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The development of biosensing electronics for real-time sweat analysis has attracted increasing research interest due to their promising applications for non-invasive health monitoring. However, one of the critical challenges lies in the sebum interference that largely limits the sensing reliability in practical scenarios. Herein, we report a flexible epidermal secretion-purified biosensing patch with a hydrogel filtering membrane that can effectively eliminate the impact of sebum and sebum-soluble substances. The as-prepared sebum filtering membranes feature a dual-layer sebum-resistant structure based on the poly(hydroxyethyl methacrylate) hydrogel functionalized with nano-brush structured poly(sulfobetaine) to eliminate interferences and provide self-cleaning capability. Furthermore, the unidirectional flow microfluidic channels design based on the Tesla valve was incorporated into the biosensing patch to prevent external sebum contamination and allow effective sweat refreshing for reliable sensing. By seamlessly combining these components, the epidermal secretion-purified biosensing patch enables continuous monitoring of sweat uric acid, pH, and sodium ions with significantly improved accuracy of up to 12 %. The proposed strategy for enhanced sweat sensing reliability without sebum interference shows desirable compatibility for different types of biosensors and would inspire the advances of flexible and wearable devices for non-invasive healthcare.

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Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.

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Tissue on a chip or organ-on-chip (OOC) is a technology that's dignified to form a transformation in drug discovery through the use of advanced platforms. These are 3D in-vitro cell culture models that mimic micro-environment of human organs or tissues on artificial microstructures built on a portable microfluidic chip without involving sacrificial humans or animals. This review article aims to offer readers a thorough and insightful understanding of technology. It begins with an in-depth understanding of chip design and instrumentation, underlining its pivotal role and the imperative need for its development in the modern scientific landscape. The review article explores into the myriad applications of OOC technology, showcasing its transformative impact on fields such as radiobiology, drug discovery and screening, and its pioneering use in space research. In addition to highlighting these diverse applications, the article provides a critical analysis of the current challenges that OOC technology faces. It examines both the biological and technical limitations that hinder its progress and efficacy and discusses the potential advancements and innovations that could drive the OOC technology forward. Through this comprehensive review, readers will gain a deep appreciation of the significance, capabilities, and evolving landscape of OOC technology.

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

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Cardiovascular disease is a major global public health challenge. Point-of-- care testing (POCT) technologies are crucial for the prevention, early diagnosis, and treatment of cardiovascular conditions. Numerous POCT technologies for cardiovascular disease are currently available, which include but are not limited to conventional methods, paper-based microfluidic technology, microfluidic chip technology, electrochemical detection technology, ultrasonic detection technology, and smartphone-based detection technology. Each method has a broad range of applications and performs differently across various detection scenarios. This article offers a comprehensive analysis of current POCT technologies for cardiovascular disease, assessing their effectiveness, limitations, and future development directions. The aim is to provide insights and theoretical references for innovative research and clinical applications in POCT methods for cardiovascular disease.

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INTRODUCTION: Designing the microfluidic channel for neonatal drug delivery requires proper considerations to enhance the efficiency and safety of drug substances when used in neonates. Thus, this research aims to evaluate high-performance materials and optimize the channel design by modeling and simulation using COMSOL multiphysics in order to deliver an optimum flow rate between 0. 3 and 1 mL/hr. METHOD: Some of the materials used in the study included PDMS, glass, COC, PMMA, PC, TPE, and hydrogels, and the evaluation criterion involved biocompatibility, mechanical properties, chemical resistance, and ease of fabrication. The simulation was carried out in the COMSOL multiphysics platform and demonstrated the fog fluid behavior in different channel geometries, including laminar flow and turbulence. The study then used systematic changes in design parameters with the aim of establishing the best implementation models that can improve the efficiency and reliability of the drug delivery system. The comparison was based mostly on each material and its appropriateness in microfluidic usage, primarily in neonatal drug delivery. The biocompatibility of the developed materials was verified using the literature analysis and adherence to the ISO 10993 standard, thus providing safety for the use of neonatal devices. Tensile strength was included to check the strength of each material to withstand its operation conditions. Chemical resistance was also tested in order to determine the compatibility of the materials with various drugs, and the possibility of fabrication was also taken into consideration to identify appropriate materials that could be used in the rapid manufacturing of the product. RESULTS: The results we obtained show that PDMS, due to its flexibility and simplicity in simulation coupled with more efficient channel designs which have been extracted from COMSOL, present a feasible solution to neonatal drug delivery. CONCLUSION: The present comparative study serves as a guide on the choice of materials and design of microfluidic devices to help achieve safer and enhanced drug delivery systems suitable for the delicate reception of fragile neonates.

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The conventional real-time screening in organs-on-chips is limited to optical tracking of pre-tagged cells and biological agents. This work introduces an efficient biofabrication protocol to integrate tunable hydrogel electrodes into 3D bioprinted-on-chips. We established our method of fabricating cell-laden hydrogel-based microfluidic chips through digital light processing-based 3D bioprinting. Our conductive ink includes poly-(3,4-ethylene-dioxythiophene)-polystyrene sulfonate (PEDOT: PSS) microparticles doped in polyethylene glycol diacrylate (PEGDA). We optimized the manufacturing process of PEDOT: PSS microparticles characterized our conductive ink for different 3D bioprinting parameters, geometries, and materials conditions. While the literature is limited to 0.5% w/v for PEDOT: PSS microparticle concentration, we increased their concentration to 5% w/v with superior biological responses. We measured the conductivity in the 3-15 m/m for a range of 0.5%-5% w/v microparticles, and we showed the effectiveness of 3D-printed electrodes for predicting cell responses when encapsulated in gelatin-methacryloyl (GelMA). Interestingly, a higher cellular activity was observed in the case of 5% w/v microparticles compared to 0.5% w/v microparticles. Electrochemical impedance spectroscopy measurements indicated significant differences in cell densities and spheroid sizes embedded in GelMA microtissues.

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The analysis of microRNAs (miRNAs) in exosomes is of great importance for noninvasive early disease diagnosis. However, current techniques to detect exosomal miRNAs is hampered either by laborious exosome isolation or low abundance of miRNAs in exosomes. Here, we developed a microfluidic chemiluminescence (CL) analysis method for the multiplexed detection of exosomal miR-21 and miR-155. The microfluidic device contained three parts: a snake-shaped channel for fully mixing chemiluminescent reagents, a ship-shaped channel modified with CD63 protein aptamer for capturing exosomes, and another two parallel ship-shaped channels for hybridization chain reaction (HCR) amplification and CL detection. The multiple signal amplification was realized by Y-shaped arrays, HCR amplification, and poly-HRP catalyzed CL reaction. Using this multiple signal amplification method, our microfluidic CL biosensor achieves a limit of detection of miRNAs of 0.49 fM, with a linear range of 1 fM-10 pM, which is better or comparable to previously reported biosensors. What's more, the proposed microfluidic biosensor exhibits great specificity and selectivity to the target miRNA. Moreover, the microfluidic CL strategy exhibited excellent accuracy and could significantly distinguish different cancer subtypes as well as cancer patients and healthy people. These results suggest that this simple, high sensitive, and more accurate analytical strategy by analyzing different types of exosomal miRNAs has the potential applications in cancer diagnosis and stage monitoring.

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Tumours often display invasive behaviours that induce fingering, branching and fragmentation processes. The phenomenon, known as diffusional instability, is driven by differential cell proliferation, migration, and death due to the presence of metabolite and catabolite concentration gradients. An understanding of the intricate dynamics of this spatially heterogeneous process plays a key role in the investigation of tumour growth and invasion. In this study, we developed an in vitro tumour invasion assay to investigate cell invasiveness in tumour spheroids under a chemotactic stimulus. Our method, employing tumour spheroids seeded in a 3D collagen gel within a microfluidic chemotaxis chamber, focuses on the role of diffusive gradients. Using Time-Lapse Microscopy, the dynamic evolution of tumour spheroids was monitored in real-time, providing a comprehensive view of the morphological changes and cell migration patterns under different chemotactic conditions. Specifically, we explored the impact of fetal bovine serum (FBS) gradients on the behaviour of CT26 mouse colon carcinoma cells and compared the effects of varying FBS concentrations to two isotropic control conditions. Furthermore, a finite element in silico model was developed to quantify the diffusive flow of nutrients in the chemotaxis chamber and obtain a detailed understanding of tumour dynamics. Our findings reveal that the presence of a chemotactic gradient significantly influences tumour invasiveness, with higher concentrations of nutrients associated with increased cancer growth and cell migration.

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Recent studies have indicated significant correlation between the concentration of immune checkpoint markers borne by extracellular vesicles (EVs) and the efficacy of immunotherapy. This study introduces a high-resolution spiral microfluidic channel-integrated electrochemical device (HiMEc), which is designed to isolate and detect EVs carrying the immune checkpoint markers programmed death ligand 1 (PD-L1) and programmed death protein 1 (PD-1), devoid of plasma-abundant lipoprotein contamination. Antigen-antibody reactions were applied to immobilize the lipoproteins on bead surfaces within the plasma, establishing a size differential with EVs. A plasma sample was then introduced into the spiral microfluidic channel, which facilitated the acquisition of nanometer-sized EVs and the elimination of micrometer-sized lipoprotein-bead complexes, along with the isolation and quantification of EVs using HiMEc. PD-L1 and PD-1 expression on EVs was evaluated in 30 plasma samples (10 from healthy donors, 20 from lung cancer patients) using HiMEc and compared to the results obtained from standard tissue-based PD-L1 testing, noting that HiMEc could be utilized to select further potential candidates. The obtained results are expected to contribute positively to the clinical assessment of potential immunotherapy beneficiaries.

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The utilization of existing Skin-on-a-Chip (SoC) is constrained by the complex structures, the multiplicity of auxiliary devices, and the inability to evaluate exogenous chemicals that are hepatotoxic after percutaneous metabolism. In this study, a gravity-driven SoC without any auxiliary devices was constructed for the hepatocytotoxicity study of exogenous chemicals. The SoC possesses 3 layers of culture chambers, from top to bottom, for human skin equivalent (HSE), Human Umbilical Vein Endothelial Cells (HUVEC) and hepatocytes (HepG2), and the maintenance and expression capacity of the corresponding cells on the SoC were verified by specificity parameters. The reactivity of the SoC to exogenous chemicals was verified by 2-aminofluorene (2-AF). The SoC can realistically simulate the in vivo exposure process of exogenous chemicals that are percutaneously exposed and metabolized into the bloodstream and then to the liver to produce toxicity, and it can achieve the same effects on transcriptome as those of animal tests at lower exposure levels while examining multiple toxicological targets of the skin, vascular endothelial cells, and hepatocytes. Both in terms of species similarity, the principles of reduction, replacement and refinement (3R), or the level of exposure suggest that the present SoC has a degree of replacement for animal models in assessing exogenous chemicals, especially those that are hepatotoxic after percutaneous metabolism.

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In-vitro maturation (IVM) is the process of cultivating early-stage follicles from the primordial to the antral stage and facilitating the maturation of oocytes outside the body within a supportive environment. This intricate procedure requires the careful coordination of various factors to replicate the natural ovarian conditions. Advanced techniques for IVM are designed to mimic the natural ovarian environment and enhance the development of follicles. Three-dimensional (3D) culture systems provide a more biologically relevant setting for follicle growth compared to traditional two-dimensional (2D) cultures. Traditional culture systems, often fail to support the complex process of follicle development effectively. However, modern engineered reproductive tissues and culture systems are making it possible to create increasingly physiological in-vitro models of folliculogenesis. These innovative methods are enabling researchers and clinicians to better replicate the dynamic and supportive environment of the ovary, thereby improving the outcomes of IVM offering new hope for fertility preservation and treatment. This paper focuses on the routine 3D culture, and innovative 3D culture of ovary and follicles, including a tissue engineering scaffolds, microfluidic (dynamic) culture system, organ-on-chip models, EVATAR system, from a clinical perspective to determine the most effective approach for achieving in-vitro maturation of follicles. These techniques provide critical support for ovarian function in various ovarian-associated disorders, including primary ovarian insufficiency (POI), premature ovarian failure (POF), ovarian cancer, and age-related infertility.

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Postoperative adhesion (POA) is a common and serious complication following various types of surgery. Current physical barriers either have a short residence time at the surgical site with a low tissue attachment capacity or are prone to undesired adhesion formation owing to the double-sided adhesive property, which limits the POA prevention efficacy of the barriers. In this study, Janus-structured microgels (Janus-MGs) with asymmetric tissue adhesion capabilities are fabricated using a novel bio-friendly gas-shearing microfluidic platform. The anti-adhesive side of Janus-MGs, which consists of alginate, hyaluronic acid, and derivatives, endows the material with separation, lubrication, and adhesion prevention properties. The adhesive side provided Janus-MGs with tissue attachment and retention capability through catechol-based adhesion, thereby enhancing the in situ adhesion prevention effect. In addition, Janus-MGs significantly reduced blood loss and shortened the hemostatic time in rats, further reducing adhesion formation. Three commonly used rat POA models with different tissue structures and motion patterns are established in this study, namely peritoneal adhesion, intrauterine adhesion, and peritendinous adhesion models, and the results showed that Janus-MGs effectively prevented the occurrence of POA in all the models. The fabrication of Janus-MGs offers a reliable strategy and a promising paradigm for preventing POA following diverse surgical procedures.

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To prepare a PLGA microsphere loaded with the antipsychotic Blonanserin without release leg period and released in a near-zero model for long time, in this study, 15 kDa and 75 kDa PLGA were chosen to be mixed with different ratios, and Blonanserin microspheres (Bn-MS) without significant differences in the particle size, drug loading capacity, and encapsulation rate were prepared by microfluidics. The release kinetic model was fitted to the release behavior by monitoring the changes in particle size and morphology during the Bn-MS release to investigate microspheres' in vitro release pattern. The results showed that the addition of appropriate ratios of mixed molecular weights to Bn-MS could eliminate the release hysteresis period. When the ratio of 15 kDa and 75 kDa was 1:9 (F3), the Bn-MS had a low burst release rate, moderate release rate, no release hysteresis period, a long release period of up to 35 days, and a stable release pattern close to the zero level. The results of the release mechanism study indicated that the hybrid PLGA improved the release behavior of the microspheres by adjusting the dissolution degradation rate of Bn-MS, which in turn affected the release mechanism of the microspheres.

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Highly efficient surface acoustic wave (SAW) transducers offer significant advantages for microfluidic atomization. Aiming at highly efficient atomization, we innovatively accomplish dual-surface simultaneous atomization by strategically positioning the liquid supply outside the IDT aperture edge. Initially, we optimize Lamb wave transducers and specifically investigate their performance based on the ratio of substrate thickness to acoustic wavelength. When this ratio h/λ is approximately 1.25, the electromechanical coupling coefficient of A0-mode Lamb waves can reach around 5.5% for 128° Y-X LiNbO3. We then study the mechanism of droplet atomization with the liquid supply positioned outside the IDT aperture edge. Experimental results demonstrate that optimized Lamb wave transducers exhibit clear dual-surface simultaneous atomization. These transducers provide equivalent amplitude acoustic wave vibrations on both surfaces, causing the liquid thin film to accumulate at the edges of the dual-surface and form a continuous mist.

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Extracellular vesicles (EVs) are considered as promising candidates for predicting patients who respond to immunotherapy. Nevertheless, simultaneous detection of multiple EVs markers still presents significant technical challenges. In this work, we developed a high-throughput microdroplet-enhanced chip (MEC) platform, which utilizes thousands of individual microchambers (∼pL) as reactors, accelerating the detection efficiency of the CRISPR/Cas systems and increasing the sensitivity by up to 100-fold (aM level). Ten biomarkers (including 5 RNAs and 5 proteins) from patients' EVs are successfully detected on one chip, and the comprehensive markers show increased accuracy (AUC 0.911) than the individual marker for the efficacy prediction of immunotherapy. This platform provides a high-throughput yet sensitive strategy for screening immunotherapy markers in clinical.

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In-vitro blood purification is essential to a wide range of medical treatments, requiring fine-grained analysis and precise separation of blood components. Despite existing methods that can extract specific components from blood by size or by magnetism, there is not yet a general approach to efficiently filter blood components on demand. In this work, we introduce the first programmable non-contact blood purification system for accurate blood component detection and extraction. To accurately identify different cells and artificial particles in the blood, we collected and annotated a new blood component object detection dataset and trained a collection of deep-learning-based object detectors upon it. To precisely capture and extract desired blood components, we fabricated a microfluidic chip and set up a customized holographic optical tweezer to trap and move cells/particles in the blood. Empirically, we demonstrate that our proposed system can perform real-time blood fractionation with high precision reaching up to 96.89%, as well as high efficiency. Its scalability and flexibility open new research directions in blood treatment.

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A novel approach combing a fluorescent microfluidic paper strip with a portable smartphone-based sensing platform is developed for rapid and sensitive detection of omethoate pesticide. The detection mechanism of the microfluidic paper strip is based on the fluorescence quenching of graphene oxide (GO) toward the cyanine 3 (Cy3)-labeled aptamer (Cy3-APT). Upon exposure to omethoate, the Cy3-APT detaches from the surface of GO, resulting in considerable fluorescence recovery, which can be visualized through the smartphone-based sensing platform. The images are analyzed through a self-developed app embedded with a pretrained convolutional neural network model, achieving a high regression coefficient of 0.9964 at an omethoate concentration range of 0-750 nM. The smartphone-based platform enables rapid on-site detection of omethoate pesticide in real samples within 10 min, with results comparable to those obtained using standard methods. In short, the proposed microfluidic paper-based fluorescent sensor combined with the smartphone-based sensing platform enhances the detection performance toward organophosphorus pesticides.

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Flexible strain sensors have been widely used in wearable electronics. However, the fabrication of flexible strain sensors with a large strain detection range, high sensitivity, and negligible hysteresis remains a formidable challenge, even after enormous advancements in the field. Herein, a flexible microfluidic strain sensor was fabricated by filling poly(3,4-ethylenedioxythiophene):polystyrenesulfonate-MXene-gold (PEDOT:PSS-MXene-Au) nanocomposites into microchannels in an elastic matrix. Owing to the unique properties of the nanofiller and Ecoflex elastomer microchannel, the microfluidic strain sensor detected a strain of 0%-500% with low hysteresis (2.4%), high sensitivity (guage factor = 25.4), short response times (∼86 ms), and good durability. Moreover, the flexible microfluidic sensor was used to detect various physiological signals and human activities, control a mechanical hand, and capture hand motions in real time. As demonstrated by its good performance, the proposed flexible microfluidic sensor holds great potential in applications such as wearable electronics, physiological signal monitoring and human-machine interactions.

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Soil nutrition is a key pillar in agricultural productivity. However, point-of-need testing for soil nutrition is not readily available in resource-limited settings such as Kenya. We set out to study the perceived need for soil testing among farmers in this country. A group of 547 farmers from Murang'a and Kiambu counties in central Kenya were recruited through multi-stage sampling to help assess the perceptions and willingness to pay (WTP) toward a prototype technology for surveillance of in-situ soil nutrition. The technology is based on a cafetière-style filter system for extraction and a microfluidic paper-based analytical device (µPAD) for nutrient readout. We employed the double bounded choice contingent valuation method (CVM) to analyze the willingness of farmers to accept and pay for the prototype if the technology was available on the market. It was found that currently, only 1.5 % of farmers carry out soil testing. The high costs of analysis at testing centers, which are often far from the farmers, are among the main reasons contributing to the majority of farmers not testing their soils. The farmers surveyed were generally willing to make their soil data publicly accessible, especially to extension officers. CVM showed that uncontrolled WTP had a 94.24 % premium above KSh1,000 ($6.60) incurred by using the existing rapid testing method. Factoring the control variables and disaggregating the model into gender categories, the findings showed that youth, women, and men had WTP values of KSh1,612.53 ($10.75), KSh1,558.68 ($10.39), and KSh1,504.83 ($10.03), respectively, indicating that farmers can indeed pay for the convenience to test their soils in situ. Through the democratization of soil nutrition data, extension agents can enhance the improvement of agricultural productivity, which implies that farmers can commercialize their agricultural activities.