Microfluidic Applications Research Articles

Enhancing fabrication of hybrid microfluidic devices through silane‐based bonding: A focus on polydimethylsiloxane‐cyclic olefin copolymer and PDMS‐lithium niobate

AbstractEffective manipulation and control of fluids in microfluidic channels requires robust bonding between the different components. Polydimethylsiloxane (PDMS) is widely employed in microchannel fabrication due to its affordability, biocompatibility, and straightforward fabrication process. However, PDMS's low surface energy poses challenges in bonding with many organic and inorganic substrates, hindering the development of hybrid microfluidic devices. In this study, a simple and versatile three step process is presented for bonding PDMS microchannels with organic (cyclic olefin copolymer (COC)) and inorganic substrates (lithium niobate (LiNbO3)) using plasma activation and a silane coupling agent. Initially, the PDMS surface undergoes oxygen/argon plasma activation, followed by functionalization with (3‐aminopropyl) triethoxysilane (APTES). Subsequently, the COC or LiNbO3 is plasma activated and brought into contact with PDMS under a load at a specific temperature. Characterization by Fourier transform infrared, scanning electron microscopy, atomic force microscopy, and contact angle measurements confirmed the successful treatment of the substrates. In addition, bonding strength of the fabricated hybrid devices was assessed through leakage and tensile tests. Under optimized conditions (100°C and 4% v/v APTES), PDMS‐COC hybrid microchannels achieved a flow rate of 600 mL/h without leakage and a tensile strength of 562 kPa. Conversely, the PDMS‐ LiNbO3 assembly demonstrated a flow rate of 216 mL/h before leakage, with a tensile strength of 334 kPa. This bonding method exhibits significant potential and versatility for various materials in microfluidic applications, ranging from biomedical research to enhanced oil recovery.

Measurement of binary diffusion at elevated Knudsen numbers using laser absorption spectroscopy

Mass diffusion coefficients of gas mixtures have been measured for more than 100 years. However, the experimental data for the mass diffusion coefficient of gas mixtures in the rarefied gas regimes at Knudsen numbers (Kn) above 0.01 are few and remain uncertain due to the inherent precision limitations of the available state-of-the-art measurement techniques. The increased frequency of gas-wall collision, wall-friction, and surface-diffusion over the wall surface at Kn > 0.01 increases the uncertainty of the diffusive mass transport processes for internal gas flow in microcapillaries. Due to the growing interest in microfluidic applications at rarefied gas conditions, accurate diffusion coefficient measurements are needed to inform theoretical predictions and empirical relations in rarefied gas regimes. Thus, this article introduces a new experiment methodology consisting of a two-bulb (TB) diffusion configuration accompanied by a tunable diode laser absorption spectroscopy (TDLAS) detection technique that uses the measured time history of path-integrated absorbance to provide a non-intrusive, species-specific, in situ measurement of mass diffusion for a He–CO2 binary gas mixture at Kn > 0.01. To demonstrate the TB-TDLAS method's capability, the effective diffusion coefficient for a He–CO2 binary gas mixture was measured in the transition gas regime at Knudsen numbers relative to the tube radius in the range 0.1 < Kn < 5.4, and the results are compared against the Bosanquet empirical relation.

Water-Wave Vortices and Skyrmions.

Topological wave structures-phase vortices, skyrmions, merons, etc.-are attracting enormous attention in a variety of quantum and classical wave fields. Surprisingly, these structures have never been properly explored in the most obvious example of classical waves: water-surface (gravity-capillary) waves. Here, we fill this gap and describe (i)water-wave vortices of different orders carrying quantized angular momentum with orbital and spin contributions, (ii)skyrmion lattices formed by the instantaneous displacements of the water-surface particles in wave interference, and (iii)meron (half-skyrmion) lattices formed by the spin-density vectors, as well as (iv)spatiotemporal water-wave vortices and skyrmions. We show that all these topological entities can be readily generated in linear water-wave interference experiments. Our findings can find applications in microfluidics and show that water waves can be employed as an attainable playground for emulating universal topological wave phenomena.

Inertial Migration in a Pressure-Driven Channel Flow: Beyond the Segre-Silberberg Pinch.

We examine theoretically the inertial migration of a neutrally buoyant rigid sphere in pressure-driven channel flow, accounting for its finite size relative to the channel width (the confinement ratio). For sufficiently large channel Reynolds numbers (Re_{c}), a small but finite confinement ratio qualitatively alters the inertial lift velocity profiles obtained using a point-particle formulation. Finite size effects lead to new equilibria, in addition to the well-known Segre-Silberberg pinch locations. Consequently, a sphere can migrate to either the near-wall Segre-Silberberg equilibria, or the new stable equilibria located closer to the channel centerline, depending on Re_{c} and its initial position. Our findings are in accord with recent experiments and simulations, and have implications for passive sorting of particles based on size, shape, and other physical characteristics, in microfluidic applications.

Surface modification of polydimethylsiloxane by the cataractous eye protein isolate

Polydimethylsiloxane (PDMS), even though widely used in microfluidic applications, its hydrophobic nature restricts its utility in some cases. To address this, PDMS may be used in conjunction with a hydrophilic material. Herein, the PDMS surface is modified by plasma treatment followed by cross-linking with the cataractous eye protein isolate (CEPI). CEPI-PDMS composites are prepared at three pH and the effects of CEPI on the chemical, physical, and electrical properties of PDMS are extensively investigated. The cross-linking between PDMS and the protein are confirmed by FTIR, and the contact angle measurements indicate the improved hydrophilic nature of the composite films as compared to PDMS. Atomic Force Microscopy results demonstrate that the surface roughness is enhanced by the incorporation of the protein and is a function of the pH. The effective elastic modulus of the composites is improved by the incorporation of protein into the PDMS matrix. Measurements of the dielectric properties of these composites indicate that they behave as capacitors at lower frequency range while demonstrating resistive characteristics at higher frequency. These composites provide preliminary ideas in developing flexible devices for potential applications in diverse areas such as energy storage materials, and thermo-elective wireless switching devices.

Tungsten Oxide Coated Liquid Metal Electrodes via Galvanic Replacement as Heavy Metal Ion Sensors.

Gallium liquid metals (LMs) like Galinstan and eutectic Gallium-Indium (EGaIn) have seen increasing applications in heavy metal ion (HMI) sensing, because of their ability to amalgamate with HMIs like lead, their high hydrogen potential, and their stable electrochemical window. Furthermore, coating LM droplets with nanopowders of tungsten oxide (WO) has shown enhancement in HMI sensing owing to intense electrical fields at the nanopowder-liquid-metal interface. However, most LM HMI sensors are droplet based, which show limitations in scalability and the homogeneity of the surface. A scalable approach that can be extended to LM electrodes is therefore highly desirable. In this work, we present, for the first time, WO-Galinstan HMI sensors fabricated via photolithography of a negative cavity, Galinstan brushing inside the cavity, lift-off, and galvanic replacement (GR) in a tungsten salt solution. Successful GR of Galinstan was verified using optical microscopy, SEM, EDX, XPS, and surface roughness measurements of the Galinstan electrodes. The fabricated WO-Galinstan electrodes demonstrated enhanced sensitivity in comparison with electrodes structured from pure Galinstan and detected lead at concentrations down to 0.1 mmol·L-1. This work paves the way for a new class of HMI sensors using GR of WO-Galinstan electrodes, with applications in microfluidics and MEMS for a toxic-free environment.

Trifurcated Splitting of Water Droplets on Engineered Lithium Niobate Surfaces.

Controlled splitting of liquid droplets is a key function in many microfluidic applications. In recent years, various methodologies have been used to accomplish this task. Here, we present an optofluidic technique based on an engineered surface formed by coating a z-cut iron-doped lithium niobate crystal with a lubricant-infused layer, which provides a very slippery surface. Illuminating the crystal with a light spot induces surface charges of opposite signs on the two crystal faces because of the photovoltaic effect. If the light spot is sufficiently intense, millimetric water droplets placed near the illuminated spot split into two charged fragments, one fragment being trapped by the bright spot and the other moving away from it. The latter fragment does not move randomly but rather follows one of three well-defined trajectories separated by 120°, which reflect the anisotropic crystalline structure of Fe:LiNbO3. Numerical simulations explain the behavior of water droplets in the framework of the forces induced by the interplay of pyroelectric, piezoelectric, and photovoltaic effects, which originate simultaneously inside the illuminated crystal. Such a synergetic effect can provide a valuable feature in applications that require splitting and coalescence of droplets, such as chemical microreactors and biological encapsulation and screening.

Controlled preparation of droplets for cell encapsulation by air-focused microfluidic bioprinting

Microfluidics is a facile platform that manipulates fluids for the production of droplets, particles, and microcapsules. However, the application of microfluidics is limited to the manipulation of the droplet position and the presence of a continuous oil phase, which needs to be removed for biomedical applications. Here, we used air as the continuous phase and developed a facile method for droplet generation and patterning by air-focused microfluidic three-dimensional (3D) droplet printing (AFMDP). By tuning the viscous drag of a focused air flow, monodisperse droplets with tunable size were generated in a microfluidic device, and droplet patterns were designed by combining the control system of the 3D printer. When using droplets as templates, hydrogel particles were prepared by AFMDP and crosslinked in a CaCl2 bath. These hydrogel particles were proven to be good carriers for the cell culture, controlled release, and immune therapy using chimeric antigen receptor (CAR) T cells. Cell viability and activity results confirmed that encapsulation of CAR-T cells in hydrogel particles did not compromise their cell activity and functionality but facilitated their manipulation and cell culture. Therefore, the AFMDP system provided a versatile platform for the design of droplets, particles, and microcapsules for biomedical applications.

Increasing particle concentration enhances particle penetration depth but slows down liquid imbibition in thin fibrous filters

The transport of particles within thin, porous media is a complex process which received growing attention due to its applications in filtration, printing and microfluidics devices. The effect of particles on liquid imbibition and particle clogging can reduce the performance and lifetime of these applications. However, these processes are still not clearly understood and are challenging to investigate. The goal of this study is to increase our understanding about the effect of particle concentration on the imbibition process in thin fibrous membrane filters. In this study, an Ultra-Fast Imaging NMR method is used to study the particle penetration inside nylon membrane filters for particle suspensions with varying particle concentrations (C0). The measurements revealed that increasing the particle concentration increases the particle penetration depth S(t) as governed by a Langmuir isotherm given by S(t)=l(t)(1+κC0)/1+κ(C0+Cb,m), with Cb,m the bound particles and κ the binding constant. Secondly, in droplet penetration, particles slow down liquid penetration in a Darcy like manner where effect on viscosity (η) and surface tension (σ) determine the penetration speed rather than changes within permeability (K0). The final liquid front (l), scaled according to l2∝σt/η. The particle penetration depths were verified using scanning electron microscopy images.

A microparticle manipulation method facilitated via microfluidic chip based on swirling flow topology design and its application in sorting

Microfluidics technology is trustworthy for microparticle operation as it doesn't involve destructive contact. Our research endeavors have encompassed microparticles manipulation by generating swirling flow region (SFR). Now we try to utilize swirl and flow topology to promote microfluidic chip design because serial operation is still not well enabled. Herein, a new model is proposed for a 6-microchannel microfluidic chip, which has realized active control of microparticles. The chip is capable of trapping, transferring, and enriching microparticles, and is applied for microparticles sorting. Simulation is performed to substantiate the viability of generating SFRs, and experiments are conducted on 3D-printed chips to validate the envisioned functions of the proposed microfluidic chip. Encouragingly, our experiments yield convincing outcomes, wherein microparticles are successfully trapped, transferred, and enriched in separated SFRs. With the help of a self-developed vision algorithm, the size sorting of microparticles is facilitated. Significantly, the manipulation of different microparticles can be achieved by tuning the microchannel velocities and tailoring the flow topology. This work presents a pioneering flow field structure and provides a feasible scheme for sorting microparticles, which is a noteworthy advance in swirl-based microfluidic chip applications. It is a potential mean for bio-/chemical analysis and fluidic-directed assembly of multiple microparticles.

Direct patterning of liquid materials on flat and curved substrates using flexible molds with through-hole and post arrays.

Liquids undergo continuous deformation in the presence of external shear stresses; however, they are pinned between structures owing to their viscosity. Therefore, reshaping the liquids using their intrinsic material properties and structural interfaces is possible. In this study, we used the template-guided forming (TGF) method to reshape and produce oil patterns on flat and curved substrates. To produce oil patterns, we developed two oil patterning methods: direct heating-based oil patterning (DHOP) and solvent evaporation-based oil patterning (SEOP), which were characterized using various oils and solvents. To overcome the limitation of relying solely on liquid patterning that undergoes complete evaporation, we successfully fabricated liquid films using oil and nonpolar organic solvents that exhibit long-term stability. Therefore, achieving durability and control over the film thickness using nonpolar organic solvents has great potential for future applications in microfluidics. Furthermore, we demonstrated that the SEOP method in conjunction with TGF can produce various and unconventional patterns of an organic photoresist (SU-8), which cannot be produced through standard photolithography. Hence, we conclude that the proposed TFG-based oil pattering methods could be highly useful for producing unconventional and unprecedented patterns on flat and curved substrates for various applications, including microelectronics, optics, filtration and separation, biomedical engineering, and nanotechnology.

Long range signature of liquid's inertia in nanoscale drainage flows.

In confinement, liquid flows are governed by a complex interplay of molecular, viscous and elastic forces. When a fluid is confined between two approaching surfaces, a transition is generally observed from a long range dynamical response dominated by viscous forces in the fluid to a short range elasto-hydrodynamic response due to the elastic deformation of the solid materials. This study investigates the behavior of fluids driven between oscillating solid surfaces using a dynamic Surface Force Apparatus. Our findings reveal that the dominant influence on fluid behavior arises from long-range inertial effects, superseding conventional elasto-hydrodynamic effects. Through systematic experimentation involving fluids of varied viscosities, diverse substrates, we identify key parameters and develop a comprehensive model which explains our measurements. Our findings not only provide insights into confined fluid dynamics but also offer practical implications for various applications in microfluidics, nanotechnology and liquid lubrication.

A continuum model for magnetic particle flows in microfluidics applicable from dilute to packed suspensions.

The manipulation of magnetic microparticles has always been pivotal in the development of microfluidic devices, as it encompasses a broad range of applications, such as drug delivery, bioanalysis, on-chip diagnostics, and more recently organ-on-chip development. However, predicting the behavior and trajectory of these particles remains a recurring and partly unresolved question. Magnetic particle-laden flows can display intricate collective behaviors, such as packed plugs, column-shaped aggregates, or fluidization, which are difficult to predict. In this study, we introduce a finite-element model to simulate highly dense flows of magnetic microparticles. Our method relies on an interpenetrating continuum approach, where both the liquid and particle phases are described by the Navier-Stokes equations, in which the magnetic force, interphase friction, and interparticle forces were included. We demonstrate its applicability across the entire range of particle packing densities and compare the results with experimental data from real microfluidic application cases. The model successfully replicates complex behaviors, such as particle aggregation, plug formation and fluidization. This approach has potential to accelerate microfluidic device development by reducing the need for costly and time-consuming experimental optimization.

Grease the gears: how lubrication of syringe pumps impacts microfluidic flow precision.

Pumps are indispensable for analytical applications and ensure controlled fluid movement. Syringe pumps are among today's most prevalent liquid delivery systems, especially for high-pressure, stable, low-flow-rate microfluidic applications. Due to moving mechanical parts of the assembly, regular maintenance is essential to ensure reliable operation and flow rates. However, lubrication of the mechanics is easily overlooked because the research focuses on novel analytical applications rather than on the maintenance of pumps. Here, we investigate the lubrication of the syringe pump guide rods with its effect on the flow rate stability after regular pump cleaning from contaminations. The guide rods of syringe pumps were thoroughly cleaned from any lubricant, and the flow rate for specified flowrates between 5 and 100 μL min-1 was measured, revealing tremendous flow rate fluctuations with a coefficient of variation (CV) value up to 0.34. In contrast, flow rate measurements of syringe pumps with lubricated guide rods show a five-fold smoother flow rate fluctuation depending on the specified flow rate with CV values below 0.07. These differences in flow rate's CV were most significant for pressure drops below 500 mbar, relevant for many lab-on-a-chip applications. In summary, we emphasize the awareness of lubricating moving parts of syringe pumps to achieve constant flow rates, minimize wear, and ensure the reliable operation of, for instance, accurate lab-on-a-chip workflows.

Spontaneous imbibition of a liquid film wetting a wall-mounted cylinder corner.

Spontaneous imbibition flows within confined geometries are commonly encountered in both natural phenomena and industrial applications. A profound knowledge of the underlying flow dynamics benefits a broad spectrum of engineering practices. Nonetheless, within this area, especially concerning complex geometries, there exists a substantial research gap. This work centers on the cylinder-plane geometry, employing a combined theoretical and numerical approach to investigate the process of a wetting film wrapping a cylinder corner. It is found that the advance of the liquid front generally follows the Lucas-Washburn kinetics, i.e., t1/2 scaling, but it also depends on the dynamics of the liquid source. Furthermore, a theoretical estimation of the timescale associated with the imbibition process is also provided, especially the merging time as an important time length characterizing the duration of the wetting process. The timescale is highly dependent on the wettability conditions and the properties of the involved liquid. The conclusion of this work lays a theoretical foundation for comprehensively understanding the capillary phenomena in complex media and shedding light on various microfluidic applications.

Nanoscale investigations of femtosecond laser induced nanogratings in optical glasses.

Femtosecond (fs) laser irradiation inside transparent materials has drawn considerable interest over the past two decades. More specifically, self-assembled nanogratings, induced by fs laser direct writing (FLDW) inside glass, enable a broad range of potential applications in optics, photonics, or microfluidics. In this work, a comprehensive study of nanogratings formed inside fused silica by FLDW is presented based on high-resolution electron microscopy imaging techniques. These nanoscale investigations reveal that the intrinsic structure of nanogratings is composed of oblate nanopores, shaped into nanoplanes, regularly spaced and oriented perpendicularly to the laser polarization. These nanoporous layers are forced-organized by light, resulting in a pseudo-organized spacing at the sub-wavelength scale, and observed in a wide range of optical glasses. In light of the current state of the art, we discuss the imprinting of nanoporous layers under thermomechanical effects induced by a plasma-mediated nanocavitation process.

Quantitative analysis of sweat evaporation loss in epidermal microfluidic patches.

Sweat analysis is identified as a promising biochemical technique for the non-invasive assessment of human health status. Epidermal microfluidic patches are the predominant sweat sampling and sensing devices. However, the sweat stored inside the patches may suffer from evaporation loss of moisture, which can increase the concentration of biomarkers and cause the biochemical analysis results of sweat to deviate from the actual results. This study focuses on quantitatively analysing the sweat evaporation loss within epidermal microfluidic patches. Analytical models based on the dissolution diffusion mechanism and corresponding partial differential equations for the diffusion process were initially developed. The analytical solution of the equation was derived using the method of separation of variables, and the steady-state concentration distribution of water in the materials of microfluidic patches was calculated when considering the application of epidermal microfluidics. Evaporation losses of sweat through different paths were quantitatively calculated and analysed, including permeation through covers, diffusion along microchannels, and absorption by sidewalls. Then, experiments on the evaporation loss of sweat within microfluidic patches were conducted to validate the theoretical calculations and analytical results. At last, the design of the anti-evaporation structure for microfluidic patches was discussed. This study can provide theoretical and experimental references for the design of water-retention structures in epidermal microfluidic patches, which significantly enhances the overall reliability of sweat biochemical analysis results.

Microfluidic programmable strategies for channels and flow.

This review summarizes programmable microfluidics, an advanced method for precise fluid control in microfluidic technology through microchannel design or liquid properties, referring to microvalves, micropumps, digital microfluidics, multiplexers, micromixers, slip-, and block-based configurations. Different microvalve types, including electrokinetic, hydraulic/pneumatic, pinch, phase-change and check valves, cater to diverse experimental needs. Programmable micropumps, such as passive and active micropumps, play a crucial role in achieving precise fluid control and automation. Due to their small size and high integration, microvalves and micropumps are widely used in medical devices and biological analysis. In addition, this review provides an in-depth exploration of the applications of digital microfluidics, multiplexed microfluidics, and mixer-based microfluidics in the manipulation of liquid movement, mixing, and splitting. These methodologies leverage the physical properties of liquids, such as capillary forces and dielectric forces, to achieve precise control over fluid dynamics. SlipChip technology, which branches into rotational SlipChip and translational SlipChip, controls fluid through sliding motion of the microchannel. On the other hand, innovative designs in microfluidic systems pursue better modularity, reconfigurability and ease of assembly. Different assembly strategies, from one-dimensional assembly blocks and two-dimensional Lego®-style blocks to three-dimensional reconfigurable modules, aim to enhance flexibility and accessibility. These technologies enhance user-friendliness and accessibility by offering integrated control systems, making them potentially usable outside of specialized technical labs. Microfluidic programmable strategies for channels and flow hold promising applications in biomedical research, chemical analysis and drug screening, providing theoretical and practical guidance for broader utilization in scientific research and practical applications.

Morphology, repulsion, and ordering of red blood cells in viscoelastic flows under confinement.

Red blood cells (RBC), the primary carriers of oxygen in the body, play a crucial role across several biomedical applications, while also being an essential model system of a deformable object in the microfluidics and soft matter fields. However, RBC behavior in viscoelastic liquids, which holds promise in enhancing microfluidic diagnostic applications, remains poorly studied. We here show that using viscoelastic polymer solutions as a suspending carrier causes changes in the clustering and shape of flowing RBC in microfluidic flows when compared to a standard Newtonian suspending liquid. Additionally, when the local RBC concentration increases to a point where hydrodynamic interactions take place, we observe the formation of equally-spaced RBC structures, resembling the viscoelasticity-driven ordered particles observed previously in the literature, thus providing the first experimental evidence of viscoelasticity-driven cell ordering. The observed RBC ordering, unaffected by polymer molecular architecture, persists as long as the surrounding medium exhibits shear-thinning, viscoelastic properties. Complementary numerical simulations reveal that viscoelasticity-induced repulsion between RBCs leads to equidistant structures, with shear-thinning modulating this effect. Our results open the way for the development of new biomedical technologies based on the use of viscoelastic liquids while also clarifying fundamental aspects related to multibody hydrodynamic interactions in viscoelastic microfluidic flows.

A novel multifunctional SERS microfluidic sensor based on ZnO/Ag nanoflower arrays for label-free ultrasensitive detection of bacteria.

This study proposes a microfluidic platform for rapid enrichment and ultrasensitive SERS detection of bacteria. The platform comprises ZnO nanoflower arrays decorated with silver nanoparticles to enhance the SERS sensitivity. The ZnO nanoflower array substrate with a 3D reticular columnar structure is prepared using the hydrothermal method. SEM analysis depicts the 3.05 μm gap distribution of the substrate array to intercept the most bacteria in the particle sizes range of 0.5 to 3 μm. Then, silver nanoparticles are deposited on the ZnO nano-array surface by liquid evaporation self-assembly. TEM and SEM analysis indicate nanosize of Ag particles, evenly distributed on the substrate, enhancing the SERS efficiency and improving sensing reproducibility. The probe molecules (R6G) are tested to demonstrate the high SERS activity of the proposed microfluidic sensor. Then, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis are selected, demonstrating the sensor's excellent bacterial capture and sensitive recognition capabilities, with a detection limit as low as 102 CFU mL-1. Additionally, the antibacterial properties of ZnO/Ag heterojunction nanostructures are studied, suggesting their ability to inactivate bacteria. Compared with the traditional Au-enhanced chip, the sensor preparation is easy, safe, reliable, and low-cost. Moreover, the ZnO nano-array exhibits a large specific surface area, high interception ability, stronger and uniform SERS performance, and effective and reliable detection of trace pathogens. This work provides potential future ZnO/Ag microfluidic SERS sensor applications for rapid, unlabeled, and trace pathogens detection in clinical and environmental applications, potentially achieving breakthroughs in early detection, prevention, and treatment.