Applications In Microfluidic Devices Research Articles

Application of Microfluidic Devices for Automated Two-Step Radiolabeling of Antibodies.

Radioimmunoconjugates (RICs) composed of tumor-targeting monoclonal antibodies and radionuclides have been developed for diagnostic and therapeutic application. A new radiolabeling method using microfluidic devices is expected to facilitate simpler and more rapid synthesis of RICs. In the microfluidic method, microfluidic chips can promote the reaction between reactants by mixing them efficiently, and pumping systems enable automated synthesis. In this study, we synthesized RICs by the pre-labeling method, in which the radiometal is coordinated to the chelator and then the radiolabeled chelator is incorporated into the antibodies, using microfluidic devices for the first time. As a result of examining the reaction parameters including the material of mixing units, reaction temperature, and flow rate, RICs with radiochemical purity (RCP) exceeding 90% were obtained. These high-purity RICs were successfully synthesized without any purification simply by pumping three solutions of a chelating agent, radiometal, and antibody into microfluidic devices. Under the same conditions, the RCP of RICs labeled by conventional methods was below 50%. These findings indicate the utility of microfluidic devices for automatic and rapid synthesis of high-quality RICs.

Double-Sided Tape in Microfluidics: A Cost-Effective Method in Device Fabrication.

The demand for easy-to-use, affordable, accessible, and reliable technology is increasing in biological, chemical, and medical research. Microfluidic devices have the potential to meet these standards by offering cost-effective, highly sensitive, and highly specific diagnostic tests with rapid performance and minimal sample volumes. Traditional microfluidic device fabrication methods, such as photolithography and soft lithography, are time-consuming and require specialized equipment and expertise, making them costly and less accessible to researchers and clinicians and limiting the applicability and potential of microfluidic devices. To address this, researchers have turned to using new low-cost materials, such as double-sided tape for microfluidic device fabrication, which offers simple and low-cost processes. The innovation of low-cost and easy-to-make microfluidic devices improves the potential for more devices to be transitioned from laboratories to commercialized products found in stores, offices, and homes. This review serves as a comprehensive summary of the growing interest in and use of double-sided tape-based microfluidic devices in the last 20 years. It discusses the advantages of using double-sided tape, the fabrication techniques used to create and bond microfluidic devices, and the limitations of this approach in certain applications.

Microfluidic paper analytic device (μPAD) technology for food safety applications.

Foodborne pathogens, food adulterants, allergens, and toxic chemicals in food can cause major health hazards to humans and animals. Stringent quality control measures at all stages of food processing are required to ensure food safety. There is, therefore, a global need for affordable, reliable, and rapid tests that can be conducted at different process steps and processing sites, spanning the range from the sourcing of food to the end-product acquired by the consumer. Current laboratory-based food quality control tests are well established, but many are not suitable for rapid on-site investigations and are costly. Microfluidic paper analytical devices (μPADs) are a fast-growing field in medical diagnostics that can fill these gaps. In this review, we describe the latest developments in the applications of microfluidic paper analytic device (μPAD) technology in the food safety sector. State-of-the-art μPAD designs and fabrication methods, microfluidic assay principles, and various types of μPAD devices with food-specific applications are discussed. We have identified the prominent research and development trends and future directions for maximizing the value of microfluidic technology in the food sector and have highlighted key areas for improvement. We conclude that the μPAD technology is promising in food safety applications by using novel materials and improved methods to enhance the sensitivity and specificity of the assays, with low cost.

Understanding droplet formation in T-shaped channels with magnetic field influence: A computational investigation

This study investigates the production of ferrofluid droplets in a T-junction geometry using the level set method and magnetic force manipulation in the three-dimensional. The analysis reveals key insights into droplet formation processes in four stages: entering, blocking, necking, and detachment. The results show that increasing the Capillary number leads to a significant decrease in volume for non-ferrofluid droplets. Application of a magnetic force enhances the balance of forces during droplet formation, directly impacting droplet volume. Moreover, increasing the magnetic Bond number substantially increases droplet volume, with a more pronounced effect at lower Capillary numbers. Modifying magnetic properties influences droplet volume, with doubling the magnetization results in a significant volume increase. Overall, magnetic forces emerge as a crucial control parameter for droplet volume in ferrofluid systems, offering potential applications in droplet-based technologies and microfluidic devices.

Gold Nanoparticles in Porous Silicon Nanotubes for Glucose Detection

Silicon nanotubes (Si NTs) have a unique structure among the silicon nanostructure family, which is useful for diverse applications ranging from therapeutics to lithium storage/recycling. Their well-defined structure and high surface area make them ideal for sensing applications. In this work, we demonstrate the formation of Au nanoparticles (NPs) functionalized with 4-Mercaptophenylboronic acid (MPBA) on porous Si NTs (pSi NTs) fabricated using ZnO nanowires as a template. The system was characterized, and the proposed structure was confirmed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Varying glucose concentrations in phosphate-buffered saline (PBS) (0.5–80 mM) were introduced to the Si NT nanocomposite system. The glucose is detectable at low concentrations utilizing surface-enhanced Raman spectroscopy (SERS), which shows a concentration-dependent peak shift in the benzene ring breathing mode (~1071 cm−1) of MPBA. Complementing these measurements are simulations of the Raman hot spots associated with plasmonic enhancement of the Au NPs using COMSOL. This biocompatible system is envisioned to have applications in nanomedicine and microfluidic devices for real-time, non-invasive glucose sensing.

Improving the water-repellent properties of carbon nanotube-polycarbonate composites by introducing nanoscale patterns into the injection molding process

In this study, we explore the impact of hydrophobic nanomaterials, specifically carbon nanotubes (CNTs), on the water repellency of composite materials. These composites are prepared by combining multilayered or single-layered CNTs with polycarbonate (PC). Our goal was to develop highly water-repellent materials by directly forming nanopatterns on the surface through injection molding to enhance water repellency. Irrespective of the CNT type, widening the spacing between surface patterns and increasing the CNT concentration from 0 to 30 wt% resulted in a notable increase in the water contact angle to 161°, surpassing that of Teflon (108°). Moreover, in the multilayered CNT/PC system, a reduction in the sliding angle was observed compared to that of pure polycarbonate, demonstrating a lotus effect-like trend. Conversely, in the case of single-layered CNTs, despite an increase in the contact angle, the sliding angle did not decrease as significantly as in the multilayered CNTs. This implies that the superior transferability during the injection molding process of multilayered CNT/PC compared to single-layered CNT/PC is the underlying factor. This technology holds promise not only in the realm of mobility, such as in the aviation and automotive industries, but also in the medical field, with applications in microfluidic devices.

A numerical and experimental analysis of CO2 laser micro-milling on PMMA sheet considering a multipass approach for microfluidic devices

Laser-assisted machining is an advanced manufacturing process that provides excellent cutting quality, flexibility, and precision. The current study used a CO2 laser to create microchannels in polymethyl methacrylate (PMMA) sheets using a series of laser passes by varyingparameters such as laser power (30–40 Watt), number of passes (1–4), and cutting speed (20–25 mm/s). A finite element analysis is performed using ABAQUS with subroutines such as Distributed Flux (DFLUX) and User Defined Field (USDFLD) to simulate and predict the upper and lower kerf width, kerf angle, and heat-affected zone (HAZ) during the process. Thermal analysis has been performed by considering the laser beam as body heat flux with a moving heat source. It has been observed that the HAZ tends to reduce with the increase of laser cutting speed. During the laser cutting process, the upper kerf width is found to increase with increasing laser power, as well as with increasing the number of passes at a given laser power and cutting speed. It is also predictedthat when laser cutting speed increases, the kerf width for a given laser power decreases. The experimental and simulation results are in good agreement and the results demonstrated thatthe average percentage error in HAZ, kerf angle,upper kerf, and lower kerf width was 3.21 %, 5.06 %, 7.60 %, and 22.2 %, respectively. The results of this study have significance for the advancement of precise and state-of-the-art manufacturing for application in microfluidic devices.

Biocatalytic Performance of β-Glucosidase Immobilized on 3D-Printed Single- and Multi-Channel Polylactic Acid Microreactors.

Microfluidic devices have attracted much attention in the current day owing to the unique advantages they provide. However, their application for industrial use is limited due to manufacturing limitations and high cost. Moreover, the scaling-up process of the microreactor has proven to be difficult. Three-dimensional (3D) printing technology is a promising solution for the above obstacles due to its ability to fabricate complex structures quickly and at a relatively low cost. Hence, combining the advantages of the microscale with 3D printing technology could enhance the applicability of microfluidic devices in the industrial sector. In the present work, a 3D-printed single-channel immobilized enzyme microreactor with a volume capacity of 30 μL was designed and created in one step via the fused deposition modeling (FDM) printing technique, using polylactic acid (PLA) as the printing material. The microreactor underwent surface modification with chitosan, and β-glucosidase from Thermotoga maritima was covalently immobilized. The immobilized biocatalyst retained almost 100% of its initial activity after incubation at different temperatures, while it could be effectively reused for up to 10 successful reaction cycles. Moreover, a multi-channel parallel microreactor incorporating 36 channels was developed, resulting in a significant increase in enzymatic productivity.

Rapid prototyping of PMMA-based microfluidic spheroid-on-a-chip models using micromilling and vapour-assisted thermal bonding

The application of microfluidic devices as next-generation cell and tissue culture systems has increased impressively in the last decades. With that, a plethora of materials as well as fabrication methods for these devices have emerged. Here, we describe the rapid prototyping of microfluidic devices, using micromilling and vapour-assisted thermal bonding of polymethyl methacrylate (PMMA), to create a spheroid-on-a-chip culture system. Surface roughness of the micromilled structures was assessed using scanning electron microscopy (SEM) and atomic force microscopy (AFM), showing that the fabrication procedure can impact the surface quality of micromilled substrates with milling tracks that can be readily observed in micromilled channels. A roughness of approximately 153 nm was created. Chloroform vapour-assisted bonding was used for simultaneous surface smoothing and bonding. A 30-s treatment with chloroform-vapour was able to reduce the surface roughness and smooth it to approximately 39 nm roughness. Subsequent bonding of multilayer PMMA-based microfluidic chips created a durable assembly, as shown by tensile testing. MDA-MB-231 breast cancer cells were cultured as multicellular tumour spheroids in the device and their characteristics evaluated using immunofluorescence staining. Spheroids could be successfully maintained for at least three weeks. They consisted of a characteristic hypoxic core, along with expression of the quiescence marker, p27kip1. This core was surrounded by a ring of Ki67-positive, proliferative cells. Overall, the method described represents a versatile approach to generate microfluidic devices compatible with biological applications.

The Physics and Manipulation of Dean Vortices in Single- and Two-Phase Flow in Curved Microchannels: A Review.

Microchannels with curved geometries have been employed for many applications in microfluidic devices in the past decades. The Dean vortices generated in such geometries have been manipulated using different methods to enhance the performance of devices in applications such as mixing, droplet sorting, and particle/cell separation. Understanding the effect of the manipulation method on the Dean vortices in different geometries can provide crucial information to be employed in designing high-efficiency microfluidic devices. In this review, the physics of Dean vortices and the affecting parameters are summarized. Various Dean number calculation methods are collected and represented to minimize the misinterpretation of published information due to the lack of a unified defining formula for the Dean dimensionless number. Consequently, all Dean number values reported in the references are recalculated to the most common method to facilitate comprehension of the phenomena. Based on the converted information gathered from previous numerical and experimental studies, it is concluded that the length of the channel and the channel pathline, e.g., spiral, serpentine, or helix, also affect the flow state. This review also provides a detailed summery on the effect of other geometric parameters, such as cross-section shape, aspect ratio, and radius of curvature, on the Dean vortices' number and arrangement. Finally, considering the importance of droplet microfluidics, the effect of curved geometry on the shape, trajectory, and internal flow organization of the droplets passing through a curved channel has been reviewed.

Microfluidic Device-Based Virus Detection and Quantification in Future Diagnostic Research: Lessons from the COVID-19 Pandemic.

The global economic and healthcare crises experienced over the past three years, as a result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted the commonplace habits of humans around the world. SARS-CoV-2, the virus responsible for the coronavirus 2019 (COVID-19) phenomenon, has contributed to the deaths of millions of people around the world. The potential diagnostic applications of microfluidic devices have previously been demonstrated to effectively detect and quasi-quantify several different well-known viruses such as human immunodeficiency virus (HIV), influenza, and SARS-CoV-2. As a result, microfluidics has been further explored as a potential alternative to our currently available rapid tests for highly virulent diseases to better combat and manage future potential outbreaks. The outbreak management during COVID-19 was initially hindered, in part, by the lack of available quantitative rapid tests capable of confirming a person's active infectiousness status. Therefore, this review will explore the use of microfluidic technology, and more specifically RNA-based virus detection methods, as an integral part of improved diagnostic capabilities and will present methods for carrying the lessons learned from COVID-19 forward, toward improved diagnostic outcomes for future pandemic-level threats. This review will first explore the context of the COVID-19 pandemic and how diagnostic technology was shown to have required even greater advancements to keep pace with the transmission of such a highly infectious virus. Secondly, the historical significance of integrating microfluidic technology in diagnostics and how the different types of genetic-based detection methods may vary in their potential practical applications. Lastly, the review will summarize the past, present, and future potential of RNA-based virus detection/diagnosis and how it might be used to better prepare for a future pandemic.

Microfluidic Wearable Devices for Sports Applications.

This study aimed to systematically review the application and research progress of flexible microfluidic wearable devices in the field of sports. The research team thoroughly investigated the use of life signal-monitoring technology for flexible wearable devices in the domain of sports. In addition, the classification of applications, the current status, and the developmental trends of similar products and equipment were evaluated. Scholars expect the provision of valuable references and guidance for related research and the development of the sports industry. The use of microfluidic detection for collecting biomarkers can mitigate the impact of sweat on movements that are common in sports and can also address the issue of discomfort after prolonged use. Flexible wearable gadgets are normally utilized to monitor athletic performance, rehabilitation, and training. Nevertheless, the research and development of such devices is limited, mostly catering to professional athletes. Devices for those who are inexperienced in sports and disabled populations are lacking. Conclusions: Upgrading microfluidic chip technology can lead to accurate and safe sports monitoring. Moreover, the development of multi-functional and multi-site devices can provide technical support to athletes during their training and competitions while also fostering technological innovation in the field of sports science.

A Review on Fluid Flow and Mixing in Microchannel and their Design and Manufacture for Microfluidic Applications

Abstract: The present time has witnessed a never-before-heard interest in and applications of microfluidic devices and systems. In microfluidic systems, fluid flows and is manipulated in microchannels. Mixing is one of the most important criteria for a majority of microfluidic systems, whose laminar nature hinders the efficiency of micromixing. The interface between the flowing fluid and the inner wall surface of the microchannel greatly influences the behaviour of fluidic flow in microfluidics. Many researchers have tried to pattern the surface, introduce obstacles to flow, and include micro- or nanoprotruded structures to enhance the mixing efficiency by manipulating the microchannel flow. New and rapid advances in MEMS and micro/nanofabrication technologies have enabled researchers to experiment with increasingly complex designs, enabling rapid transformation and dissemination of new knowledge in the field of microfluidics. Here, we report the fluid flow characteristics, mixing, and associated phenomena about microfluidic systems. Microfluidic systems and components such as microreactors, micromixers, and microchannels are reviewed in this work. We review active and passive micromixers, with a primary focus on widely used passive micromixers. Various microchannel geometries and their features, mixing efficiencies, numerical analysis, and fabrication methods are reviewed. Applications as well as possible future trends and advancements in this field, are included too. It is expected to make the reader curious and more familiar with the interesting field of microfluidics.

Application of Paper-Based Microfluidic Analytical Devices (µPAD) in Forensic and Clinical Toxicology: A Review.

The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, µPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma-hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors.

Application of microfluidic technologies on COVID-19 diagnosis and drug discovery.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has boosted the development of antiviral research. Microfluidic technologies offer powerful platforms for diagnosis and drug discovery for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis and drug discovery. In this review, we introduce the structure of SARS-CoV-2 and the basic knowledge of microfluidic design. We discuss the application of microfluidic devices in SARS-CoV-2 diagnosis based on detecting viral nucleic acid, antibodies, and antigens. We highlight the contribution of lab-on-a-chip to manufacturing point-of-care equipment of accurate, sensitive, low-cost, and user-friendly virus-detection devices. We then investigate the efforts in organ-on-a-chip and lipid nanoparticles (LNPs) synthesizing chips in antiviral drug screening and mRNA vaccine preparation. Microfluidic technologies contribute to the ongoing SARS-CoV-2 research efforts and provide tools for future viral outbreaks.

A layout-dependent formula for the critical separation size of parallelogram-type deterministic lateral displacement arrays

The accurate and general formulation of the critical separation size is crucial for the effective design and application of passive microfluidic devices. However, the current formulas for the deterministic lateral displacement (DLD) technique are inadequate in accounting for its structural complexity. To address this limitation, we conducted mesoscopic hydrodynamics simulations to assess the separation performance of various parallelogram-type circular post arrays. Based on the simulation results, we developed a new layout-dependent formula that takes into account key geometric parameters, such as the lateral gap size, row shift fraction, and aspect ratio of downstream and lateral post-post distances, to characterize the lateral gap dimension, periodicity, and asymmetry of DLD arrays, respectively. This formula demonstrated high accuracy over a wide design space, precisely predicting the critical separation sizes of many asymmetric DLD devices in experiments. Furthermore, it is worth noting that when the downstream gap size expands, the veering flow strengthens, which, in turn, results in an increase in the critical separation size. These findings shed light on the unique separation mechanism induced by array asymmetry and present a powerful design tool for maximizing the potential of asymmetric DLD devices.

Advances in Integration, Wearable Applications, and Artificial Intelligence of Biomedical Microfluidics Systems.

Microfluidics attracts much attention due to its multiple advantages such as high throughput, rapid analysis, low sample volume, and high sensitivity. Microfluidics has profoundly influenced many fields including chemistry, biology, medicine, information technology, and other disciplines. However, some stumbling stones (miniaturization, integration, and intelligence) strain the development of industrialization and commercialization of microchips. The miniaturization of microfluidics means fewer samples and reagents, shorter times to results, and less footprint space consumption, enabling a high throughput and parallelism of sample analysis. Additionally, micro-size channels tend to produce laminar flow, which probably permits some creative applications that are not accessible to traditional fluid-processing platforms. The reasonable integration of biomedical/physical biosensors, semiconductor microelectronics, communications, and other cutting-edge technologies should greatly expand the applications of current microfluidic devices and help develop the next generation of lab-on-a-chip (LOC). At the same time, the evolution of artificial intelligence also gives another strong impetus to the rapid development of microfluidics. Biomedical applications based on microfluidics normally bring a large amount of complex data, so it is a big challenge for researchers and technicians to analyze those huge and complicated data accurately and quickly. To address this problem, machine learning is viewed as an indispensable and powerful tool in processing the data collected from micro-devices. In this review, we mainly focus on discussing the integration, miniaturization, portability, and intelligence of microfluidics technology.

Flexible and Photo-responsive superwetting surfaces based on porous materials coated with Mussel-Inspired Azo-Copolymer

The decoration of porous materials with stimulus-responsive polymers is an efficient strategy for the fabrication of superwetting surfaces; however, the weak interfacial interaction between the polymers and the substrates limits their application. Herein, inspired by the molecular structure of the mussel foot protein, a series of catechol-functionalized azobenzene-containing copolymers with diverse chain structures are synthesized via solution radical polymerization and used for the preparation of smart superwetting surfaces. After dip-coating with the mussel-inspired azo-copolymers, the modified cotton fabrics and melamine sponges possessed smart surfaces with photo-switchable wettability. These as-prepared flexible smart surfaces exhibited rapid wettability transition between high hydrophobicity and superhydrophilicity with alternating ultraviolet (UV) and visible light irradiation. Meanwhile, these superwetting surfaces were also experimentally found to be robust without apparent degradation in their photo-responsiveness, even after being soaked in acid/base solutions and subjected to repetitive mechanical deformation. Especially, the functionalized melamine sponges as bulk superwetting materials have excellent mechanical stability, which can tolerate harsh abrasion cycles and repetitive compressive deformations. More importantly, it was also confirmed that the mussel-inspired azo-copolymers exhibited excellent adhesion properties at the interface of various substrates. This bioinspired strategy and developed functional copolymers paves the way for facile and large-scale fabrication of superwetting surfaces, which may find a wide range of advanced potential applications in microfluidic devices, biomedicine and sensors.

Recent Progress and Perspectives on Neural Chip Platforms Integrating PDMS-Based Microfluidic Devices and Microelectrode Arrays

Recent years have witnessed a spurt of progress in the application of the encoding and decoding of neural activities to drug screening, diseases diagnosis, and brain–computer interactions. To overcome the constraints of the complexity of the brain and the ethical considerations of in vivo research, neural chip platforms integrating microfluidic devices and microelectrode arrays have been raised, which can not only customize growth paths for neurons in vitro but also monitor and modulate the specialized neural networks grown on chips. Therefore, this article reviews the developmental history of chip platforms integrating microfluidic devices and microelectrode arrays. First, we review the design and application of advanced microelectrode arrays and microfluidic devices. After, we introduce the fabrication process of neural chip platforms. Finally, we highlight the recent progress on this type of chip platform as a research tool in the field of brain science and neuroscience, focusing on neuropharmacology, neurological diseases, and simplified brain models. This is a detailed and comprehensive review of neural chip platforms. This work aims to fulfill the following three goals: (1) summarize the latest design patterns and fabrication schemes of such platforms, providing a reference for the development of other new platforms; (2) generalize several important applications of chip platforms in the field of neurology, which will attract the attention of scientists in the field; and (3) propose the developmental direction of neural chip platforms integrating microfluidic devices and microelectrode arrays.

Application of a novel rectangular filtering microfluidic device for microfilarial detection.

The rectangular filtering microfluidic chip was invented using microfluidics device fabrication technology and can separate living microfilariae from blood samples without a syringe pump. The diagnostic results are highly effective. The device is based on the principle of separating millions of blood cells from microfilariae using a rectangular filter structure. It disperses fluid evenly into the flow-passage channel, and its rectangular filter structure is the key to success in reducing the pressure and separating blood cells from microfilariae effectively. The flow rate and blood cell concentration were optimized in our study. The chip is intended to be a point-of-care device that can reduce the use of superfluous instrumentation in the field. The technology is designed to be rapid, accurate, and easy-to-use for all users, especially those in remote areas.