Search

Simple Summary: Interactions between breast cancer (BCa) cells and carcinoma-associated fibroblasts (CAFs) in the tumor microenvironment (TME) are critical for cancer development and progression and can mitigate responses to therapies. Historically, it has been difficult to replicate in vivo long-term interactions between BCa cells and CAFs for in vitro studies and to define the precise roles of CAFs in BCa cell progression. Our novel microfluidic-capable culture devices called TAME (tissue architecture and microenvironment engineering) devices enable us to study cell-cell interactions of human breast cancer (BCa) cells and human CAFs through their secretome in 3D cultures for extended periods, up to and beyond 70 days. Using these systems, we observed that CAFs enhance BCa cell progression to an invasive phenotype. Moreover, secretome-mediated reciprocal interactions of BCa cells and CAFs promote their migration toward each other, suggesting that targeting signaling pathways to mediate interactions between BCa cells and CAFs could be a potential therapeutic approach for the prevention of BCa progression. Background/Objectives: Carcinoma-associated fibroblasts (CAFs), a prominent cell type in the tumor microenvironment (TME), significantly contributes to cancer progression through interactions with cancer cells and other TME components. Consequently, targeting signaling pathways driven by CAFs has potential to yield new therapeutic approaches to inhibit cancer progression. However, the mechanisms underlying their long-term interactions with cancer cells in vivo remains poorly understood. Methods: To address this, we developed a three-dimensional (3D) parallel coculture model of human triple-negative breast cancer (TNBC) cells and CAFs using our innovative TAME devices. This model allowed for the analysis of TNBC paracrine interactions via their secretome over extended culture periods (at least 70 days). Results: Using TNBC cell lines (MDA-MB-231, MCF10.DCIS, and HCC70), we found that TNBC spheroids in 3D parallel cocultures with CAFs exhibited more pronounced invasive finger-like outgrowths than those in cocultures of TNBC cells and normal fibroblasts (NFs) over a period of 50–70 days. We also established that the CAF-derived secretome affects TNBC migration towards the CAF secretome region. Additionally, we observed a preferential migration of CAFs, but not NFs, toward TNBC spheroids. Conclusions: Overall, our results suggest that paracrine interactions between TNBC cells and CAFs enhance TNBC invasive phenotypes and promote reciprocal migration. [ABSTRACT FROM AUTHOR]

Shear stress plays a crucial role in modulating cell adhesion and signaling. We present a microfluidic shear stress generator used to investigate the adhesion dynamics of Dictyostelium discoideum, an amoeba cell model organism with well-characterized adhesion properties. We applied shear stress and tracked cell adhesion, motility, and detachment using time-lapse videomicroscopy. In the precise shear conditions generated on-chip, our results show cell migration patterns are influenced by shear stress, with cells displaying an adaptive response to shear forces as they alter their adhesion and motility behavior. Additionally, we observed that DH1-10 wild-type D. discoideum cells exhibit stronger adhesion and resistance to shear-induced detachment compared to phg2 adhesion-defective mutant cells. We also highlight the influence of cell density on detachment kinetics. [ABSTRACT FROM AUTHOR]

Technologies for rapid and high-throughput separation of rare cells from large populations of other types of cells have recently attracted much attention in the field of bioengineering. Among the various cell separation technologies proposed in the past, dielectrophoresis has shown particular promise because of its preciseness of manipulation and noninvasiveness to cells. However, one drawback of dielectrophoresis devices is that their application of high voltage generates Joule heat that exposes the cells within the device to high temperatures. To further explore this problem, this study investigated the temperature field in a previously developed cell separation device in detail. The temperature rise at the bottom of the microfluidic channel in the device was measured using a micro-LIF method. Moreover, the thermofluidic behavior of the cell separation device was numerically investigated by adopting a heat generation model that takes the electric-field-dependent heat generation term into account in the energy equation. Under the operating conditions of the previously developed cell separation device, the experimentally obtained temperature rise in the device was approximately 20 °C, and the numerical simulation results generally agreed well. Next, parametric calculations were performed with changes in the flow rate of the cell sample solution and the solution conductivity, and a temperature increase of more than 40 °C was predicted. The results demonstrated that an increase in temperature within the cell separation device may have a significant impact on the physiological functions of the cells, depending on the operating conditions of the device. [ABSTRACT FROM AUTHOR]

Complement C5a protein has been shown to play a major role in tissue regeneration through interaction with its receptor (C5aR) on target cells. Expression of this receptor has been reported in the nervous system which, upon injury, has no treatment to restore the lost functions. This work aimed at investigating the Complement C5a effect on axonal growth after axotomy in vitro. Primary hippocampal neurons were isolated from embryonic Wistar rats. Cell expression of C5aR mRNA was verified by RT-PCR while its membrane expression, localization, and phosphorylation were investigated by immunofluorescence. Then, the effects of C5a on injured axonal growth were investigated using a 3D-printed microfluidic device. Immunofluorescence demonstrated that the primary cultures contained only mature neurons (93%) and astrocytes (7%), but no oligodendrocytes or immature neurons. Immunofluorescence revealed a co-localization of NF-L and C5aR only in the mature neurons where C5a induced the phosphorylation of its receptor. C5a application on injured axons in the microfluidic devices significantly increased both the axonal growth speed and length. Our findings highlight a new role of C5a in regeneration demonstrating an enhancement of axonal growth after axotomy. This may provide a future therapeutic tool in the treatment of central nervous system injury. [ABSTRACT FROM AUTHOR]

In this work, a microfluidic paper-based analytical device (µPAD) for simultaneous detection of Fe, Zn, and Mn ions using immobilized chromogenic reagents Ferene S, xylenol orange, and 1-(2-pyridylazo)-2-naphthol, respectively, is presented. As the effective recognition of analytes via respective chromogens takes place under extremely different pH conditions, experiments reported in this publication are focused on optimization of the µPAD architecture allowing for the elimination of potential cross effects. The paper-based microfluidic device was fabricated using low-cost and well-reproducible wax-printing technology. For optical detection of color changes, an ordinary office scanner and self-made RGB-data processing program were applied. Optimized and stable over time, µPADs allow fast, selective, and reproducible multianalyte determinations at submillimolar levels of respective heavy metal ions, which was confirmed by results of the analysis of solutions mimicking real samples of wastewater. The presented concept of simultaneous determination of different analytes that required extremely different conditions for detection can be useful for the development of other multianalyte microfluidic paper-based devices in the µPAD format. [ABSTRACT FROM AUTHOR]

The radiometal gallium-68 (Ga-68) has garnered significant interest due to its convenient production via compact and widely available generators and the high performance of 68Ga-labeled compounds for positron-emission tomography (PET) imaging for cancer diagnosis and management of patients undergoing targeted radionuclide therapy. Given the short half life of Ga-68 (68 min), microfluidic-based radiosynthesis is a promising avenue to establish very rapid, efficient, and routine radiolabeling with Ga-68; however, the typical elution volume of Ga-68 from a generator (4–10 mL) is incompatible with the microliter reaction volumes of microfluidic devices. To bridge this gap, we developed a microscale cartridge-based approach to concentrate Ga-68. By optimizing cartridge design, resin type, resin mass, and eluent composition, Ga-68 was reliably concentrated from ~6 mL to ~80 µL with high recovery efficiency (>97%, n = 14). Furthermore, this method is suitable for both single- and dual-generator setups. To demonstrate suitability of the concentrated radiometal for radiolabeling, we performed microdroplet synthesis of [68Ga]Ga-PSMA-11, achieving high radiochemical yield (83 ± 11%, n = 3), excellent radiochemical purity (>99%), and high apparent specific activity (255–320 MBq/μg). The entire process, including Ga-68 concentration, radiosynthesis, purification, and formulation, was completed in 12 min. Starting with activity of 0.81–0.84 GBq, 0.51–0.64 GBq of product was produced, sufficient for multiple patient doses. This work paves the way to clinical-scale production of other 68Ga-labeled compounds using droplet microreactor methods, or high-throughput labeling optimization or compound screening of 68Ga-labeled probes using droplet reaction arrays. [ABSTRACT FROM AUTHOR]

The inception of microfluidic devices marks a confluence of diverse scientific domains, including physics, biology, chemistry, and fluid mechanics. These multidisciplinary roots have catalyzed the evolution of microfluidic devices, which serve as versatile platforms for various chemical and biological processes. Notably, microfluidic devices have garnered attention as efficient reactors, offering distinct benefits such as minimized spatial requirements for reactions, reduced equipment costs, and accelerated residence times. These advantages, among others, have ignited a compelling interest in harnessing microfluidic technology for the conception, refinement, and production of various nanomaterials and nanocomposites, pivotal within both industrial and medicinal sectors. This comprehensive exposition delves into multifaceted aspects of nanomaterial synthesis, underscoring the transformative role of microfluidic methodologies as a departure from conventional techniques. The discourse navigates through intricate considerations surrounding the preparation of nanomaterials, elucidating how the microfluidic paradigm has emerged as a promising alternative. This paper serves as an illuminating exploration of the juncture between microfluidic innovation and nanomaterial synthesis. It traverses the transformative potential of microfluidics in revolutionizing traditional approaches, heralding a new era of precision engineering for advanced materials with applications spanning industrial to medicinal domains. [ABSTRACT FROM AUTHOR]

The Special Issue of Micromachines, titled "Nanomaterials for Micro/Nanodevices," explores the advancements and applications of nanomaterials in micro- and nano-scale devices. The issue features ten papers that highlight the unique properties of nanomaterials and their role in enhancing device performance. From bio-inspired nanomaterials to superhydrophobic surfaces and novel materials like nanostructured spinel chromites, the issue covers a wide range of topics that showcase the potential of nanomaterials in driving future technological innovations. Researchers and practitioners can gain valuable insights from these studies to further develop nanomaterial applications in various fields. [Extracted from the article]

The velocity and trajectory of particles moving along the corrugated (rough) surface under the action of gravity is obtained by a modified Method of Fundamental Solutions (MFS). This physical situation is found often in biological systems and microfluidic devices. The Stokes equations with no-slip boundary conditions are solved using the Green's function for Stokeslets. In the present study, the velocity of a moving particle under the action of the gravity force is not known and becomes a part of the MFS solution. This requires an adjustment of the matrix of the MFS linear system to include the unknown particle velocity and incorporate in the MFS the balance of hydrodynamic and gravity forces acting on the particle. The study explores the combination of the regularization of Stokeslets and placement of Stokeslets outside the flow domain to ensure the accuracy and stability of computations for particles moving in proximity to the wall. The MFS results are compared to prior published approximate analytical and experimental results to verify the effectiveness of this methodology to predict the trajectory of particles, including their deviation from the vertical trajectory, and select the optimal set of computational parameters. The developed MFS methodology is then applied to the sedimentation of a pair of two spherical particles in proximity to the corrugated wall, in which case, the analytical solution is not available. The MFS results show that particles in the pair deviate from the trajectory of a single particle: the particle located below moves farther away from vertical wall, and the particle located above shifts closer to the wall. [ABSTRACT FROM AUTHOR]

Long-term live cell imaging requires sophisticated and fully automated commercial-stage incubators equipped with specified inverted microscopes to regulate temperature, CO2 content, and humidity. In this study, we present a CO2-free on-stage incubator specifically designed for use across various cell culture platforms, enabling live cell imaging applications. A simple and transparent incubator was fabricated from acrylic sheets to be easily placed on the stages of most inverted microscopes. We successfully performed live-cell imaging of cholangiocarcinoma (CCA) cells and HeLa cell dynamics in both 2D and 3D microenvironments over three days. We also analyzed directed cell migration under high serum induction within a microfluidic device. Interesting phenomena such as "whole-colony migration", "novel type of collective cell migration" and "colony formation during cell and colony migration" are reported here for the first time, to the best of our knowledge. These phenomena may improve our understanding of the nature of cell migration and cancer metastasis. [ABSTRACT FROM AUTHOR]

This review examines recent advancements in electrochemical immunosensors for the detection of organophosphate pesticides, focusing on strategies to enhance sensitivity and selectivity. The widespread use of these pesticides has necessitated the development of rapid, accurate, and field-deployable detection methods. We discuss the fundamental principles of electrochemical immunosensors and explore innovative approaches to improve their performance. These include the utilization of nanomaterials such as metal nanoparticles, carbon nanotubes, and graphene for signal amplification; enzyme-based amplification strategies; and the design of three-dimensional electrode architectures. The integration of these sensors into microfluidic and lab-on-a-chip devices has enabled miniaturization and automation, while screen-printed and disposable electrodes have facilitated on-site testing. We analyze the challenges faced in real sample analysis, including matrix effects and the stability of biological recognition elements. Emerging trends such as the application of artificial intelligence for data interpretation and the development of aptamer-based sensors are highlighted. The review also considers the potential for commercialization and the hurdles that must be overcome for widespread adoption. Future research directions are identified, including the development of multi-analyte detection platforms and the integration of sensors with emerging technologies like the Internet of Things. This comprehensive overview provides insights into the current state of the field and outlines promising avenues for future development in organophosphate pesticide detection. [ABSTRACT FROM AUTHOR]

Microfluidics are crucial for managing small-volume analytical solutions for various applications, such as disease diagnostics, drug efficacy testing, chemical analysis, and water quality monitoring. The precise control of flow control devices can generate diverse flow patterns using pneumatic control with solenoid valves and a microcontroller. This system enables the active modulation of the pneumatic pressure through Arduino programming of the solenoid valves connected to the pressure source. Additionally, the incorporation of solenoid valve sets allows for multichannel control, enabling simultaneous creation and manipulation of various microflows at a low cost. The proposed microfluidic flow controller facilitates accurate flow regulation, especially through periodic flow modulation beneficial for droplet generation and continuous production of microdroplets of different sizes. Overall, we expect the proposed microfluidic flow controller to drive innovative advancements in technology and medicine owing to its engineering precision and versatility. [ABSTRACT FROM AUTHOR]

Particle separation and sorting techniques based on microfluidics have found extensive applications and are increasingly gaining prominence. This research presents the design and fabrication of a microfluidic device for separating cells using deterministic lateral displacement (DLD), enabling accuracy and continuity while being size-based. Nevertheless, it remains demanding, to completely reverse the detrimental effects of the boundaries that disturb the fluidic flow in the channel and reduce particle separation efficiency. This study introduces a novel approach to enhance the boundary structure of channels. By using this design, separation efficiency is boosted, and the fluid behavior around the walls is improved. The boundary correction (BC) enhances the operation of the microchannel and is very effective in microchannels. With boundary correction, the device exhibited improved separation efficiencies, but in its absence, separation efficiencies dropped. The collected microscopic images of the isolation of prostate cancer cell lines and red blood cells revealed promising outcomes. The efficiency of circulating tumor cell (CTC) throughput in the microfluidic channel, quantified as the ratio or proportion of tumor cells exiting the channel to cells entering it, exceeds 93%. Moreover, the efficiency of CTC isolation, expressed as the proportion of tumor cells from the upper outlet of the microfluidic channel to all cells, is over 89%. Additionally, the efficiency of red blood cell isolation, evaluated as the ratio of red blood cells from the lower outlet of the microfluidic channel to all cells, surpasses 77%. While using the same DLD separator without boundary correction reduced the separation efficiency by around 5%. [ABSTRACT FROM AUTHOR]

This paper presents a novel centrifugal microfluidic approach (so-called lab-on-a-CD) for magnetic circulating tumor cell (CTC) separation from the other healthy cells according to their physical and acquired chemical properties. This study enhances the efficiency of CTC isolation, crucial for cancer diagnosis, prognosis, and therapy. CTCs are cells that break away from primary tumors and travel through the bloodstream; however, isolating CTCs from blood cells is difficult due to their low numbers and diverse characteristics. The proposed microfluidic device consists of two sections: a passive section that uses inertial force and bifurcation law to sort CTCs into different streamlines based on size and shape and an active section that uses magnetic forces along with Dean drag, inertial, and centrifugal forces to capture magnetized CTCs at the downstream of the microchannel. The authors designed, simulated, fabricated, and tested the device with cultured cancer cells and human cells. We also proposed a cost-effective method to mitigate the surface roughness and smooth surfaces created by micromachines and a unique pulsatile technique for flow control to improve separation efficiency. The possibility of a device with fewer layers to improve the leaks and alignment concerns was also demonstrated. The fabricated device could quickly handle a large volume of samples and achieve a high separation efficiency (93%) of CTCs at an optimal angular velocity. The paper shows the feasibility and potential of the proposed centrifugal microfluidic approach to satisfy the pumping, cell sorting, and separating functions for CTC separation. [ABSTRACT FROM AUTHOR]

Vascular diseases are widespread, and sometimes such life-threatening medical disorders cause abnormal blood flow, blood particle damage, changes to flow dynamics, restricted blood flow, and other adverse effects. The study of vascular flow is crucial in clinical practice because it can shed light on the causes of stenosis, aneurysm, blood cancer, and many other such diseases, and guide the development of novel treatments and interventions. Microfluidics and computational fluid dynamics (CFDs) are two of the most promising new tools for investigating these phenomena. When compared to conventional experimental methods, microfluidics offers many benefits, including lower costs, smaller sample quantities, and increased control over fluid flow and parameters. In this paper, we address the strengths and weaknesses of computational and experimental approaches utilizing microfluidic devices to investigate the rheological properties of blood, the forces of action causing diseases related to cardiology, provide an overview of the models and methodologies of experiments, and the fabrication of devices utilized in these types of research, and portray the results achieved and their applications. We also discuss how these results can inform clinical practice and where future research should go. Overall, it provides insights into why a combination of both CFDs, and experimental methods can give even more detailed information on disease mechanisms recreated on a microfluidic platform, replicating the original biological system and aiding in developing the device or chip itself. [ABSTRACT FROM AUTHOR]

The microfluidic measurement of capillary flow can be used to evaluate the response of biological samples to stimulation, where distance and velocity are altered. Melt-extruded multi-bored microfluidic capillaries allow for high-throughput testing with low device cost, but simple devices may limit control over sample flow when compared to the more complex "lab-on-a-chip" devices produced using advanced microfluidic fabrication methods. Previously, we measured the dynamics of global haemostasis stimulated by thrombin by dipping straight vertical microcapillaries into blood, but only the most rapid response could be monitored, as flow slowed significantly within 30 s. Here, we show an innovative method to extend both the stimulation process and flow measurement time without increasing the cost of the device by adding simple loops to the flexible extruded device. The loops enable longer time-scale measurements by increasing resistance to flow, thereby reducing the dependence on high stimulus concentrations for rapid reactions. The instantaneous velocity and equilibrium heights of straight and looped vertical microcapillary films were assessed with water, plasma and whole blood, showing that the loops create additional frictional resistances, reduce flow velocity and prolong residence times for increased time scales of the stimulation process. A modified pressure balance model was used to capture flow dynamics with the added loop. Looped devices loaded with thrombin and collagen showed an improved detection of blood stimulation responses even with lower stimulus concentrations, compared to straight vertical capillaries. Thrombin-activated blood samples in straight capillaries provided a maximum measurement zone of only 4 mm, while the looped design significantly increased this to 11 mm for much longer time scale measurements. Our results suggest that extending stimulation times can be achieved without complex microfluidic fabrication methods, potentially improving concentration–response blood stimulation assays, and may enhance the accuracy and reliability. We conclude adding a loop to low-cost extruded microfluidic devices may bring microfluidic devices closer to delivering on their promise of widespread, decentralized low-cost evaluation of blood response to stimulation in both research and clinical settings. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most severe form of brain cancer in adults, characterized by its complex vascular network that contributes to resistance to conventional therapies. Thermal therapies, such as magnetic hyperthermia (MHT), emerge as promising alternatives, using heat to selectively target tumor cells while minimizing damage to healthy tissues. The organ-on-a-chip can replicate this complex vascular network of GBM, allowing for detailed investigations of heat dissipation in MHT, while computational simulations refine treatment parameters. In this in silico study, tumor-on-a-chip models were used to optimize MHT therapy by comparing heat dissipation in normal and abnormal vascular networks, considering geometries, flow rates, and concentrations of magnetic nanoparticles (MNPs). In the high vascular complexity model, the maximum velocity was 19 times lower than in the normal vasculature model and 4 times lower than in the low-complexity tumor model, highlighting the influence of vascular complexity on velocity and temperature distribution. The MHT simulation showed greater heat intensity in the central region, with a flow rate of 1 µL/min and 0.5 mg/mL of MNPs being the best conditions to achieve the therapeutic temperature. The complex vasculature model had the lowest heat dissipation, reaching 44.15 °C, compared to 42.01 °C in the low-complexity model and 37.80 °C in the normal model. These results show that greater vascular complexity improves heat retention, making it essential to consider this heterogeneity to optimize MHT treatment. Therefore, for an efficient MHT process, it is necessary to simulate ideal blood flow and MNP conditions to ensure heat retention at the tumor site, considering its irregular vascularization and heat dissipation for effective destruction. [ABSTRACT FROM AUTHOR]

Metal micro-droplet ejection technology has attracted attention for its potential applications in the rapid prototyping of micro-metal parts and microelectronic packaging. The current micro-droplet ejection device developed based on this technology faces challenges such as the requirement of a micro-oxygen ejection environment, a complex feeding structure, and high costs. Therefore, a drop-on-demand droplet generator for metallic pellets with impact feed ejection is designed in this paper. This device has a simple and compact structure, does not require a high-cost heat source, and can perform drop-on-demand ejection of metallic pellets in an atmospheric environment. A micro-channel feeding method based on piezoelectric ceramic actuator drives is proposed. A rigid dynamics metallic pellet flight trajectory model is established to analyze the relationships between the driving voltage and the flight trajectory of the pellets. With the help of Fluent to simulate and analyze the melting and ejection processes of the pellets inside the nozzle, the changes in the variable parameters of the flow field in the process of the melting and flight of a single molten drop are studied. The droplet generator produces stable droplets with a 500 µs pulse width and 1100 mm/s initial velocity of the projectile. The simulation results show that a single projectile has to go through three stages including feeding, melting, and ejecting, which take 39.5 ms, 7.85 ms, and 17.65 ms. The total simulation time is 65.0 ms. It is expected that the injection frequency of the metal projectile droplet-generating device will reach 15 Hz. [ABSTRACT FROM AUTHOR]

This review explores significant advancements in polymer science and fabrication processes that have enhanced the performance and broadened the application scope of microfluidic devices. Microfluidics, essential in biotechnology, medicine, and chemical engineering, relies on precise fluid manipulation in micrometer-sized channels. Recent innovations in polymer materials, such as flexible, biocompatible, and structurally robust polymers, have been pivotal in developing advanced microfluidic systems. Techniques like replica molding, microcontact printing, solvent-assisted molding, injection molding, and 3D printing are examined, highlighting their advantages and recent developments. Additionally, the review discusses the diverse applications of polymer-based microfluidic devices in biomedical diagnostics, drug delivery, organ-on-chip models, environmental monitoring, and industrial processes. This paper also addresses future challenges, including enhancing chemical resistance, achieving multifunctionality, ensuring biocompatibility, and scaling up production. By overcoming these challenges, the potential for widespread adoption and impactful use of polymer-based microfluidic technologies can be realized. [ABSTRACT FROM AUTHOR]

This study investigates the fabrication of 3D-printed microfluidic devices for solid/liquid separation, focusing on additive manufacturing technologies. Stereolithography (SLA) and fused filament fabrication (FFF) were used to create microseparators with intricate designs optimized for separation efficiency. Model suspensions containing quartz sand, nano-calcium carbonate, and talc-based baby powder in water were prepared using an electric magnetic stirrer and conveyed into the microseparator via a peristaltic pump. Different flow rates were tested to evaluate their influence on the separation efficiency. The highest separation efficiency for the model systems was observed at a flow rate of 200 mL min−1. This was due to the increased turbulence at higher flow rates, which hindered the secondary flow perpendicular to the primary flow direction. The particle size distribution before and after separation was analyzed using sieve and laser diffraction, and particle morphology was inspected by scanning electron microscopy. The laser diffraction analysis revealed post-separation particle size distributions, indicating that Outlet 1 (external stream) consistently captured larger particles more effectively than Outlet 2 (internal stream). This work highlights the potential of additive manufacturing to produce customized microfluidic devices, enabling rapid prototyping and fine-tuning of complex geometries, thus enhancing separation efficiency across various industrial applications. [ABSTRACT FROM AUTHOR]

Gastrointestinal cell culture technology has evolved in the past decade with the integration of microfluidic technologies, bringing advantages with greater selectivity and cost effectiveness. Herein, these technologies are sorted into three categories, namely the cell-culture insert devices, conventional microfluidic devices, and 3D-printed microfluidic devices. Each category is discussed in brief with improvements also discussed here. Introduction of different companies and applications derived from each are also provided to encourage uptake. Subsequently, future perspectives of integrating microfluidics with trending topics like stool-derived in vitro communities and gut–immune–tumor axis investigations are discussed. Insights on modular microfluidics and its implications on gastrointestinal cell cultures are also discussed here. Future perspectives on point-of-care (POC) applications in relations to gastrointestinal microfluidic devices are also discussed here. In conclusion, this review presents an introduction of each microfluidic platform with an insight into the greater contribution of microfluidics in gastrointestinal cell cultures. [ABSTRACT FROM AUTHOR]

The rapid and sensitive detection of bacterial contaminants using low-cost and portable point-of-need (PoN) biosensors has gained significant interest in water quality monitoring. Cell-imprinted polymers (CIPs) are emerging as effective and inexpensive materials for bacterial detection as they provide specific binding sites designed to capture whole bacterial cells, especially when integrated into PoN microfluidic devices. However, improving the sensitivity and detection limits of these sensors remains challenging. In this study, we integrated CIP-functionalized stainless steel microwires (CIP-MWs) into a microfluidic device for the impedimetric detection of E. coli bacteria. The sensor featured two parallel microchannels with three-electrode configurations that allowed simultaneous control and electrochemical impedance spectroscopy (EIS) measurements. A CIP-MW and a non-imprinted polymer (NIP)-MW suspended perpendicular to the microchannels served as the working electrodes in the test and control channels, respectively. Electrochemical spectra were fitted with equivalent electrical circuits, and the charge transfer resistances of both cells were measured before and after incubation with target bacteria. The charge transfer resistance of the CIP-MWs after 30 min of incubation with bacteria was increased. By normalizing the change in charge transfer resistance and analyzing the dose–response curve for bacterial concentrations ranging from 0 to 107 CFU/mL, we determined the limits of detection and quantification as 2 × 102 CFU/mL and 1.4 × 104 CFU/mL, respectively. The sensor demonstrated a dynamic range of 102 to 107 CFU/mL, where bacterial counts were statistically distinguishable. The proposed sensor offers a sensitive, cost-effective, durable, and rapid solution for on-site identification of waterborne pathogens. [ABSTRACT FROM AUTHOR]

Lactate is a critical regulatory factor secreted by tumors, influencing tumor development, metastasis, and clinical prognosis. Precise analysis of tumor-cell-secreted lactate is pivotal for early cancer diagnosis. This study describes a paper-based microfluidic chip to enable the detection of lactate levels secreted externally by living cells. Under optimized conditions, the lactate biosensor can complete the assay in less than 30 min. In addition, the platform can be used to distinguish lactate secretion levels in different cell lines and can be applied to the screening of antitumor drugs. Through enzymatic chemical conversion, this platform generates fluorescent signals, enabling qualitative assessment under a handheld UV lamp and quantitative analysis via grayscale intensity measurements using ImageJ (Ver. 1.50i) software. The paper-based platform presented in this study is rapid and highly sensitive and does not necessitate other costly and intricate instruments, thus making it applicable in resource-constrained areas and serving as a valuable tool for investigating cell lactate secretion and screening various anti-cancer drugs. [ABSTRACT FROM AUTHOR]

Loop-mediated isothermal amplification (LAMP) has attracted significant attention for rapid and accurate point-of-care diagnostics. However, integrating sample introduction, lysis, amplification, and detection steps into an easy-to-use, disposable system has so far been challenging. This has limited the uptake of the technique in practical applications. In this study, we developed a colourimetric one-step LAMP assay that combines thermolysis and LAMP reaction, to detect the SARS-CoV-2 virus in nasopharyngeal swab samples from COVID-19-infected individuals. The limit of detection was 500 copies per reaction at 65 °C for 25 min in reaction tubes. Additionally, we developed a finger-operated capillary-driven microfluidic device with selective PVA coating. This finger-actuated microfluidic device could self-dose the required sample amount for the LAMP reaction and inhibit sample evaporation. Finally, we integrated the LAMP assay into the microfluidic device by short-term pre-storage of the LAMP master mix. Using this device, nasopharyngeal swab samples from COVID-19-infected individuals showed positive results at a reaction time of 35 min at 65 °C. This integrated device may be adapted to detect other RNA viruses of interest rapidly. [ABSTRACT FROM AUTHOR]

In experiments considering cell handling in microchannels, cell sedimentation in the storage container is a key problem because it affects the reproducibility of the experiments. Here, a simple and low-cost cell mixing device (CMD) is presented; the device is designed to prevent the sedimentation of cells in a syringe during their injection into a microfluidic channel. The CMD is based on a slider crank device made of 3D-printed parts that, combined with a permanent magnet, actuate a stir bar placed into the syringe containing the cells. By using A549 cell lines, the device is characterized in terms of cell viability (higher than 95%) in different mixing conditions, by varying the oscillation frequency and the overall mixing time. Then, a dedicated microfluidic experiment is designed to evaluate the injection frequency of the cells within a microfluidic chip. In the presence of the CMD, a higher number of cells are injected into the microfluidic chip with respect to the static conditions (2.5 times), proving that it contrasts cell sedimentation and allows accurate cell handling. For these reasons, the CMD can be useful in microfluidic experiments involving single-cell analysis. [ABSTRACT FROM AUTHOR]

pH-responsive hydrogels have numerous applications in tissue engineering, drug delivery systems, and diagnostics. Gelatin methacryloyl (GelMA) is a biocompatible, semi-synthetic polymer prepared from gelatin. When combined with aqueous solvents, GelMA forms hydrogels that have extensive applications in biomedical engineering. GelMA can be produced with different degrees of methacryloyl substitution; however, the synthesis of this polymer has not been tuned towards producing selectively modified materials for single-component pH-responsive hydrogels. In this work, we have explored two different synthetic routes targeting different gelatin functional groups (amine, hydroxyl, and/or carboxyl) to produce two GelMA analogs: gelatin A methacryloyl glycerylester (polymer A) and gelatin B methacrylamide (polymer B). Polymers A and B were used to fabricate pH-responsive hydrogel microspheres in a flow-focusing microfluidic device. At neutral pH, polymer A and B microspheres displayed an average diameter of ~40 µm. At pH 6, microspheres from polymer A showed a swelling ratio of 159.1 ± 11.5%, while at pH 10, a 288.6 ± 11.6% swelling ratio was recorded for polymer B particles. [ABSTRACT FROM AUTHOR]

Although methods for generating human induced pluripotent stem cell (hiPSC)-derived motor nerve organoids are well established, those for sensory nerve organoids are not. Therefore, this study investigated the feasibility of generating sensory nerve organoids composed of hiPSC-derived sensory neurons using a microfluidic approach. Notably, sensory neuronal axons from neurospheres containing 100,000 cells were unidirectionally elongated to form sensory nerve organoids over 6 mm long axon bundles within 14 days using I-shaped microchannels in microfluidic devices composed of polydimethylsiloxane (PDMS) chips and glass substrates. Additionally, the organoids were successfully cultured for more than 60 days by exchanging the culture medium. The percentage of nuclei located in the distal part of the axon bundles (the region 3−6 mm from the entrance of the microchannel) compared to the total number of cells in the neurosphere was 0.005% for live cells and 0.008% for dead cells. Molecular characterization confirmed the presence of the sensory neuron marker ISL LIM homeobox 1 (ISL1) and the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Moreover, capsaicin stimulation activated TRPV1 in organoids, as evidenced by significant calcium ion influx. Conclusively, this study demonstrated the feasibility of long-term organoid culture and the potential applications of sensory nerve organoids in bioengineered nociceptive sensors. [ABSTRACT FROM AUTHOR]

Flexible manufacturing cells provide significant advantages in low-volume mass-customization production but also induce added complexity and technical challenges in terms of integration, control, and extensibility. The variety of closed-source industrial protocols, the heterogeneous equipment, and the product's manufacturing specifications are main points of consideration in the development of such a system. This study aims to describe the approach, from concept to implementation, for the development of the controller for a flexible manufacturing cell consisting of heterogeneous equipment in terms of functions and communication interfaces. Emphasis is put on the considerations and challenges for effective integration, extensibility, and interoperability. Scheduling and monitoring performed by the developed controller are demonstrated for a manufacturing cell producing microfluidic devices (bioMEMS) that consists of six workstations and a robot-based handling system. Communication between the system controller and the workstations was based on open-source technologies instead of proprietary software and protocols, to support interoperability and, to a considerable extent, code reusability. [ABSTRACT FROM AUTHOR]

Two-layer microfluidic devices with porous membranes have been widely used in bioapplications such as microphysiological systems (MPS). Porous electrodes, instead of membranes, have recently been incorporated into devices for electrochemical cell analysis. Generally, microfluidic channels are prepared using soft lithography and assembled into two-layer microfluidic devices. In addition to soft lithography, three-dimensional (3D) printing has been widely used for the direct fabrication of microfluidic devices because of its high flexibility. However, this technique has not yet been applied to the fabrication of two-layer microfluidic devices with porous electrodes. This paper proposes a novel fabrication process for this type of device. In brief, Pluronic F-127 ink was three-dimensionally printed in the form of sacrificial layers. A porous Au electrode, fabricated by sputtering Au on track-etched polyethylene terephthalate membranes, was placed between the top and bottom sacrificial layers. After covering with polydimethylsiloxane, the sacrificial layers were removed by flushing with a cold solution. To the best of our knowledge, this is the first report on the sacrificial approach-based fabrication of two-layer microfluidic devices with a porous electrode. Furthermore, the device was used for electrochemical assays of serotonin and could successfully measure concentrations up to 5 µM. In the future, this device can be used for MPS applications. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide micro- and nanoparticles have significant applications in biomedical and chemical engineering. This study presents the development and evaluation of a novel low-cost microfluidic device for the purification and hyperconcentration of these magnetic particles. The device, fabricated using laser ablation of polymethyl methacrylate (PMMA), leverages precise control over fluid dynamics to efficiently separate magnetic particles from non-magnetic ones. We assessed the device's performance through Multiphysics simulations and empirical tests, focusing on the separation of magnetite nanoparticles from blue carbon dots and magnetite microparticles from polystyrene microparticles at various total flow rates (TFRs). For nanoparticle separation, the device achieved a recall of up to 93.3 ± 4% and a precision of 95.9 ± 1.2% at an optimal TFR of 2 mL/h, significantly outperforming previous models, which only achieved a 50% recall. Microparticle separation demonstrated an accuracy of 98.1 ± 1% at a TFR of 2 mL/h in both simulations and experimental conditions. The Lagrangian model effectively captured the dynamics of magnetite microparticle separation from polystyrene microparticles, with close agreement between simulated and experimental results. Our findings underscore the device's robust capability in distinguishing between magnetic and non-magnetic particles at both micro- and nanoscales. This study highlights the potential of low-cost, non-cleanroom manufacturing techniques to produce high-performance microfluidic devices, thereby expanding their accessibility and applicability in various industrial and research settings. The integration of a continuous magnet, as opposed to segmented magnets in previous designs, was identified as a key factor in enhancing magnetic separation efficiency. [ABSTRACT FROM AUTHOR]

Passive fluid control has mostly been used for valves, pumps, and mixers in microfluidic systems. The basic principle is to generate localized losses in special channel structures, such as branches, grooves, or spirals. The flow field in two-dimensional space can be easily calculated using the typical Stokes formula, but it is challenging in three-dimensional space. Moreover, the flow field with periodic variable cross-sections channeled of polyhedral units has been neglected in this research field due to previous limitations in manufacturing technology. With the continuous progress of 3D printing technology, the field of microfluidic devices ushered in a new era of manufacturing three-dimensional irregular channels. In this study, we present finite analysis results for a periodic nodular-like channel. The experiments involve variations in the Reynold number (Re), periodic frequency, and comparative analyses with conventional structures. The findings indicate that this variable 3D cross-section structure can readily achieve performance comparable to other passive fluid control methods in valve applications. A 3D model of the periodic tetrahedron channel was fabricated using 3D printing to validate these conclusions. This research has the potential to significantly enhance the performance of passive fluid control units that have long been constrained by manufacturing dimensions. [ABSTRACT FROM AUTHOR]

Microfluidics have revolutionized cell culture by allowing for precise physical and chemical environmental control. Coupled with electrodes, microfluidic cell culture can be activated or have its changes sensed in real-time. We used our previously developed reliable and stable microfluidic device for cell growth and monitoring to design, fabricate, and characterize a whole-channel impedance-based sensor and used it to systematically assess the electrical and electrochemical influences of microfluidic channel boundaries coupled with varying electrode sizes, distances, coatings, and cell coverage. Our investigation includes both theoretical and experimental approaches to investigate how design parameters and insulating boundary conditions change impedance characteristics. We examined the system with various solutions using a frequency range of 0.5 Hz to 1 MHz and a modulation voltage of 50 mV. The results show that impedance is directly proportional to electrode distance and inversely proportional to electrode coating, area, and channel size. We also demonstrate that electrode spacing is a dominant factor contributing to impedance. In the end, we summarize all the relationships found and comment on the appropriateness of using this system to investigate barrier cells in blood vessel models and organ-on-a-chip devices. This fundamental study can help in the careful design of microfluidic culture constructs and models that require channel geometries and impedance-based biosensing. [ABSTRACT FROM AUTHOR]

We propose a nucleic acids dilution-induced assembly (NADIA) method for the preparation of lipid nanoparticles. In the conventional method, water-soluble polymers such as nucleic acids and proteins are mixed in the aqueous phase. In contrast, the NADIA method, in which self-assembly is triggered upon dilution, requires dispersion in an alcohol phase without precipitation. We then investigated several alcohols and discovered that propylene glycol combined with sodium chloride enabled the dispersion of plasmid DNA and protamine sulfate in the alcohol phase. The streamlined characteristics of the NADIA method enable the preparation of extracellular vesicles-mimicking lipid nanoparticles (ELNPs). Among the mixing methods using a micropipette, a syringe pump, and a microfluidic device, the lattermost was the best for decreasing batch-to-batch differences in size, polydispersity index, and transfection efficiency in HepG2 cells. Although ELNPs possessed negative ζ-potentials and did not have surface antigens, their transfection efficiency was comparable to that of cationic lipoplexes. We observed that lipid raft-mediated endocytosis and macropinocytosis contributed to the transfection of ELNPs. Our strategy may overcome the hurdles linked to supply and quality owing to the low abundance and heterogeneity in cell-based extracellular vesicles production, making it a reliable and scalable method for the pharmaceutical manufacture of such complex formulations. [ABSTRACT FROM AUTHOR]

Water pollution greatly impacts humans and ecosystems, so a series of policies have been enacted to control it. The first step in performing pollution control is to detect contaminants in the water. Various methods have been proposed for water quality testing, such as spectroscopy, chromatography, and electrochemical techniques. However, traditional testing methods require the utilization of laboratory equipment, which is large and not suitable for real-time testing in the field. Microfluidic devices can overcome the limitations of traditional testing instruments and have become an efficient and convenient tool for water quality analysis. At the same time, artificial intelligence is an ideal means of recognizing, classifying, and predicting data obtained from microfluidic systems. Microfluidic devices based on artificial intelligence and machine learning are being developed with great significance for the next generation of water quality monitoring systems. This review begins with a brief introduction to the algorithms involved in artificial intelligence and the materials used in the fabrication and detection techniques of microfluidic platforms. Then, the latest research development of combining the two for pollutant detection in water bodies, including heavy metals, pesticides, micro- and nanoplastics, and microalgae, is mainly introduced. Finally, the challenges encountered and the future directions of detection methods based on industrial intelligence and microfluidic chips are discussed. [ABSTRACT FROM AUTHOR]

The capability to record data in passive, image-based wearable sensors can simplify data readouts and eliminate the requirement for the integration of electronic components on the skin. Here, we developed a skin-strain-actuated microfluidic pump (SAMP) that utilizes asymmetric aspect ratio channels for the recording of human activity in the fluidic domain. An analytical model describing the SAMP's operation mechanism as a wearable microfluidic device was established. Fabrication of the SAMP was achieved using soft lithography from polydimethylsiloxane (PDMS). Benchtop experimental results and theoretical predictions were shown to be in good agreement. The SAMP was mounted on human skin and experiments conducted on volunteer subjects demonstrated the SAMP's capability to record human activity for hundreds of cycles in the fluidic domain through the observation of a stable liquid meniscus. Proof-of-concept experiments further revealed that the SAMP could quantify a single wrist activity repetition or distinguish between three different shoulder activities. [ABSTRACT FROM AUTHOR]

Microfluidic separators play a pivotal role in the biomedical and chemical industries by enabling precise fluid manipulations. Traditional fabrication of these devices typically requires costly cleanroom facilities, which limits their broader application. This study introduces a novel microfluidic device that leverages the passive Zweifach–Fung principle to overcome these financial barriers. Through Lagrangian computational simulations, we optimized an eleven-channel Zweifach–Fung configuration that achieved a perfect 100% recall rate for particles following a specified normal distribution. Experimental evaluations determined 2 mL/h as the optimal total flow rate (TFR), under which the device showcased exceptional performance enhancements in precision and recall for micrometer-sized particles, achieving an overall accuracy of 94% ± 3%. Fabricated using a cost-effective, non-cleanroom method, this approach represents a significant shift from conventional practices, dramatically reducing production costs while maintaining high operational efficacy. The cost of each chip is less than USD 0.90 cents and the manufacturing process takes only 15 min. The development of this device not only makes microfluidic technology more accessible but also sets a new standard for future advancements in the field. [ABSTRACT FROM AUTHOR]

Microfluidics is an important technology for the biomedical industry and is often utilised in our daily lives. Recent advances in micro-milling technology have allowed for rapid fabrication of smaller and more complex structures, at lower costs, making it a viable alternative to other fabrication methods. The microfluidic chip fabrication developed in this research is a step-by-step process with a self-contained wet milling chamber. Additionally, ethanol solvent bonding is used to allow microfluidic chips to be fully fabricated within approximately an hour. The effect of using this process is tested with quantitative contact profileometery data to determine the expected surface roughness in the microchannels. The effect of surface roughness on the controllability of microparticles is tested in functional microfluidic chips using image processing to calculate particle velocity. This process can produce high-quality channels when compared with similar studies in the literature and surface roughness affects the control of microparticles. Lastly, we discuss how the outcomes of this research can produce rapid and higher-quality microfluidic devices, leading to improvement in the research and development process within the fields of science that utilise microfluidic technology. Such as medicine, biology, chemistry, ecology, and aerospace. [ABSTRACT FROM AUTHOR]

With the rapid development and commercial interest in the organ-on-a-chip (OoC) field, there is a need for materials addressing key experimental demands and enabling both prototyping and large-scale production. Here, we utilized the gas-permeable, thermoplastic material polymethylpentene (PMP). Three methods were tested to prototype transparent PMP films suitable for transmission light microscopy: hot-press molding, extrusion, and polishing of a commercial, hazy extruded film. The transparent films (thickness 20, 125, 133, 356, and 653 µm) were assembled as the cell-adhering layer in sealed culture chamber devices, to assess resulting oxygen concentration after 4 days of A549 cell culture (cancerous lung epithelial cells). Oxygen concentrations stabilized between 15.6% and 11.6%, where the thicker the film, the lower the oxygen concentration. Cell adherence, proliferation, and viability were comparable to glass for all PMP films (coated with poly-L-lysine), and transparency was adequate for transmission light microscopy of adherent cells. Hot-press molding was concluded as the preferred film prototyping method, due to excellent and reproducible film transparency, the possibility to easily vary film thickness, and the equipment being commonly available. The molecular orientation in the PMP films was characterized by IR dichroism. As expected, the extruded films showed clear orientation, but a novel result was that hot-press molding may also induce some orientation. It has been reported that orientation affects the permeability, but with the films in this study, we conclude that the orientation is not a critical factor. With the obtained results, we find it likely that OoC models with relevant in vivo oxygen concentrations may be facilitated by PMP. Combined with established large-scale production methods for thermoplastics, we foresee a useful role for PMP within the OoC field. [ABSTRACT FROM AUTHOR]

The evolution in the biomedical engineering field boosts innovative technologies, with microfluidic systems standing out as transformative tools in disease diagnosis, treatment, and monitoring. Numerical simulation has emerged as a tool of increasing importance for better understanding and predicting fluid-flow behavior in microscale devices. This review explores fabrication techniques and common materials of microfluidic devices, focusing on soft lithography and additive manufacturing. Microfluidic systems applications, including nucleic acid amplification and protein synthesis, as well as point-of-care diagnostics, DNA analysis, cell cultures, and organ-on-a-chip models (e.g., lung-, brain-, liver-, and tumor-on-a-chip), are discussed. Recent studies have applied computational tools such as ANSYS Fluent 2024 software to numerically simulate the flow behavior. Outside of the study cases, this work reports fundamental aspects of microfluidic simulations, including fluid flow, mass transport, mixing, and diffusion, and highlights the emergent field of organ-on-a-chip simulations. Additionally, it takes into account the application of geometries to improve the mixing of samples, as well as surface wettability modification. In conclusion, the present review summarizes the most relevant contributions of microfluidic systems and their numerical modeling to biomedical engineering. [ABSTRACT FROM AUTHOR]

In microfluidic systems, it is important to maintain flow stability to execute various functions, such as chemical reactions, cell transportation, and liquid injection. However, traditional flow sources, often bulky and prone to unpredictable fluctuations, limit the portability and broader application of these systems. Existing fluidic stabilizers, typically designed for specific flow sources, lack reconfigurability and adaptability in terms of the stabilization ratios. To address these limitations, a modular and standardized stabilizer system with tunable stabilization ratios is required. In this work, we present a Lego-like modular microfluidic stabilizer system, which is fabricated using 3D printing and offers multi-level stabilization combinations and customizable stabilization ratios through the control of fluidic RC constants, making it adaptable to various microfluidic systems. A simplified three-element circuit model is used to characterize the system by straightforwardly extracting the RC constant without intricate calculations of the fluidic resistance and capacitance. By utilizing a simplified three-element model, the stabilizer yields two well-fitted operational curves, demonstrating an R-square of 0.95, and provides an optimal stabilization ratio below 1%. To evaluate the system's effectiveness, unstable input flow at different working frequencies is stabilized, and droplet generation experiments are conducted and discussed. The results show that the microfluidic stabilizer system significantly reduces flow fluctuations and enhances droplet uniformity. This system provides a new avenue for microfluidic stabilization with a tunable stabilization ratio, and its plug-and-play design can be effectively applied across diverse applications to finely tune fluid flow behaviors in microfluidic devices. [ABSTRACT FROM AUTHOR]

In situ electroporation, a non-invasive technique for enhancing the permeability of cell membranes, has emerged as a powerful tool for intracellular delivery and manipulation. This method allows for the precise introduction of therapeutic agents, such as nucleic acids, drugs, and proteins, directly into target cells within their native tissue environment. Herein, we introduce an innovative electroporation strategy that employs a Janus particle (JP)-based microelectrode to generate a localized and controllable electric field within a microfluidic chip. The microfluidic device is engineered with an indium tin oxide (ITO)-sandwiched microchannel, where the electric field is applied, and suspended JP microelectrodes that induce a stronger localized electric field. The corresponding simulation model is developed to better understand the dynamic electroporation process. Numerical simulations for both single-cell and chain-assembled cell electroporation have been successfully conducted. The effects of various parameters, including pulse voltage, duration medium conductivity, and radius of Janus microelectrode, on cell membrane permeabilization are systematically investigated. Our findings indicate that the enhanced electric intensity near the poles of the JP microelectrode significantly contributes to the electroporation process. In addition, the distribution for both transmembrane voltage and the resultant nanopores can be altered by conveniently adjusting the relative position of the JP microelectrode, demonstrating a selective and in situ electroporation technique for spatial control over the delivery area. Moreover, the obtained differences in the distribution of electroporation between chain cells can offer insightful directives for the electroporation of tissues or cell populations, enabling the precise and targeted modulation of specific cell populations. As a proof of concept, this work can provide a robust alternative technique for the study of complex and personalized cellular processes. [ABSTRACT FROM AUTHOR]

This study presents a novel absorption cell with a circular geometry that can be integrated into microfluidic devices for optical spectroscopy applications. The absorption cell is made of PDMS/SU8 and offers an optical path length that is 8.5 times its diameter, resulting in a significant increase in the sensitivity of the measurements. Overall, this design provides a reliable and efficient solution for optical spectroscopy in microfluidic systems, enabling the precise detection and analysis of small quantities of analytes. [ABSTRACT FROM AUTHOR]

The document discusses the advancements in microfluidics for biomedical applications, highlighting innovations in areas such as cell co-culture, 3D printing for microfluidic devices, CTC separation, resistive pulse sensors, nanopore technology, magnetic particles detection, droplet generation, mechanoporation, paper microfluidics, and organ-on-a-chip systems. The authors present various research papers that explore these topics, emphasizing the potential of microfluidics to revolutionize biological research and disease diagnosis. The document showcases a diverse range of contributions from different researchers in the field, demonstrating the interdisciplinary nature of microfluidics in biomedical applications. [Extracted from the article]

Organ-on-a-chip technologies show exponential growth driven by the need to reduce the number of experimental animals and develop physiologically relevant human models for testing drugs. In vitro, microfluidic devices should be carefully designed and fabricated to provide reliable tools for modeling physiological or pathological conditions and assessing, for example, drug delivery through biological barriers. The aim of the current study was to optimize the utilization of three existing skin-on-a-chip microfluidic diffusion chambers with various designs. For this, different perfusion flow rates were compared using cellulose acetate membrane, polyester membrane, excised rat skin, and acellular alginate scaffold in the chips. These diffusion platforms were integrated into a single-channel microfluidic diffusion chamber, a multi-channel chamber, and the LiveBox2 system. The experimental results revealed that the 40 µL/min flow rate resulted in the highest diffusion of the hydrophilic model formulation (2% caffeine cream) in each system. The single-channel setup was used for further analysis by computational fluid dynamics simulation. The visualization of shear stress and fluid velocity within the microchannel and the presentation of caffeine progression with the perfusion fluid were consistent with the measured data. These findings contribute to the development and effective application of microfluidic systems for penetration testing. [ABSTRACT FROM AUTHOR]

The Fusarium fungi is found in cereals and feedstuffs and may produce mycotoxins, which are secondary metabolites, such as the T-2 toxin (T-2). In this work, we explored the hepatotoxicity of T-2 using microfluidic 3D hepatic cultures. The objectives were: (i) exploring the benefits of microfluidic 3D cultures compared to conventional 3D cultures available commercially (Aggrewell plates), (ii) establishing 3D co-cultures of hepatic cells (HepG2) and stellate cells (LX2) and assessing T-2 exposure in this model, (iii) characterizing the induction of metabolizing enzymes, and (iv) evaluating inflammatory markers upon T-2 exposure in microfluidic hepatic cultures. Our results demonstrated that, in comparison to commercial (large-volume) 3D cultures, spheroids formed faster and were more functional in microfluidic devices. The viability and hepatic function decreased with increasing T-2 concentrations in both monoculture and co-cultures. The RT-PCR analysis revealed that exposure to T-2 upregulates the expression of multiple Phase I and Phase II hepatic enzymes. In addition, several pro- and anti-inflammatory proteins were increased in co-cultures after exposure to T-2. [ABSTRACT FROM AUTHOR]

Dimensional measurements are fundamental in microfluidic device manufacturing and performance. The main focus of this study is the measurement of the connection port sizes in microfluidic devices and components and, accordingly, the possible existence of fluid leaks determined using the flow rate error. The sizes associated with three different microfluidic systems were determined using laser interferometry and through an optical measuring instrument, with metrological traceability to national length standards. It was possible to infer the method with the greatest accuracy and lowest measurement uncertainty for characterizing this kind of system. In conclusion, the results of this work directly address the current lack of dimensions measuring methods of microfluidic components by providing a comprehensive comparison of different protocols, ultimately suggesting a preferred option for immediate application within the microfluidic industry. [ABSTRACT FROM AUTHOR]

Microfluidic devices have long been useful for both the modeling and diagnostics of numerous diseases. In the past 20 years, they have been increasingly adopted for helping to study those in the family of breast cancer through characterizing breast cancer cells and advancing treatment research in portable and replicable formats. This paper adds to the body of work concerning cancer-focused microfluidics by proposing a simulation of a hypothetical bi-ended three-pronged device with a single channel and 16 electrodes with 8 pairs under different voltage and frequency regimes using COMSOL. Further, a study was conducted to examine the frequencies most effective for ACEO to separate cancer cells and accompanying particles. The study revealed that the frequency of EF has a more significant impact on the separation of particles than the inlet velocity. Inlet velocity variations while holding the frequency of EF constant resulted in a consistent trend showing a direct proportionality between inlet velocity and net velocity. These findings suggest that optimizing the frequency of EF could lead to more effective particle separation and targeted therapeutic interventions for breast cancer. This study hopefully will help to create targeted therapeutic interventions by bridging the disparity between in vitro and in vivo models. [ABSTRACT FROM AUTHOR]

World-to-chip interfacing remains a critical issue for microfluidic devices. Current solutions to connect tubing to rigid microfluidic chips remain expensive, laborious, or require specialized skills and precision machining. Here, we report reusable, inexpensive, and easy-to-use connectors that enable monitoring of the connection ports. Our magnetic connectors benefit from a simple one-step fabrication process and low dead volume. They sustain pressures within the high range of microfluidic applications. They represent an essential tool for rapid thermoplastic (PMMA, PC, COC) prototyping and can also be used with glass, pressure-sensitive adhesive, or thin PDMS devices. [ABSTRACT FROM AUTHOR]

Microfluidic devices promise to overcome the limitations of conventional hemodialysis and oxygenation technologies by incorporating novel membranes with ultra-high permeability into portable devices with low blood volume. However, the characteristically small dimensions of these devices contribute to both non-physiologic shear that could damage blood components and laminar flow that inhibits transport. While many studies have been performed to empirically and computationally study hemolysis in medical devices, such as valves and blood pumps, little is known about blood damage in microfluidic devices. In this study, four variants of a representative microfluidic membrane-based oxygenator and two controls (positive and negative) are introduced, and computational models are used to predict hemolysis. The simulations were performed in ANSYS Fluent for nine shear stress-based parameter sets for the power law hemolysis model. We found that three of the nine tested parameters overpredict (5 to 10×) hemolysis compared to empirical experiments. However, three parameter sets demonstrated higher predictive accuracy for hemolysis values in devices characterized by low shear conditions, while another three parameter sets exhibited better performance for devices operating under higher shear conditions. Empirical testing of the devices in a recirculating loop revealed levels of hemolysis significantly lower (<2 ppm) than the hemolysis ranges observed in conventional oxygenators (>10 ppm). Evaluating the model's ability to predict hemolysis across diverse shearing conditions, both through empirical experiments and computational validation, will provide valuable insights for future micro ECMO device development by directly relating geometric and shear stress with hemolysis levels. We propose that, with an informed selection of hemolysis parameters based on the shear ranges of the test device, computational modeling can complement empirical testing in the development of novel high-flow blood-contacting microfluidic devices, allowing for a more efficient iterative design process. Furthermore, the low device-induced hemolysis measured in our study at physiologically relevant flow rates is promising for the future development of microfluidic oxygenators and dialyzers. [ABSTRACT FROM AUTHOR]

This work reports a simple bubble generator for the high-speed generation of microbubbles with constant cumulative production. To achieve this, a gas–liquid co-flowing microfluidic device with a tiny capillary orifice as small as 5 μm is fabricated to produce monodisperse microbubbles. The diameter of the microbubbles can be adjusted precisely by tuning the input gas pressure and flow rate of the continuous liquid phase. The co-flowing structure ensures the uniformity of the generated microbubbles, and the surfactant in the liquid phase prevents coalescence of the collected microbubbles. The diameter coefficient of variation (CV) of the generated microbubbles can reach a minimum of 1.3%. Additionally, the relationship between microbubble diameter and the gas channel orifice is studied using the low Capillary number (Ca) and Weber number (We) of the liquid phase. Moreover, by maintaining a consistent gas input pressure, the CV of the cumulative microbubble volume can reach 3.6% regardless of the flow rate of the liquid phase. This method not only facilitates the generation of microbubbles with morphologic stability under variable flow conditions, but also ensures that the cumulative microbubble production over a certain period of time remains constant, which is important for the volume-dominated application of chromatographic analysis and the component analysis of natural gas. [ABSTRACT FROM AUTHOR]