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We fabricated a microfluidic chip (osteoblast [OB]–osteoclast [OC] chip) that could regulate the mixture amounts of OB and OC supernatants to investigate the effect of different supernatant distributions on osteogenesis or osteoclastogenesis. Computer-aided design was used to produce an OB–OC chip from polydimethylsiloxane. A pressure controller was assembled and different blends of OB and OC supernatants were correctly determined. OB and OC supernatants were placed on the upper panels of the OB–OC chip after differentiation for an in vitro evaluation. We then tested the changes in osteogenesis using MC3T3-E1 cells in the middle chambers. We observed that a 75:25 distribution of OB and OC supernatants was the most potent in osteogenesis. We then primed the osteogenic differentiation of MC3T3-E1 cells using an OB–OC mixed supernatant or an OB supernatant alone (supernatant ratios of 75:25 or 100:0, respectively). These cells were placed on the calvarial defect sites of rats. Microcomputed tomography and histological analyses determined a significantly higher bone formation in the group exposed to the OB–OC supernatant at a ratio of 75:25. In this study, we demonstrate the applicability of an OB–OC chip to evaluate the effect of different supernatant distributions of OB and OC. We observed that the highest bone-forming potential was in MC3T3-E1 cells treated with conditioned media, specifically the OB–OC supernatant at a ratio of 75:25. [ABSTRACT FROM AUTHOR]

Circulating tumor cells are typically found in the peripheral blood of patients, offering a crucial pathway for the early diagnosis and prediction of cancer. Traditional methods for early cancer diagnosis are inefficient and inaccurate, making it difficult to isolate tumor cells from a large number of cells. In this paper, a new spiral microfluidic chip with asymmetric cross-section is proposed for rapid, high-throughput, label-free enrichment of CTCs in peripheral blood. A mold of the desired flow channel structure was prepared and inverted to make a trapezoidal cross-section using a micro-nanotechnology process of 3D printing. After a systematic study of how flow rate, channel width, and particle concentration affect the performance of the device, we utilized the device to simulate cell sorting of 6 μm, 15 μm, and 25 μm PS (Polystyrene) particles, and the separation efficiency and separation purity of 25 μm PS particles reached 98.3% and 96.4%. On this basis, we realize the enrichment of a large number of CTCs in diluted whole blood (5 mL). The results show that the separation efficiency of A549 was 88.9% and the separation purity was 96.4% at a high throughput of 1400 μL/min. In conclusion, we believe that the developed method is relevant for efficient recovery from whole blood and beneficial for future automated clinical analysis. [ABSTRACT FROM AUTHOR]

The flash organometallic catalysis is a new concept that refers to the study of fast and controlled organometallic catalytic reactions by using microfluidic devices. Flash reactions' kinetics (ms‐s scale) is often ignored due to the lack of proper research tool in organometallic chemistry. The development of microfluidic systems offers the opportunity to discover under‐studied mechanisms and new reactions. In this concept, the basic theory of kinetic measurement in a microreactor is briefly reviewed and then two examples on studying flash organometallic catalytic transformation are introduced. One example is the discovery of a highly active palladium catalytic species for Suzuki Coupling and the other example is the study of a neglected isomerization catalytic cycle with a time scale of seconds before isomerization‐hydroformylation by customized microfluidic devices. The last part is summary and prospect of this new area. Customizing a microfluidic device with good engineering design for a target reaction supports flash reactions' kinetic experimentation and could become a general strategy in chemistry lab. [ABSTRACT FROM AUTHOR]

Nanoliposomes are nano-sized vesicles that can be used as drug delivery carriers with the ability to encapsulate both hydrophobic and hydrophilic compounds. Moreover, their lipid compositions facilitate their internalization by cells. However, the interaction between nanoliposomes and the membrane barrier of the human body is not well-known. If cellular tests and animal testing offer a solution, their lack of physiological relevance and ethical concerns make them unsuitable to properly mimic human body complexity. Microfluidics, which allows the environment of the human body to be imitated in a controlled way, can fulfil this role. However, existing models are missing the presence of something that would mimic a basal membrane, often consisting of a simple cell layer on a polymer membrane. In this study, we investigated the diffusion of nanoliposomes in a microfluidic system and found the optimal parameters to maximize their diffusion. Then, we incorporated a custom made GelMA with a controlled degree of substitution and studied the passage of fluorescently labeled nanoliposomes through this barrier. Our results show that highly substituted GelMA was more porous than lower substitution GelMA. Overall, our work lays the foundation for the incorporation of a hydrogel mimicking a basal membrane on a drug delivery microfluidic platform. [ABSTRACT FROM AUTHOR]

Rapamycin (RAP) is currently being developed as potential antibreast cancer drug. However, its poor solubility completely limits its use. The aim of this study was to develop polyethylene glycol-poly(lactide-co-glycolide) (PEG-PLGA)-based nanoparticles (NPs) to load RAP via microfluidics with an appropriate polyethylene glycol (PEG) content to enhance the bioavailability of RAP. Polydimethylsiloxane (PDMS) chips with a Y-shaped channel were designed to obtain RAP-loaded PEG-PLGA NPs (RAP-PEG-PLGA). The entrapment efficiency (EE) and drug loading (DL) as well as release profile of RAP-PEG-PLGA were evaluated, and their resistance to plasma albumin adsorption of NPs with different PEG contents was evaluated and compared. RAW264.7 and 4T1 cells were used to assess the antiphagocytic and anticancer cells effect of NPs, respectively. RAP-PEG-PLGA of around 124 nm in size were successfully prepared with the EE of 82.0% and DL of 12.3%, and sustained release for around 40 d. A PEG relative content of 10% within the PEG-PLGA molecule was shown superior in resisting protein adsorption. RAP-PEG-PLGA inhibited the growth of breast cancer cells when the concentration was over 10 μg/mL, and the inhibition efficiency was significantly higher than free RAP. Hence, the current RAP-PEG-PLGA could be a potential therapeutic system for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The separation of particles such as cells and bacteria in viscoelastic fluids has significant applications in biomedical fields. At present, one of the main challenges that limit the application of microfluidic technology is to separate particles in the viscoelastic fluids with different rheological properties. For instance, most existing microfluidic devices can only work in the fluid with a specific rheological property, resulting in the requirement of time-consuming design, manufacturing, testing, and optimization of different devices to separate particles in the fluids with different rheological properties. In this work, a novel hybrid three-stage microfluidic device that was made up of a micropore structure and two gradually contracted microchannels was designed to achieve efficient continuous separation of particles in the viscoelastic fluid over a wide range of rheological properties (0.07 < El < 340.41). Different separation strategies including first focusing, then initial separation, and then precise separation (FISPS) and initial separation and then precise separation (ISPS) were found. The separation strategy ISPS occurred at El < 0.14 while the separation strategy FISPS occurred at El > 8.43. In addition, the transformation of the separation mechanism from ISPS to FISPS was found under different flow conditions in the fluid with the transitional rheological properties (0.21 < El < 1.10). The effect of the flow rate and the rheological property of the fluid on microparticle separation were systematically studied by the experiment. With simple structure, easy operation, high separation efficiency, the present microfluidic device would have great potentials in the biomedical and clinical applications, such as the separation of cells for different patients. [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]

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]

Conventional microfluidic systems that rely on capillary force have a fixed structure and limited sensitivity, which cannot meet the demands of clinical applications. Herein, we propose a dual-drive microfluidic device for sensitive and flexible detection of multiple pathogenic microorganisms antigens/antibodies. The device comprises a portable microfluidic analyzer and a dual-drive microfluidic chip. Along with capillary force, a second active driving force is provided by a removable self-driving valve in the waste chamber. The interval between these two driving forces can be adjusted to control the reaction time in the microchannel, optimizing the formation of antigen-antibody complexes and enhancing sensitivity. Moreover, the material used in the self-driving valve can be changed to adjust the active force strength needed for different tests. The device offers quantitative analysis for respiratory syncytial virus antigen and SARS-CoV-2 antigen using a 35 μL sample, delivering results within 5 min. The detection limits of the system were 1.121 ng/mL and 0.447 ng/mL for respiratory syncytial virus recombinant fusion protein and SARS-CoV-2 recombinant nucleoprotein, respectively. Although the dual-drive microfluidic device has been used for immunoassay for respiratory syncytial virus and SARS-CoV-2 in this study, it can be easily adapted to other immunoassay applications by changing the critical reagents. [ABSTRACT FROM AUTHOR]

Paper with its mechanical strength as well as due to its microfluidic properties has emerged as an interesting sustainable material for future high-tech applications. Examples include paper-based sensors and actuators, paper-based construction materials and paper-based membranes. These examples have in common that a precise control of the water distribution inside the paper sheet during fluid water imbibition, water vapor adsorption, or drying affects the fluidic properties of the paper, which are crucial for its performance. Here silica-based coatings are applied to control the water distribution in the paper sheet during imbibition, adsorption and drying. By using dense silica coatings, the fibers are shielded from water penetration which limits the water distribution into the fiber–fiber voids. Whereas with a mesoporous silica coating, mesopores can be inserted into the paper, providing an additional space for water imbibition and adsorption. Water location upon imbibition, adsorption and drying were investigated using small angle x-ray scattering and gravimetric water vapor adsorption. Thereby, water distribution upon imbibition and adsorption depends on the type of silica coating. In addition, the drying mechanism and water distribution during drying is as well determined by the silica-based coating. The obtained results allow to deduce design criteria for local water management in paper sheets. [ABSTRACT FROM AUTHOR]

Electrochemistry is a hotspot in today's research arena. Many different domains have been extended for their role towards the Internet of Things, digital health, personalized nutrition, and/or wellness using electrochemistry. These advances have led to a substantial increase in the power and popularity of electroanalysis and its expansion into new phases and environments. The recent COVID-19 pandemic, which turned our lives upside down, has helped us to understand the need for miniaturized electrochemical diagnostic platforms. It also accelerated the role of mobile and wearable, implantable sensors as telehealth systems. The major principle behind these platforms is the role of electrochemical immunoassays, which help in overshadowing the classical gold standard methods (reverse transcriptase polymerase chain reaction) in terms of accuracy, time, manpower, and, most importantly, economics. Many research groups have endeavoured to use electrochemical and bio-electrochemical tools to overcome the limitations of classical assays (in terms of accuracy, accessibility, portability, and response time). This review mainly focuses on the electrochemical technologies used for immunosensing platforms, their fabrication requirements, mechanistic objectives, electrochemical techniques involved, and their subsequent output signal amplifications using a tagged and non-tagged system. The combination of various techniques (optical spectroscopy, Raman scattering, column chromatography, HPLC, and X-ray diffraction) has enabled the construction of high-performance electrodes. Later in the review, these combinations and their utilization will be explained in terms of their mechanistic platform along with chemical bonding and their role in signal output in the later part of article. Furthermore, the market study in terms of real prototypes will be elaborately discussed. [ABSTRACT FROM AUTHOR]

Transcriptomics and metabolomics, two biological research fields that need large numbers of zebrafish embryos, require the removal of unfertilised or nonviable zebrafish embryos. Biologists routinely conduct the tedious, error-prone, and time-consuming manual sorting of embryos. We suggest a novel approach that combines deep learning and microfluidics for automated sorting to overcome this difficulty. To determine the developmental stage and viability of zebrafish eggs, we trained an optimized YOLOv5 model with 95.8% accuracy and a processing speed of 10.6 ms per frame, classifying them as dead, unfertilised, or alive. The eggs are contained in traps on a microfluidic chip using micro-pumps. After that, the deep learning system can identify and automatically sort the eggs according to their viability by positioning this chip on an XYZ motorized stage. The sorting experiment was conducted in two modes: without feedback and with feedback while using the dead egg position. The first one had a sorting success rate of 90% as opposed to 97.9% for the feedback mode with 3 seconds required for each dead egg. This automated approach provides a precise and efficient way to handle a large number of zebrafish embryos while also greatly reducing the workload associated with manual sorting. The success rates attained demonstrate the usefulness and effectiveness of our suggested methodology, opening new avenues for biological research involving accurate embryo selection. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Explosives & Propellants is the property of Chinese Journal of Explosives & Propellants Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Explosives & Propellants is the property of Chinese Journal of Explosives & Propellants Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Explosives & Propellants is the property of Chinese Journal of Explosives & Propellants Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To enable the detection and modulation of modularized neural networks in vitro, this study proposes a microfluidic microelectrode array chip for the cultivation, compartmentalization, and control of neural cells. The chip was designed based on the specific structure of neurons and the requirements for detection and modulation. Finite-element analysis of the chip's flow field was conducted using the COMSOL Multiphysics software, and the simulation results show that the liquid within the chip can flow smoothly, ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels. By employing MEMS technology in combination with nanomaterial modification techniques, the microfluidic microelectrode array chip was fabricated successfully. Primary hippocampal neurons were cultured on the chip, forming a well-defined neural network. Spontaneous electrical activity of the detected neurons was recorded, exhibiting a 23.7% increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array. This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro, potentially serving as a novel tool in neuroscience research. ARTICLE HIGHLIGHTS: HIGHLIGHTS • A microfluidic microelectrode array chip is proposed for detecting electrophysiological signals in patterned neuronal networks. • The chip's feasibility is verified via fluid dynamical simulation, and fabrication is accomplished. • The chip is used for the compartmentalized culture and electrophysiology detection of primary hippocampal neurons, and spontaneous discharge is obtained. [ABSTRACT FROM AUTHOR]

A microfluidic immuno-biosensor detection system consisting of a microfluidic spectrum chip and a micro-spectrometer detection device is presented for the rapid point-of-care (POC) detection and quantification of high-sensitivity C-reactive protein (hs-CRP) in urine. The detection process utilizes a highly specific enzyme-linked immunosorbent assay (ELISA) method, in which capture antibodies and detection antibodies are pre-deposited on the substrate of the microchip and used to form an immune complex with the target antigen. Horseradish peroxidase (HRP) is added as a marker enzyme, followed by a colorimetric reaction using 3,3′,5,5′-tetramethylbenzidine (TMB). The absorbance values (a.u.) of the colorimetric reaction compounds are measured using a micro-spectrometer device and used to measure the corresponding hs-CRP concentration according to the pre-established calibration curve. It is shown that the hs-CRP concentration can be determined within 50 min. In addition, the system achieves recovery rates of 93.8–106.2% in blind water samples and 94.5–104.6% in artificial urine. The results showed that the CRP detection results of 41 urine samples from patients with chronic kidney disease (CKD) were highly consistent with the conventional homogeneous particle-enhanced turbidimetric immunoassay (PETIA) method's detection results (R2 = 0.9910). The experimental results showed its applicability in the detection of CRP in both urine and serum. Overall, the results indicate that the current microfluidic ELISA detection system provides an accurate and reliable method for monitoring the hs-CRP concentration in point-of-care applications. [ABSTRACT FROM AUTHOR]

Abstract Metasurfaces, as 2D artificial electromagnetic materials, play a pivotal role in manipulating electromagnetic waves by controlling their amplitude, phase, and polarization. Achieving this control involves designing subwavelength meta‐molecules with specific geometries and periodicities. In the context of microfluidic metasurfaces, optical properties can be dynamically modulated by altering either the geometric structure of liquid meta‐molecules or the refractive index of the liquid medium. Leveraging the fluidity of liquid materials, microfluidic metasurfaces exhibit remarkable performance in terms of reconfigurability and flexibility. These properties not only establish a cutting‐edge research area but also broaden the scope of applications for active metasurface devices. Additionally, the integration of metasurfaces within microfluidic systems has led to novel functionalities, including enhanced particle manipulation and sensor technologies. Compared to conventional solid‐material‐based metasurfaces, microfluidic metasurfaces offer greater design freedom, making them advantageous for diverse fields such as electromagnetic absorption, optical sensing, holographic displays, and tunable optical meta‐devices like flat lenses and polarizers. This review provides insights into the characteristics, modulation techniques, and potential applications of microfluidic metasurfaces, illuminating both the current research landscape and promising avenues for further explorations.

Abstract Screening liters of blood (i.e., apheresis) represents a generalized approach to promote the reliable access to circulating tumor cell clusters (CTCCs), which are known to be highly metastasis‐competent, yet ultrarare. However, no existing CTCC sorting technology has demonstrated high throughput, high yield, low shear stress, and minimal blood dilution simultaneously as required in apheresis. Here, a label‐free method is introduced termed Precision Apheresis for Non‐invasive Debulking of cell Aggregates (PANDA) to continuously isolate CTCCs from undiluted blood to clean buffer through size sorting, processing 1.4 billion cells per second. The cell focusing is optimized within whole blood leveraging secondary transverse flow and margination. The PANDA chip recovers >90% of spiked ≈24 rare HeLa cell clusters from 100 mL undiluted blood samples (equivalent to ≈500 billion blood cells) at 1 L h−1 throughput, with ≤20s device residence time, ≤15 Pa shear stress, and >99.9% return of blood components. The technology lays the groundwork for future routine isolation to increase the recovery of these ultrarare yet clinically significant tumor cell populations from large volumes of blood to advance cancer research, early detection, and treatment.

Abstract Graphene field‐effect transistors (GFETs) are widely used in biosensing due to their excellent properties in biomolecular signal amplification, exhibiting great potential for high‐sensitivity and point‐of‐care testing in clinical diagnosis. However, difficulties in complicated fabrication steps are the main limitations for the further studies and applications of GFETs. In this study, a modular fabrication technique is introduced to construct microfluidic GFET biosensors within 3 independent steps. The low‐melting metal electrodes and intricate flow channels are incorporated to maintain the structural integrity of graphene and facilitate subsequent sensing operations. The as‐fabricated GFET biosensor demonstrates excellent long‐term stability, and performs effectively in various ion environments. It also exhibits high sensitivity and selectivity for detecting single‐stranded nucleic acids at a 10 fm concentration. Furthermore, when combined with the CRISPR/Cas12a system, it facilitates amplification‐free and rapid detection of nucleic acids at a concentration of 1 fm. Thus, it is believed that this modular‐fabricated microfluidic GFET may shed light on further development of FET‐based biosensors in various applications.

In this review, we discuss recent reproductive organ-on-a-chip (OoC) experiments that encompass multiple target areas of investigation, including model fabrication strategies, transport mechanisms, and immunology. We highlight fetal membrane and placental biology, OoC history and background, and the designs of reproductive OoC platforms. Reproductive OoC designs include fetal membrane models such as the Fetal Membrane-on-a-chip (FMOC) and others, placental models such as the placenta on-a-chip, and full reproductive tract models such as EVATAR. Diverse fabrication strategies and the integration of multiple model materials are explored. OoC samples can be analyzed with many analytical techniques, including mass spectrometry, fluorescence microscopy, ELISAs, impedance spectroscopy, and electrochemical techniques. The future of reproductive OoC models is a promising technology for advancing preterm birth (PTB) research, pharmacology studies, and fertility technologies.

Infectious diseases remain a public healthcare concern worldwide. Amidst the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, increasing resources have been diverted to investigate therapeutics targeting the COVID-19 spike glycoprotein and to develop various classes of vaccines. Most of the current investigations employ two-dimensional (2D) cell culture and animal models. However, 2D culture negates the multicellular interactions and three-dimensional (3D) microenvironment, and animal models cannot mimic human physiology because of interspecies differences. On the other hand, organ-on-a-chip (OoC) devices introduce a game-changer to model viral infections in human tissues, facilitating high-throughput screening of antiviral therapeutics. In this context, this review provides an overview of thein vitroOoC-based modeling of viral infection, highlighting the strengths and challenges for the future.

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.

Elisabetta Esposito,1 Elena Pozza,2 Catia Contado,1 Walter Pula,1 Olga Bortolini,3 Daniele Ragno,1 Sofia Toldo,3 Fabio Casciano,4 Agnese Bondi,1 Enrico Zauli,2 Paola Secchiero,4 Giorgio Zauli,3 Elisabetta Melloni4 1Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara, I-44121, Italy; 2Department of Translational Medicine, University of Ferrara, Ferrara, I-44121, Italy; 3Department of Environmental Sciences and Prevention, University of Ferrara, Ferrara, I-44121, Italy; 4Department of Translational Medicine and LTTA Centre, University of Ferrara, Ferrara, I-44121, ItalyCorrespondence: Elisabetta Esposito; Elisabetta Melloni, Tel +39 0532 455230 ; +39 0532 455936, Email ese@unife.it; elisabetta.melloni@unife.itPurpose: Proliferative vitreoretinal diseases (PVDs) represent a heterogeneous group of pathologies characterized by the presence of retinal proliferative membranes, in whose development retinal pigment epithelium (RPE) is deeply involved. As the only effective treatment for PVDs at present is surgery, we aimed to investigate the potential therapeutic activity of Nutlin-3a, a small non-genotoxic inhibitor of the MDM2/p53 interaction, on ARPE-19 cell line and on human RPE primary cells, as in vitro models of RPE and, more importantly, to formulate and evaluate Nutlin-3a loaded liposomes designed for ophthalmic administration.Methods: Liposomes were produced using an innovative approach by a microfluidic device under selection of different conditions. Liposome size distribution was evaluated by photon correlation spectroscopy and centrifugal field flow fractionation, while the liposome structure was studied by transmission electron microscopy and Fourier-transform infrared spectroscopy. The Nutlin-3a entrapment capacity was evaluated by ultrafiltration and HPLC. Nutlin-3a biological effectiveness as a solution or loaded in liposomes was evaluated by viability, proliferation, apoptosis and migration assays and by morphological analysis.Results: The microfluidic formulative study enabled the selection of liposomes composed of phosphatidylcholine (PC) 5.4 or 8.2 mg/mL and 10% ethanol, characterized by roundish vesicular structures with 150– 250 nm mean diameters. Particularly, liposomes based on the lower PC concentration were characterized by higher stability. Nutlin-3a was effectively encapsulated in liposomes and was able to induce a significant reduction of viability and migration in RPE cell models.Conclusion: Our results lay the basis for a possible use of liposomes for the ocular delivery of Nutlin-3a. Keywords: Nutlin-3a, liposomes, microfluidic, PVDs, CFFF

Abstract Optical biosensors based on plasmonic nanostructures have attracted great interest due to their ability to detect small refractive index changes with high sensitivity. In this work, a novel plasmonic coupled cavity waveguide is proposed for refractive index sensing applications. The structure consists of a metal–insulator–metal waveguide side coupled to an array of asymmetric H-shape element, designed to provide dual-band resonances. The sharp transmission dips and large field enhancements associated with dual-band resonances can enable sensitive detection of material under test. The resonator array creates a slow light effect to improve light-matter interactions. The structure was simulated using the finite integration technique as the full-wave technique, and the sensitivity and figure of merit were extracted for different ambient refractive indices. The maximum sensitivity of 1774 nm/RIU and high figure of merit of 2 × 104 RIU−1 for the basic model and 1.15 × 105 RIU−1 for the modified model were achieved, demonstrating the potential for high-performance sensing. The unique transmission characteristics also allow for combined spectral shaping and detection over a broad bandwidth. The simple, compact geometry makes the design suitable for on-chip integration. This work demonstrates a promising refractive index sensor based on coupled dual-band resonators in a plasmonic waveguide.

ABSTRACTChronic digestive disorders are of increasing incidence worldwide with expensive treatments and no available cure. Available therapeutic schemes mainly rely on symptom relief, with large degrees of variability in patients’ response to such treatments, underlining the need for new therapeutic strategies. There are strong indications that the gut microbiota’s contribution seems to be a key modulator of disease activity and patients’ treatment responses. Hence, efforts have been devoted to understanding host–microbe interactions and the mechanisms underpinning such variability. Animal models, being the gold standard, provide valuable mechanistic insights into host–microbe interactions. However, they are not exempt from limitations prompting the development of alternative methods. Emerging microfluidic technologies and gut-on-chip models were shown to mirror the main features of gut physiology and disease state, reflect microbiota modification, and include functional readouts for studying host responses. In this commentary, we discuss the relevance of animal models in understanding host–microbe interactions and how gut-on-chip technology holds promises for addressing patient variability in responses to chronic digestive disease treatment.

A new and efficient technique is developed by combining the hyphenated microfluidic‐ and aerosol‐based synthesis with the coupled differential mobility analysis for the effective and continuous synthesis and simultaneous analysis of metal–organic frameworks (MOFs)‐derived hybrid nanostructured products. HKUST‐1, a copper‐based MOF, is chosen as the representative to fabricate Cu‐based hybrid catalysts for reverse water‐gas shift (RWGS) reaction, an effective route for CO2 utilization. The effect of precursor concentration and carrier selection on the properties of the resulting products, including mobility size distribution, crystallization degree, surface area, and metal dispersion are investigated, as well as the correlation between the material properties of the synthesized catalysts and their catalytic performance in RWGS reaction in terms of conversion ratio/rate, selectivity, and operational stability. The results indicate that the continuous microfluidic droplet system can successfully synthesize MOF colloids, followed by the continuous production of MOF‐derived hybrid materials through the tandem aerosol spray‐drying‐reaction system. High catalytic activity and low initiate temperature toward RWGS (turnover frequency = 0.0074 s−1; 450 °C) are achievable. The work facilitates the production and the designed concept of relevant MOF‐derived hybrid nanostructured catalysts in the continuous synthesis system and the enhancement of applications in CO2 capture and utilization. [ABSTRACT FROM AUTHOR]

In this work, liquid metal was introduced into a simple co‐flow microfluidic system, and we successfully fabricated the liquid metal droplets fiber by solidifying the continuous phase. The law of liquid metal droplet generation was discussed by theoretical analysis, simulations and experiment results, which is a critical guidance for fabricating liquid metal droplets fibers with various parameters. The liquid metal droplets can be selectively exposed to the air during the dehydration process of the continuous phase. In this way, fibers with different morphologies were fabricated, including symmetric mode and asymmetric mode. These kinds of fibers are easily fabricated in large quantities and can be potentially used in water transportation, fog harvesting, soft robots, etc. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

The therapeutic effect of gefitinib on colorectal cancer (CRC) is unclear, but it has been reported that stromal cells in the tumor microenvironment may have an impact on drug sensitivity. Herein, we established a microfluidic co-culture system and explored the sensitivity of CRC cells co-cultured with cancer-associated fibroblasts (CAFs) to gefitinib. The system consisted of a multichannel chip and a Petri dish. The chambers in the chip and dish were designed to continuously supply nutrients for long-term cell survival and create chemokine gradients for driving cell invasion without any external equipment. Using this system, the proliferation and invasiveness of cells were simultaneously evaluated by quantifying the area of cells and the migration distance of cells. In addition, the system combined with live cell workstation could evaluate the dynamic drug response of co-cultured cells and track individual cell trajectories in real-time. When CRC cells were co-cultured with CAFs, CAFs promoted CRC cell proliferation and invasion and reduced the sensitivity of cells to gefitinib through the exosomes secreted by CAFs. Furthermore, the cells that migrated out of the chip were collected, and EMT-related markers were determined by immunofluorescent and western blot assays. The results demonstrated that CAFs affected the response of CRC cells to gefitinib by inducing EMT, providing new ideas for further research on the resistance mechanism of gefitinib. This suggests that targeting CAFs or exosomes might be a new approach to enhance CRC sensitivity to gefitinib, and our system could be a novel platform for investigating the crosstalk between tumor cells and CAFs and understanding multiple biological changes of the tumor cells in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Single-cell analysis provides a groundbreaking avenue for exploring cell-to-cell variation, the heterogeneity of cell responses to stimuli, and the impact of DNA sequence variations on cell phenotypes. A crucial facet of this analytical approach involves the refinement of techniques for effective single-cell trapping and sustained culture. This study introduces a microfluidic platform based on micropillars for hydrodynamic trapping and prolonged cultivation of individual cells. The proposed biochip design, termed three-micropillars based microfluidic (3µPF) structure, incorporates interleaved trap units, each featuring three-micropillars based microfluidic structure strategically designated to trap single cells, enhance the surface area of cells exposed to the culture medium, and enable dynamic culture, continuous waste removal. This configuration aims to mitigate adverse effects associated with bioparticle collisions compared to conventional trap units. The study employs finite element method to conduct a comprehensive numerical investigation into the operational mechanism of the microfluidic device. The simulation results show that the filled trap unit demonstrates a low-velocity magnitude, reducing shear stress on cells and facilitating extended culture. The hydrodynamic single-cell trap mechanism of the proposed device was also verified. The insights derived from this work are pivotal for optimizing the device and guiding future experimental examinations, thus contributing significantly to the progression of single-cell analysis techniques. [ABSTRACT FROM AUTHOR]

Nanofluids are widely used in seawater desalination, energy conversion, and ion circuits, and the ordered channel structure can improve the ion transport properties of such nanofluids. Biomass-based nanofluids has revealed flaws, such as uncontrollable construction of nanostructure, the weak interaction of structural components, low ionic conductivity, unsatisfactory long-term reliability underwater, and insufficient energy conversion efficiency. Herein, in this study, micronano channel fiber was constructed by self-twisting microfluidic spinning cellulose nanocrystals (CNCs) to obtain aligned nanostructures with an orientation of 0.77. An ordered arrangement and stable bonding formed between the CNCs make their mechanical properties and electrical conductivity improve significantly. It exhibited excellent mechanical properties, with a tensile strength of 450 MPa. The cellulose fibers had a conductivity of 5.5 mS/cm in a 10−5 M KCl solution. The steady-state ordered arrangement micronano channels and regularly arranged hydroxyl functional groups formed by self-twisting effect, which promotes ion transport with higher diffusion coefficient of K+ than Cl−. This work can promote the application of pure cellulose in high-performance osmotic energy conversion systems. [ABSTRACT FROM AUTHOR]

The disruption of the blood–brain barrier (BBB) in Alzheimer's Disease (AD) is largely influenced by amyloid beta (Aβ). In this study, we developed a high-throughput microfluidic BBB model devoid of a physical membrane, featuring endothelial cells interacting with an extracellular matrix (ECM). This paper focuses on the impact of varying concentrations of Aβ1–42 oligomers on BBB dysfunction by treating them in the luminal. Our findings reveal a pronounced accumulation of Aβ1–42 oligomers at the BBB, resulting in the disruption of tight junctions and subsequent leakage evidenced by a barrier integrity assay. Additionally, cytotoxicity assessments indicate a concentration-dependent increase in cell death in response to Aβ1–42 oligomers (LC50 ~ 1 µM). This study underscores the utility of our membrane-free vascular chip in elucidating the dysfunction induced by Aβ with respect to the BBB. [ABSTRACT FROM AUTHOR]

Surfactant injection is a promising method for enhanced oil recovery (EOR) due to its effective micro‐displacement mechanisms. However, understanding the interaction of a surfactant solution with heavy oil in porous media is neither straightforward nor well understood, particularly in heterogeneous systems. By enabling in‐situ real‐time monitoring of flow transport, microfluidic studies have provided novel insights into the underlying multiphase physics of flow at the pore scale. This paper examines the two‐phase displacement efficiency of a new surfactant in layered–fractured porous microfluidic patterns, a topic seldom discussed in the literature. To evaluate the performance of the proposed surfactant, we considered several heterogeneous media with varying layer and fracture geometrical characteristics, quantifying displacement efficiency for each case. Based on the analysis of pore‐scale snapshots, it was inferred that the primary mechanisms responsible for EOR during surfactant flooding into heavy oil include pore wall transportation, emulsifications, the deformation of residual oil, inter‐pore or intra‐pore bridging, and wettability alteration. Macroscopic displacement experiments revealed that the width of the swept area from surfactant injection significantly exceeded that of water injection, resulting in a substantially higher oil recovery. Furthermore, it was demonstrated that the direction of fluid flow in relation to fracture orientation plays a critical role in the dynamics of surfactant solution movement and, consequently, the ultimate oil production. [ABSTRACT FROM AUTHOR]

Intracellular delivery, the process of transporting substances into cells, is crucial for various applications, such as drug delivery, gene therapy, cell imaging, and regenerative medicine. Among the different approaches of intracellular delivery, mechanoporation stands out by utilizing mechanical forces to create temporary pores on cell membranes, enabling the entry of substances into cells. This method is promising due to its minimal contamination and is especially vital for stem cells intended for clinical therapy. In this review, we explore various mechanoporation technologies, including microinjection, micro–nano needle arrays, cell squeezing through physical confinement, and cell squeezing using hydrodynamic forces. Additionally, we highlight recent research efforts utilizing mechanoporation for stem cell studies. Furthermore, we discuss the integration of mechanoporation techniques into microfluidic platforms for high-throughput intracellular delivery with enhanced transfection efficiency. This advancement holds potential in addressing the challenge of low transfection efficiency, benefiting both basic research and clinical applications of stem cells. Ultimately, the combination of microfluidics and mechanoporation presents new opportunities for creating comprehensive systems for stem cell processing. [ABSTRACT FROM AUTHOR]

Combinatorial drug therapy has emerged as a critically important strategy in medical research and patient treatment and involves the use of multiple drugs in concert to achieve a synergistic effect. This approach can enhance therapeutic efficacy while simultaneously mitigating adverse side effects. However, the process of identifying optimal drug combinations, including their compositions and dosages, is often a complex, costly, and time-intensive endeavor. To surmount these hurdles, we propose a novel microfluidic device capable of simultaneously generating multiple drug concentration gradients across an interlinked array of culture chambers. This innovative setup allows for the real-time monitoring of live cell responses. With minimal effort, researchers can now explore the concentration-dependent effects of single-agent and combination drug therapies. Taking neural stem cells (NSCs) as a case study, we examined the impacts of various growth factors—epithelial growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF)—on the differentiation of NSCs. Our findings indicate that an overdose of any single growth factor leads to an upsurge in the proportion of differentiated NSCs. Interestingly, the regulatory effects of these growth factors can be modulated by the introduction of additional growth factors, whether singly or in combination. Notably, a reduced concentration of these additional factors resulted in a decreased number of differentiated NSCs. Our results affirm that the successful application of this microfluidic device for the generation of multi-drug concentration gradients has substantial potential to revolutionize drug combination screening. This advancement promises to streamline the process and accelerate the discovery of effective therapeutic drug combinations. [ABSTRACT FROM AUTHOR]