Microfluidic Applications Research Articles

Modular and extendable 1D-simulation for microfluidic devices

Microfluidic devices have been the subject of considerable attention in recent years. The development of novel microfluidic devices, their evaluation, and their validation requires simulations. While common methods based on Computational Fluid Dynamics (CFD) can be time-consuming, 1D simulation provides an appealing alternative that leads to efficient results with reasonable quality. Current 1D simulation tools cover specific microfluidic applications; however, these tools are still rare and not widely adopted. There is a need for a more versatile and adaptable tool that covers novel applications, like mixing and the addition of membranes, and allows easy extension, resulting in one comprehensive 1D simulation tool for microfluidic devices. In this work, we present an open-source, modular, and extendable 1D simulation approach for microfluidic devices, which is available as an open-source software package at https://github.com/cda-tum/mmft-modular-1D-simulator. To this end, we propose an implementation that consists of a base module (providing the core functionality) that can be extended with dedicated application-specific modules (providing dedicated support for common microfluidic applications such as mixing, droplets, membranes, etc.). Case studies show that this indeed allows to efficiently simulate a broad spectrum of microfluidic applications in a quality that matches previous results or even fabricated devices.

Programmable and flexible wood-based origami electronics

Natural polymer substrates are gaining attention as substitutes for plastic substrates in electronics, aiming to combine high performance, intricate shape deformation, and environmental sustainability. Herein, natural wood veneer is converted into a transparent wood film (TWF) substrate. The combination of 3D printing and origami technique is established to create programmable wood-based origami electronics, which exhibit superior flexibility with high tensile strength (393 MPa) due to the highly aligned cellulose fibers and the formation of numerous intermolecular hydrogen bonds between them. Moreover, the flexible TWF electronics exhibit editable multiplexed configurations and maintain stable conductivity. This is attributed to the strong adhesion between the cellulose-based ink and TWF substrate by non-covalent bonds. Benefiting from its anisotropic structure, the programmability of TWF electronics is achieved through sequentially folding into predesigned shapes. This design not only promotes environmental sustainability but also introduces its customizable shapes with potential applications in sensors, microfluidics, and wearable electronics.

Design and Analysis of a Thermal Flowmeter for Microfluidic Applications: A Study on Sensitivity at Low Flow Rates

To address the challenge of precise flow rate measurement in microchannels, this research details the conceptualization and comprehensive evaluation of a thermal flowmeter which works on the principle of calorimetry for measuring small flow rates between 0.1 and 180 mL/h. The thermal flowmeter is composed of a silicone pipe, a heater, three platinum thermal sensors (T1, T2, T3), and water as the working fluid. The flowmeter is strategically placed to monitor the complex thermodynamics between upstream and downstream flows. The analysis revealed a notable decay in the slope of the temperature differences beyond a flow rate of 40 mL/h, indicating the exceptional sensitivity of the device at lower flow rates and making it an ideal choice for medical applications. Parametric analysis was also carried out to place the sensors at optimized locations for better sensitivity.

A multilayered homogeneous hydrodynamic cloak realized in a free fluid flow

In recent years, hydrodynamic invisibility cloaks have attracted significant attention from the scientific and engineering communities due to their potential in applications such as fluid flow manipulation, drag reduction, submarine stealth, and biomedical engineering. However, cloaks based on transformation mapping theory typically require porous medium flow, limiting practical implementation. To address this, we draw inspiration from Hele-Shaw flow and develop a homogeneous hydrodynamic cloak composed of multiple layers in free fluid flow at low Reynolds numbers (Re≪1). Through structural optimization, we construct a cloaking shell with ten concentric layers of alternating heights, achieving near-perfect cloaking as demonstrated by simulations and experiments. This non-porous cloak design offers valuable insights into the rapidly advancing field of hydrodynamic metamaterials and enables methods for controlling fluid flow at the microscale, with promising applications in microfluidics.

Single-Cell Microfluidics: A Primer for Microbiologists.

Recent advances in microfluidic technology have made it possible to image live bacterial cells with a high degree of precision and control. In particular, single-cell microfluidic designs have created new opportunities to study phenotypic variation in bacterial populations. However, the development and use of microfluidic devices require specialized resources, and these can be practical barriers to entry for microbiologists. With this review, our intentions are to help demystify the design, construction, and application of microfluidics. Our approach is to present design elements as building blocks from which a multitude of microfluidics applications can be imagined by the microbiologist.

Reconfigurable Antireflection Coatings Enabled by PDMS Oligomer Infusion in Templated Nanoporous Polymer Films.

The diffusion of uncured polydimethylsiloxane (PDMS) oligomers out of bulk PDMS elastomers is usually detrimental to many biomedical and microfluidic applications due to the inevitable contamination of the contacting fluids and substrates. Here, we transform this detrimental process into an enabling technology for achieving novel reconfigurable antireflection (AR) coatings, which are of great technological importance in the development of new nano-optical and optoelectronic applications. Self-assembled monolayer silica colloidal crystals are first used as sacrificial templates in fabricating nanoporous polymer AR coatings. When air in the templated nanopores is replaced with infused PDMS oligomers simply by pressing a PDMS stamp on a nanoporous AR film, the original antireflection conditions are lost, and the coating transforms from a low-reflection configuration to a high-reflection state. The original antireflection performance can be fully recovered by dissolving the infused oligomers in the appropriate solvents (e.g., hexane). This novel tuning mechanism for achieving reconfigurable AR properties has been confirmed by systematic investigations using various microscopes, optical spectroscopy, nanoindentation, thermomechanical tests, and X-ray photoelectron spectroscopy. Complex micropatterns with micrometer-scale spatial resolution and drastically different AR performances can be easily printed on nanoporous AR films by using a soft lithography-based microcontact printing process. Numerical finite-difference time-domain simulations match well with experimental antireflection measurements and reveal a linear relationship between the optical transmission and the amount of infused PDMS oligomers in nanopores.

Deformation and enclosed volume change of axisymmetric non-linear dielectric elastomer membrane pump: a theoretical study

Abstract This work investigates the change in the enclosed volume of an axisymmetric non-linear hyper-elastic membrane pump subjected to dielectric actuation. The equilibrium equations in cylindrical coordinates, coupled with non-linear constitutive relations, are solved numerically to obtain the deformed membrane geometry under pressure loading (using Variational Calculus). The effect of dielectric actuation is then incorporated by considering the change in material properties and deformation induced by the applied electric field. The deformed geometry under dielectric actuation is determined, and the change in enclosed volume is calculated by comparing the deformed states with and without the applied electric field. The proposed approach enables quantifying the volumetric change in non-linear hyper-elastic membrane pumps due to dielectric actuation for potential applications in soft robotics, adaptive optics, and microfluidics. By non-dimensionalizing variables, key dimensionless parameters governing the problem are identified for broader applicability. Furthermore, this methodology can estimate volume changes for different electric actuations when a specific material is chosen with experimentally derived parameter trends, facilitating material selection or synthesis to meet targeted volumetric requirements.

Flow analysis and fabrication of micro scale controlled surfaces by ultrashort pulse laser for microfluidic device applications

Microfluidics finds a wide range of industrial applications mainly in fields such as biomedical, clinical, electrical, and thermal engineering. Microchannels are the building blocks of most microfluidic devices. Thus, it becomes evident to understand the properties and the effect of the surfaces on the outcomes of devices. In this study, the effect of the shape of microchannels and the roughness elements on the flow is evaluated. Microchannels with three cross-sections and roughness elements of three different geometries are considered. The effect of varying Reynolds numbers on the flow parameters such as Friction factor, Nusselt number, Poiseuille number, pressure drop and surface temperature at the base of the substrate is studied. It is observed that rough microchannels and rectangular roughness elements showed a higher Nusselt number than smooth microchannels. The rough microchannels with triangular roughness elements showed higher friction factors. The surface temperature is higher for the smooth microchannels with triangular roughness elements. Furthermore, to demonstrate the manufacturability of microfluidic channels with controlled surfaces and to validate the preliminary results of the numerical simulations, the ultrashort pulse laser micromachining technique is used to fabricate the microchannels with structures on Polymethyl Methacrylate (PMMA) material.

Microbial single-cell applications under anoxic conditions.

The field of microbiology traditionally focuses on studying microorganisms at the population level. Nevertheless, the application of single-cell level methods, including microfluidics and imaging techniques, has revealed heterogeneity within populations, making these methods essential to understand cellular activities and interactions at a higher resolution. Moreover, single-cell sorting has opened new avenues for isolating cells of interest from microbial populations or complex microbial communities. These isolated cells can be further interrogated in downstream single-cell "omics" analyses, providing physiological and functional information. However, applying these methods to study anaerobic microorganisms under in situ conditions remains challenging due to their sensitivity to oxygen. Here, we review the existing methodologies for the analysis of viable anaerobic microorganisms at the single-cell level, including live-imaging, cell sorting, and microfluidics (lab-on-chip) applications, and we address the challenges involved in their anoxic operation. Additionally, we discuss the development of non-destructive imaging techniques tailored for anaerobes, such as oxygen-independent fluorescent probes and alternative approaches.

Microfluidic Applications in Prostate Cancer Research.

Prostate cancer is a disease in which cells in the prostate, a gland in the male reproductive system below the bladder, grow out of control and, among men, it is the second-most frequently diagnosed cancer (other than skin cancer). In recent years, prostate cancer death rate has stabilized and, currently, it is the second-most frequent cause of cancer death in men (after lung cancer). Most deaths occur due to metastasis, as cancer cells from the original tumor establish secondary tumors in distant organs. For a long time, classical cell cultures and animal models have been utilized in basic and applied scientific research, including clinical applications for many diseases, such as prostate cancer, since no better alternatives were available. Although helpful in dissecting cellular mechanisms, these models are poor predictors of physiological behavior mainly because of the lack of appropriate microenvironments. Microfluidics has emerged in the last two decades as a technology that could lead to a paradigm shift in life sciences and, in particular, controlling cancer. Microfluidic systems, such as organ-on-chips, have been assembled to mimic the critical functions of human organs. These microphysiological systems enable the long-term maintenance of cellular co-cultures in vitro to reconstitute in vivo tissue-level microenvironments, bridging the gap between traditional cell cultures and animal models. Several reviews on microfluidics for prostate cancer studies have been published focusing on technology advancement and disease progression. As metastatic castration-resistant prostate cancer remains a clinically challenging late-stage cancer, with no curative treatments, we expanded this review to cover recent microfluidic applications related to prostate cancer research. The review includes discussions of the roles of microfluidics in modeling the human prostate, prostate cancer initiation and development, as well as prostate cancer detection and therapy, highlighting potentially major contributions of microfluidics in the continuous march toward eradicating prostate cancer.

Utilization of Microfluidic Droplet-Based Methods in Diagnosis and Treatment Methods of Hepatocellular Carcinoma: A Review.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is associated with high morbidity and mortality. One of the main challenges in the management of HCC is late clinical presentation and thus diagnosis of the disease, which results in poor survival. The pathogenesis of HCC is complex and involves chronic liver injury and genetic alterations. Diagnosis of HCC can be made either by biopsy or imaging; however, conventional tissue-based biopsy methods and serological biomarkers such as AFP have limited clinical applications. While hepatocellular carcinoma is associated with a range of molecular alterations, including the activation of oncogenic signaling pathways, such as Wnt-TGFβ, PI3K-AKT-mTOR, RAS-MAPK, MET, IGF, and Wnt-β-catenin and TP53 and TERT promoter mutations, microfluidic applications have been limited. Early diagnosis is crucial for advancing treatments that would address the heterogeneity of HCC. In this context, microfluidic droplet-based methods are crucial, as they enable comprehensive analysis of the genome and transcriptome of individual cells. Single-cell RNA sequencing (scRNA-seq) allows the examination of individual cell transcriptomes, identifying their heterogeneity and cellular evolutionary relationships. Other microfluidic methods, such as Drop-seq, InDrop, and ATAC-seq, are also employed for single-cell analysis. Here, we examine and compare these microfluidic droplet-based methods, exploring their advantages and limitations in liver cancer research. These technologies provide new opportunities to understand liver cancer biology, diagnosis, treatment, and prognosis, contributing to scientific efforts in combating this challenging disease.

Analysis of electroviscous effects in electrolyte liquid flow through a heterogeneously charged uniform microfluidic device

Charge-heterogeneity (i.e., surface charge variation in the axial direction of the device) introduces non-uniformity in flow characteristics in the microfluidic device. Thus, it can be used for controlling practical microfluidic applications, such as mixing, mass, and heat transfer processes. This study has numerically investigated the charge-heterogeneity effects in the electroviscous (EV) flow of symmetric (1:1) electrolyte liquid through a uniform slit microfluidic device. The Poisson’s, Nernst-Planck (N-P), and Navier–Stokes (N-S) equations are numerically solved using the finite element method (FEM) to obtain the flow fields, such as total electrical potential (U), excess charge (n *), induced electric field strength (E x), and pressure (P) fields for following ranges of governing parameters: inverse Debye length (2 ≤ K ≤ 20), surface charge density (4 ≤ S 1 ≤ 16), and surface charge-heterogeneity ratio (0 ≤ S rh ≤ 2). Results have shown that the total potential (∣ΔU∣) and pressure (∣ΔP∣) drop maximally increase by 99.09% (from 0.1413 to 0.2812) (at K = 20, S 1 = 4) and 12.77% (from 5.4132 to 6.1045) (at K = 2, S 1 = 8), respectively with overall charge-heterogeneity (0 ≤ S rh ≤ 2). Electroviscous correction factor (Y, i.e., ratio of effective to physical viscosity) maximally enhances by 12.77% (from 1.2040 to 1.3577) (at K = 2, S 1 = 8), 40.98% (from 1.0026 to 1.4135) (at S 1 = 16, S rh = 1.50), and 41.35% (from 1 to 1.4135) (at K = 2, S rh = 1.50), with the variation of S rh (from 0 to 2), K (from 20 to 2), and S 1 (from 0 to 16), respectively. Further, a simple pseudo-analytical model is developed to estimate the pressure drop in EV flow, accounting for the influence of charge-heterogeneity based on the Poiseuille flow in a uniform channel. This model predicts the pressure drop ± 2%–4% within the numerical results. The robustness and simplicity of this model enable the present numerical results for engineering and design aspects of microfluidic applications.

Digital core on a chip: Surfactant flooding in low-permeability reservoir

The development of hard-to-recover reserves every year requires ever-more-innovative industrial and laboratory approaches for efficient production of hydrocarbons. Oil industry has recently turned to the use of microfluidic technology to investigate the flow paths and interactions of reservoir fluids under high pressures and temperatures. The present study describes elaboration of a digital core on a chip, i.e. a microfluidic chip with the structure that replicates the void space of a selected reservoir and is designed based on the computed tomography images of core samples. Similarity of core samples and 2D generated structure was controlled through average pore diameter and structure morphology. The manufactured micromodels were used for surfactant compositions screening aiming to demonstrate the technology capabilities for further testing of various enhanced oil recovery (EOR) chemicals.Thus, several surfactants were examined in bulk employing standard screening procedures (stability evaluation, interfacial tension (IFT) measurements and phase behavior test with oil), and then were investigated in transparent microfluidic chips. Visualization of fluid flow in the porous structure is a primary advantage of microfluidics application for EOR. Hence, surfactant coreflooding-on-a-chip enabled correlation of IFT behavior of various surfactants with recovery efficiency, fast detection of in-situ emulsification and fluid flow distribution analysis in the porous media. Generally, symbiosis of two advanced technologies, i.e. microfluidics and digital core modeling, facilitated significant speed up of laboratory tests and reduce of their cost.

Understanding error rejection of differential impedance spectroscopy for the in situ characterization of highly conductive fluids

Abstract Differential impedance spectroscopy (DIS) can offer distinct advantages over conventional impedance spectroscopy (IS), particularly for the in situ characterization of highly conductive, corrosive fluids. To enhance the understanding of DIS and determine the conditions under which this method is preferable over conventional IS with fixed electrode positions, error calculations were performed. Two scenarios were analyzed, one accounting solely for random instrument errors and the other including random errors as well as systematic errors from a serial offset impedance. Our analyses reveal that while permittivity measurements of highly conductive media remain challenging regardless of whether a conventional or differential impedance approach is used, DIS enables highly accurate conductivity measurements across a wide frequency and conductivity range. Studying different cell dimensions with equal cell constants revealed that despite the increased influence of systematic errors at small scales, conductivity can still be accurately measured, underscoring the applicability of DIS for microfluidic applications. Other potential parasitic effects, such as those arising from the electromagnetic skin effect, stray capacitances, electrode size, and temperature gradients, are discussed, providing a comprehensive framework for sample characterization with DIS.

Deep learning enabled label-free microfluidic droplet classification for single cell functional assays.

Droplet-based microfluidics techniques coupled to microscopy allow for the characterization of cells at the single-cell scale. However, such techniques generate substantial amounts of data and microscopy images that must be analyzed. Droplets on these images usually need to be classified depending on the number of cells they contain. This verification, when visually carried out by the experimenter image-per-image, is time-consuming and impractical for analysis of many assays or when an assay yields many putative droplets of interest. Machine learning models have already been developed to classify cell-containing droplets within microscopy images, but not in the context of assays in which non-cellular structures are present inside the droplet in addition to cells. Here we develop a deep learning model using the neural network ResNet-50 that can be applied to functional droplet-based microfluidic assays to classify droplets according to the number of cells they contain with >90% accuracy in a very short time. This model performs high accuracy classification of droplets containing both cells with non-cellular structures and cells alone and can accommodate several different cell types, for generalization to a broader array of droplet-based microfluidics applications.

Glucose Oxidase-Based Glucose Biosensing with a Simple Dual Ag/AgCl Probe Conductivity Readout.

We describe a conductometric assay of the enzymatic conversion of glucose to gluconic acid by dissolved glucose oxidase (GOx), using the generation of proton and gluconate from the reaction product dissociation for glucose detection. Simple basics of ionic conductivity, a silver/silver chloride wire pair, and a small applied potential translate glucose-dependent GOx activity into a scalable cell current. Enzyme immobilization and complex sensor design, involving extra nanomaterials or microfabrication of electrode structures, are entirely avoided, in contrast to all modern electrochemical glucose biosensors. Assay calibration showed a response linearity up to 500 μM, with a sensitivity of about 1.3 nA/μM. Selectivity tests excluded signals from sugars other than glucose, and glucose quantifications with recovery rates close to 100% were reached with a model sample and a beverage. Easy use of elementary physicochemical phenomena and a satisfactory performance are assets of the proposed non-amperometric glucose biosensing strategy. Assay integration into a planar dual electrode platform, with or without microfluidic application option, is feasible because of the simplicity of the sensor readout and suggests a route to affordable glucose analysis in beverage, food, and body fluid samples.

Dimension compensation of printed master molds by a desktop LCD 3D printer for high-precision microfluidic applications.

Recent advances in low-cost liquid crystal display (LCD) 3D printing have popularized its use in creating microfluidic master molds and complete devices. However, the quality and precision of these fabrications often fall short of the rigorous standards required for advanced microfluidic applications. This study introduces a novel approach to enhance the dimensional accuracy of microchannels produced using a desktop LCD 3D printer. We propose a method for dimension compensation, optimize the printing parameters, and provide a straightforward post-treatment technique to ensure high-quality curing of polydimethylsiloxane (PDMS) in master molds made from photosensitive resin. Our investigation assesses the precision of 3D printing across three different scales of square cross-section microchannels by measuring their widths and heights, leading to the determination of optimal printing parameters that minimize dimensional errors. The dimensional errors are further reduced by introducing a series of dimension compensation factors, which correct the nominal dimensions of the microchannels by using the compensation factors in 3D printing. The dimensional accuracy is significantly improved after compensation even in fabricating complex microchannels of triangular cross-sections. Finally, a spiral channel of trapezoidal-like cross-section with tilted edges is fabricated for microfluidic application, and highly efficient particle separation is realized in the channel. The proposed method provides new insights for utilizing desktop LCD 3D printers to achieve high-accuracy microstructures necessary for advanced microfluidic applications.

Microfluidic supercritical CO2 applications: Solvent extraction, nanoparticle synthesis, and chemical reaction

Supercritical CO2, known for its non-toxic, non-flammable and abundant properties, is well-perceived as a green alternative to hazardous organic solvents. It has attracted considerable interest in food, pharmaceuticals, chromatography, and catalysis fields. When supercritical CO2 is integrated into microfluidic systems, it offers several advantages compared to conventional macro-scale supercritical reactors. These include optical transparency, small volume, rapid reaction, and precise manipulation of fluids, making microfluidics a versatile tool for process optimization and fundamental studies of extraction and reaction kinetics in supercritical CO2 applications. Moreover, the small length scale of microfluidics allows for the production of uniform nanoparticles with reduced particle size, beneficial for nanomaterial synthesis. In this perspective, we review microfluidic investigations involving supercritical CO2, with a particular focus on three primary applications, namely, solvent extraction, nanoparticle synthesis, and chemical reactions. We provide a summary of the experimental innovations, key mechanisms, and principle findings from these microfluidic studies, aiming to spark further interest. Finally, we conclude this review with some discussion on the future perspectives in this field.

Fabrication of microchannels on silica glass by femtosecond laser multi-scan: From surface generation mechanism to morphology control

Femtosecond laser processing has become a critical technique for the microfabrication of hard and brittle materials, particularly in microfluidic device applications. This study focuses on the fabrication of microchannels with controllable cross-sectional profiles in silica glass, a material known for its excellent physical and chemical properties. Through a combination of experimental research and theoretical analysis, the surface generation mechanisms governing microchannel morphology are investigated, alongside the influence of various processing parameters on the surface roughness at the microchannel bottom. A comprehensive optimization method is developed to control sidewall taper and surface roughness by adjusting laser scanning paths and modes. Utilizing a composite scanning approach, the study achieves near-rectangular microchannels with average sidewall taper angles below 5° and surface roughness (Sa) of 2.53 μm. These results provide a new strategy for precise control of microchannel morphology in silica glass, offering significant potential to enhance the efficiency and precision of microfluidic device fabrication, with broad applications in both industrial and research settings.

Breakup regimes and heat transfer of an isolated bubble and Taylor bubble flow in the T-type microchannel

Current research on Taylor bubble flow heat transfer mainly focuses on straight channels, with less emphasis on the transport characteristics and heat transfer regimes of Taylor bubble flow in branching channels. Understanding the flow and heat transfer regimes of Taylor bubble flow in branching channels is crucial for enhancing microfluidic and microchemical applications. Numerical simulations can provide detailed flow information that experiments might miss, deepening our understanding of Taylor bubble flow for enhanced heat transfer. The research results indicate the presence of three bubble breakup regimes at the T-junction: Non-breakup (NB), Tunnel breakup (TB), and Obstructed breakup (OB). The phase diagrams were established based on Capillary number and bubble length to predict the transitions between these three breakup regimes. Pressure within the channel increases with bubble deformation but decreases after breakup. Bubble breakup converts potential energy to kinetic energy, enhancing the heat transfer coefficient in the branching microchannels. The stagnation of bubbles at the T-junction temporarily reduces the heat transfer coefficient but increases after the breakup. Up to 115 % of the best performance improvement was achieved for Taylor bubble flow when the channel width ratio was 1.2. When the channel width ratio was greater than or equal to 1, the TB regime influenced bubble breakup within the channel, resulting in asymmetric breakups and uneven heat transfer. When employing tree-like branched microchannels and Taylor flow for enhanced heat transfer, a channel width ratio of 0.8 is recommended.