Microfluidic Materials Research Articles

Reducing Cathodic Drift during Isoelectric Focusing Using Microscale Immobilized pH Gradient Gels.

Microfluidic analytical tools play an important role in miniaturizing targeted proteomic assays for improved detection sensitivity, throughput, and automation. Microfluidic isoelectric focusing (IEF) can resolve proteoforms in lysate from low-to-single cell numbers. However, IEF assays often use carrier ampholytes (CAs) to establish a pH gradient for protein separation, presenting limitations like pH instability in the form of cathodic drift (migration of focused proteins toward the cathode). Immobilized pH gradient (IPG) gels reduce cathodic drift by covalently immobilizing the pH buffering components to a matrix. To our knowledge, efforts to implement IPG gels at the microscale have been limited to glass microdevices. To adapt IEF using IPGs to widely used microfluidic device materials, we introduce a polydimethylsiloxane (PDMS)-based microfluidic device and compare the microscale pH gradient stability of IEF established with IPGs, CAs, and a hybrid formulation of IPG gels and CAs (mixed-bed IEF). The PDMS-based IPG microfluidic device (μIPG) resolved analytes differing by 0.1 isoelectric point within a 3.5 mm separation lane over a 20 min focusing duration. During the 20 min duration, we observed markedly different cathodic drift velocities among the three formulations: 60.1 μm/min in CA-IEF, 2.5 μm/min in IPG-IEF (∼24-fold reduction versus CA-IEF), and 1.4 μm/min in mixed-bed IEF (∼43-fold reduction versus CA-IEF). Lastly, mixed-bed IEF in a PDMS device resolved green fluorescent protein (GFP) proteoforms from GFP-expressing human breast cancer cell lysate, thus establishing stability in lysate from complex biospecimens. μIPG is a promising and stable technique for studying proteoforms from small volumes.

Study of Advanced Techniques for Inquisition, Segregation and Removal of Microplastics from Water Streams: Current Insights and Future Directions

The present research covers different analytical methods utilized for the diagnosis and characterization of microplastics (MPs) in water and wastewater, such as particle size distribution analysis, and focuses on the sources and forms of MPs in receiving environments. First, we look at the most recent collection techniques, which include a variety of spectroscopic, chromatographic, and microscopic approaches used to identify and measure microplastics in water samples. We then investigate separation techniques designed to separate microplastics from diverse environmental matrices. This involves applying existing methods of separation based on density, such as centrifugation, flotation, and sedimentation, as well as more recent ones, like the use of microfluidic devices and materials for selective adsorption. Lastly, we look into removal methods aimed to reduce the buildup of microplastics in aquatic environments. These include enzymatic breakdown, coagulation/flocculation, and filtering, among other physical, chemical, and biological techniques.

Microfluidic devices, materials, and recent progress for petroleum applications: A review

AbstractMicrofluidic devices are miniaturized systems that manipulate fluids on a small scale, typically at microlitre or nanolitre volumes. They have received significant attention in various industries, including petroleum applications. The recent advancements in microfluidic devices for petroleum applications have the potential to improve oil recovery efficiency, reduce costs, and provide valuable insights into fluid behaviour and reservoir characterization. This paper aims to provide a comprehensive overview of microfluidic devices, their materials, and their applications in the petroleum industry. The first section of the paper focuses on describing the materials used in microfluidic devices specifically tailored for energy sector applications. In the second section, the paper highlights relevant applications and discoveries in petroleum research, showcasing the innovative techniques and special features enabled by microfluidic devices. These applications include but are not limited to asphaltenes characterization, enhanced oil recovery (EOR), and water treatment. The versatility and customization of microfluidic devices have allowed researchers to accurately represent fractures, ensure chemical conformance, simulate high pressure–high temperature conditions and reservoir heterogeneity, and study geochemical interaction. Additionally, molecular tagging and machine learning techniques have been employed for image analysis, further enhancing the capabilities of microfluidic devices. Throughout the paper, the advantages and disadvantages of implementing microfluidic devices and utilizing specific materials are thoroughly discussed. This analysis provides valuable insights into the challenges and potential limitations associated with this technology. To conclude, the paper offers suggestions, ideas, and highlights for future research paths, pointing toward promising directions for further exploration in this field.

Utilization of charged microdroplets for the controlled rapid synthesis of hollow sodium chloride single crystals.

Charged microdroplets are favored in microfluidic control, biomedicine, chemistry and materials processing due to their unique physicochemical environment, including interface double layers, high electric fields, surface concentration enrichment, and more. Herein, we investigated the crystallization of charged sodium chloride microdroplets and achieved the formation of hollow single crystals in a single-step process lasting only a few seconds, without the use of templates. Additionally, we discussed the plausible crystal growth mechanism, which appears to be an unconventional outward-inward growth process.

Surface-segregating zwitterionic copolymers to control poly(dimethylsiloxane) surface chemistry.

The use of microfluidic devices in biomedicine is growing rapidly in applications such as organs-on-chip and separations. Polydimethylsiloxane (PDMS) is the most popular material for microfluidics due to its ability to replicate features down to the nanoscale, flexibility, gas permeability, and low cost. However, the inherent hydrophobicity of PDMS leads to the adsorption of macromolecules and small molecules on device surfaces. This curtails its use in "organs-on-chip" and other applications. Current technologies to improve PDMS surface hydrophilicity and fouling resistance involve added processing steps or do not create surfaces that remain hydrophilic for long periods. This work describes a novel, simple, fast, and scalable method for improving surface hydrophilicity and preventing the nonspecific adsorption of proteins and small molecules on PDMS through the use of a surface-segregating zwitterionic copolymer as an additive that is blended in during manufacture. These highly branched copolymers spontaneously segregate to surfaces and rearrange in contact with aqueous solutions to resist nonspecific adsorption. We report that mixing a minute amount (0.025 wt%) of the zwitterionic copolymer in PDMS considerably reduces hydrophobicity and nonspecific adsorption of proteins (albumin and lysozyme) and small molecules (vitamin B12 and reactive red). PDMS blended with these zwitterionic copolymers retains its mechanical and physical properties for at least six months. Moreover, this approach is fully compatible with existing PDMS device manufacture protocols without additional processing steps and thus provides a low-cost and user-friendly approach to fabricating reliable biomicrofluidics.

Fabrication and Validation of a 3D Portable PEGDA Microfluidic Chip for Visual Colorimetric Detection of Captured Breast Cancer Cells.

To guide therapeutic strategies and to monitor the state changes in the disease, a low-cost, portable, and easily fabricated microfluidic-chip-integrated three-dimensional (3D) microchamber was designed for capturing and analyzing breast cancer cells. Optimally, a colorimetric sensor array was integrated into a microfluidic chip to discriminate the metabolites of the cells. The ultraviolet polymerization characteristic of poly(ethylene glycol) diacrylate (PEGDA) hydrogel was utilized to rapidly fabricate a three-layer hydrogel microfluidic chip with the designed structure under noninvasive 365 nm laser irradiation. 2-Hydroxyethyl methacrylate (HEMA) was added to the prepolymer in order to increase the adhesive capacity of the microchip's surface for capturing cells. 1-Vinyl-2-pyrrolidone (NVP) was designed to improve the toughness and reduce the swelling capacity of the hydrogel composite. A non-toxic 3D hydrogel microarray chip (60 mm × 20 mm × 3 mm) with low immunogenicity and high hydrophilicity was created to simulate the real physiological microenvironment of breast tissue. The crisscross channels were designed to ensure homogeneous seeding density. This hydrogel material displayed excellent biocompatibility and tunable physical properties compared with traditional microfluidic chip materials and can be directly processed to obtain the most desirable microstructure. The feasibility of using a PEGDA hydrogel microfluidic chip for the real-time online detection of breast cancer cells' metabolism was confirmed using a specifically designed colorimetric sensor array with 16 kinds of porphyrin, porphyrin derivatives, and indicator dyes. The results of the principal component analysis (PCA), the hierarchical cluster analysis (HCA), and the linear discriminant analysis (LDA) suggest that the metabolic liquids of different breast cells can be easily distinguished with the developed PEGDA hydrogel microfluidic chip. The PEGDA hydrogel microfluidic chip has potential practicable applicability in distinguishing normal and cancerous breast cells.

Research progress on pesticide residue detection based on microfluidic technology.

The problem of pesticide residue contamination has attracted widespread attention and poses a risk to human health. The current traditional pesticide residue detection methods have difficulty meeting rapid and diverse field screening requirements. Microfluidic technology integrates functions from sample preparation to detection, showing great potential for quick and accurate high-throughput detection of pesticide residues. This paper reviews the latest research progress on microfluidic technology for pesticide residue detection. First, the commonly used microfluidic materials are summarized, including silicon, glass, paper, polydimethylsiloxane, and polymethyl methacrylate. We evaluated their advantages and disadvantages in pesticide residue detection applications. Second, the current pesticide residue detection technology based on microfluidics and its application to real samples are summarized. Finally, we discuss this technology's present challenges and future research directions. This study is expected to provide a reference for the future development of microfluidic technology for pesticide residue detection.

A Systematic Analysis of Recent Technology Trends of Microfluidic Medical Devices in the United States.

In recent years, the U.S. Food and Drug Administration (FDA) has seen an increase in microfluidic medical device submissions, likely stemming from recent advancements in microfluidic technologies. This recent trend has only been enhanced during the COVID-19 pandemic, as microfluidic-based test kits have been used for diagnosis. To better understand the implications of this emerging technology, device submissions to the FDA from 2015 to 2021 containing microfluidic technologies have been systematically reviewed to identify trends in microfluidic medical applications, performance tests, standards used, fabrication techniques, materials, and flow systems. More than 80% of devices with microfluidic platforms were found to be diagnostic in nature, with lateral flow systems accounting for about 35% of all identified microfluidic devices. A targeted analysis of over 40,000 adverse event reports linked to microfluidic technologies revealed that flow, operation, and data output related failures are the most common failure modes for these device types. Lastly, this paper highlights key considerations for developing new protocols for various microfluidic applications that use certain analytes (e.g., blood, urine, nasal-pharyngeal swab), materials, flow, and detection mechanisms. We anticipate that these considerations would help facilitate innovation in microfluidic-based medical devices.

Parylene C as a Multipurpose Material for Electronics and Microfluidics.

Poly(p-xylylene) derivatives, widely known as Parylenes, have been considerably adopted by the scientific community for several applications, ranging from simple passive coatings to active device components. Here, we explore the thermal, structural, and electrical properties of Parylene C, and further present a variety of electronic devices featuring this polymer: transistors, capacitors, and digital microfluidic (DMF) devices. We evaluate transistors produced with Parylene C as a dielectric, substrate, and encapsulation layer, either semitransparent or fully transparent. Such transistors exhibit steep transfer curves and subthreshold slopes of 0.26 V/dec, negligible gate leak currents, and fair mobilities. Furthermore, we characterize MIM (metal-insulator-metal) structures with Parylene C as a dielectric and demonstrate the functionality of the polymer deposited in single and double layers under temperature and AC signal stimuli, mimicking the DMF stimuli. Applying temperature generally leads to a decrease in the capacitance of the dielectric layer, whereas applying an AC signal leads to an increase in said capacitance for double-layered Parylene C only. By applying the two stimuli, the capacitance seems to suffer from a balanced influence of both the separated stimuli. Lastly, we demonstrate that DMF devices with double-layered Parylene C allow for faster droplet motion and enable long nucleic acid amplification reactions.

Chemical Imaging of Mass Transport Near the No-Slip Interface of a Microfluidic Device using Attenuated Total Reflection–Fourier Transform Infrared Spectroscopy

Mass transport in geometrically confined environments is fundamental to microfluidic applications. Measuring the distribution of chemical species on flow requires the use of spatially resolved analytical tools compatible with microfluidic materials and designs. Here, the implementation of an attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) imaging (macro-ATR) approach for chemical mapping of species in microfluidic devices is described. The imaging method is configurable between a large field of view, single-frame imaging, and the use of image stitching to build composite chemical maps. Macro-ATR is used to quantify transverse diffusion in the laminar streams of coflowing fluids in dedicated microfluidic test devices. It is demonstrated that the ATR evanescent wave, which primarily probes the fluid within ∼500 nm of the channel surface, provides accurate quantification of the spatial distribution of species in the entire microfluidic device cross section. This is the case when flow and channel conditions promote vertical concentration contours in the channel as verified by three-dimensional numeric simulations of mass transport. Furthermore, the validity of treating the mass transport problem in a simplified and faster approach using reduced dimensionality numeric simulations is described. Simplified one-dimensional simulations, for the specific parameters used herein, overestimate diffusion coefficients by a factor of approximately 2, whereas full three-dimensional simulations accurately agree with experimental results.

Facile Microembossing Process for Microchannel Fabrication for Nanocellulose-Paper-Based Microfluidics.

Nanofibrillated cellulose paper (nanopaper) has gained growing interest as one promising substrate material for paper-based microfluidics, thanks to its ultrasmooth surface, high optical transparency, uniform nanofiber matrix with nanoscale porosity, and tunable chemical properties. Recently, research on nanopaper-based microfluidics has quickly advanced; however, the current technique of patterning microchannels on nanopaper (i.e., 3D printing, spray coating, or manual cutting and sticking), that is fundamental for application development, still has some limitations, such as ease-of-contamination, and more importantly, only enabling millimeter-scale channels. This paper reports a facile process that leverages the simple operations of microembossing with the convenient plastic micro-molds, for the first time, patterning nanopaper microchannels downing to 200 μm, which is 4 times better than the existing methods and is time-saving (<45 mins). We also optimized the patterning parameters and provided one quick look-up table as the guideline for application developments. As proof-of-concept, we first demonstrated two fundamental microfluidic devices on nanopaper, the laminar-mixer and droplet generator, and two functional nanopaper-based analytical devices (NanoPADs) for glucose and Rhodamine B (RhB) sensing based on optical colorimetry and surface-enhanced Raman spectroscopy, respectively. The two NanoPADs showed outstanding performance with low limits of detection (2 mM for glucose and 19fM for RhB), which are 1.25× and 500× fold improvement compared to the previously reported values. This can be attributed to our newly developed highly accurate microchannel patterning process that enables high integration and fine-tunability of the NanoPADs along with the superior optical properties of nanopaper.

Traditional vs. Microfluidic Synthesis of ZnO Nanoparticles.

Microfluidics provides a precise synthesis of micro-/nanostructures for various applications, including bioengineering and medicine. In this review article, traditional and microfluidic synthesis methods of zinc oxide (ZnO) are compared concerning particle size distribution, morphology, applications, reaction parameters, used reagents, and microfluidic device materials. Challenges of traditional synthesis methods are reviewed in a manner where microfluidic approaches may overcome difficulties related to synthesis precision, bulk materials, and reproducibility.

Alignment-free construction of double emulsion droplet generation devices incorporating surface wettability contrast.

Although polydimethylsiloxane (PDMS) is a versatile and easy-to-use material for microfluidics, its inherent hydrophobicity often necessitates specific hydrophilic treatment to fabricate microchip architectures for generating double emulsions. These additional processing steps frequently lead to increased complexity, potentially creating barriers to the wider use of promising microfluidic techniques. Here we describe an alignment-free spatial hydrophilic PDMS patterning technique to produce devices for the creation of double emulsions using combinations of PDMS and PDMS/surfactant bilayers. The technique enables us to achieve selective patterning and alignment-free bonding, producing reliable and reproducible water-in-oil-in-water W/O/W droplet emulsions. Our method involves processing devices in a vertical orientation, with the wetting transition contrast being achieved simply by imaging whilst adjusting the PDMS pouring speed (using a mobile phone, for example). We successfully obtain hydrophilic surfaces without distinguishable hydrophobic recovery using a range of surfactant concentrations. Droplet emulsions were produced with low coefficients of variation aligned with those generated with other, more complex, techniques (e.g. 3.8% and 3.1% for the inner and outer diameters, respectively). As a further example, the methods were also demonstrated for liposome production. In future we anticipate that the technique may be applied to other fields, including e.g. reagent delivery, DNA amplification, and encapsulated cell studies.

Assessment of silicon, glass, FR4, PDMS and PMMA as a chip material for acoustic particle/cell manipulation in microfluidics

In the present study, the capabilities of different chip materials for acoustic particle manipulation have been assessed with the same microfluidic device architecture, under the same actuator and flow conditions. Silicon, glass, epoxy with fiberglass filling (FR4), polydimethylsiloxane (PDMS) and polymethyl methacrylate (PMMA) are considered as chip materials. The acoustophoretic chips in this study were manufactured with four different fabrication methods: plasma etching, chemical etching, micromachining and molding. A novel chip material, FR4, has been employed as a microfluidic chip material in acoustophoretic particle manipulation for the first time in literature, which combines the ease of manufacturing of polymer materials with improved acoustic performance. The acoustic particle manipulation performance is evaluated through acoustophoretic focusing experiments with 2μm and 12μm polystyrene microspheres and cultured breast cancer cell line (MDA-MB-231). Unlike the common approach in the literature, the piezoelectric materials were actuated with partitioned cross-polarized electrodes which allowed effective actuation of different family of chip materials. Different from previous studies, this study evaluates the performance of each acoustophoretic device through the perspective of synchronization of electrical, vibrational and acoustical resonances, considers the thermal performance of the chip materials with their effects on cell viability as well as manufacturability and scalability of their fabrication methods. We believe our study is an essential work towards the commercialization of acoustophoretic devices since it brings a critical understanding of the effect of chip material on device performance as well as the cost of achieving that performance.

Current Advancements and Future Road Map to Develop ASSURED Microfluidic Biosensors for Infectious and Non-Infectious Diseases.

Better diagnostics are always essential for the treatment and prevention of a disease. Existing technologies for detecting infectious and non-infectious diseases are mostly tedious, expensive, and do not meet the World Health Organization’s (WHO) ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to end user) criteria. Hence, more accurate, sensitive, and faster diagnostic technologies that meet the ASSURED criteria are highly required for timely and evidenced-based treatment. Presently, the diagnostics industry is finding interest in microfluidics-based biosensors, as this integration comprises all qualities, such as reduction in the size of the equipment, rapid turnaround time, possibility of parallel multiple analysis or multiplexing, etc. Microfluidics deal with the manipulation/analysis of fluid within micrometer-sized channels. Biosensors comprise biomolecules immobilized on a physicochemical transducer for the detection of a specific analyte. In this review article, we provide an outline of the history of microfluidics, current practices in the selection of materials in microfluidics, and how and where microfluidics-based biosensors have been used for the diagnosis of infectious and non-infectious diseases. Our inclination in this review article is toward the employment of microfluidics-based biosensors for the improvement of already existing/traditional methods in order to reduce efforts without compromising the accuracy of the diagnostic test. This article also suggests the possible improvements required in microfluidic chip-based biosensors in order to meet the ASSURED criteria.

Microfabrication Bonding Process Optimization for a 3D Multi-Layer PDMS Suspended Microfluidics

Microfluidic systems have received increased attention due to their wide variety of applications, from chemical sensing to biological detection to medical analysis. Microfluidics used to be fabricated by using etching techniques that required cleanroom and aggressive chemicals. However, another microfluidic fabrication technique, namely, soft lithography, is less expensive and safer compared to former techniques. Polydimethylsiloxane (PDMS) has been widely employed as a fabrication material in microfluidics by using soft lithography as it is transparent, soft, bio-compatible, and inexpensive. In this study, a 3D multi-layer PDMS suspended microfluidics fabrication process using soft lithography is presented, along with its manufacturing issues that may deteriorate or compromise the microsystem’s test results. The main issues considered here are bonding strength and trapped air-bubbles, specifically in multi-layer PDMS microfluidics. In this paper, these two issues have been considered and resolved by optimizing curing temperature and air-vent channel integration to a microfluidic platform. Finally, the suspended microfluidic system has been tested in various experiments to prove its sensitivity to different fluids and flow rates.

Directional droplet transfer on micropillar-textured superhydrophobic surfaces fabricated using a ps laser

Directional droplet transfer is essential for water collection, microfluidic and remote material transfer. Laser-enabled 2.5-dimensional fabrication of micropillars on shape-memory-polymers transfers the surface wettability from hydrophilicity to superhydrophobicity in a simple, fast, and large-scale manner. The surface wettability exhibits a tight relationship with the topographic features of the surface microstructures. By adjusting the height, diameter, bending angle of the micropillars as well as superhydrophobic chemical treatment, the contact angles of water droplets on the micropillar-textured surfaces exceed 160° and exhibit finely-tunable sliding angles from 5.4 ± 1.9° to 71.8 ± 5.9°. A water droplet on a surface textured with bended micropillar shows anisotropic sliding behavior depending on the sliding direction and the micropillar bending angle. By properly design and assembly of straight and bended micropillars, speedy sliding tracks are constructed and directional droplet transfer is demonstrated, suggesting great potential in the fields of lossless material transportation, biomedical testing and microfluidic devices.

Recent Advances in Thermoplastic Microfluidic Bonding.

Microfluidics is a multidisciplinary technology with applications in various fields, such as biomedical, energy, chemicals and environment. Thermoplastic is one of the most prominent materials for polymer microfluidics. Properties such as good mechanical rigidity, organic solvent resistivity, acid/base resistivity, and low water absorbance make thermoplastics suitable for various microfluidic applications. However, bonding of thermoplastics has always been challenging because of a wide range of bonding methods and requirements. This review paper summarizes the current bonding processes being practiced for the fabrication of thermoplastic microfluidic devices, and provides a comparison between the different bonding strategies to assist researchers in finding appropriate bonding methods for microfluidic device assembly.

Superwetting patterned PDMS/PMMA materials by facile one-step electro-spraying for signal expression and liquid transportation

• Patterned PDMS/PMMA coating with asymmetrical wettability has been constructed by electro-spraying technique. • Membrane filters with high wetting contrast demonstrate high separation efficiency and good cycling ability. • Patterned surfaces with anisotropic adhesion show promising on-demand droplet manipulation ability. • Real-time liquid signal expression is realized on such wetting-patterned membrane with high efficiency. Superwetting materials with multiple functions have drawn heightened attention due to their delicately adjustable surface wettability. However, realizing the full potential of diversified functions is often hampered by the usually symmetrical wetting state. Herein, we introduce a versatile electro-spraying technique to construct a patterned PDMS/PMMA coating with asymmetrical wettability. The tunable superwetting patterns are able to achieve the required functional diversity. The as-prepared superhydrophobic fabric can act as a separation filter with a high separation efficiency and satisfactory cycling ability. With the wettability difference, such patterned surfaces can also manipulate the successive drops motions, and relation between the surface patterns and the controllable movement is demonstrated. In addition, the patterned surface can serve as a smart signal-expression membrane, thereby enabling real-time variable liquid signal expression with alterable signals. The exciting results have paved the way for expanding the application foreground of smart superwetting materials in microfluidics and signal-detection.

Microfluidic Particle Reactors: From Interface Characteristics to Cells and Drugs Related Biomedical Applications

AbstractFunctional microfluidic particle reactors (MPRs), prepared with microfluidic emulsions with biomaterials as the templates, can directly encapsulate bioactive substances to achieve different biomedical applications. Different types of MPRs (such as single structure MPRs, mixed structure MPRs, and all‐aqueous structure MPRs) have multifarious functions owing to the prominent interface characteristics endowed by emulsion templates with exquisite controlled fluid components and interface structures, as well as functional biomaterials with attractive properties. Notably, the constructed MPRs are endowed with better controllability, biocompatibility, and injectability with the significant advances in the burgeoning droplet microfluidic technology and material science. This contributes to the improvement of the flexibility and degree of freedom of the MPRs supporting cell and drug‐related biomedical applications (such as 3D cell culture, cell/drug delivery, and controlled drug release), leading to more effective diagnosis and treatment. In this paper, the correlation between the particle structure, determined by optimizing emulsion template fluid components and interfacial complexity, and the interface characteristics of the MPRs are primarily investigated. Next, the interface characteristics of the MPRs expanded by functional biomaterials are reviewed, as well as the distinct properties of MPRs in the biomedical applications related to cells and drugs. Finally, the existing challenges and future perspectives are discussed to improve the unique interface characteristics of MPRs in broader biomedical applications.