Microfluidic Applications Research Articles

Electrical Impedance Correlated to Flow Rate in Elastomeric Valves: An Analog Material Memory.

Elastomeric valves are used regularly in microfluidic applications as monolithic control elements to direct, arrest, and drive fluid flow. However, normally closed elastomeric microvalves constructed in polydimethylsiloxane (PDMS) appear to exhibit a material memory property in which flow rate information is stored in the electrical properties of the PDMS device. Flow rate through the open valves shows high correlation with the subsequent impedance measured across the closed valve, with a constant of proportionality as high as 7.61 kΩ per μL/min at 100 Hz. The memory effect is relatively nonvolatile, maintaining linearity for greater than 10 min and is resilient to mechanical perturbation. Overwrite times are characterized, and the memory effect is observed across multiple devices and stimulus frequencies. These characteristics as a nonvolatile analog memory element show promise for applications in neuromorphic computing systems.

Design and optimization of electrode-integrated microfluidic chips for enhanced electrochemical impedance spectroscopy assessments

Abstract Electrode-integrated microfluidic chips play a pivotal role in applying electrochemical impedance spectroscopy (EIS) across various domains. This technology has significantly transformed biomedical research, facilitating progress in drug discovery, diagnostics, and cell analysis. The architecture of these chips integrated with electrodes critically influences the precision and dependability of EIS outcomes. This study developed diverse microfluidic chip designs, including circular, deltoid, and deltoid-like shapes, to explore microenvironmental dynamics on EIS assessments. Moreover, computational fluid dynamics (CFD) was utilized to examine the flow properties within the proposed chip designs by investigating the relationship between pressure and velocities in the microenvironment. The study also assessed the effects of varying flow rates (1, 10, 100 µL) on EIS analysis and the simulation studies. Findings indicated that there were empty spaces in the circular design, which is commonly used, and it was not suitable for EIS experiments. Furthermore, it was noted that even with reduced altitude in the EIS measurement area, the environment remained conducive to more accurate measurements. A flow rate of 10 µL/min was identified as optimal in this research, as it offered the best balance among charge transfer resistance (Rct), capacitance (Q), and open circuit potential (OCP) values, while also minimizing the sample volume which is very important for microfluidic chip design and applications. This study demonstrated a strong interaction between microfluidic chip designs for electrode integration and EIS outcomes. On the other hand, it has yielded a reliable, cost-effective, rapid, practical, reusable, and portable platform after choosing an appropriate architecture for the electrode housing.

Integrated CAD/CAM Approach for Parametric Design and High-Precision Microfabrication of Planar Functional Structures Comprising Radially Oriented V-Grooves

High-precision microfabrication is essential for enhancing or enabling new functionalities in parts and tooling surfaces. V-groove structures are commonly used in surface engineering for diverse applications. Selecting the optimal V-groove shape, array, and fabrication method is crucial for achieving the desired performance. This study integrates the parametric definition of V-groove structures in both design and fabrication modules using three main function blocks (MFBs). MFB1 defines a single V-groove’s parametric model using specific input parameters. MFB2 transforms these parameters into equations to generate a CAD model of the surface. MFB3 combines inputs from MFB1 with parameters related to cutting tool geometry, cutting strategy, and process planning, producing functional NC code for the machine tool. The approach focuses on micromachining radial V-grooves on planar surfaces, requiring precise alignment and multi-axis single-point diamond cutting (SPDC) with rotation tool center point (RTCP) support. Testing on acrylic samples achieved ±0.1° orientation accuracy and ±2 μm positional accuracy, demonstrating potential for applications in drag reduction, fouling resistance, light guiding, and open microfluidics.

Silica Glass-Based Droplet Generation Microfluidic Chips Enabled by Femtosecond Laser: Simulation Analysis, Controllable Fabrication, and Performance Evaluation.

Microdroplet technology is widely used in biomedicine, material synthesis, and the petrochemical industry due to its unique biological and mechanical properties. Silica glass has emerged as a key substrate for droplet microfluidic chips because of its excellent physical, chemical, and biocompatible characteristics. However, its intrinsic hardness and brittleness create significant challenges in fabrication. This study investigates the use of femtosecond laser processing for the fabrication of silica glass-based microfluidic devices for droplet generation. A combined approach of simulation, numerical calculations, and experimental validation is employed to investigate key factors influencing droplet size and generation frequency, including channel wall wettability and phase flow rates. The results demonstrate that femtosecond laser direct writing enables the high-precision fabrication of microfluidic structures, such as microchannels and functional features at the channel bottom and through holes. Furthermore, ultrafast laser processing allows the creation of a cross-junction microfluidic device with superhydrophobic walls, confirming its feasibility for liquid-liquid droplet generation. This work highlights the potential of femtosecond laser processing for manufacturing high-performance microfluidic devices with exceptional precision, efficiency, and functionality, providing valuable insights for advancing microfluidic applications.

Low-Cost, Open-Source, High-Precision Pressure Controller for Multi-Channel Microfluidics

Microfluidics is a technology that manipulates liquids on the scales ranging from microliters to femtoliters. Such low volumes require precise control over pressures that drive their flow into the microfluidic chips. This article describes a custom-built pressure controller for driving microfluidic chips. The pressure controller features piezoelectrically controlled pressure regulation valves. As an open-source system, it offers high customizability and allows users to modify almost every aspect. The cost is roughly a third of what similar, alternative, commercially available piezoelectrically controlled pressure regulators could be purchased for. The measured output pressure values of the device vary less than 0.7% from the device’s reported pressure values when the requested pressure is between −380 and 380 mbar. Importantly, the output pressure the device creates fluctuates only ±0.2 mbar when the pressure is cycled between 10 and 500 mbar. The pressure reading accuracy and stability validation suggest that the device is highly feasible for many advanced (low-pressure) microfluidic applications. Here, we compare the main features of our device to commercially and non-commercially available alternatives and further demonstrate the device’s performance and accessibility in successful microfluidic hydrodynamic focusing (MHF)-based synthesis of large unilamellar vesicles (LUVs).

Smart biomaterials in healthcare: Breakthroughs in tissue engineering, immunomodulation, patient-specific therapies, and biosensor applications

Smart biomaterials have significantly impacted human healthcare by advancing the development of medical devices designed to function within human tissue, mimicking the behavior of natural tissues. While the intelligence of biomaterials has evolved from inert to active over the past few decades, smart biomaterials take this a step further by making their surfaces or bulk respond based on interactions with surrounding tissues, imparting outcomes similar to natural tissue functions. This interaction with the surrounding tissue helps in creating stimuli-responsive biomaterials, which can be useful in tissue engineering, regenerative medicine, autonomous drug delivery, orthopedics, and much more. Traditionally, material engineering focused on refining the static properties of biomaterials to accommodate them within the body without evoking an immune response, which was a major obstacle to their unrestricted operation. This review highlights and explains various engineering approaches currently under research for developing stimuli-responsive biomaterials that tune their outcomes based on responses to bodily factors like temperature, pH, and ion concentration or external factors like magnetism, light, and conductivity. Applications in soft and hard tissue engineering, 4D printing, and scaffold design are also discussed. The advanced application of microfluidics, like organ-on-a-chip models, extensively benefits from the intrinsic smart properties of biomaterials, which are also discussed below. The review further elaborates on how smart biomaterial engineering could revolutionize biosensor applications, thereby improving patient care quality. We delineate the limitations and key challenges associated with biomaterials, providing insights into the path forward and outlining future directions for developing next-generation biomaterials that will facilitate clinical translation.

Development and optimization of a precision and reliable particle dispensing system integrated with a pendulum motion dispensing module

Abstract This study presents a novel approach to enhancing microparticle dispersion and ejection performance by utilizing a pendulum motion of a particle reservoir. Owing to their tendency to sediment in suspension, microparticles pose significant challenges in achieving consistent and repeatable ejections, often leading to nozzle clogging. To overcome these challenges, a three-axis automated particle dispensing system integrated with a rotational dispensing module was developed. The pendulum motions of the dispensing module were investigated to assess their impact on particle dispersion, including 90-degree, 180-degree, and 360-degree swings. The 360-degree pendulum motion sustained particle dispersion, leading to the consistent and reliable ejection of particles during continuous droplet ejection. Moreover, we evaluated a novel particle dispensing system, including the effects of particle suspension density and dispensing parameters on the ejection performance and dead volume of minute particle samples. Stable particle dispensing was achieved, with a CV below 7%, even at high concentrations (14% w/v). The number of ejected particles exhibited a linear relationship (R 2 = 99%) with suspension densities ranging from 1%–14% w/v. Furthermore, dispensing parameters such as the amplitude and duration of the applied pressure showed a linear correlation with both the number of ejected particles and the volume of ejected droplets (R 2 = 99%). The dead volume was 2 μl, representing 10% of the 20 μl small sample used. These results demonstrate the flexibility of the system in maintaining a high performance across a range of operational conditions. The findings highlight the potential of this rotational approach for enhancing the reliability and accuracy of particle dispensing in microfluidic applications.

Dewetting Fingering Instability in Capillary Suspensions: Role of Particles and Liquid Bridges.

This study investigates the fingering instability that forms during the stretching of capillary suspensions with and without added nanoparticles. The dewetting process is observed using a transparent lifted Hele-Shaw cell. The liquid bridge is stretched under constant acceleration, and the resulting instability patterns are recorded using two high-speed cameras. Finger-like structures, characteristic of the Saffman-Taylor instability, are observed. The total length of the dendrites and the intersecting number of branches are quantified. We reveal the roles of microparticles, nanoparticles, and the secondary liquid during the fingering instability. The addition of microparticles to pure liquid enhanced finger length due to increased particle interactions and nucleation sites for bubbles. The addition of secondary fluid reduces fingering length by forming a strong interparticle network. Incorporation of nanoparticles induces an early onset of cavitation and enhances fingering instability. However, nanoparticles make the capillary suspensions' overall microstructure more homogeneous, reduce the sample variation in fingering patterns, and promote the even distribution of gel on both slides during splitting. These findings highlight the complex interactions governing dewetting in capillary (nano)suspensions. This knowledge has potential applications in microfluidics, 3D printing, and thin-film coatings, where controlling dewetting is crucial.

Isogeometric boundary element formulation to simulate droplets in microchannel confinement

Purpose This study aims to present an isogeometric boundary element formulation that stably and accurately models the motion of a droplet with arbitrary viscosity in free flows and microchannel confinements. Design/methodology/approach Like other numerical methods, isogeometric boundary element formulation also suffers from mesh distortion; therefore, volume correction and mesh relaxation are also required for efficient and stable simulations of deformable particles in Stokes flow with high accuracy. To improve the stability and accuracy of the proposed formulation, (i) volume correction and (ii) mesh relaxation algorithms to prevent mesh distortion are implemented. Findings Several test cases for a droplet in free-space shear flow are demonstrated for different Ca and viscosity ratio values which determine the deformability of a droplet. The results reveal that the drift of the enclosed volume inside a droplet and the mesh distortion becomes severe at low viscosity ratios and high Ca values, i.e. in the high deformability regime. The proposed numerical method integrating the stabilization algorithm enables the simulations at low spatiotemporal resolutions, even in extreme cases. The proposed method provides more than 10× speed-up compared to high-fidelity simulations without mesh relaxation. Efficient and accurate 3D simulations of droplets are also presented for simulations in microfluidic confinement. Practical implications The current formulation can be applied for many different microfluidic applications, and can be extended to tackle multiphysics simulations of multiple droplets in microchannel confinement. Originality/value The paper presents an isogeometric boundary element formulation with volume correction and mesh relaxation to model the motion of a droplet with arbitrary viscosity in free flows and microchannel confinements.

Characterizing Recent PDMS Changes in Electrokinetic-Based Microfluidic Devices' Performance and Manufacturing for Cell Sorting Applications.

Understanding cells from complex biological samples is vital to understanding cellular biology and medical applications. One evolving tool for cell sorting is the use of microfluidic devices to achieve higher precision and remove the need for labeling cell subpopulations. However, few microfluidic devices have been translated commercially beyond academic research often due to challenges in larger scale fabrication. Here, we initially investigated a compelling label-free microfluidic device with complex geometries to perform contactless dielectrophoresis (cDEP) for applications in enriching cell subpopulations in oncology, neurology, stem cells, and sample preparation. We began scaling the manufacturing of cDEP devices using Dow Sylgard 184, more commonly referred to as PDMS (polydimethylsiloxane). However, we began observing a new, dynamic bubble formation phenomenon which had significant impacts on device performance. Within just 5 min of exposure at typical experimental values, cell death was nearly 100%. Variables related to manufacturing, environment, equipment, personnel, raw materials sourcing, lithography methods and experimental conditions/parameters were systematically evaluated to find the root cause of the exacerbated bubble formation observed. Further, alternate polymers were sourced for manufacturing and experimental performance comparisons. All variables investigated failed to solve the significant decline in device performance and increase in cell death. Upon completing chemical analysis in this work, we conclude that the decline in device performance was a direct result of changes to the expected PDMS properties and composition. Despite these challenges, our robust quality control combined with experimental protocols to remove bubbles from the cDEP devices achieved consistent experimental performance including 2-3 h run times and >90% cell viability after sorting. These new PDMS behaviors will need to continue to be monitored and controlled to ensure consistency in experimentation, application and commercialization feasibility for a wide variety of microfluidic device designs and applications.

Investigations on tool electrode wear during ultrasonic assisted ECDM process

The electrochemical discharge machining (ECDM) process is one of the emerging methods to fabricate microfeatures on glass, which is widely accepted in the pharmaceutical industry for microfluidic applications. A slight deviation in geometry may significantly affect the microfluidic device’s functioning. As the machined dimension of the feature depends on tool geometry, understanding the tool electrode wear (TEW) and its effect on machined geometry is necessary. In the present investigation, ultrasonic energy is coupled to the ECDM process, and a mathematical model has been developed for TEW. The dependency of the tool wear on machining time was examined, and a mathematical model was developed for tool wear. Further, a parametric investigation was performed to identify TEW and geometrical characteristics of the machined features. Post-machining, tool and machined features were examined under FE-SEM for geometrical alterations, depositions and inclusions. Further, multi-objective optimization was used to find the optimal parameters to achieve minimum TEW, minimal thermal damages and maximum material removal rate (MRR) during the ECDM process. Applying ultrasonic energy assistance (at 15% power rating) to the tool during the process has reduced the TEW by 73.17% and increased the MRR by 11.08% compared to the conventional without ultrasonic assistance.

Microfluidics for Electrochemical Energy Conversion and Storage: Prospects Toward Sustainable Ammonia Production.

Ammonia is a key chemical in the production of fertilizers, refrigeration and an emerging hydrogen-carrying fuel. However, the Haber-Bosch process, the industrial standard for centralized ammonia production, is energy-intensive and indirectly generates significant carbon dioxide emissions. Electrochemical nitrogen reduction offers a promising alternative for green ammonia production. Yet, current reaction rates remain well below economically feasible targets. This work examines the application of electrochemical microfluidics for the enhancement of the rates of electrochemical ammonia synthesis. The review is built on the introduction to electrochemical microfluidics, corresponding cell designs, and the main applications of microfluidics in electrochemical energy conversion/storage. Based on recent advances in electrochemical ammonia synthesis, with an emphasis on the critical role of robust experimental controls, electrochemical microfluidics represents a promising route to environmentally friendly, on-site and on-demand ammonia production. This review aims to bridge the knowledge gap between the disciplines of electrochemistry and microfluidics and promote interdisciplinary understanding and innovation in this transformative field.

Dynamics of active poroelastic filaments in Stokes flow.

Active particles are self-propelled microswimmers with potential applications in biomedicine and microfluidics. With recent advances in manufacturing technology, it is now possible to experimentally realize soft and flexible artificial microswimmers, which afford more complex dynamics and offer exciting new routes for trajectory control versus traditional rigid designs. Inspired by landmark work simulating the dynamics of flexible active filaments, we present a simple method to study the dynamics of active poroelastic microbots of general shape. Focusing on filament designs, we predict that sufficiently flexible "Janus pusher" filaments may exhibit oscillating dynamics as they swim forward and that under certain conditions, "Saturn" filaments may perform locomotion on spiral trajectories and exhibit "run-and-tumble" dynamics reminiscent of bacterial motion. Finally, we consider a simple extension of our framework that qualitatively incorporates stimuli-responsive hydrogel behavior, which we demonstrate may be used to steer Janus rods. Our results suggest that flexibility and responsivity may play a key role in expanding the functionality of active particles in intelligent artificial microswimming studies.

Autonomous inverse encoding guides 4D nanoprinting for highly programmable shape morphing

Abstract Highly programmable shape morphing of 4D-printed micro/nanostructures are urgently desired for applications in robotics and intelligent systems. However, due to the lack of autonomous holistic strategies throughout the target shape input, optimal material distribution generation, and fabrication program output, 4D nanoprinting that permits arbitrary shape morphing remains a challenging task for manual design. In this study, we report an autonomous inverse encoding strategy to decipher the genetic code for material property distributions that can guide the encoded modeling toward arbitrarily pre-programmed 4D shape morphing. By tuning the laser power of each voxel at the nanoscale, the genetic code can be spatially programmed and controllable shape morphing can be realized through the inverse encoding process. Using this strategy, the 4D-printed structures can be designed and accurately shift to the target morphing of arbitrarily hand-drawn lines under stimulation. Furthermore, as a proof-of-concept, a flexible fiber micromanipulator that can approach the target region through pre-programmed shape morphing is autonomously inversely encoded according to the localized spatial environment. This strategy may contribute to the modeling and arbitrary shape morphing of micro/nanostructures fabricated via 4D nanoprinting, leading to cutting-edge applications in microfluidics, micro-robotics, minimally invasive robotic surgery, and tissue engineering.

Unveiling the complex morphologies of sessile droplets on heterogeneous surfaces

Droplets exhibiting a myriad of shapes on surfaces are ubiquitous in both nature and industrial applications. In high-resolution manufacturing processes, e.g., semiconductor chips, precise control over wetting shapes is crucial for production accuracy. Despite the high demand for describing droplet wetting shapes and their transformations across a wide range of applications, a robust model for precisely depicting complex three-dimensional (3D) wetting droplet shapes on heterogeneous surfaces remains elusive. Herein, we fill this gap by developing a universal, high-precision model that accurately describes wetting shapes, including those with polygonal baselines and irregular footprints. Our model reveals the intricate wetting morphologies beyond the classic Young’s law and Cassie-Baxter-Wenzel models. Besides, it aligns quantitatively with physical simulations for various droplet volumes. This work provides a potential method to achieve highly complex morphologies of droplets via low-cost beforehand design of the surfaces, thereby opening up potential applications in 3D printing, printed electronics, and microfluidics.

Microfluidics Based Particle and Droplet Generation for Gene and Drug Delivery Approaches.

Microfluidics-based droplets have emerged as a powerful technology for biomedical research, offering precise control over droplet size and structure, optimal mixing of solutions, and prevention of cross-contamination. It is a major branch of microfluidic technology with applications in diagnostic testing, imaging, separation, and gene amplification. This review discusses the different aspects of microfluidic devices, droplet generation techniques, droplet types, and the production of micro/nano particles, along with their advantages and limitations. Passive and active methods for droplet formation are discussed, as well as the manipulation of droplet shape and content. This review also highlights the potential applications of droplet microfluidics in tissue engineering, cancer therapy, and drug delivery systems. The use of microfluidics in the production of lipid nanoparticles and polymeric microparticles is also presented, with emphasis on their potential in drug delivery and biomedical research. Finally, the contributions of microfluidics to vaccines, gene therapy, personalized medicine, and future perspectives are discussed, emphasizing the need for continuous innovation and integration with other technologies, such as AI and wearable devices, to further enhance its potential in personalized medicine and drug delivery. However, it is also noted that challenges in commercialization and widespread adoption still need to be addressed.

Resolution study of jamg he 10k resin for the manufacture of microfluidics moulds

Abstract Introduction New trends in lab-on-a-chip mould fabrication rely on 3D printing technologies using stereolithography (SLA). However, the small size of the channels requires precise control of the printing parameters. For this reason, we propose a calibration procedure for the exposure time of a specific resin intended for microfluidic applications. Methods Several standard calibration tests were printed using an Elegoo MARS Ultra and a high-resolution resin JAMG HE 10K. The model was printed with various details to calibrate the exposure time, including lines and holes of different widths, as well as pins and holes of various diameters. Each model was printed three times, with the exposure time varied from 2 to 4 seconds. After printing, the models were cleaned in a 2-propanol bath for 20 minutes and light-cured for 60 minutes at room temperature. The details were measured using an optical microscope with a digital camera and compared to the digital model. Results The results indicate that the optimum exposure time is just over 2 seconds. Increasing the exposure time resulted in finer details protruding from the base, with lines and pins measuring approximately 100 µm and 200 µm, respectively. In contrast, reducing the exposure time led to gaps and holes with finer details, ranging from 250 µm to 500 µm at 2 seconds. Conclusion In conclusion, proper calibration of the resin exposure time is essential to achieve the desired dimensions for the expected microfluidic mould.

Liquid crystal torons in Poiseuille-like flows

Three-dimensional (3D) simulations of the structure of liquid crystal (LC) torons, topologically protected distortions of the LC director field, under material flows are rare but essential in microfluidic applications. Here, we show that torons adopt a steady-state configuration at low flow velocity before disintegrating at higher velocities, in line with experimental results. Furthermore, we show that under partial slip conditions at the boundaries, the flow induces a reversible elongation of the torons, also consistent with the experimental observations. These results are in contrast with previous simulation results for 2D skyrmions under similar flow conditions, highlighting the need for a 3D description of this LC soliton in relation to its coupling to the material flow. These findings pave the way for future studies of other topological solitons, like hopfions and heliknotons, in flowing soft matter systems.

Quantifying surface wettability in textured surfaces using two-dimensional pseudo-potential multiphase lattice Boltzmann model

Surface wettability plays a critical role in microfluidic applications, enabling enhanced fluid flow control, minimizing sample waste, and improving efficiency across various fields, including drying technology, food processing, chemical manufacturing, and ­environmental engineering. This study presents a numerical investigation of surface wettability on textured surfaces utilizing a two-dimensional (2D) pseudo-potential multiphase lattice Boltzmann method (LBM) with a D2Q9 model. The analysis is conducted for a range of solid-fluid interaction parameters (Gads ), varying between −2.50 and −1.40. Initially, the equilibrium state of a water droplet on a flat surface is simulated for different interaction parameters to validate the accuracy of the numerical model. Subsequently, micropillars are introduced on the bottom wall of the surface with varying heights and spacings to create hydrophobic and superhydrophobic textures, resulting in enhanced contact angles. The wettability of these surfaces is analyzed by placing a water droplet with a radius of 30 lattice units at the center of a computational domain sized 200 × 200 lattice units. The findings reveal that increasing the interaction parameter on textured surfaces significantly reduces the contact area between the droplet and the solid surface due to the momentum redirection effect, thereby increasing surface surface wettability. Similarly, greater spacing between micropillars enhances surface surface wettability. The simulated contact angles for various interaction strengths have been qualitatively validated with previously reported results, confirming the robustness of the present numerical model.

Modulating the Selective Enrichment and Depletion of Ions Using Electrorheological Fluids in Variable-Area Microchannels.

Electrorheological fluids are suspensions that are characterized by a strong functional dependence of their constitutive behavior on the local electric field. While such fluids are known to be promising in different applications of microfluidics including electrokinetic flows, their capabilities of controlling ion transport and preferential solute segregation in confined fluidic systems remain to be explored. In this work, we bring out the unique role of electrorheological fluids in orchestrating the selective enrichment and depletion of charged species in variable area microfluidic channels. Our reported phenomenon is fundamentally distinctive from other types of nonlinear electrokinetic effects previously reported, in a sense that here the dependence of the flow rheology on the electric field turns out to be the central mechanism toward orchestrating the observed nonlinear ion transport. Our results indicate exclusive features of the resulting ion concentration polarization, such as more pronounced ion concentration polarization, controlled largely by the influence of the variations in the channel cross section on the driving electrokinetic forces and the resistive viscous interactions. The underlying physical mechanism is captured aptly by a simple one-dimensional area-averaged model, and validated by full-scale three-dimensional simulations. Our illustrative case study for a converging-diverging microchannel with cross-sectionally uniform solute concentrations reveals that electrorheological effect with greater contrast between the deep and shallow region depths, greater solute concentration, and larger applied axial electric field, all acting in tandem, magnifies the solute enrichment and depletion in the respective segregation zones, bearing significant implications in analytical chemistry, bioanalysis, and beyond.