Microfluidic Flow Research Articles

Facile synthesis of aryl and benzyl substituted 2-methylquinazolin-4(3H)-one ring by microfluidic flow reaction chemistry

This study describes the development of a new and rapid synthesis procedure for performing the aryl and benzyl substituted 2-methylquinazolin-4(3H)-one ring cyclization reaction. We utilized a continuous-flow microfluidic reactor for the production of quinazolinone derivatives of a humanin peptide mimetic screening hit in a facile manner, offering a cleaner reaction profile, high yield, and quick scalability. Our results show the power of flow chemistry to this reaction and can be of general utility for synthesizing quinazolinone-containing intermediates and final products of industrial importance in a continuous and safe manner.

Fluid Slip and Drag Reduction on Liquid-Infused Surfaces under High Static Pressure.

Liquid-infused surfaces (LIS) have been shown to reduce the huge frictional drag affecting microfluidic flow and are expected to be more robust than superhydrophobic surfaces when exposed to external pressure as the lubricant in LIS is incompressible. Here, we investigate the effect of applying static pressure on the effective slip length measured on Teflon wrinkled surfaces infused with silicone oil through pressure measurements in microfluidic devices. The effect of static pressure on LIS was found to depend on air content in the flowing water: for degassed water, the average effective slip length was beff = 2.16 ± 0.90 μm, irrespective of applied pressure. In gassed water, the average effective slip length was beff = 4.32 ± 1.06 μm at zero applied pressure, decreased by 55% to 2.37 ± 0.90 μm when the pressure was increased to 50 kPa, and then remained constant up to 200 kPa. The result is due to nanobubbles present on LIS, which are compressed or partially dissolved under pressure, and the effect is more evident when the size and portion of surface nanobubbles are higher. In contrast, on superhydrophobic wrinkles, the decline in beff was more sensitive to applied pressure, with beff = 6.8 ± 1.4 μm at 0 kPa and, on average, beff = -1 ± 3 μm for pressures higher than 50 kPa for both gassed and degassed water. Large fluctuations in the experimental measurements were observed on superhydrophobic wrinkles, suggesting the nucleation of large bubbles on the surface. The same pressure increase did not affect the flow on smooth substrates, on which gas nanobubbles were not observed. Contrary to expectations, we observed that drag reduction in LIS is affected by applied pressure, which we conclude is because, in a similar manner to superhydrophobic surfaces, they lose the interfacial gas, which lubricates the flow.

Multiplex Profiling of Biomarker and Drug Uptake in Single Cells Using Microfluidic Flow Cytometry and Mass Spectrometry.

To perform multiplex profiling of single cells and eliminate the risk of potential sample loss caused by centrifugation, we developed a microfluidic flow cytometry and mass spectrometry system (μCytoMS) to evaluate the drug uptake and induced protein expression at the single cell level. It involves a microfluidic chip for the alignment and purification of single cells followed by detection with laser-induced fluorescence (LIF) and inductively coupled plasma mass spectrometry (ICP-MS). Biofunctionalized nanoprobes (BioNPs), conjugating ∼3000 6-FAM-Sgc8 aptamers on a single gold nanoparticle (AuNP) (Kd = 0.23 nM), were engineered to selectively bind with protein tyrosine kinase 7 (PTK7) on target cells. PTK7 expression induced by oxaliplatin (OXA) uptake was assayed with LIF, while ICP-MS measurement of 195Pt revealed OXA uptake of the drug in individual cells, which provided further in-depth information about the drug in relation to PTK7 expression. At an ultralow flow of ∼0.043 dyn/cm2 (20 μL/min), the chip facilitates the extremely fast focusing of BioNPs labeled single cells without the need for centrifugal purification. It ensures multiplex profiling of single cells at a throughput speed of 500 cells/min as compared to 40 cells/min in previous studies. Using a machine learning algorithm to initially profile drug uptake and marker expression in tumor cell lines, μCytoMS was able to perform in situ profiling of the PTK7 response to the OXA at single-cell resolution for tests done on clinical samples from 10 breast cancer patients. It offers great potential for multiplex single-cell phenotypic analysis and clinical diagnosis.

Precise control of microfluidic flow conditions is critical for harnessing the in vitro transfection capability of pDNA-loaded lipid-Eudragit nanoparticles.

Microfluidics is widely regarded as a leading technology for industrial-scale manufacture of multicomponent, gene-based nanomedicines in a reproducible manner. Yet, very few investigations detail the impact of flow conditions on the biological performance of the product, particularly biocompatibility and therapeutic efficiency. Herein, this study investigated the engineering of a novel lipid-Eudragit hybrid nanoparticle in a bifurcating microfluidics micromixer for plasmid DNA (pDNA) delivery. Nanoparticles of ~150 nm in size, with uniform polydispersity index (PDI = 0.2) and ξ-potential of 5-11 mV were formed across flow rate ratios (FRR, aqueous to organic phase) of 3:1 and 5:1, respectively. The hybrid nanoparticles maintained colloidal stability and structural integrity of loaded pDNA following recovery by ultracentrifugation. Importantly, in vitro testing in human embryonic kidney cell line (HEK293T) revealed significant differences in biocompatibility and transfection efficiency (TE). Lipid-Eudragit nanoparticles produced at FRR 3:1 displayed high cellular toxicity (0-30% viability), compared with nanoparticles prepared at FRR 5:1 (50-100% viability). Red fluorescent protein (RFP) expression was sustained for 24-72 h following exposure of cells to nanoparticles, indicating controlled release of pDNA and trafficking to the nucleus. Nanoparticles produced at FRR 5:1 resulted in markedly higher TE (12%) compared with those prepared at FRR 3:1 (2%). Notably, nanoparticles produced using the bench-scale nanoprecipitation method resulted in lower biocompatibility (30-90%) but higher RFP expression (25-38%). These findings emphasize the need for in-depth analysis of the effect of formulation and flow conditions on the physicochemical and biological performance of gene nanomedicines when transitioning from bench to clinic.

Towards Automation in 3D Cell Culture: Selective and Gentle High-Throughput Handling of Spheroids and Organoids via Novel Pick-Flow-Drop Principle.

3D cell culture is becoming increasingly important for mimicking physiological tissue structures in areas such as drug discovery and personalized medicine. To enable reproducibility on a large scale, automation technologies for standardized handling are still a challenge. Here, a novel method for fully automated size classification and handling of cell aggregates like spheroids and organoids is presented. Using microfluidic flow generated by a piezoelectric droplet generator, aggregates are aspirated from a reservoir on one side of a thin capillary and deposited on the other side, encapsulated in free-flying nanoliter droplets to a target. The platform has aggregate aspiration and plating efficiencies of 98.1% and 98.4%, respectively, at a processing throughput of up to 21 aggregates per minute. Cytocompatibility of the method is thoroughly assessed with MCF7, LNCaP, A549 spheroids and colon organoids, revealing no adverse effects on cell aggregates as shear stress is reduced compared to manual pipetting. Further, generic size-selective handling of heterogeneous organoid samples, single-aggregate-dispensing efficiencies of up to 100% and the successful embedding of spheroids or organoids in a hydrogel with subsequent proliferation is demonstrated. This platform is a powerful tool for standardized 3D in vitro research.

Electrohydrodynamic (In)Stability of Microfluidic Channel Flows: Analytical Expressions in the Limit of Small Reynolds Number

We study electrohydrodynamic (EHD) linear (in)stability of microfluidic channel flows, i.e., the stability of interface between two shearing viscous (perfect) dielectrics exposed to an electric field in large aspect ratio microchannels. We then apply our results to particular microfluidic systems known as two-liquid electroosmotic (EO) pumps. Our novel results are detailed analytical expressions for the growth rate of two-dimensional EHD modes in Couette–Poiseuille flows in the limit of small Reynolds number (R); the expansions to both zeroth and first order in R are considered. The growth rates are complicated functions of viscosity-, height-, density-, and dielectric-constant ratio, as well as of wavenumbers and voltages. To make the results useful to experimentalists, e.g., for voltage-control EO pump operations, we also derive equations for the impending voltages of the neutral stability curves that divide stable from unstable regions in voltage–wavenumber stability diagrams. The voltage equations and the stability diagrams are given for all wavenumbers. We finally outline the flow regimes in which our first-order-R voltage corrections could potentially be experimentally measured. Our work gives insight into the coupling mechanism between electric field and shear flow in parallel-planes channel flows, correcting an analogous EHD expansion to small R from the literature. We also revisit the case of pure shear instability, when the first-order-R voltage correction equals zero, and replace the renowned instability mechanism due to viscosity stratification at small R with the mechanism due to discontinuity in the slope of the unperturbed velocity profile.

A low-cost microfluidic flow stabilizer for enhancing QCM measurement stability in in-liquid bio-applications

Quartz crystal microbalance (QCM) is a powerful sensing technique widely used in various applications, including biosensing, chemical analysis, and material science. In in-liquid applications, QCM measurements are susceptible to fluctuations in fluid flow rate, which can introduce unwanted noise and compromise the accuracy and reliability of the measurements. In this work, we present an approach to enhance the stability of QCM measurements by utilizing a microfluidic flow stabilizer. The flow stabilizer is designed to minimize flow rate fluctuations, thereby reducing the impact of hydrodynamic effects on the QCM frequency response. We employ a comprehensive methodology that combines computational fluid dynamics (CFD) simulations using ANSYS Fluent software, microfabrication, and experimental testing to evaluate the effectiveness of the flow stabilizer in mitigating flow-induced fluctuations and improving the reliability of QCM measurements. For fabrication, we use direct engraving with a CO2 laser beam on polymethyl methacrylate (PMMA) material to drastically reduce the fabrication cost (to <40 cents) and fabrication time (to 35 min) of the microfluidic chip. Two different designs have been presented and tested: one with a single air reservoir and the other with two reservoirs. Two distinct setups employing a peristaltic pump and a micropump, along with a high fundamental frequency of 50 MHz QCM sensor, were utilized for comprehensive testing in this study. The experimental results demonstrated that the first and second designs of the microfluidic flow stabilizer effectively reduced the fluctuation amplitude in QCM measurements from 100% (input) to 23% and 19% (output), respectively.

Ultraviolet laser-etched Norland optical adhesive 81 micromodel for studying two-phase flow experiments

As the global energy demand grows, maximizing oil extraction from known reserves has become critical. The study of microfluidic flow and transport in porous media has become a key direction for future subsurface energy technologies. However, the high requirements of fabrication techniques and materials have constrained the progress of micro-scale experiments. In this study, we have innovatively proposed a microfluidic chip fabrication method based on ultraviolet laser, and a set of visualized microdrive platforms is developed to allow direct observation of two-phase flow processes at the pore scale. In this study, two pore structures—one with low porosity and high connectivity and the other with high porosity but low connectivity—were constructed to investigate the effect of pore structure on recovery. Two micromodels with different pore structures were fabricated, and water and surfactant drive experiments were conducted at different drive rates, respectively. The results show that increasing the replacement rate and introducing surfactant can somewhat improve the final recovery. Using surfactant is more effective in enhancing the recovery rate than increasing the replacement rate. The complexity of pore structure is one of the main factors affecting the formation of residual oil. The microfluidic experimental setup proposed in this study reduces the time and cost of conventional practical methods. It permits visualization of the oil drive process, demonstrating that the Norland Optical Adhesive 81 (NOA81) micromodel is a valuable tool in two-phase flow studies and its applications.

Realizing the multifunctional microfluidic flow manipulation based on hydrodynamic metamaterials

From their initial application to the fields of chemistry and biology, microfluidic chips used as micro total analysis systems have developed into new technologies to satisfy the requirements of various societal industries. Microchannels are essential components of microfluidic chips; they play a vital role in connecting the inlet and outlet as well as determining the flow distribution and reagent mixing. Microfluidic research has always been devoted to minimizing energy dissipation, fluid resistance, and pressure drop to realize energy-efficient microfluidic chips. This study proposes a new theory for manipulating the flow in microchannels based on hydrodynamic metamaterials according to the spatial transformation theory. In particular, hydrodynamic metamaterials are specifically designed to construct flow shifters, flow splitters, and flow combiners, and theoretical and numerical simulations are performed to assess their hydrodynamic performance. The systematic design of hydrodynamic metamaterial devices proposed in this work establishes a theoretical framework to achieve a steady flow state without inducing unstable flow disturbances in complex-shape microchannels.

Flow‐Induced Microfluidic Assembly for Advanced Biocatalysis Materials

AbstractExploring the potential of microfluidic systems, this study presents a groundbreaking approach harnessing energy in microfluidic flows within a purpose‐built microreactor, enabling precise deposition of functional biomaterials. Upon optimizing reactor dimensions and integrating it into a microfluidic system, sequentially flow‐induced deposition of DNA hydrogels and transformation into DNA‐protein hybrid materials with SpyTag/SpyCatcher technology is investigated. However, limited functionalization rates restrict its viability for targeted biocatalytic processes. Therefore, the direct deposition of a phenolic acid decarboxylase is investigated, which is efficiently deposited but shows limited biocatalytic performance due to shear‐induced denaturation. This challenge is overcome by a two‐step immobilization process, resulting in microfluidic bioreactors demonstrating initial high space‐time yields of up to 7000 g L−1 d−1, but whose process stability proves unsatisfactory. However, by exploiting the principle of flow‐induced deposition to immobilize recombinant E. coli cells as functional living materials overexpressing biocatalytically relevant enzymes, bioreactors are produced that show equally high space‐time yields in continuous whole‐cell catalysis which remain constant over periods of up to 10 days. The insights gained offer optimization strategies for advanced functional materials and innovative reactor systems holding promise for applications in fundamental materials science, biosensing, and scalable production of microreactors for biocatalysis and bioremediation.

A microfluidic card-based electrochemical assay for the detection of sulfonamide resistance genes

Most electroanalytical detection schemes for DNA markers require considerable time and effort from expert personnel to thoroughly follow the analysis and obtain reliable outcomes. This work aims to present an electrochemical assay performed inside a small card-based platform powered by microfluidic manipulation, requiring minimal human intervention and consumables. The assay couples a sample/signal dual amplification and DNA-modified magnetic particles for the detection of DNA amplification products. Particularly, the sul1 and sul4 genes involved in the resistance against sulfonamide antibiotics were analyzed. As recognized by the World Health Organization, antimicrobial resistance threatens global public health by hampering medication efficacy against infections. Consequently, analytical methods for the determination of such genes in environmental and clinical matrices are imperative. Herein, the resistance genes were extracted from E. coli cells and amplified using an enzyme-assisted isothermal amplification at 37 °C. The amplification products were analyzed in an easily-produced, low-cost, card-based set-up implementing a microfluidic system, demanding limited manual work and small sample volumes. The target amplicon was thus captured and isolated using versatile DNA-modified magnetic beads injected into the microchannel and exposed to the various reagents in a continuously controlled microfluidic flow. After the optimization of the efficiency of each phase of the assay, the platform achieved limits of detections of 44.2 pmol L−1 for sul1 and 48.5 pmol L−1 for sul4, and was able to detect down to ≥500-fold diluted amplification products of sul1 extracted from E. coli living cells in around 1 h, thus enabling numerous end-point analyses with a single amplification reaction.

Convective Drying of Porous Media: Comparison of Phase-Field Simulations with Microfluidic Experiments

Convective drying of porous media is central to many engineering applications, ranging from spray drying over water management in fuel cells to food drying. To improve these processes, a deep understanding of drying phenomena in porous media is crucial. Therefore, detailed simulation of multiphase flows with phase change is of great importance to investigate the complex processes involved in drying porous media. While many studies aim to access the phenomena solely by simulations, here we succeed to compare comprehensively simulations with an experimental methodology based on microfluidic multiphase flow studies in engineered porous media. In this contribution, we propose a Navier–Stokes Cahn–Hilliard model coupled with balance equations for heat and moisture to simulate the two-phase flow with phase change. The phase distribution of the two fluids air and water is modeled by the Phase-Field equation. Comparisons with experiments are rare in the literature and usually involve very simple cases. We compare our simulation with convective drying experiments of porous media. Experimentally, the interface propagation of the water–air interface was visualized in detail during drying in a structured microfluidic cell made from PDMS. The drying pattern and the drying time in the experiment are very well reproduced by our simulation. This validation will enable the application for the presented Navier–Stokes Cahn–Hilliard model in more complex cases focused more on applications, e.g., in the field of fibrous materials.

Numerical investigation of the effect of microfluidic flow parameters and physical properties on double emulsion droplet forming

Numerical investigation of the effect of microfluidic flow parameters and physical properties on double emulsion droplet forming

Electrohydrodynamic peristaltic microfluidic flow with thermal and molecular analysis featuring sloped configurations

This study examines the simultaneous impacts of thermal and molecular transfer of non-Newtonian fluid propelled by the collective impact of electroosmosis and peristaltic pumping via inclined channel. Internal frictional heating and heat generation are also taken into consideration. The electrohydrodynamic phenomenon is described by the nonlinear Poisson–Boltzmann equation. The problem is modulated mathematically through a system of coupled non-linear differential equations in wave frame of reference. Using the regular perturbation method around a small wave number δ, we obtain sequential solutions for stream function ψ, electric potential ϕ, velocity u, pressure gradient dpdx, temperature θ and concentration Ω distributions. The influences of newly arising parameters such as the electroosmotic parameter me, relaxation time parameter λ1, retardation time parameter λ2, wave number δ, Reynold’s number Re, heat generation parameter β, Prandtl number Pr, Schmidt number Sc, Froude number Fr and Soret number Sr on physical characteristics are analyzed graphically. There is an inverse correlation between the parameters of relaxation time and retardation time and their effects on axial velocity, concentration, and temperature distributions. In particular, the temperature of the fluid increases as the EDL parameter, relaxation time parameter, viscous dissipation parameter, and Reynolds number increase, but decreases as the retardation time parameter increases. Moreover, the axial pressure gradient increases as Reynolds number and inclination angle increase, while it decreases as Froude number increases. The current model has applicability in the chemical industry, reservoir engineering, micro-fabrication, and biomedical applications, where electroosmotic effects on heat and mass movement are crucial.

Magnetic Microbead-Based Herringbone Chip for Sensitive Detection of Human Immunodeficiency Virus.

The microfluidic chip-based nucleic acid detection method significantly improves the sensitivity since it precisely controls the microfluidic flow in microchannels. Nonetheless, significant challenges still exist in improving the detection efficiency to meet the demand for rapid detection of trace substances. This work provides a novel magnetic herringbone (M-HB) structure in a microfluidic chip, and its advantage in rapid and sensitive detection is verified by taking complementary DNA (cDNA) sequences of human immunodeficiency virus (HIV) detection as an example. The M-HB structure is designed based on controlling the magnetic field distribution in the micrometer scale and is formed by accumulation of magnetic microbeads (MMBs). Hence, M-HB is similar to a nanopore microstructure, which has a higher contact area and probe density. All of the above is conducive to improving sensitivity in microfluidic chips. The M-HB chip is stable and easy to form, which can linearly detect cDNA sequences of HIV quantitatively ranging from 1 to 20 nM with a detection limit of 0.073 nM. Compared to the traditional herringbone structure, this structure is easier to form and release by controlling the magnetic field, which is flexible and helps in further study. Results show that this chip can sensitively detect the cDNA sequences of HIV in blood samples, demonstrating that it is a powerful platform to rapidly and sensitively detect multiple nucleic acid-related viruses of infectious diseases.

Tired and stressed: direct holographic quasi-static stretching of aging echinocytes and discocytes in plasma using optical tweezers [Invited

Red blood cells (RBCs) undergo a progressive morphological transformation from smooth biconcave discocytes into rounder echinocytes with spicules on their surface during cold storage. The echinocytic morphology impacts RBCs' ability to flow through narrow sections of the circulation and therefore transfusion of RBC units with a high echinocytic content are thought to have a reduced efficiency. We use an optical tweezers-based technique where we directly trap and measure linear stiffness of RBCs under stress without the use of attached spherical probe particles or microfluidic flow to induce shear. We study RBC deformability with over 50 days of storage performing multiple stretches in blood plasma (serum with cold agglutinins removed to eliminate clotting). In particular, we find that discocytes and echinocytes do not show significant changes in linear stiffness in the small strain limit ( change in length) up to day 30 of the storage period, but do find differences between repeated stretches. By day 50 the linear stiffness of discocytes had increased to approximately that measured for echinocytes throughout the entire period of measurements. These changes in stiffness corresponded to recorded morphological changes in the discocytes as they underwent storage lesion. We believe our holographic trapping and direct measurement technique has applications to directly control and quantify forces that stretch other types of cells without the use of attached probes.

Machine learning classification of cellular states based on the impedance features derived from microfluidic single-cell impedance flow cytometry.

Mitosis is a crucial biological process where a parental cell undergoes precisely controlled functional phases and divides into two daughter cells. Some drugs can inhibit cell mitosis, for instance, the anti-cancer drugs interacting with the tumor cell proliferation and leading to mitosis arrest at a specific phase or cell death eventually. Combining machine learning with microfluidic impedance flow cytometry (IFC) offers a concise way for label-free and high-throughput classification of drug-treated cells at single-cell level. IFC-based single-cell analysis generates a large amount of data related to the cell electrophysiology parameters, and machine learning helps establish correlations between these data and specific cell states. This work demonstrates the application of machine learning for cell state classification, including the binary differentiations between the G1/S and apoptosis states and between the G2/M and apoptosis states, as well as the classification of three subpopulations comprising a subgroup insensitive to the drug beyond the two drug-induced states of G2/M arrest and apoptosis. The impedance amplitudes and phases used as input features for the model training were extracted from the IFC-measured datasets for the drug-treated tumor cells. The deep neural network (DNN) model was exploited here with the structure (e.g., hidden layer number and neuron number in each layer) optimized for each given cell type and drug. For the H1650 cells, we obtained an accuracy of 78.51% for classification between the G1/S and apoptosis states and 82.55% for the G2/M and apoptosis states. For HeLa cells, we achieved a high accuracy of 96.94% for classification between the G2/M and apoptosis states, both of which were induced by taxol treatment. Even higher accuracy approaching 100% was achieved for the vinblastine-treated HeLa cells for the differentiation between the viable and non-viable states, and between the G2/M and apoptosis states. We also demonstrate the capability of the DNN model for high-accuracy classification of the three subpopulations in a complete cell sample treated by taxol or vinblastine.

Microfluidic extensional flow device to study mass transfer dynamics in the polymer microparticle formation process.

Polymer microparticles are often used to encapsulate drugs for sustained drug-release treatments. One of the ways they are manufactured is by using a solvent extraction process, in which the polymer solution is emulsified into an aqueous bulk phase using a surfactant as a stabilizing agent, followed by the removal of the solvent. The radius of a polymer drop decreases as a function of time until the polymer reaches the gelling point, after which it is separated and dried. Among the various operating parameters, the rate of solvent extraction is a critical step that affects the morphology and porosity, and consequently, the kinetics of drug release. But a fundamental mechanistic understanding of the solvent extraction dynamics as a function of shear is still unexplored. In this study, we have developed an experimental mass transfer model to predict the extraction by using the microfluidic extensional flow device (MEFD) to probe the shear and extraction dynamics at the level of a single drop in a linear extensional flow field. We used a computer-controlled feedback algorithm to manipulate the flow field and hydrodynamically trap a Hele-Shaw drop and observe the extraction process. For the polymer solution, we used a biocompatible polymer, poly-lactic-co-glycolic acid (PLGA) with ethyl acetate (EtOAc) as the solvent. Our experiments were conducted by varying the extensional rate (G) in the channel from ∼0.1 s-1 to ∼10 s-1, and using an analytical solution of the flow field, we captured the dissolution process and measured the change in drop radius (R) with time (t). Interestingly, we initially observed a short-time asymptote R ∼ t, and later the long-time asymptote of R = constant; both trends were physically explained. The transport model developed in this work can be used to predict extraction rates and polymer microparticle composition for any polymer-solvent system. This work is also an important contribution to the literature on convective mass transfer in partially miscible emulsions.

A microfluidic scanning flow cytometer with superior signal-to-noise-ratio for label-free characterization of small particles

Single-cell analysis without immune-specific labelling is essential across research fields, but conventional flow cytometers (FCMs) struggle with label-free analysis. We introduce a novel microfluidic scanning flow cytometer (μSFC) designed for label-free analysis within a simple microfluidic chip. Our system outperforms traditional FCMs for label-free analysis but its signal-to-noise ratio (SNR) limits the minimum detectable size. We present three modifications to enhance SNR and improve the smallest detectable particle size: additional neutral optical density filtering, a lower noise-equivalent-power photoreceiver, and laser spot size reduction. These improvements enable reliable characterization of particles as small as 3 μm. Experimental results validate the correlation between angular profile oscillations and particle size. While reliable detection down to 1 μm is achieved, further refinement is needed. The simplicity and low setup of the μSFC make it promising for integration into multi-parametric single-cell analysis systems, facilitating comprehensive cellular characterization for diagnostic and point-of-care applications.

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.