Low yield stress measurements with a microfluidic rheometer.

Yield stress, τy, is a key rheological property of complex materials such as gels, dense suspensions, and dense emulsions. While there is a range of established techniques to measure τy in the order of tens to thousands of pascals, the measurement of low τy, specifically below 1 Pa, remains underexplored. In this article, we present the measurement of low apparent τy using a Hele-Shaw microfluidic extensional flow device (MEFD). Using the MEFD, we observe a gradient in shear stress, τ, such that τ is lower near the center or stagnation point, and higher away from the stagnation point. For a yield stress fluid, we observe that, below a certain flow rate, τ exceeds τy only in the outer region, leading to stagnation or unyielding of the fluid in the inner region. We use scaling analysis based on a Hele-Shaw linear extensional flow to deduce τy by measuring the size of the unyielded region, S. We validate this scaling relationship using Carbopol solutions with concentrations ranging between 0.015 to 0.3%, measuring τy as low as ∼10 mPa to ∼1 Pa, and comparing it with τy measured using a standard rheometer. While the experimental lower limit of our technique is 5 mPa, modifying the geometry or improving the image analysis can reduce this limit to the order of 10-4 Pa. The MEFD facilitates rapid measurement of τy, allowing for its real-time assessment. We further report τy of human blood samples between 30 to 80 mPa with their hematocrit ranging between 14 to 63%. Additionally, we determine τy for a mucus simulant (∼0.7 Pa), and lactic drink (∼7 mPa) to demonstrate the versatility of the MEFD technique.

The yielding behaviour of human mucus.

Mucus is a viscoelastic material with non-linear rheological properties such as a yield stress of the order of a few hundreds of millipascals to a few tens of pascals, due to a complex network of mucins in water along with non-mucin proteins, DNA and cell debris. In this review, we discuss the origin of the yield stress in human mucus, the changes in the rheology of mucus with the occurrence of diseases, and possible clinical applications in disease detection as well as cure. We delve into the domain of mucus rheology, examining both macro- and microrheology. Macrorheology involves investigations conducted at larger length scales (∼ a few hundreds of µm or higher) using traditional rheometers, which probe properties on a bulk scale. It is significant in elucidating various mucosal functions within the human body. This includes rejecting unwanted irritants out of lungs through mucociliary and cough clearance, protecting the stomach wall from the acidic environment as well as biological entities, safeguarding cervical canal from infections and providing a swimming medium for sperms. Additionally, we explore microrheology, which encompasses studies performed at length scales ranging from a few tens of nm to a µm. These microscale studies find various applications, including the context of drug delivery. Finally, we employ scaling analysis to elucidate a few examples in lung, cervical, and gastric mucus, including settling of irritants in lung mucus, yielding of lung mucus in cough clearance and cilial beating, spreading of exogenous surfactants over yielding mucus, swimming of Helicobacter pylori through gastric mucus, and lining of protective mucus in the stomach. The scaling analyses employed on the applications mentioned above provide us with a deeper understanding of the link between the rheology and the physiology of mucus.

Affinity-controlled release of rod-derived cone viability factor enhances cone photoreceptor survival.

Retinitis pigmentosa (RP) is a group of genetic diseases that results in rod photoreceptor cell degeneration, which subsequently leads to cone photoreceptor cell death, impaired vision and eventual blindness. Rod-derived cone viability factor (RdCVF) is a protein which has two isoforms: a short form (RdCVF) and a long form (RdCVFL) which act on cone photoreceptors in the retina. RdCVFL protects photoreceptors by reducing hyperoxia in the retina; however, sustained delivery of RdCVFL remains challenging. We developed an affinity-controlled release strategy for RdCVFL. An injectable physical blend of hyaluronan and methylcellulose (HAMC) was covalently modified with a peptide binding partner of the Src homology 3 (SH3) domain. This domain was expressed as a fusion protein with RdCVFL, thereby enabling its controlled release from HAMC-binding peptide. Sustained release of RdCVFL was demonstrated for the first time as RdCVFL-SH3 from HAMC-binding peptide for 7 d in vitro. To assess bioactivity, chick retinal dissociates were harvested and treated with the affinity-released recombinant protein from the HAMC-binding peptide vehicle. After 6 d in culture, cone cell viability was greater when cultured with released RdCVFL-SH3 relative to controls. We utilized computational fluid dynamics to model release of RdCVFL-SH3 from our delivery vehicle in the vitreous of the human eye. We demonstrate that our delivery vehicle can prolong the bioavailability of RdCVFL-SH3 in the retina, potentially enhancing its therapeutic effects. Our affinity-based system constitutes a versatile delivery platform for ultimate intraocular injection in the treatment of retinal degenerative diseases. STATEMENT OF SIGNIFICANCE: Retinitis pigmentosa (RP) is the leading cause of inherited blindness in the world. Rod-derived cone viability factor (RdCVF), a novel protein paracrine factor, is effective in preclinical models of RP. To extend its therapeutic effects, we developed an affinity-controlled release strategy for the long form of RdCVF, RdCVFL. We expressed RdCVFL as a fusion protein with an Src homology 3 domain (SH3). We then utilized a hydrogel composed of hyaluronan and methylcellulose (HAMC) and modified it with SH3 binding peptides to investigate its release in vitro. Furthermore, we designed a mathematical model of the human eye to investigate delivery of the protein from the delivery vehicle. This work paves the way for future investigation of controlled release RdCVF.

Pathophysiology of outer retinal corrugations: Imaging dataset and mechanical models.

This article presents high-resolution swept-source optical coherence tomography (SS-OCT) imaging data used to elaborate a mechanical model that elucidates the formation of outer retinal corrugations (ORCs) in rhegmatogenous retinal detachments (RRD). The imaging data shared in the repository and presented in this article is related to the research paper entitled "Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory" (Muni et al., AJO, 2022). The dataset consists of 69 baseline cross-sectional SS-OCT scans from 66 patients that were assessed for the presence of ORCs and analyzed considering the clinical features of each case. From the 66 cases, we selected SS-OCT images of 4 RRD patients with visible ORCs and no cystoid macular edema (CME) to validate the mechanical model. We modelled the retina as a composite material consisting of the outer retinal layer (photoreceptor layer) and the inner retinal layer (the part of the retina that excludes the photoreceptor layer) with thicknesses T o and T i and elastic modulus E o and E i , respectively. The thickness of the outer and inner retinal layers and the relative increase in the length of the outer retinal layer (γ) were measured from the SS-OCT images. Measurements from the SS-OCT images of patients with RRD demonstrated a 30% increase (γ=0.3) in the length of the outer retinal layer and a 400% increase in the thickness of the outer retinal layer (To). Using the mathematical model, Eo/Ei ranged between 0.05 to 0.5 to result in ORCs with a similar frequency to those observed in the SS-OCT scans.

IMMEDIATE SUBRETINAL FLUID DISPLACEMENT FROM THE BUOYANT FORCE OF A SMALL GAS BUBBLE IN PNEUMATIC RETINOPEXY: INSIGHTS INTO THE POTENTIAL MECHANISM OF RETINAL DISPLACEMENT AFTER RETINAL DETACHMENT REPAIR.

PURPOSE: To demonstrate how a small gas bubble injected into the vitreous cavity in pneumatic retinopexy for rhegmatogenous retinal detachment causes immediate displacement of subretinal fluid and to gain insights into the potential mechanism of retinal displacement. METHODS: Three patients with rhegmatogenous retinal detachment who underwent pneumatic retinopexy were enrolled and prospectively followed. All patients underwent ultra-widefield fundus photography at baseline and at 1 to 2 minutes after intravitreal gas injection. RESULTS: In all cases, the ultra-widefield fundus photograph demonstrated immediate displacement of subretinal fluid, suggesting that the buoyant force applied to the retina by the bubble was responsible for the displacement of subretinal fluid. The results were extrapolated to determine the buoyant force applied by a small and large gas bubble as in pneumatic retinopexy and pars plana vitrectomy. We determined that the buoyant force applied with a larger bubble in pars plana vitrectomy was substantially greater, and this may lead to retinal displacement. CONCLUSION: Intravitreal gas applies significant buoyant force to the detached retina and subretinal fluid that leads to substantial and rapid displacement of subretinal fluid. Understanding the affect of the buoyant force of the gas bubble on the detached retina can provide insight into possible mechanisms of retinal displacement.

Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory.

PURPOSE: Outer retinal folds occur when outer retinal corrugations (ORCs) persist after retinal reattachment with worse functional outcomes. We investigate the pathophysiology of ORCs in vivo. DESIGN: Prospective cohort study. METHODS: Patients with rhegmatogenous retinal detachment (RRD) presenting to St. Michael's Hospital, Toronto, Ontario, Canada, between August 2020 and February 2022 were assessed with swept-source optical coherence tomography (SS-OCT) and ultra-widefield SS-OCT for ORCs. Clinical characteristics of eyes with/without ORCs were compared. Mathematical models were used to deduce mechanical properties leading to ORCs. RESULTS: Sixty-six patients were included. More than half (60.6%, 40/66) were fovea-off and 48.4% (32/66) had ORCs at presentation. All eyes (32/32) with ORCs had retinal pigment epithelium (RPE)-photoreceptor dysregulation for at least 2 days, defined as loss of RPE control with acute, progressive, and extensive RRDs. In all (34/34) eyes without ORCs the RPE was in relative control of the subretinal space with nonprogressive subclinical or small localized or resolving RRDs, or with RPE-photoreceptor dysregulation for fewer than 2 days. Mathematical models indicate that a modulus of elasticity of the outer retina relative to the inner retina of 0.05 to 0.5 leads to ORCs. CONCLUSIONS: ORCs develop with (1) acute exposure of subretinal space to liquified vitreous, (2) for >2 days, that (3) overwhelms RPE capacity, leading to progressive and extensive RRD. Mathematical models suggest that a reduction in the modulus of elasticity of the outer retina occurs such that intrinsic compressive forces, likely related to progressive outer retinal hydration and lateral expansion, lead to ORCs. Understanding the pathophysiology of ORCs has implications for management.

A paradigm shift in retinal detachment repair: The concept of integrity.

The management of rhegmatogenous retinal detachment has rapidly evolved over recent decades. A range of surgical techniques exist, all of which can achieve retinal reattachment in most cases. In recent years there have also been vast technical advances in retinal imaging that have introduced novel ways of visualizing and studying the retinal macro and microstructural anatomy following retinal detachment repair. Recent clinical trial data demonstrates that functional and patient-reported outcomes of retinal reattachment differ with surgical technique, accompanied by differences in anatomic biomarkers of retinal recovery or 'integrity'. We discuss recent insights into the physiology of retinal reattachment gleaned from multimodal imaging, which shed light on the pathophysiology of various post-operative anatomic abnormalities. The ideal scenario is to achieve retinal reattachment as soon as possible, without retinal displacement, outer retinal folds or discontinuity of the external limiting membrane, ellipsoid zone and interdigitation zone, with an intact foveal bulge. To this end, we present an in-depth contemporary account of current concepts and mechanisms involved during retinal reattachment surgery, supported by clinical data and mathematical modelling, awareness of which can help the vitreoretinal surgeon achieve better post-operative outcomes. In this review we substantiate the case for a paradigm shift in rhegmatogenous retinal detachment repair; beyond the emphasis on single-operation reattachment rates, and instead striving to maximize functional outcomes using minimally invasive techniques. This can only be achieved if vitreoretinal surgeons embrace all of the available techniques, with individualized selection of surgical approach and the resolute goal of optimizing the 'integrity' of retinal reattachment.

Fibrous hydrogels under biaxial confinement.

Confinement of fibrous hydrogels in narrow capillaries is of great importance in biological and biomedical systems. Stretching and uniaxial compression of fibrous hydrogels have been extensively studied; however, their response to biaxial confinement in capillaries remains unexplored. Here, we show experimentally and theoretically that due to the asymmetry in the mechanical properties of the constituent filaments that are soft upon compression and stiff upon extension, filamentous gels respond to confinement in a qualitatively different manner than flexible-strand gels. Under strong confinement, fibrous gels exhibit a weak elongation and an asymptotic decrease to zero of their biaxial Poisson's ratio, which results in strong gel densification and a weak flux of liquid through the gel. These results shed light on the resistance of strained occlusive clots to lysis with therapeutic agents and stimulate the development of effective endovascular plugs from gels with fibrous structures for stopping vascular bleeding or suppressing blood supply to tumors.

Emulsion characterization via microfluidic devices: A review on interfacial tension and stability to coalescence.

Emulsions have gained significant importance in many industries including foods, pharmaceuticals, cosmetics, health care formulations, paints, polymer blends and oils. During emulsion generation, collisions can occur between newly-generated droplets, which may lead to coalescence between the droplets. The extent of coalescence is driven by the properties of the dispersed and continuous phases (e.g. density, viscosity, ion strength and pH), and system conditions (e.g. temperature, pressure or any external applied forces). In addition, the diffusion and adsorption behaviors of emulsifiers which govern the dynamic interfacial tension of the forming droplets, the surface potential, and the duration and frequency of the droplet collisions, contribute to the overall rate of coalescence. An understanding of these complex behaviors, particularly those of interfacial tension and droplet coalescence during emulsion generation, is critical for the design of an emulsion with desirable properties, and for the optimization of the processing conditions. However, in many cases, the time scales over which these phenomena occur are extremely short, typically a fraction of a second, which makes their accurate determination by conventional analytical methods extremely challenging. In the past few years, with advances in microfluidic technology, many attempts have demonstrated that microfluidic systems, characterized by micrometer-size channels, can be successfully employed to precisely characterize these properties of emulsions. In this review, current applications of microfluidic devices to determine the equilibrium and dynamic interfacial tension during droplet formation, and to investigate the coalescence stability of dispersed droplets applicable to the processing and storage of emulsions, are discussed.

Understanding the mechanism of retinal displacement following rhegmatogenous retinal detachment repair: A computer simulation model.

PURPOSE: Retinal displacement is common following rhegmatogenous retinal detachment (RRD) repair. A computer simulation was developed to assess forces applied by a gas tamponade of various sizes in the setting of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV). DESIGN: Computer simulation model. METHODS: The contact angle and pressure between the tamponade and the retina were calculated using interfacial tension and the densities of gas and vitreous. A simulation determined the dynamics of fluid motion in the subretinal space and calculated deformations of the retina. RESULTS: Bulk flow of fluid away from the tamponade in a direction along gravity stretched the retina and caused displacement in the simulations. Extent of displacement is attributable to the subretinal fluid layer thickness, and area of contact and contact pressure applied by the tamponade. Larger gas tamponades have greater contact pressure applied to the retina. Reducing gas bubble size from 93% to 6.25% with PPV versus PnR, there was a 79% reduction in the mean contact pressure (1.4 mmHg-0.29 mmHg), and a 93% reduction in the surface area of contact (11 cm2 -0.8 cm2 ). Therefore, the contact force applied to the entire retina decreases by 97% from 83 mN (PPV) to 2.9 mN (PnR). The model resembling PnR had more than three times less displacement compared to PPV. CONCLUSIONS: This model provides a framework to study retinal displacement. Our findings suggest that proportional to their size, gas tamponades stretched the retina by displacing subretinal fluid following RRD repair.

Substrate colonization by an emulsion drop prior to spreading.

In classical wetting, the spreading of an emulsion drop on a surface is preceded by the formation of a bridge connecting the drop and the surface across the sandwiched film of the suspending medium. However, this widely accepted mechanism ignores the finite solubility of the drop phase in the medium. We present experimental evidence of a new wetting mechanism, whereby the drop dissolves in the medium, and nucleates on the surface as islands that grow with time. Island growth is predicated upon a reduction in solubility near the contact line due to attractive interactions between the drop and the surface, overcoming Ostwald ripening. Ultimately, wetting is manifested as a coalescence event between the parent drop and one of the islands, which can result in significantly large critical film heights and short hydrodynamic drainage times prior to wetting. This discovery has broad relevance in areas such as froth flotation, liquid-infused surfaces, multiphase flows and microfluidics.

h-FIBER: Microfluidic Topographical Hollow Fiber for Studies of Glomerular Filtration Barrier.

Kidney-on-a-chip devices may revolutionize the discovery of new therapies. However, fabricating a 3D glomerulus remains a challenge, due to a requirement for a microscale soft material with complex topography to support cell culture in a native configuration. Here, we describe the use of microfluidic spinning to recapitulate complex concave and convex topographies over multiple length scales, required for biofabrication of a biomimetic 3D glomerulus. We produced a microfluidic extruded topographic hollow fiber (h-FIBER), consisting of a vessel-like perfusable tubular channel for endothelial cell cultivation, and a glomerulus-like knot with microconvex topography on its surface for podocyte cultivation. Meter long h-FIBERs were produced in microfluidics within minutes, followed by chemically induced inflation for generation of topographical cues on the 3D scaffold surface. The h-FIBERs were assembled into a hot-embossed plastic 96-well plate. Long-term perfusion, podocyte barrier formation, endothelialization, and permeability tests were easily performed by a standard pipetting technique on the platform. Following long-term culture (1 month), a functional filtration barrier, measured by the transfer of albumin from the blood vessel side to the ultrafiltrate side, suggested the establishment of an engineered glomerulus.

3D Printing of Vascular Tubes Using Bioelastomer Prepolymers by Freeform Reversible Embedding.

Bioelastomers have been extensively used in tissue engineering applications because of favorable mechanical stability, tunable properties, and chemical versatility. As these materials generally possess low elastic modulus and relatively long gelation time, it is challenging to 3D print them using traditional techniques. Instead, the field of 3D printing has focused preferentially on hydrogels and rigid polyester materials. To develop a versatile approach for 3D printing of elastomers, we used freeform reversible embedding of suspended prepolymers. A family of novel fast photocrosslinakble bioelastomer prepolymers were synthesized from dimethyl itaconate, 1,8-octanediol, and triethyl citrate. Tensile testing confirmed their elastic properties with Young's moduli in the range of 11-53 kPa. These materials supported cultivation of viable cells and enabled adhesion and proliferation of human umbilical vein endothelial cells. Tubular structures were created by embedding the 3D printed microtubes within a secondary hydrogel that served as a temporary support. Upon photocrosslinking and porogen leaching, the polymers were permeable to small molecules (TRITC-dextran). The polymer microtubes were assembled on the 96-well plates custom made by hot-embossing, as a tool to connect multiple organs-on-a-chip. The endothelialization of the tubes was performed to confirm that these microtubes can be utilized as vascular tubes to support parenchymal tissues seeded on them.

Interfacial Tension of the Water-Diluted Bitumen Interface at High Bitumen Concentrations Measured Using a Microfluidic Technique.

The interfacial tension (IFT) is a critical parameter to inform our understanding of the phenomena of drop breakup and droplet-droplet coalescence in sheared water-in-diluted bitumen (dilbit) emulsions. A microfluidic extensional flow device (MEFD) was used to determine the IFT of the dilbit-water emulsion system for bitumen concentrations of 33%, 50%, and 67% by weight (solvent to bitumen ratio (S/B) = 2, 1, and 0.5, respectively) and two different pH values of water: 8.3 and 9.9. The IFT was observed to increase with the bitumen concentration and decrease significantly upon lowering the water pH. The time scale for achieving the steady state IFT increased with bitumen concentration and was less sensitive to the water pH. But the most important feature of our measurements is that the IFTs recorded were significantly smaller than the values reported in the literature. We recognized two important differences between our studies and prior investigations: measurement of the IFT of water drops in dilbit as opposed to dilbit drops in water in earlier studies, and time scales of measurement of IFT that ranged from hundreds of milliseconds to a few seconds, as compared to a minute or longer in past investigations. These differences were examined carefully, but neither was found to explain the low IFTs measured in our studies. Our work leads to the following hypothesis: the mechanical properties of the interface of a sheared water drop in bitumen are significantly different from a stagnant one.

Novel Activated Microbubbles-based Strategy to Coat Nanoparticles on Root Canal Dentin: Fluid Dynamical Characterization.

INTRODUCTION: Activated microbubbles (MBs) have the potential to deliver nanoparticles in complex microspaces such as root canals. The objective of the study is to determine the fluid dynamical parameters associated with ultrasonic, sonic, and manual activation of MBs in simulated root canals and to assess the effectiveness of surface coating formed by delivering chitosan nanoparticles using activated MBs within root canals in extracted teeth. METHODS: In stage 1, polydimethylsiloxane models were fabricated to determine the physical effects of MBs agitated manually (MM), sonically (MS), and ultrasonically (MU). Spherical tracer particles were used to visualize and record the fluid motion using an inverted microscope linked to a high-speed camera. The velocity, wall stress, and penetration depth were analyzed at regions of interest. In stage 2, 35 extracted human incisors were divided into 7 groups to evaluate the effectiveness of chitosan nanoparticle delivery using activated MBs (MM, MS, and MU groups). Field emission scanning electron microscopy and energy-dispersive X-rays were used to characterize the nanoparticle coating on root canal dentin and the degree of dentinal tubule occlusion. RESULTS: In stage 1, velocity, wall stress, and penetration depth increased significantly in the MB groups compared with the control (P < .01). In stage 2, 70% of the dentin surface was coated, and 65% of the dentinal tubule was occluded with nanoparticle-based coating in the MM, MU, and water ultrasonic groups. Element analysis displayed the presence of dentin smear on the root canal surface for the MU and water ultrasonic groups. CONCLUSIONS: Activated MBs enhanced fluid dynamical parameters when compared with water in simulated root canal models. Manual activation of MBs resulted in uniform and significant nanoparticle-based surface coating and tubule blockage in root canal dentin without dentin smear formation.

Mass transfer dynamics in the dissolution of Taylor bubbles.

The knowledge of thermodynamic and mass transfer parameters in gas-liquid systems is critical for the design of macroscale units for separation and reaction processes. The phenomenon of shrinkage of Taylor bubbles upon dissolution has the capability of supplying these design parameters, provided a reliable mathematical model is available for data deconvolution. Unfortunately, the existing models in the literature suffer from at least one of the following three major limitations. First, mass transfer between the bulk liquid segment and the surrounding liquid film has been incorrectly estimated. Second, the liquid segment is assumed to be well mixed, even though there is clear evidence of the contrary in the literature [Yang et al., Chem. Eng. Sci., 2017, 169, 106]. Third, an average mass transfer coefficient is assumed to be valid throughout the dissolution process, despite the fact that bubble velocities can change significantly during dissolution. In this work, we have rectified these limitations and developed a detailed model that takes into account the local concentration gradients and the flow profiles, without resorting to the computationally expensive, full numerical simulations of the fluid flow and concentration distribution equations. To validate the model, experiments were carried out in circular, silica capillaries of different radii by generating segmented flow of CO2 in physical solvents, and the diffusivity and the solubility were subsequently extracted with an error of less than 5%. This work can be extended to the study of gas-liquid-solid reactions in the Taylor flow configuration, and applied to the design of catalyst-coated monolithic reactors.

Near-infrared incoherent broadband cavity enhanced absorption spectroscopy (NIR-IBBCEAS) for detection and quantification of natural gas components.

The principle of near-infrared incoherent broadband cavity enhanced absorption spectroscopy was employed to develop a novel instrument for detecting natural gas leaks as well as for testing the quality of natural gas mixtures. The instrument utilizes the absorption features of methane, butane, ethane, and propane in the wavelength region of 1100 nm to 1250 nm. The absorption cross-section spectrum in this region for methane was adopted from the HITRAN database, and those for the other three gases were measured in the laboratory. A singular-value decomposition (SVD) based analysis scheme was employed for quantifying methane, butane, ethane, and propane by performing a linear least-square fit. The developed instrument achieved a detection limit of 460 ppm, 141 ppm, 175 ppm and 173 ppm for methane, butane, ethane, and propane, respectively, with a measurement time of 1 second and a cavity length of 0.59 m. These detection limits are less than 1% of the Lower Explosive Limit (LEL) for each gas. The sensitivity can be further enhanced by changing the experimental parameters (such as cavity length, lamp power etc.) and using longer averaging intervals. The detection system is a low-cost and portable instrument suitable for performing field monitorings. The results obtained on the gas mixture emphasize the instrument's potential for deployment at industrial facilities dealing with natural gas, where potential leaks pose a threat to public safety.

An exploration of the reflow technique for the fabrication of an in vitro microvascular system to study occlusive clots.

Embolic ischemia and pulmonary embolism are health emergencies that arise when a particle such as a blood clot occludes a smaller blood vessel in the brain or the lungs, and restricts flow of blood downstream of the vessel. In this work, the reflow technique (Wang et al. Biomed. Microdevices 2007, 9, 657) was adapted to produce a microchannel network that mimics the occlusion process. The technique was first revisited and a simple geometrical model was developed to quantitatively explain the shapes of the resulting microchannels for different reflow parameters. A critical modification was introduced to the reflow protocol to fabricate nearly circular microchannels of different diameters from the same master, which is not possible with the traditional reflow technique. To simulate the phenomenon of occlusion by clots, a microchannel network with three generations of branches with different diameters and branching angles was fabricated, into which fibrin clots were introduced. At low constant pressure drop (ΔP), a clot blocked a branch entrance only partially, while at higher ΔP, the branch was completely blocked. Instances of simultaneous blocking of multiple channels by clots, and the consequent changes in the flow rates in the unblocked branches of the network, were also monitored. This work provides the framework for a systematic study of the distribution of clots in a network, and the rate of dissolution of embolic clots upon the introduction of a thrombolytic drug into the network.

The hydrodynamics of segmented two-phase flow in a circular tube with rapidly dissolving drops.

This article discusses boundary integral simulations of dissolving drops flowing through a cylindrical tube for large aspect ratio drops. The dynamics of drop dissolution is determined by three dimensionless parameters: λ, the viscosity of the drop fluid relative to the suspending fluid; Ca, the capillary number defining the ratio of the hydrodynamic force to the interfacial tension force; and k, a dissolution constant based on the velocity of dissolution. For a single dissolving drop, the velocity in the upstream region is greater than the downstream region, and for sufficiently large k, the downstream velocity can be completely reversed, particularly at low Ca. The upstream end of the drop travels faster and experiences greater deformation than the downstream end. The film thickness, δ, between the drop and the tube wall is governed by a delicate balance between dissolution and changes in the outer fluid velocity resulting from a fixed pressure drop across the tube and mass continuity. Therefore, δ, and consequently, the drop average velocity, can increase, decrease or be relatively invariant in time. For two drops flowing in succession, while low Ca drops maintain a nearly constant separation distance during dissolution, at sufficiently large Ca, for all values of k, dissolution increases the separation distance between drops. Under these conditions, the liquid segments between two adjacent drops can no longer be considered as constant volume stirred tanks. These results will guide the choices of geometry and operating parameters that will facilitate the characterization of fast gas-liquid reactions via two-phase segmented flows.