with very good agreements with the measured experimental data.

Observations and modeling of tidally generated high-frequency velocity fluctuations downstream of a channel constriction

Abstract. We investigate data from an acoustic Doppler current profiler deployed in a constricted ocean channel showing a tidally dominated flow with intermittent velocity extrema during outflow from the constriction but not during inflow. A 2D numerical ocean model forced by tides is used to examine the spatial flow structure and underlying dynamical processes. We find that flow-separation eddies generated near the tightest constriction point form a dipole pair which propagates downstream and drives the observed intermittent flow variability. The eddies, which are generated by an along-channel adverse pressure gradient, spin up for some time near the constriction until they develop local low pressures in their centers that are strong enough to modify the background along-channel pressure gradient significantly. When the dipole has propagated some distance away from the constriction, the conditions for flow separation are recovered, and new eddies are formed.

Dynamics of two unequal micron-sized viscous emulsion drops flowing in a two-dimensional constricted microcapillary channel: A numerical study

Emulsions containing unequal-sized droplets are ubiquitous. Compared to the equal-sized emulsion droplet coalescence process in porous media, unequal-sized emulsion droplets show distinctly different dynamics and features when flowing through the capillary channel. In this paper, we numerically studied the flow of two unequal small micron-size emulsion drops flowing in a two-dimensional (2D) half-sine pulse shape constricted tube. The finite element method solves the momentum, continuity, and level set equations. The oil–water interface is tracked using the level set method. Effects of drop size, capillary number (interfacial tension), viscosity ratio, and geometrical shape constriction effects on the droplets' flow behavior across the throat, its flow velocities, and average viscous pressure across the tube were investigated. It is found when there is a significant difference in diameters of the two un-equalized droplets, they will flow separately through the throat, whereas when the two un-equalized droplets’ size is close to each other, they coalescence with each other after passing through the constriction. Higher interfacial tension leads unequal-sized droplets to coalescence more readily while droplets pass without coalescence at low interfacial tension cases. The highest pressure drop is recorded at the critical point where the two unequal-sized droplets begin to merge in the constriction throat. Increasing droplet viscosity reduces the chances of coalescence and increases the average viscous pressure drop hence leading to mobility reduction. In the case of geometrical constrictions, circular-shaped contracted tubes offer the least resistance to fluid flow and are more appropriate for enhanced oil recovery processes. We hope our numerical findings will provide more information to facilitate the enhanced oil recovery process.

The Surfactant Role on a Droplet Passing through a Constricted Microchannel in a Pressure-Driven Flow: A Lattice Boltzmann Study.

The role of surfactants in the flow of a droplet driven by a pressure gradient through a constricted microchannel is simulated by using our recently developed lattice Boltzmann method. We first study the surfactant role on a droplet flowing through a microchannel with a shrunken square section under different surfactant concentrations and capillary numbers (i.e., imposed pressure gradients). As the surfactant concentration increases, the droplet flow regime first changes from the flow regime I of the droplet getting stuck at the entrance of the constricted channel to the flow regime II of the droplet flowing through the constricted channel with breakup, and then to the flow regime III of the droplet flowing through the constricted channel without breakup. As the capillary number increases, the surfactant role on the number of mother droplets breaking up and the time of mother droplets completely flowing through the constricted section tend to decrease, suggesting that the surfactant effects are gradually weakened. Then, a phase diagram describing how the surfactant concentration and capillary number affect the droplet flow regime is presented. As the surfactant concentration increases, the critical capillary number that distinguishes droplet flow regimes I from II gradually decreases, while the critical capillary number that distinguishes droplet flow regimes II from III first increases and then decreases.

Cell-free layer of red blood cells in a constricted microfluidic channel under steady and time-dependent flow conditions

Cell-free layer of red blood cells in a constricted microfluidic channel under steady and time-dependent flow conditions

Numerical study of droplet behavior passing through a constricted square channel

Snap-off is a crucial mechanism for drop breakup in multiphase flow within porous media. However, the systematic investigation of snap-off dynamics in constricted capillaries with varying pore and throat heights remains limited. In this study, we conducted three-dimensional simulations of drop behavior in a constricted square capillary with non-uniform depth, employing a color-gradient lattice Boltzmann model. Our analysis encompassed a comprehensive range of parameters, including geometrical factors and physical properties, such as capillary number, initial drop size, viscosity ratio, constriction length, and the presence of soluble surfactants. Depending on these parameters, the drop exhibited either breakup or deformation as it traversed the constriction. Upon snap-off occurrence, we quantified two significant aspects: the snap-off time t̂b, which represents the time interval between the drop front passing the constriction center and the snap-off event, and the volume of the first daughter drop V̂d generated by the breakup mechanism. Consistently, we observed a power-law relationship between t̂b and the capillary number Ca. However, the variation of V̂d with Ca exhibited a more complex behavior, influenced by additional factors, such as the viscosity ratio and the presence of surfactants, which break the linear increase in V̂d with Ca. Notably, the inclusion of surfactants is able to homogenize the volume of the first daughter drop. Through our comprehensive numerical study, we provide valuable insight into the snap-off process in constricted capillaries. This research contributes to the understanding of multiphase flow behavior and facilitates the optimization of processes involving snap-off in porous media.

The dynamic behavior of a droplet flows through a constricted splitting channel: a lattice Boltzmann study

In this paper, a lattice Boltzmann method is used to simulate the dynamic behavior of a droplet flows through a constricted channel, where an obstacle is placed in the center of the constricted channel to split the droplet. The method is first used to simulate the effect of the capillary number on the volume of the divided daughter droplets. Results show that the volume difference between the daughter droplets above and below the obstacle increases as increases. We also find that reducing the capillary number is conducive to the droplet splitting into two daughter droplets with similar volume. The method is then used to simulate the influence of the viscosity ratio on the droplet flows through a constricted channel. As increases, the volume difference between the daughter droplets above and below the obstacle decreases. Finally, the influence of the confinement ratio on the evolution of the droplet morphology is investigated. With increase in , the volume difference between the daughter droplets above and below the obstacle increases. When , the droplet does not break up and completely enters the bottom channel. Comparing with the converging-diverging and ratchet channels, the constricted splitting channel is more conductive to the breakup of the droplet neck.

Effects of induced magnetic field on conducting viscous fluid flowing in a constricted channel

We report the effects of an externally applied magnetic field on an electrically conducting fluid flow in a locally constricted channel. With the use of finite-difference discretization and the ADI (Alternating directions implicit) scheme, the non-linear coupled magnetohydrodynamic (MHD) equations in two dimensions were numerically solved. When the magnetic Reynolds number RM >> 1, an induced magnetic field forms in the motion and significantly affects flow. The electromagnetic force (Lorentz force) is developed and acts as a damping force. It results the suppression of flow separation regions developed due to the channel constrictions. It delays the onset of flow separation and the flow become stable. By employing suitable value of magnetic field one can completely suppress the flow separation. The induced magnetic field and current density vectors are dense at the constriction site due to high velocity shear in the downstream of the constriction, resulting in the creation of high shear magnetic and electric fields.

Two-dimensional numerical modelling of viscous emulsion drops coalescence in a constricted capillary channel

We study numerically the coalescence of viscous emulsion drops in a two-dimensional semi-elliptical shape constricted channel. The Navier-Stokes equations are solved using the finite element method and the oil-water interface is tracked using the level-set techniques. Effects of interfacial tension, inertia, viscosity ratio, droplet size, and constriction shape on the droplet coalescence and average viscous pressure drop along the channel are investigated. It is found that at high interfacial tension, droplets are circular, approach each other more quickly, coalesce at the constriction entrance, and give higher pressure drops. At intermediate interfacial tension, the onset of coalescence occurs downstream of the constriction entrance while at very low interfacial tension, no coalescence of the droplets was observed. Inertia is found to be negligible effects on the coalescence of the droplets. High inertia gives less viscous pressure drop. Less viscous droplets are more likely to quickly coalesce compared to high viscous drops. Higher viscous drops create more resistance to flow. Moreover, larger size drops are responsible for more quick coalescence and tend to create more viscous pressure drops. In addition, we found that circular constriction offers less resistance to fluid flow. We hope that these numerical results would be beneficial while displacing oil from the underground reservoirs.

Finite droplets vs long droplets: Discrepancy in release conditions in a microscopic constricted channel

Conditions of release of trapped droplets in constricted channels are of great significance in various domains, including microfluidic development and enhanced oil recovery. In our previous studies, a detailed and quantitative analysis of the threshold pressure needed to release a droplet from a constricted channel has been performed. However, droplets may exist in real applications as long droplets, which may exhibit different behavior than finite droplets. Therefore, in this study, direct numerical simulations, combining the fluid flow equations and the phase-field method, have been conducted on three-dimensional constrained channels to investigate discrepancies in release conditions of finite droplets and long droplets. The results have shown that for a finite droplet, the maximum pressure increases with the increase in the contact angle, whereas for a long droplet, the maximum pressure is almost the same both in the water-wet and neutral-wet conditions. Effects of droplet size on the release pressure have also been studied. For the finite droplet and at the water-wet condition (θ = 45°), the minimum release pressure increases linearly with the droplet length, while for the long droplet at similar conditions, the minimum release pressure does not change much as the length of the droplet increases. Furthermore, the release pressure decreases with the increased tapering angle.

A computational model for the transit of a cancer cell through a constricted microchannel.

We propose a three-dimensional computational model to simulate the transient deformation of suspended cancer cells flowing through a constricted microchannel. We model the cell as a liquid droplet enclosed by a viscoelastic membrane, and its nucleus as a smaller stiffer capsule. The cell deformation and its interaction with the suspending fluid are solved through a well-tested immersed boundary lattice Boltzmann method. To identify a minimal mechanical model that can quantitatively predict the transient cell deformation in a constricted channel, we conduct extensive parametric studies of the effects of the rheology of the cell membrane, cytoplasm and nucleus and compare the results with a recent experiment conducted on human leukaemia cells. We find that excellent agreement with the experiment can be achieved by employing a viscoelastic cell membrane model with the membrane viscosity depending on its mode of deformation (shear versus elongation). The cell nucleus limits the overall deformation of the whole cell, and its effect increases with the nucleus size. The present computational model may be used to guide the design of microfluidic devices to sort cancer cells, or to inversely infer cell mechanical properties from their flow-induced deformation.

Salt fingers in a constricted channel

Constriction of a channel dominates fluid flow and the salt finger, double-diffusive instability.

Numerical Investigation of the Pulsatile Flow of Viscous Fluid in Constricted Wall Channel with Thermal Radiation

Numerical Investigation of the Pulsatile Flow of Viscous Fluid in Constricted Wall Channel with Thermal Radiation

The human pre-replication complex is an open complex

In eukaryotes, DNA replication initiation requires assembly and activation of the minichromosome maintenance (MCM) 2-7 double hexamer (DH) to melt origin DNA strands. However, the mechanism for this initial melting is unknown. Here, we report a 2.59-Å cryo-electron microscopy structure of the human MCM-DH (hMCM-DH), also known as the pre-replication complex. In this structure, the hMCM-DH with a constricted central channel untwists and stretches the DNA strands such that almost a half turn of the bound duplex DNA is distorted with 1 base pair completely separated, generating an initial open structure (IOS) at the hexamer junction. Disturbing the IOS inhibits DH formation and replication initiation. Mapping of hMCM-DH footprints indicates that IOSs are distributed across the genome in large clusters aligning well with initiation zones designed for stochastic origin firing. This work unravels an intrinsic mechanism that couples DH formation with initial DNA melting to license replication initiation in human cells.

Deformation of a compound droplet in a wavy constricted channel

Deformation of a compound droplet in a wavy constricted channel

Trans-9,10-Dihydro-9,10-ethanoanthracene-11,12-dicarboxylic Acid: Remarkable Host Selectivities in the Presence of Mixtures of Anisole and Bromoanisole Isomers

In this work, trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic acid (DED), a host compound that formed complexes with anisole (ANI), 2-bromoanisole (2-BA), and 4-bromoanisole (4-BA), was revealed to possess a remarkable affinity (93.1–98.6%) for 4-BA when recrystallized from any mixtures containing this guest species, be these binary (ANI/4-BA, 2-BA/4-BA, or 3-BA/4-BA), ternary (ANI/2-BA/4-BA, ANI/3-BA/4-BA, or 2-BA/3-BA/4-BA), or quaternary (ANI/2-BA/3-BA/4-BA) in nature. Furthermore, this striking host selectivity persisted even in binary solutions containing low concentrations of 4-BA (18–25%); near-complete selectivities in favor of 4-BA were observed here too. Single crystal X-ray diffraction analyses showed that the favored guest species, 4-BA, was the only one to experience short intermolecular contacts, through its phenyl ring, with the host molecule’s carbonyl oxygen atom and the host hydrogen atom on the carbon bearing the second carboxylic acid group. Furthermore, ANI and 2-BA were accommodated in wide open channels, while the guest accommodation type for 4-BA was significantly more constricted. Thermal analyses confirmed that 2(DED)·3(ANI) and DED·2-BA, having the disfavored guests in open channels, were unstable at room temperature, while the preferred guest species, 4-BA, in its decidedly constricted channels, was only released at significantly higher temperatures (116.8 °C). Therefore, by employing host–guest chemistry strategies, DED has the ability to purify and separate any of these 4-BA-containing mixtures, a distinct advantage over fractional distillations which are cumbersome owing to physical property similarities of 2-, 3-, and 4-BA.

Host Compound DED: Guest Accommodation Type, Noncovalent Host···Guest Interactions, Crystal Densities, and Thermal Stabilities Ensure High Host Selectivities for 4-Methylanisole in Anisole and Methylanisole Mixtures

trans-9,10-Dihydro-9,10-ethanoanthracene-11,12-dicarboxylic acid (DED), dimethyl trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylate (H1), and trans-α,α,α′,α′-tetraphenyl-9,10-dihydro-9,10-ethanoanthracene-11,12-dimethanol (H2) formed complexes with anisole (ANI) and 2-, 3-, and 4-methylanisole (2-, 3-, and 4-MA) in single-solvent recrystallization experiments. DED was observed to possess an overwhelming selectivity for 4-MA when recrystallized from equimolar binary, ternary, and quaternary mixtures (82.2–99.3%) and nonequimolar binary solutions where this guest species was present. It was therefore demonstrated that DED may serve as an efficient host compound for the separation and purification of many of the mixtures employed in this investigation; extremely high K values (K is a measure of the selectivity of the host compound) were calculated in many instances (137.9, 190.7). However, the selectivity behavior of H1 and H2 in analogous experimental conditions could not be established owing to the extremely slow (months) crystal growth process from these mixtures. Single-crystal X-ray diffraction (SCXRD) experiments revealed that 4-MA interacted with DED via two short stabilizing (host)C–O···π(guest) contacts (3.2782(17), 3.3780(17) Å, 145, 138°). This interaction type was absent in 2(DED)·3-MA and weaker in 2(DED)·2-MA (and only one interaction of this kind was present in the latter complex). Additionally, the crystal density of 2(DED)·4-MA (1.335 g·cm–1) was greater than those of 2(DED)·3(ANI) (1.277 g·cm–1), 2(DED)·2-MA (1.257 g·cm–1), and 2(DED)·3-MA (1.283 g·cm–1), alluding to a tighter packing in the complex with the preferred guest species owing to the shorter contacts in this crystal. The higher density was also explained by a significantly shorter intermolecular (host)π···π(host) interaction in the 4-MA-containing complex. Furthermore, 4-MA experienced more constricted channel accommodation compared with ANI, 2- and 3-MA. Finally, 2(DED)·4-MA possessed the greater thermal stability (the onset of the guest release process, Ton = 101.8 °C) compared with 2(DED)·3(ANI) (unstable at room temperature), 2(DED)·2-MA (Ton = 90.4 °C), and 2(DED)·3-MA (Ton = 85.3 °C).