Narrow Constriction Research Articles

Optimum flow rate of actively deformable particles in the overdamped regime

In this study, we investigate the behavior of actively deformable particles in a two-dimensional system as they flow through a narrow constriction under overdamped conditions. The model simulates particles that oscillate by harmonically changing their radius over time, with dynamics and interaction forces reflecting general cellular systems. We identify an optimal self-oscillation frequency at which the flow rate is maximized, occurring when the oscillation period matches the time needed for a particle to traverse a few of its own radii. While the model is a highly simplified abstraction and not intended to replicate the complexity of biological systems, it offers valuable insights into the mechanisms that may underlie efficient movement in crowded cellular contexts.

Investigation of Mode-Induced Spin Wave Transmission Blockage by In Situ Nanoscale Grooves.

In the pursuit of advancing spin-wave optics, the propagation of magnetostatic surface spin-waves is investigated in a uniform permalloy waveguide with in-situ nanopatterned grooves created through Atomic Force Microscopy nanolithography and Focused Ion Beam etching. The study unveils that the introduction of narrow constrictions and grooves leads to a non-monotonic reduction of the transmitted spin-wave signal intensity as the spin-wave pathway is shrinked. The remarkable feature that a stronger signal extinction is obtained for a narrow groove compared to a spin-waveguide interrupted by a full gap, where only inefficient transport through dipolar coupling is allowed, is highlighted. Combining experimental and numerical analyses, the intricate interplay between spin-wave diffraction and reflection at the waveguide edges is unraveled, being at the origin of a transverse-mode variation responsible for the signal extinction when detected using coplanar antennas. The findings offer insights into the controllable manipulation of detected spin-wave intensity, thereby opening promising avenues for the improvement of spin-wave switches and interferometers, and for the nanopatterning of graded indexmagnonics.

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.

Confined migration: Microtubules control the cell rear

Cell migration through complex 3D environments relies on the interplay between actin and microtubules. A new study shows that, when cells pass through narrow constrictions, CLASP-dependent microtubule stabilisation at the cell rear controls actomyosin contractility to enable nuclear translocation and preserve cell integrity.

Clogging of Noncohesive Suspension Flows

Abstract When flowing through narrow channels or constrictions, many-body systems exhibit various flowing patterns, yet they can also get stuck. In many of these systems, the flowing elements remain as individuals (they do not aggregate or merge), sharing strong analogies among each other. This is the case for systems as contrasting as grains in a silo and pedestrians passing through tight spaces. Interestingly, when these entities flow within a fluid medium, numerous similarities persist. However, the fluid dynamics aspects of such clogging events, such as interstitial flow, liquid pressure, and hydrodynamic interactions, has only recently begun to be explored. In this review, we describe parallels with dry granular clogging and extensively analyze phenomena emerging when particles coexist with fluid in the system. We discuss the influence of diverse flow drive, particle propulsion mechanisms, and particle characteristics, and we conclude with examples from nature.

FLN-2 functions in parallel to linker of nucleoskeleton and cytoskeleton complexes and CDC-42/actin pathways during P-cell nuclear migration through constricted spaces in Caenorhabditis elegans.

Nuclear migration through narrow constrictions is important for development, metastasis, and proinflammatory responses. Studies performed in tissue culture cells have implicated linker of nucleoskeleton and cytoskeleton (LINC) complexes, microtubule motors, the actin cytoskeleton, and nuclear envelope repair machinery as important mediators of nuclear movements through constricted spaces. However, little is understood about how these mechanisms operate to move nuclei in vivo. In Caenorhabditis elegans larvae, six pairs of hypodermal P cells migrate from lateral to ventral positions through a constricted space between the body wall muscles and the cuticle. P-cell nuclear migration is mediated in part by LINC complexes using a microtubule-based pathway and by an independent CDC-42/actin-based pathway. However, when both LINC complex and actin-based pathways are knocked out, many nuclei still migrate, suggesting the existence of additional pathways. Here, we show that FLN-2 functions in a third pathway to mediate P-cell nuclear migration. The predicted N-terminal actin-binding domain in FLN-2 that is found in canonical filamins is dispensable for FLN-2 function; this and structural predictions suggest that FLN-2 does not function as a filamin. The immunoglobulin-like repeats 4-8 of FLN-2 were necessary for P-cell nuclear migration. Furthermore, in the absence of the LINC complex component unc-84, fln-2 mutants had an increase in P-cell nuclear rupture. We conclude that FLN-2 functions to maintain the integrity of the nuclear envelope in parallel with the LINC complex and CDC-42/actin-based pathways to move P-cell nuclei through constricted spaces.

An Overview of Transferosomal Technology

Abstract: Ever since the invention of liposomes by Bangham in 1963, researchers have been fascinated by the vesicular carriers. Liposomes and niosomes have been used extensively by researchers for various routes such as oral and nasal. However, lately, it has been understood that traditional liposomes are not very significant when it comes to penetration. The use of nanovesicles in transdermal drug delivery systems has been enhanced exponentially ever since the discovery of ultra- deformable liposomes known as transfersomes or transferosomes. Transferosomes have numerous advantages, such as biocompatibility, biodegradability, flexibility, and deformability, so that they can pass through narrow constrictions. They have good entrapment efficiency and can act as a depot to sustain the release of drugs. The methods of preparation include the rotary film evaporation method, reverse phase evaporation method, vortexing sonication method, ethanol injection method, and freeze-thaw method. Transfersomes are characterized by particle size, zeta potential, polydispersity index, surface morphology, and encapsulation efficiency. Transferosomes have been successfully exploited for the enhancement of efficacy of many drugs like Hydroquinone, Itraconazole, Ivabradine, lornoxicam, minoxidil etc., via transdermal and nasal routes. The technology is easy to scale up. Consequently, it can be inferred that transfersomes are the future of transdermal drug delivery systems.

High-Resolution and Low-Noise Single-Molecule Sensing with Bio-Inspired Solid-State Nanopores.

Solid-state nanopores have been extensively explored as single-molecule sensors, bearing the potential for the sequencing of DNA. Although they offer advantages in terms of high mechanical robustness, tunable geometry, and compatibility with existing semiconductor fabrication techniques in comparison with their biological counterparts, efforts to sequence DNA with these nanopores have been hampered by insufficient spatial resolution and high noise in the measured ionic current signal. Here we show that these limitations can be overcome by the use of solid-state nanopores featuring a thin, narrow constriction as the sensing region, inspired by biological protein nanopores that have achieved notable success in DNA sequencing. Our extensive molecular dynamics simulations show that these bio-inspired nanopores can provide high spatial resolution equivalent to 2D material nanopores and, meanwhile, significantly inhibit noise levels. A theoretical model is also provided to assess the performance of the bio-inspired nanopore, which could guide its design and optimization.

Super-Suppression of Long-Wavelength Phonons in Constricted Nanoporous Geometries.

In a typical semiconductor material, the majority of the heat is carried by long-wavelength, long-mean-free-path phonons. Nanostructuring strategies to reduce thermal conductivity, a promising direction in the field of thermoelectrics, place scattering centers of size and spatial separation comparable to the mean free paths of the dominant phonons to selectively scatter them. The resultant thermal conductivity is in most cases well predicted using Matthiessen's rule. In general, however, long-wavelength phonons are not as effectively scattered as the rest of the phonon spectrum. In this work, using large-scale molecular-dynamics simulations, non-equilibrium Green's function simulations, and Monte Carlo simulations, we show that specific nanoporous geometries that create narrow constrictions in the passage of phonons lead to anticorrelated heat currents in the phonon spectrum. This effect results in super-suppression of long-wavelength phonons due to heat trapping and reductions in the thermal conductivity to values well below those predicted by Matthiessen's rule.

On the coupling of magnetic moments to superconducting quantum interference devices

We investigate the coupling factor φ µ that quantifies the magnetic flux Φ per magnetic moment µ of a point-like magnetic dipole that couples to a superconducting quantum interference device (SQUID). Representing the dipole by a tiny current-carrying (Amperian) loop, the reciprocity of mutual inductances of SQUID and Amperian loop provides an elegant way of calculating ϕμ(r,eˆμ) vs. position r and orientation eˆμ of the dipole anywhere in space from the magnetic field BJ(r) produced by a supercurrent circulating in the SQUID loop. We use numerical simulations based on London and Ginzburg–Landau theory to calculate φ µ from the supercurrent density distributions in various superconducting loop geometries. We treat the far-field regime ( r≳a= inner size of the SQUID loop) with the dipole placed on (oriented along) the symmetry axis of circular or square shaped loops. We compare expressions for φ µ from simple filamentary loop models with simulation results for loops with finite width w (outer size A > a), thickness d and London penetration depth λ L and show that for thin ( d≪a ) and narrow (w < a) loops the introduction of an effective loop size aeff in the filamentary loop-model expressions results in good agreement with simulations. For a dipole placed right in the center of the loop, simulations provide an expression ϕμ(a,A,d,λL) that covers a wide parameter range. In the near-field regime (dipole centered at small distance z above one SQUID arm) only coupling to a single strip representing the SQUID arm has to be considered. For this case, we compare simulations with an analytical expression derived for a homogeneous current density distribution, which yields excellent agreement for λL>w,d . Moreover, we analyze the improvement of φ µ provided by the introduction of a narrow constriction in the SQUID arm below the magnetic dipole.

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.

High throughput intracellular delivery by viscoelastic mechanoporation

Brief pulses of electric field (electroporation) and/or tensile stress (mechanoporation) have been used to reversibly permeabilize the plasma membrane of mammalian cells and deliver materials to the cytosol. However, electroporation can be harmful to cells, while efficient mechanoporation strategies have not been scalable due to the use of narrow constrictions or needles which are susceptible to clogging. Here we report a high throughput approach to mechanoporation in which the plasma membrane is stretched and reversibly permeabilized by viscoelastic fluid forces within a microfluidic chip without surface contact. Biomolecules are delivered directly to the cytosol within seconds at a throughput exceeding 250 million cells per minute. Viscoelastic mechanoporation is compatible with a variety of biomolecules including proteins, RNA, and CRISPR-Cas9 ribonucleoprotein complexes, as well as a range of cell types including HEK293T cells and primary T cells. Altogether, viscoelastic mechanoporation appears feasible for contact-free permeabilization and delivery of biomolecules to mammalian cells ex vivo.

Flow and clogging of capillary droplets.

Capillary droplets form due to surface tension when two immiscible fluids are mixed. We describe the motion of gravity-driven capillary droplets flowing through narrow constrictions and obstacle arrays in both simulations and experiments. Our new capillary deformable particle model recapitulates the shape and velocity of single oil droplets in water as they pass through narrow constrictions in microfluidic chambers. Using this experimentally validated model, we simulate the flow and clogging of single capillary droplets in narrow channels and obstacle arrays and find several important results. First, the capillary droplet speed profile is nonmonotonic as the droplet exits the narrow orifice, and we can tune the droplet properties so that the speed overshoots the terminal speed far from the constriction. Second, in obstacle arrays, we find that extremely deformable droplets can wrap around obstacles, which leads to decreased average droplet speed in the continuous flow regime and increased probability for clogging in the regime where permanent clogs form. Third, the wrapping mechanism causes the clogging probability in obstacle arrays to become nonmonotonic with surface tension Γ. At large Γ, the droplets are nearly rigid and the clogging probability is large since the droplets can not squeeze through the gaps between obstacles. With decreasing Γ, the clogging probability decreases as the droplets become more deformable. However, in the small-Γ limit, the clogging probability increases since the droplets are extremely deformable and wrap around the obstacles. The results from these studies are important for developing a predictive understanding of capillary droplet flows through complex and confined geometries.

Gate-defined quantum point contacts in a germanium quantum well.

We report an experimental study of quantum point contacts defined in a high-quality strained germanium quantum well with layered electric gates. At a zero magnetic field, we observed quantized conductance plateaus in units of 2e2/h. Bias-spectroscopy measurements reveal that the energy spacing between successive one-dimensional subbands ranges from 1.5 to 5 meV as a consequence of the small effective mass of the holes and the narrow gate constrictions. At finite magnetic fields perpendicular to the device plane, the edges of the conductance plateaus get split due to the Zeeman effect and Landé g factors were estimated to be ∼6.6 for the holes in the germanium quantum well. We demonstrate that all quantum point contacts in the same device have comparable performances, indicating a reliable and reproducible device fabrication process. Thus, our work lays a foundation for investigating multiple forefronts of physics in germanium-based quantum devices that require quantum point contacts as building blocks.

Hydrodynamics of a multicomponent vesicle under strong confinement.

We numerically investigate the hydrodynamics and membrane dynamics of a multicomponent vesicle in two strongly confined geometries. This serves as a simplified model for red blood cells undergoing large deformations while traversing narrow constrictions. We propose a new parameterization for the bending modulus that remains positive for all lipid phase parameter values. For a multicomponent vesicle passing through a stenosis, we establish connections between various properties: lipid phase coarsening, size and flow profile of the lubrication layers, excess pressure, and the tank-treading velocity of the membrane. For a multicomponent vesicle passing through a contracting channel, we find that the lipid always phase separates so that the vesicle is stiffer in the front as it passes through the constriction. For both cases of confinement we find that lipid coarsening is arrested under strong confinement, and resumes at a high rate upon relief from extreme confinement. The results may be useful for efficient sorting lipid domains using microfluidic flows by controlled release of vesicles passing through strong confinement.

Examining the anatomy of the upper airways and soft tissues in healthy people and patients with sleep disorders.

Objective: To assessed upper airway differences between individuals with and without obstructive sleep apnea (OSA). The study Investigated upper airway differences in OSA. Study Design: Comparative cross sectional study. Setting: Hayatabad Medical Complex, Khyber Girls Medical College. Period: January, 2022 to October, 2022. Material &amp; Methods: 68 participants examined with results: "Anterior-posterior (AP) respiratory tract dimension" consistent across groups. Mandible rami dimension uniform, indicating no bony contribution to lateral narrowing. OSA patients displayed narrower lateral respiratory tracts due to enlarged lateral pharyngeal walls. OSA patients didn't exhibit larger fat pads in the minimal respiratory tract compared to healthy individuals. Results: Our findings reveal that the upper airways of apneic patients exhibit distinct characteristics compared to those of individuals without apnea. Specifically, these differences manifest in the lateral and narrow constriction of the apneic airway. The study's results underscore the significance of examining delicate tissue elements surrounding the upper respiratory tract to comprehend these variations in apneic respiratory tract dimensions. Conclusion: This study highlights OSA-related upper airway differences, primarily attributed to enlarged lateral pharyngeal walls. Understanding these distinctions may aid OSA diagnosis and management.

Effect of physical properties on the dynamics of an isolated bubble squeezing through a narrow constriction

Effect of physical properties on the dynamics of an isolated bubble squeezing through a narrow constriction

Enhanced Broadband Photodetection with Geometry and Interface Engineered Nanocrystalline Graphite

AbstractPhotodetection across the near‐infrared (NIR) to short‐wavelength infrared (SWIR) spectrum is important for many applications. This study explores photodetection using nanocrystalline graphite (NCG) in a suspended, narrow constriction configuration for improved performance. Bowtie constrictions are fabricated in both suspended and substrate‐supported NCG devices, allowing for accurate comparison. It shows that the suspended constriction enhances the bolometric photoresponse and sensor detectivity by several orders of magnitude compared to the substrate‐supported counterparts, attributed to reduced thermalization and electric field concentration. The suspended configuration preserves a spectrally flat photoresponse while reducing operating voltage through a tailored NCG layer thickness. Chromatic aberration‐corrected photocurrent spectroscopy is used to measure the photoresponse from 1100 to 1700 nm, and diffraction‐limited hyperspectral photocurrent imaging is conducted to measure the local photocurrent generation across the device. Bolometric and photo‐thermoelectric currents are restricted to the suspended central constriction due to electric field concentration and thermal decoupling and the direction of the photocurrents within the sensor is revealed. The experimental data is complemented by simulations of the light absorption and the electric field distribution. This work indicates the importance of geometry and thermal decoupling for boosting device performance, offering promising prospects for sensitive and low‐power NCG‐based photodetectors in the NIR‐SWIR range.

STEM-01. PLEXIN-B2 DRIVES CONFINED MIGRATION OF GLIOBLASTOMA STEM CELLS THROUGH MEMBRANE TENSION, ENDOCYTOSIS, AND MECHANO-ELECTRO REGULATION

Abstract Glioblastoma is a malignant brain tumor of uncontrolled proliferation and infiltration. GBM stem cells (GSCs) are constantly challenged by confined spaces during their migration through the brain parenchyma. Understanding the factors that drive GSC confined migration (CM) is thus critical for effective drug development. Using microchannel devices, we showed that GSCs are adept at squeezing through narrow constrictions at faster speed than through non-constricted spaces. During CM, cytoskeletal components and plasma membrane self-organize to establish polarity and propel the cell through the constrictions. Among the mechanical plasticity observed for meeting the challenges of CM the cells remodel their shape and plasma membrane through increased endocytosis. Rapid endocytosis of inner leaflet anionic phospholipids-such as PI(4,5)P2 and phosphatidylserine at the front of the cell collectively contribute to drive positive-charged actin filaments and calcium to the rear end of cells, abruptly leading to localized changes in membrane potential and propelling the cell. Correspondingly, inhibiting endocytosis abrogates polarity and results in failure to CM. These effects were recapitulated by deletion of the cell surface receptor Plexin-B2. Plexin-B2-CRISPR knockout (KO) GSCs displayed reduced capability to squeeze through constrictions in microchannel devices. Mechanistically, Plexin-B2 KO in GSCs compromised membrane dynamics and reduced endocytosis as consequence of low cell stiffness and membrane tension. Computational simulations demonstrated that membrane tension couples with cell stiffness in feedback loops and support the model that Plexin-B2 controls membrane tension through actomyosin contractility. On a molecular level, the locked extracellular ring domain of Plexin-B2 prevents GSCs to migrate through constrictions and recapitulates the defects associated with Plexin-B2 KO phenotype, indicating that ring bending is required for membrane tension. Thus, our results describe critical mechano-electro events necessary to establish polarity and prompt GSCs migration under confinement and provide a mechanism by which a single mechanosensor exert regulation at the cytoskeletal and membrane levels.

Sideways maneuvers enable narrow aperture negotiation by free-flying hummingbirds.

Many birds routinely fly fast through dense vegetation characterized by variably sized structures and voids. Successfully negotiating these cluttered environments requires maneuvering through narrow constrictions between obstacles. We show that Anna's hummingbirds (Calypte anna) can negotiate apertures less than one wingspan in diameter using a novel sideways maneuver that incorporates continuous, bilaterally asymmetric wing motions. Crucially, this maneuver allows hummingbirds to continue flapping as they negotiate the constriction. Even smaller openings are negotiated via a faster ballistic trajectory characterized by tucked and thus non-flapping wings, which reduces force production and increases descent rate relative to the asymmetric technique. Hummingbirds progressively shift to the swept method as they perform hundreds of consecutive transits, suggesting increased locomotor performance with task familiarity. Initial use of the slower asymmetric transit technique may allow birds to better assess upcoming obstacles and voids, thereby reducing the likelihood of subsequent collisions. Repeated disruptions of normal wing kinematics as birds negotiate tight apertures may determine the limits of flight performance in structurally complex environments. These strategies for aperture transit and associated flight trajectories can inform designs and algorithms for small aerial vehicles flying within cluttered environments.