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The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous cells such as fibroblasts, pericytes, endothelial cells and immune cells. The intricate cellular interactions within the TME hold a central role in shaping the dynamics of cancer progression, influencing pivotal aspects such as tumor initiation, growth, invasion, response to therapeutic interventions, and the emergence of drug resistance. In immunologically 'cold' tumors, the TME is marked by a scarcity of infiltrating immune cells, limited antigen presentation in the absence of potent immune-stimulating signals, and an abundance of immunosuppressive factors. While strategies targeting the TME as a therapeutic avenue in 'cold' tumors have emerged, there is a pressing need for novel approaches that faithfully replicate the complex cellular and non-cellular interactions in order to develop targeted therapies that can effectively stimulate immune responses and improve therapeutic outcomes in patients. Microfluidic devices offer distinct advantages over traditional in vitro 3D co-culture models and in vivo animal models, as they better recapitulate key characteristics of the TME and allow for precise, controlled insights into the dynamic interplay between various immune, stromal and cancerous cell types at any timepoint. This review aims to underscore the pivotal role of microfluidic systems in advancing our understanding of the TME and presents current microfluidic model systems that aim to dissect tumor-stromal, tumor-immune and immune-stromal cellular interactions in various 'cold' tumors. Understanding the intricacies of the TME in 'cold' tumors is crucial for devising effective targeted therapies to reinvigorate immune responses and overcome the challenges of current immunotherapy approaches.

Microfluidic-engineered hydrogel microspheres have emerged as a promising avenue for advancements in tissue engineering and regenerative medicine, particularly through the precise manipulation of fluids to achieve personalized composite biomaterials. In this study, we employed microfluidic technology to fabricate hydrogel microspheres (HMs) using Chinese herbal Bletilla striata polysaccharide (BSP) as the primary material. Concurrently, the natural active ingredient 20(S)-protopanaxadiol (PPD) was encapsulated within the HMs in the form of liposomes (PPD-Lipo), resulting in the formation of nanocomposite hydrogel microspheres (PPD-Lipo@HMs) intended for diabetic wound tissue repair. PPD-Lipo@HMs are characterized by the expansive specific surface area, adjustable mechanical properties, and exceptional biocompatibility. PPD-Lipo@HMs can stimulate the production of vascular endothelial factors, which in turn enhances the migration of endothelial cells, the creation of tubes, angiogenesis, and tissue repair. Moreover, the PPD-Lipo@HMs accumulation produces a microsphere scaffold that effectively covers damaged tissues, promoting the attachment, spread, and multiplication of fibroblast and endothelial cells. The polysaccharide material BSP within PPD-Lipo@HMs can modulate the immune microenvironment of the damaged tissue, reducing inflammation, encouraging re-epithelialization and granulation tissue formation, accelerating angiogenesis and collagen deposition, ultimately leading to tissue repair. The findings highlight the superior therapeutic efficacy of the microfluidic-engineered PPD-Lipo@HMs in addressing the complex challenges of diabetic wound tissue repair, thereby affirming the significant potential of microfluidic engineering technology in tissue repair applications. Highlights: Microfluidic-engineered nano-composite microspheres are extensively explored for tissue engineering. Microfluidic and photocrosslinking techniques were used to construct Bletilla striata polysaccharide nano-composite microspheres for the first time. Tissue-engineered nano-composite microspheres efficiently fill irregular wounds to promote cell migration and proliferation. 20(S)-protopanaxadiol combined with Bletilla striata polysaccharide synergistic angiogenesis and immune regulation to promote diabetic wound tissue regeneration. [ABSTRACT FROM AUTHOR]

The presence of bacterial persisters is a key factor contributing to chronic infection. However, no effective treatment methods are currently available. Thus, a platform is developed, called reactive oxygen species (ROS) bomb, based on microenvironment‐adaptive hydrogel microspheres, to oxidize the cell membranes of persisters in chronic periprosthetic joint infection (PJI). Fenton reagent hydroxy iron oxide (FeOOH) and a glucose oxidase (GOx)/calcium phosphate (CaP) acid‐responsive shell are sequentially induced on the surface of mesoporous polydopamine (PDA) nanoparticles by the PDA‐mediated ion precipitation and interfacial adhesion, followed by the coloaded with glucose into microfluidic hyaluronic acid hydrogel microspheres. Hydroxyl radicals are explosively generated through GOx‐mediated glucose oxidase, H2O2 production, and its Fenton‐like reactions with FeOOH, which also benefit from the weakly acidic microenvironment around persisters, result in the destruction of bacterial cell membrane, and subsequent overflow of cellular contents such as dsDNA, proteins, and K+. The bactericidal rates of methicillin‐resistant Staphylococcus aureus and Staphylococcus epidermidis persisters are up to 99.14% and 98.96%, and the bacterial loads in lesion location are significantly decreased after ROS bombs treated, effectively alleviated the inflammation and bone resorption damage. This work provides a new strategy toward persisters clearance and shows great application potential in other chronic infection‐related diseases. [ABSTRACT FROM AUTHOR]

Plant-based biotechnology is crucial for developing renewable biofuels, enhancing bioremediation, and improving the food supply chain. Modern agricultural technologies often face limitations due to variable weather conditions and significant infrastructure costs. Addressing these challenges, smaller-scale biotechnologies optimize plant production through controlled lighting and nutrient supply, mitigating the impact of adverse weather. In vitro technologies are particularly effective for promoting plant growth with desirable phenotypic traits under controlled conditions, though they bring challenges related to sustainability and costs. Recent innovations in microfabrication have led to the miniaturization of traditional in vitro technologies, significantly reducing both sample volumes and costs. This review explores the advancements in microfluidic systems for plant studies, covering a range from single plant cells to mature plants, and discusses the common materials and integrated technologies employed in microfabrication for in-depth in vitro studies. • Small-scale biotechnologies address agricultural problems. • Single-plant cell positioning and observation are possible with microfluidics. • Miniaturized Optimized in vitro conditions improve plant development. • Advanced miniaturized in vitro technology reduced sample volume and cost. • Plant research uses microfluidics for macro and micro inspection. [ABSTRACT FROM AUTHOR]

The demand for rapid, high-quality, and controlled mixing at the microscale has led to the development of various types of micromixers. Micromixers are commonly categorised as active, or passive based on whether they utilise external energy to enhance mixing. Passive micromixers utilise a complex geometry to enhance the diffusion coefficient at lower Reynolds numbers and induce chaotic advection at higher Reynolds numbers for effectively mixing fluids without external energy. Active micromixers, on the other hand, achieve precise, fast, and controllable mixing by employing external energy sources such as pressure, electric, magnetic, or acoustic fields. Some active methods such as magnetic field-driven micromixers need fluids with specific properties. Others, such as acoustic field-driven micromixers apply to various types of fluids. Bubbles can be used as membranes or stirrers in microfluidic devices for both passive and active micromixers. They are easy to use, compatible with microfluidic systems, low cost, and effective. Improvements in manufacturing methods, notably, 3D printing have emerged as promising methods for the development of new micromixer designs. In this paper, a wide range of micromixer types is reviewed and the main mechanism for enhanced mixing is investigated. This study aims to guide researchers proposing innovative designs. Furthermore, it is shown that combining different methods can lead to the development of more effective micromixers, promising further advancements in microscale mixing technology. [ABSTRACT FROM AUTHOR]

Sea squirts (Tunicata) are chordates and develop a swimming larva with a small and defined number of individually identifiable cells. This offers the prospect of connecting specific stimuli to behavioral output and characterizing the neural activity that links these together. Here, we describe the development of a microfluidic chip that allows live larvae of the sea squirt Ciona intestinalis to be immobilized and recorded. By generating transgenic larvae expressing GCaAMP6m in defined cells, we show that calcium ion levels can be recorded from immobilized larvae, while microfluidic control allows larvae to be exposed to specific waterborne stimuli. We trial this on sea water carrying increased levels of carbon dioxide, providing evidence that larvae can sense this gas. Research Highlights: Development of a microfluidic chip in which Ciona larvae can be immobilized, exposed to controlled stimuli, and recorded.A transgenic construct was designed to drive expression of the live cell calcium ion reporter GCaMP in Ciona palp cells and other sensory cells.Exposure of Ciona larvae to carbon dioxide‐enriched sea water leads to detectable changes in GCaMP activity. [ABSTRACT FROM AUTHOR]

This research introduced a microfluidic kit for rapid and economic detection of melamine (MLM) and sodium hypochlorite (NaOCl) in milk samples. The kit allows for simultaneous identification of MLM and NaOCl by reacting with cyanuric acid-modified Au nanoparticles (Au@Ca) and N, N-diethyl-p-phenylenediamine, respectively. The resulting color changes are used as the analytical signal for detection. All of the effective operational parameters were optimized by a one-factor-at-a-time approach. Under the optimum conditions (pH 6.5, path length = 50 mm, flow rate = 0.1 ml/min) a linear relationship between the concentrations of MLM and NaOCl and the blue component of the analyzed RGB pixels of the images captured with a smartphone camera was observed. The linear ranges for MLM and NaOCl were obtained in the concentration ranges of 0.1–1 and 0.1–4.5 µM, respectively, with 0.040 µM and 0.078 µM detection limits, consecutively. The results indicate that the proposed microfluidic kit provides strong selectivity and high reproducibility for detecting MLM and NaOCl in milk samples. To validate the performance of the method, the microfluidic kit was employed for analyzing five different milk samples, yielding recovery values between 94.0% and 105.0% and relative standard deviation values lower than 4.12% indicating the proposed system has admissible accuracy for both analytes. Besides, the results were compared to those obtained using high-performance liquid chromatography, as a standard reference method, and a good agreement between the two approaches was found. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The challenge of producing polymer vesicles remains difficult, despite numerous attempts to modulate the kinetics of polymer vesicle budding and achieve precise control over the membrane characteristics. An innovative approach that incorporates the use of copolymer-loaded single-emulsion droplets is proposed to address this challenge. This method enables the precise manipulation of micelles and polymer vesicles' composition, structures and dimensions. The emulsion contracts and forms microspheres when the copolymer concentrations exceed > 0.5 wt%, resulting in the formation of nano polymer vesicles. Conversely, the copolymer spontaneously forms micro polymer vesicles and micelles through vesicle budding at lower concentrations. The spontaneous production of vesicles and micelles can be induced by modifying the copolymer concentration in the emulsion. Our discoveries have a significant impact relative to the development of copolymer membranes and contribute to an enhanced comprehension of the mass manufacturing of polymer vesicles from single emulsions. [ABSTRACT FROM AUTHOR]

The intensive development of tight reservoirs has positioned them as a strategic alternative to conventional oil and gas resources. Existing enhanced oil recovery (EOR) methods struggle to effectively exploring reservoir oil, resulting in low recovery rates. Novel and effective means of developing tight reservoirs are urgently needed. Nanomaterials have shown promising applications in improving water flooding efficiency, with in-depth research into mechanisms that lower injection pressure and increase water injection volumes. However, the extent of improvement remains limited. In this study, a silicon quantum dots (Si-QDs) material was synthesized via a hydrothermal synthesis method and used to prepare a nanofluid for the efficient recovery of tight reservoir. The Si-QDs, with an approximate diameter of 3 nm and a spherical structure, were surface functionalized with benzenesulfonic acid groups to enhance the performance. The developed nanofluid demonstrated stability without aggregation at 120 °C and a salinity of 60000 mg/L. Core flooding experiments have demonstrated the attractive EOR capabilities of Si-QDs, shedding light of the EOR mechanisms. Si-QDs effectively improve the wettability of rocks, enhancing the sweeping coefficient of injected fluids and expanding sweeping area. Within this sweeping region, Si-QDs efficiently stripping adsorbed oil from the matrix, thus increasing sweeping efficiency. Furthermore, Si-QDs could modify the state of pore-confined crude oil, breaking it down into smaller particles that are easier to displacement in subsequent stages. Si-QDs exhibit compelling EOR potential, positioning them as a promising approach for effectively developing tight oil reservoirs. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor cell therapy is a successful immunotherapy for the treatment of blood cancers. However, hurdles in their manufacturing remain including efficient isolation and purification of the T-cell starting material. Herein, we describe a one-step separation based on inertial spiral microfluidics for efficient enrichment of T-cells in B-cell acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia patient's samples. In healthy donors used to optimize the process, the lymphocyte purity was enriched from 65% (SD ± 0.2) to 91% (SD ± 0.06) and T-cell purity was enriched from 45% (SD ± 0.1) to 73% (SD ± 0.02). Leukemic samples had higher starting B-cells compared to the healthy donor samples. Efficient enrichment and recovery of lymphocytes and T-cells were achieved in ALL samples with B-cells, monocytes and leukemic blasts depleted by 80% (SD ± 0.09), 89% (SD ± 0.1) and 74% (SD ± 0.09), respectively, and a 70% (SD ± 0.1) T-cell recovery. Chronic lymphocytic leukemia samples had lower T-cell numbers, and the separation process was less efficient compared to the ALL. This study demonstrates the use of inertial microfluidics for T-cell enrichment and depletion of B-cell blasts in ALL, suggesting its potential to address a key bottleneck of the chimeric antigen receptor-T manufacturing workflow. [ABSTRACT FROM AUTHOR]

Recent research has focused on the methods for administration of medications in a controlled manner while minimizing side effects. Cross-linked hydrogels have wide application area as nanocarriers. There are many approaches for developing suitable methods to produce ideal particles. Advances in microtechnology have been considered as a solution to produce controlled drug delivery systems, however, it is limited due to the necessity for specialized laboratories. In this study, a simple method to produce antibiotic-loaded chitosan particles is proposed. Production was carried out with two different designs, a syringe-based flow focusing system (outer diameter of 1 mm, inner diameter of 120 µm) and microchannel with 250 µm width and 100 µm height fabricated with the computer numerical control (CNC). Sodium Triphosphate (TPP) was used as cross-linking agent for the production of particles and the effects of the concentration and flow rates on the particle formation was investigated. It has been observed that particles can be produced in a syringe-based system, but the resulting particles are not homogeneous. In the studies carried out with CNC microchannel, it was determined by SEM analysis that the obtained particles ranged in size from 39 to 771 nm, and it was seen that the CNC microchannel was more effective at low and equal flow rates (25 µl/min). It has been found that increasing the flow rate and concentration of chitosan increases the particle size. It was determined that Ampicillin loaded particles synthesized with the CNC microchannel exhibited high inhibition against Gram positive and Gram negative bacteria. These results show that the proposed approaches for the design of microsystems can be used in the formation of drug carriers without the need for specialized laboratories and expertise. [ABSTRACT FROM AUTHOR]

This pafa considers a three-dimensional micropump based on a piezoelectric actuator. COMSOL software version 6.5 is used to simulate the faformance of the micropump. At first, a reference micropump is defined, which works at a frequency of 60 Hz and a voltage of 1500 V that is capable of pumping a maximum flow rate of 0.038 ml/s. The influence of frequency, voltage, the axial position of input and output of micropump, dimensions of piezoelectric actuator and membrane, and shape of the actuator on the fluid output flow rate and pumped fluid volume is investigated. The results demonstrate that the frequency, voltage, dimensions of the piezoelectric actuator and the membrane has a direct effect on the output flow rate and the pumped fluid volume so that the output flow rate of the fluid and the volume of the pumped fluid increase with the increase of these parameters. For example, the output flow rate of the micropump at 100 and 20 Hz frequency is 0.065 and 0.011 ml/s, respectively. By increasing the voltage from 1500 to 1875 V, the micropump output flow rate increases to 0.047 ml/s. The results show that the rectangular piezoelectric actuator has a lower efficiency than the circular one. [ABSTRACT FROM AUTHOR]

Cold‐induced vasoconstriction is a significant contributor that leads to chilblains and hypothermia in humans. However, current animal models have limitations in replicating cold‐induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel‐on‐a‐chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of N‐isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature set at 30°C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37°C to 4°C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel‐on‐a‐chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel‐on‐a‐chip led to cell necrosis, mitochondrial membrane potential (ΔΨm) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold‐induced endothelial injury, this groundbreaking thermosensitive vessel‐on‐a‐chip technology offers promising advancements in the study of cold‐induced cardiovascular diseases, including pathogenesis and therapeutic drug screening. [ABSTRACT FROM AUTHOR]

A novel microfluidic ractopamine (RAC) detection platform consisting of a microfluidic RAC chip and a smart analysis device is proposed for the determination of RAC concentration in meat samples. This technology utilizes gold nanoparticles (AuNPs) modified with glutamic acid (GLU) and polyethyleneimine (PEI) to measure RAC concentration in food products. When RAC is present, AuNPs aggregate through hydrogen bonding, causing noticeable changes in their optical properties, which are detected using a self-built UV–visible micro-spectrophotometer. Within the range of 5 to 80 ppb, a linear relationship exists between the absorbance ratio (A693nm/A518nm) (Y) and RAC concentration (X), expressed as Y = 0.0054X + 0.4690, with a high coefficient of determination (R2 = 0.9943). This method exhibits a detection limit of 1.0 ppb and achieves results within 3 min. The practical utility of this microfluidic assay is exemplified through the evaluation of RAC concentrations in 50 commercially available meat samples. The variance between concentrations measured using this platform and those determined via liquid chromatography–tandem mass spectrometry (LC-MS/MS) is less than 8.33%. These results underscore the viability of the microfluidic detection platform as a rapid and cost-effective solution for ensuring food safety and regulatory compliance within the livestock industry. [ABSTRACT FROM AUTHOR]

Biosecurity encompasses the health and safety of humans, animals, plants, and the environment. In this article, "biosecurity" is defined as encompassing the comprehensive aspects of human, animal, plant, and environmental safety. Reliable biosecurity testing technology is the key point for effectively assessing biosecurity risks and ensuring biosecurity. Therefore, it is crucial to develop excellent detection technologies to detect risk factors that can affect biosecurity. An electrochemical microfluidic biosensing platform integrates fluid control, target recognition, signal transduction, and output and incorporates the advantages of electrochemical analysis technology and microfluidic technology. Thus, an electrochemical microfluidic biosensing platform, characterized by exceptional analytical sensitivity, portability, rapid analysis speed, low reagent consumption, and low risk of contamination, shows considerable promise for biosecurity detection compared to traditional, more complex, and time-consuming detection technologies. This review provides a concise introduction to electrochemical microfluidic biosensors and biosecurity. It highlights recent research advances in utilizing electrochemical microfluidic biosensing platforms to assess biosecurity risk factors. It includes the use of electrochemical microfluidic biosensors for the detection of risk factors directly endangering biosecurity (direct application: namely, risk factors directly endangering the health of human, animals, and plants) and for the detection of risk factors indirectly endangering biosecurity (indirect application: namely, risk factors endangering the safety of food and the environment). Finally, we outline the current challenges and future perspectives of electrochemical microfluidic biosensing platforms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In microfluidic reactors designed for the synthesis of nanomaterials, hydrodynamics and mixing performance play a crucial role in the characteristics of the synthesized nanoparticles. In the current study, CFD simulation is utilized to shed light on flow characteristics inside a spiral microfluidic device and the way it affects the mixing during ZnO synthesis. Before microfabrication, the optimal number of spiral loops and flow rate in the microfluidic reactor was determined through mixing index calculation according to the CFD results in terms of the concentration distribution. Furthermore, this synthesis method is compared with batch nanoparticle fabrication techniques. In the microfluidic system, the concentrations of precursors were 50 times more diluted rather than batch methods. The droplet-based microfluidic ZnO synthesis was eight-fold faster than batch synthesis. The ZnO nanoparticles were characterized by XRD, SEM, and FTIR techniques. The outcomes of the FTIR analysis demonstrated that both the batch and microfluidic samples exhibit identical vibrational peaks. The experiments showed that the microfluidic system is reliable for controlling size. Besides, the CFD results indicated that a spiral micromixer with five loops provides sufficient mixing. The acquired findings from the characterization analyses can lead us toward a clue that once the ZnCl 2 /NaOH concentration ratio is greater than unity, a narrower size distribution of ZnO particles is probable. Consequently, the microfluidic reactor can be an efficient method for nanomaterial construction owing to the minimization of energy consumption and independence of the operational synthesis temperature. [ABSTRACT FROM AUTHOR]

This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre‐clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from the THP‐1 cell line, creating a physiological biological microenvironment. To mimic the three‐dimensional architecture and dynamic expansion and relaxation of the air‐blood‐barrier, they are grown on a stretchable microphysiological lung‐on‐chip. For validating the in vitro model, three different protocols have been developed to demonstrate the clinically established anti‐inflammatory effect of glucocorticoids to reduce certain inflammatory markers after different pro‐inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) to simulate an LPS‐induced acute lung injury measured best with cytokine IL‐6 release; (2) an inflammation caused by LPS at ALI (air‐liquid interface) to investigate aerosolized anti‐inflammatory treatment, measured with chemokine IL‐8 release; and (3) an inflammation with a combination of human inflammatory cytokines TNFα and IFNγ to simulate a critical cytokine storm leading to epithelial barrier disruption, where the eventual weakening or protection of the epithelial barrier can be measured. In all cases, the presence of macrophages appeared to be crucial to mediating inflammatory changes in the alveolar epithelium. LPS induction led to inflammatory changes independently of stretch conditions. Dynamic stretch, emulating breathing‐like mechanics, was essential for in vitro modeling of the clinically relevant outcome of epithelial barrier disruption upon TNFα/IFNγ‐induced inflammation. [ABSTRACT FROM AUTHOR]

In order to solve the obvious nonlinear problem of temperature and complex structure of PCR instrument during nucleic acid amplification. In this paper, a new nucleic acid amplification device and temperature control algorithm were proposed. In the device, in order to improve the rise and fall rate and make the whole reaction device smaller and simpler, this paper uses a microfluidic chip for nucleic acid reaction. At the same time, in the warming and cooling module, the temperature is controlled by the semiconductor chilling plate, the air‐cooled cooling device and the heat sink structure, which greatly improves the speed of nucleic acid amplification. In the algorithm, a hybrid algorithm is designed, using Particle Swarm Optimization (PSO) to optimize PID algorithm parameters, and then based on fuzzy theory, according to the temperature control requirements of nucleic acid amplification, fuzzy rules are analyzed and fuzzy reasoning is carried out, and then combined with PID to achieve rapid response and overshooting control of temperature control. Finally, the measurement noise is filtered by Kalman filter. Finally, COMSOL and MATLAB software are used to simulate and compare, and it is proved that the device has a certain heat dissipation effect in the process of nucleic acid amplification. This algorithm can improve the accuracy and robustness of the control system, improve the response speed, reduce the overshoot, shorten the adjustment time, and restrain the interference. [ABSTRACT FROM AUTHOR]

Transport and alignment of microscopic chips are important steps in microelectronics component integration with common approaches being pick‐and‐place, microfluidics, parallel transfer and self‐assembly. An alternate transport approach of microscopic chips is proposed using patterned liquid micro rails as chaperones. The surface free energy and interfacial free energy minimization of all constituents enable the creation of stable pathways. This allows for chip‐attachment to rails, while the liquid layer lubricates chip‐sliding. Monorails, digital monorails, and digital birails are investigated for chip movement behavior. Chip position and speed can be controlled using liquid flow in closed chambers. Speeds from 10 to 400 mm s−1 are achieved with translation distances as long as 50 mm. It is discovered that chips can selectively cross rail discontinuities of up to 500 µm, allowing for chip position control through a stop‐and‐go motion. A programmable liquid rails‐based chip conveyor system is demonstrated by transporting diodes to receptor sites where they undergo self‐assembly. [ABSTRACT FROM AUTHOR]

The choroid plexus (CP), a highly vascularized endothelial–epithelial convolute, is placed in the ventricular system of the brain and produces a large part of the cerebrospinal fluid (CSF). Additionally, the CP is the location of a blood–CSF barrier (BCSFB) that separates the CSF from the blood stream in the CP endothelium. In vitro models of the CP and the BCSFB are of high importance to investigate the biological functions of the CP and the BCSFB. Since the CP is involved in several serious diseases, these in vitro models promise help in researching the processes contributing to the diseases and during the development of treatment options. In this review, we provide an overview on the available models and the advances that have been made toward more sophisticated and "in vivo near" systems as organoids and microfluidic lab-on-a-chip approaches. We go into the applications and research objectives for which the various modeling systems can be used and discuss the possible future prospects and perspectives. [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]

The use of stem cell-based treatment systems is prevalent in regenerative medicine. To enhance the regenerative capabilities of stem cells, growth factors are typically incorporated into the treatment system. Nonetheless, traditional hydrogel-encapsulated or heparinized scaffolds that bind factors have limitations. In this study, we prepared a biomaterial strategy using uniform poly(lactic-co-glycolic) acid (PLGA) microspheres (uPLGA-Ms) fabricated by microfluidic to sustain delivery of insulin-like growth factor 1 (IGF-1), a critical protein for hMSCs biological functions. The uPLGA-Ms loaded IGF-1 were highly monodispersed through precise manipulation of the flow rate of the two-phase of the flow-focusing microchannle. The results showed that the uPLGA-Ms stabilize IGF-1 and provide a more efficient sustained delivery and cost-effective of growth factor. Gene expression analysis demonstrated the uPLGA delivery of IGF-1 results in a (enhanced) supported hMSCs expansion, survival, stemness, and secretion abilities comparable with the conventional soluble IGF-1 group. In summary, this material-based strategy to stabilize and sustain delivery of growth factor has broad potential to regeneration of various tissues and organs.

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. [ABSTRACT FROM AUTHOR]

Abstract Chemical bioreactions play a significant role in many of the microfluidic devices, and their applications in biomedical science have seen substantial growth. Given that effective mixing is vital for initiating biochemical reactions in many applications, micromixers have become increasingly prevalent for high-throughput assays. In this research, a numerical study using the finite element method was conducted to examine the fluid flow and mass transfer characteristics in novel micromixers featuring an array of pillars. The study utilized two-dimensional geometries. The impact of pillar configuration on mixing performance was evaluated using concentration distribution and mixing index as key metrics. The study explores the effects of pillar array design on mixing performance and pressure drop, drawing from principles such as contraction–expansion and split-recombine. Two configurations of pillar arrays, slanted and arrowhead, are introduced, each undergoing investigation regarding parameters such as pillar diameter, gap size between pillar groups, distance between pillars, and vertical shift in pillar groups. Subsequently, optimal micromixers are identified, exhibiting mixing efficiency exceeding 99.7% at moderate Reynolds number (Re = 1), a level typically challenging for micromixers to attain high mixing efficiency. Notably, the pressure drop remains low at 1102 Pa. Furthermore, the variations in mixing index over time and across different positions along the channel are examined. Both configurations demonstrate short mixing lengths and times. At a distance of 4300 μm from the inlet, the slanted and arrowhead configurations yielded mixing indices of 97.2% and 98.9%, respectively. The micromixers could provide a mixing index of 99.5% at the channel’s end within 8 s. Additionally, both configurations exceeded 90% mixing indices by the 3 s. The combination of rapid mixing, low pressure drop, and short mixing length positions the novel micromixers as highly promising for microfluidic applications.

Natural bone is a material with a hierarchical porous structure; therefore, the pore size of bone tissue at the micro-scale is crucial for osteoblast function and osteogenesis. However, the physiological mechanisms behind pore size-regulated osteogenesis remain unclear. Trabecular separation is one of the main parameters of bone trabeculae structure, which is the gap between the trabeculae and can be understood as porosity. This study uses a bioinspired bone chip made from polydimethylsiloxane (PDMS) to mimic the multiscale microstructures of healthy and osteoporotic bone tissue based on data on trabecular separation from healthy and osteoporotic mice. Microchannels in the chip were made in the same topology and substrate but at different micro-scales. The result showed that osteoblasts seeded into the smaller microchannel (200 μm in diameter, mimicking healthy bone) demonstrate greater osteogenic capability and autophagy than in the larger one (350 μm in diameter, mimicking osteoporotic bone). In addition, changes in osteogenesis between each microchannel after using the autophagy inhibitor chloroquine (CQ) indicated that osteogenesis was accelerated by autophagy in the 200 μm microchannel. Finally, we found stronger osteogenesis in the 200 μm microchannel, which depends on the activation of Hippo/YAP signaling. This bioinspired bone chip, which mimics the cellular behavioral changes in the osteoporotic microenvironment at the tissue level during the transition from healthy to osteoporotic bone, is expected to be the ideal in vitro platform for studying osteoporosis (OP).

Hydrogen peroxide (H2O2) is an essential molecule to various physiological processes and is commonly used for the detection and monitoring of glucose and cell viability.  Furthermore, it is identified as a signal of oncogenic growth due to its widespread presence within the cancer cell environment. However, the low concentrations of H2O2 released by cancer cells' metabolism challenge current detection methods' capabilities and their practicality for translation to clinical applications. Colorimetric assays with simple readouts are a promising solution, provided that their sensitivity and rapidity in detecting H2O2 improve.  Here, a plasmonic enhanced nanopatterned platform is proposed coupled with an Amplex Red assay to monitor the color change of H2O2 released from cancer cells. The nanopatterned platform embedded into a multiplexed microfluidic device enhances the kinetics of the reaction ≈7 times. This approach has reached a limit of detection of 1 pm when tested in breast (MCF‐7) and prostate (PC‐3) cancer media. The collected color images are processed and analyzed by a machine learning algorithm that categorizes them into “high” or “low‐to‐no” concentrations of H2O2 with 91% accuracy. This study is a step toward developing a device for highly sensitive H2O2 detection that is easily adaptable, user‐friendly, portable, and automated. [ABSTRACT FROM AUTHOR]

Viral RNA detection is crucial in preventing and treating early infectious diseases. Traditional methods of RNA detection require a large amount of equipment and technical personnel. In this study, proposed a programmable controlled surface acoustic wave (SAW)‐based RNA detecting device has been proposed. The proposed device can perform the entire viral RNA detection process, including cell lysis by cell‐microparticle collision through SAW‐induced liquid whirling, RNA capture by SAW‐suspended magnetic beads, RNA elution through SAW‐induced high streaming force, and PCR thermal cycling through SAW‐generated heat. The device has completed all RNA detection steps in one mini chamber, requiring only 489 µl reagents for RNA extraction, much smaller than the amount used in manual RNA extraction (2065 µl). The experimental results have shown that PCR results from the device are comparable to those achieved via commercial qPCR instrumental detection. This work has demonstrated the potential of SAW‐based lab‐on‐a‐chip devices for point‐of‐care testing and provided a novel approach for rapidly detecting infectious diseases. [ABSTRACT FROM AUTHOR]

This study presents a portable, low-cost, point-of-care (POC) system for the simultaneous detection of blood glucose and hematocrit. The system consists of a disposable origami microfluidic paper-based analytical device (μPAD) for plasma separation, filtration, and reaction functions and a 3D-printed cassette for hematocrit and blood glucose detection using a smartphone. The origami μPAD is patterned using a cost-effective label printing technique instead of the conventional wax printing method. The 3D-printed cassette incorporates an array of LED lights, which mitigates the effects of intensity variations in the ambient light and hence improves the accuracy of the blood glucose and hematocrit concentration measurements. The hematocrit concentration is determined quantitatively by measuring the distance of plasma wicking along the upper layer of the origami μPAD, which is pretreated with sodium chloride and Tween 20 to induce dehydration and aggregation of the red blood cells. The filtered plasma also penetrates to the lower layer of the origami μPAD, where it reacts with embedded colorimetric assay reagents to produce a yellowish-brown complex. A color image of the reaction complex is captured using a smartphone inserted into the 3D-printed cassette. The image is analyzed using self-written RGB software to quantify the blood glucose concentration. The calibration results indicate that the proposed detection platform provides an accurate assessment of the blood glucose level over the range of 45–630 mg/dL (R2 = 0.9958). The practical feasibility of the proposed platform is demonstrated by measuring the blood glucose and hematocrit concentrations in 13 human whole blood samples. Taking the measurements obtained from commercial glucose and hematocrit meters as a benchmark, the proposed system has a differential of no more than 6.4% for blood glucose detection and 9.1% for hematocrit detection. Overall, the results confirm that the proposed μPAD is a promising solution for cost-effective and reliable POC health monitoring. [ABSTRACT FROM AUTHOR]

Microstructured reactors offer fast chemical engineering transfer and precise microfluidic control, enabling the determination of reactions' kinetic parameters. This review examines recent advancements in measuring microreaction kinetics. It explores kinetic modeling, reaction mechanisms, and intrinsic kinetic equations pertaining to two types of microreaction: esterification and transesterification reactions involving acids, bases, or biocatalysts. The utilization of a micro packed-bed reactor successfully achieves a harmonious combination of the micro-dispersion state and the reaction kinetic characteristics. Additionally, this review presents micro-process simulation software and explores the advanced integration of microreactors with spectroscopic analyses for reaction monitoring and data acquisition. Furthermore, it elaborates on the control principles of the micro platform. The superiority of online measurement, automation, and the digitalization of the microreaction process for kinetic measurements is highlighted, showcasing the vast prospects of artificial intelligence applications. [ABSTRACT FROM AUTHOR]

We developed a surface-enhanced Raman scattering (SERS)-active plasmonic core-satellite nanostructure and incorporated it into a membrane filter-integrated microfluidic device for continuous monitoring of molecules in solution. The core-satellite nanostructures were fabricated by immobilizing a high number density of gold nanoparticles (AuNPs) on silica beads.to create many nanogaps among the AuNPs. The sizes of the nanogaps were fine-tuned by adding a silver (Ag) shell to optimize the SERS activity. In addition, citrate molecule, the capping agent of the nanoparticles, was displaced by alkali halides. The displacement not only reduced the SERS signals of citrate but also enhanced the adsorption of target molecules. The alkali halide-treated core-satellite nanostructures were accumulated onto a membrane filter integrated into a microfluidic device, serving as a uniform and sensitive SERS substrate. By increasing the volume of the sample solution flowing through the membrane filter, we increased the number of molecules adsorbed to the nanostructures, amplifying the intensities of their characteristic Raman peaks. Our microfluidic SERS device demonstrated continuous SERS detection of malachite green at a concentration as low as 500 fM. In summary, while various core-satellite nanostructures and microfluidic SERS devices have been reported, the integration of the membrane filter-containing microfluidic device with the core-satellite nanostructures facilitated sensitive and continuous molecule detection in our study. [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]

Three-dimensional (3D) spheroid models are crucial for cancer research, offering more accurate insights into tumour biology and drug responses than traditional 2D cell cultures. However, inconsistent and low-throughput spheroid production has hindered their application in drug screening. Here, we present an automated high-throughput platform for a spheroid selection, fabrication, and sorting system (SFSS) to produce uniform gelatine-encapsulated spheroids (GESs) with high efficiency. SFSS integrates advanced imaging, analysis, photo-triggered fabrication, and microfluidic sorting to precisely control spheroid size, shape, and viability. Our data demonstrate that our SFSS can produce over 50 GESs with consistent size and circularity in 30 min with over 97% sorting accuracy while maintaining cell viability and structural integrity. We demonstrated that the GESs can be used for drug screening and potentially for various assays. Thus, the SFSS could significantly enhance the efficiency of generating uniform spheroids, facilitating their application in drug development to investigate complex biological systems and drug responses in a more physiologically relevant context. [ABSTRACT FROM AUTHOR]

Introduction: Damage to the corneal nerves can result in discomfort and chronic pain, profoundly impacting the quality of life of patients. Development of novel in vitro method is crucial to better understand corneal nerve regeneration and to find new treatments for the patients. Existing in vitro models often overlook the physiology of primary sensory neurons, for which the soma is separated from the nerve endings. Methods: To overcome this limitation, our novel model combines a compartmentalized microfluidic culture of trigeminal ganglion neurons from adult mice with live-imaging and automated 3D image analysis offering robust way to assess axonal regrowth after axotomy. Results: Physical axotomy performed by a two-second aspiration led to a reproducible 70% axonal loss and altered the phenotype of the neurons, increasing the number of substance P-positive neurons 72h post-axotomy. To validate our new model, we investigated axonal regeneration after exposure to pharmacological compounds. We selected various targets known to enhance or inhibit axonal regrowth and analyzed their basal expression in trigeminal ganglion cells by scRNAseq. NGF/GDNF, insulin, and Dooku-1 (Piezo1 antagonist) enhanced regrowth by 81, 74 and 157%, respectively, while Yoda-1 (Piezo1 agonist) had no effect. Furthermore, SARM1-IN-2 (Sarm1 inhibitor) inhibited axonal regrowth, leading to only 6% regrowth after 72h of exposure (versus 34% regrowth without any compound). Discussion: Combining compartmentalized trigeminal neuronal culture with advanced imaging and analysis allowed a thorough evaluation of the extent of the axotomy and subsequent axonal regrowth. This innovative approach holds great promise for advancing our understanding of corneal nerve injuries and regeneration and ultimately improving the quality of life for patients suffering from sensory abnormalities, and related conditions. [ABSTRACT FROM AUTHOR]

Introduction: Self-coalescing microfluidic devices represent an exciting opportunity for leveraging viscous dominated flow phenomena to reconstitute a series of reagents with a single sample infusion. In a self-coalescing microfluidic device, spatially separated dried reagents are reconstituted using a single infusion. Due to the unique device geometry, the reagents remain spatially separated after infusion. As such, self-coalescing microfluidic devices have the potential to simplify point-of-care testing by simultaneously performing multiple colorimetric tests in one device. The current versions of these devices use standard, more costly microfabrication processes and are too small to be easily read by eye. Methods: Here, we created a low cost and scaled up version of a self-coalescing microfluidic device by using laser-cut-roll-based silicone tape. In addition to eliminating the need for cleanrooms, our approach simplifies the integration of assay reagents since they can be spotted onto a coverslip and covered with the tape microfluidic device. We empirically optimized our device, finding that flow rate significantly influenced the formation of self-coalescence as well as proper reagent reconstitution. Results and Discussion: When flow rates were too slow or fast, reagents would streak, leading to inadvertent mixing between different spatial locations. Our studies further revealed that geometry had a stronger influence on device operation in low-flow conditions. Our final optimized device exhibited a 100% success rate, demonstrated through self-coalescence with no reagent streaking at 100 μL/min, which enabled the isotropic diffusion of reagents. Furthermore, the spots are spatially separated and large enough to be visualized by the naked eye and captured by a smartphone camera for downstream analysis. Taken together, our innovative device leverages the advantages of sticker microfluidics and low-cost manufacturing methods to offer standalone functionality. This approach has the potential to significantly impact point-ofcare diagnostics, particularly in resource-limited regions. By enabling multiplexed diagnostic assays through our novel technology, we aim to provide accessible and affordable healthcare solutions. [ABSTRACT FROM AUTHOR]

Chemical bioreactions play a significant role in many of the microfluidic devices, and their applications in biomedical science have seen substantial growth. Given that effective mixing is vital for initiating biochemical reactions in many applications, micromixers have become increasingly prevalent for high-throughput assays. In this research, a numerical study using the finite element method was conducted to examine the fluid flow and mass transfer characteristics in novel micromixers featuring an array of pillars. The study utilized two-dimensional geometries. The impact of pillar configuration on mixing performance was evaluated using concentration distribution and mixing index as key metrics. The study explores the effects of pillar array design on mixing performance and pressure drop, drawing from principles such as contraction–expansion and split-recombine. Two configurations of pillar arrays, slanted and arrowhead, are introduced, each undergoing investigation regarding parameters such as pillar diameter, gap size between pillar groups, distance between pillars, and vertical shift in pillar groups. Subsequently, optimal micromixers are identified, exhibiting mixing efficiency exceeding 99.7% at moderate Reynolds number (Re = 1), a level typically challenging for micromixers to attain high mixing efficiency. Notably, the pressure drop remains low at 1102 Pa. Furthermore, the variations in mixing index over time and across different positions along the channel are examined. Both configurations demonstrate short mixing lengths and times. At a distance of 4300 μm from the inlet, the slanted and arrowhead configurations yielded mixing indices of 97.2% and 98.9%, respectively. The micromixers could provide a mixing index of 99.5% at the channel’s end within 8 s. Additionally, both configurations exceeded 90% mixing indices by the 3 s. The combination of rapid mixing, low pressure drop, and short mixing length positions the novel micromixers as highly promising for microfluidic applications. [ABSTRACT FROM AUTHOR]

Pathogenic microorganisms play a crucial role in the global disease burden due to their ability to cause various diseases and spread through multiple transmission routes. Immunity tests identify antigens related to these pathogens, thereby confirming past infections and monitoring the host's immune response. Traditional pathogen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs), are often labor-intensive, slow, and reliant on sophisticated equipment and skilled personnel, which can be limiting in resource-poor settings. In contrast, the development of microfluidic technologies presents a promising alternative, offering automation, miniaturization, and cost efficiency. These advanced methods are poised to replace traditional assays by streamlining processes and enabling rapid, high-throughput immunity testing for pathogens. This review highlights the latest advancements in microfluidic systems designed for rapid and high-throughput immunity testing, incorporating immunosensors, single molecule arrays (Simoas), a lateral flow assay (LFA), and smartphone integration. It focuses on key pathogenic microorganisms such as SARS-CoV-2, influenza, and the ZIKA virus (ZIKV). Additionally, the review discusses the challenges, commercialization prospects, and future directions to advance microfluidic systems for infectious disease detection. [ABSTRACT FROM AUTHOR]

Introduction: As the body's first line of defense against disease and infection, neutrophils must efficiently navigate to sites of inflammation; however, neutrophil dysregulation contributes to the pathogenesis of numerous diseases that leave people susceptible to infections. Many of these diseases are also associated with changes to the protein composition of the extracellular matrix. While it is known that neutrophils and endothelial cells, which play a key role in neutrophil activation, are sensitive to the mechanical and structural properties of the extracellular matrix, our understanding of how protein composition in the matrix affects the neutrophil response to infection is incomplete. Methods: To investigate the effects of extracellular matrix composition on the neutrophil response to infection, we used an infection-on-a-chip microfluidic device that replicates a portion of a blood vessel endothelium surrounded by a model extracellular matrix. Model blood vessels were fabricated by seeding human umbilical vein endothelial cells on 2, 4, or 6 mg/mL type I collagen hydrogels. Primary human neutrophils were loaded into the endothelial lumens and stimulated by adding the bacterial pathogen Pseudomonas aeruginosa to the surrounding matrix. Results: Collagen concentration did not affect the cell density or barrier function of the endothelial lumens. Upon infectious challenge, we found greater neutrophil extravasation into the 4 mg/mL collagen gels compared to the 6 mg/mL collagen gels. We further found that extravasated neutrophils had the highest migration speed and distance in 2mg/mL gels and that these values decreased with increasing collagen concentration. However, these phenomena were not observed in the absence of an endothelial lumen. Lastly, no differences in the percent of extravasated neutrophils producing reactive oxygen species were observed across the various collagen concentrations. Discussion: Our study suggests that neutrophil extravasation and migration in response to an infectious challenge are regulated by collagen concentration in an endothelial cell-dependent manner. The results demonstrate how the mechanical and structural aspects of the tissue microenvironment affect the neutrophil response to infection. Additionally, these findings underscore the importance of developing and using microphysiological systems for studying the regulatory factors that govern the neutrophil response. [ABSTRACT FROM AUTHOR]

Endothelial programmed death‐ligand 1 (PD‐L1) expression is higher in tumors than in normal tissues. Also, tumoral vasculatures tend to be leakier than normal vessels leading to a higher trans‐endothelial or transmural fluid flow. However, it is not clear whether such elevated transmural flow can control endothelial PD‐L1 expression. Here, a new microfluidic device is developed to investigate the relationship between transmural flow and PD‐L1 expression in microvascular networks (MVNs). After treating the MVNs with transmural flow for 24 h, the expression of PD‐L1 in endothelial cells is upregulated. Additionally, CD8 T cell activation by phytohemagglutinin (PHA) is suppressed when cultured in the MVNs pre‐conditioned with transmural flow. Moreover, transmural flow is able to further increase PD‐L1 expression in the vessels formed in the tumor microenvironment. Finally, by utilizing blocking antibodies and knock‐out assays, it is found that transmural flow‐driven PD‐L1 upregulation is controlled by integrin αVβ3. Overall, this study provides a new biophysical explanation for high PD‐L1 expression in tumoral vasculatures. [ABSTRACT FROM AUTHOR]

As(III) determination is of great importance in various industries such as environmental monitoring, pharmaceuticals, and metallurgy. In this respect, a nanocomposite of sucrose-modified gold nanoparticles (Au@Suc) was synthesized and characterized by UV-visible spectrophotometry and transmission electron microscopy (TEM) methods. Then, the applicability of the synthesized nanocomposite for the development of a microfluidic kit for the colorimetric point-of-care (POC) detection of As(III) ions was scrutinized. The experimental parameters for the microfluidic kit were optimized using the one-factor-at-a-time (OFAT) approach. The effective conditions for the microfluidic kit were found to be a flow rate of 0.15 ml min-1, a path length of 5.50 cm, and a pH of 7.0. The resulting microfluidic kit indicated a direct correlation between the red component of RGB pixels in images captured by a smartphone and the concentration of As(III) ions in the range of 0.09-1.20 µM, with a detection limit of 0.054 µM. Evaluation of the microfluidic kit's selectivity revealed no significant interference. Additionally, the microfluidic kit was successfully employed to analyze As(III) in various drinking water samples, with recovery values ranging between 95.01% and 105.00%. [ABSTRACT FROM AUTHOR]

In recent years, highly specialized nanoscopic drug carriers have been developed, which can, e.g., traverse biological barriers, protect drugs against harsh physiological conditions, and release such drugs in a controlled manner. However, for the delivery of particles via the respiratory pathway, aerodynamic diameters in the range of several micrometers are required to achieve good lung deposition and biodistribution. To combine the favorable properties of inhalable, micron‐sized particles with the advantages of nanosized drug carriers, herein, dry‐powder, hybrid microparticles (h‐μPs), which disintegrate upon contact with moist surfaces (as present in the lung) to release the embedded nanoparticles into the mucosa, are introduced. Furthermore, a microfluidic setup, which mimics the air–gel interface of the mucosal airway epithelium, is presented. With this setup, the interaction of airborne h‐μPs with the mucosal interface on a microscopic level is investigated. In detail, the influence of the h‐μP charge on their deposition efficiency is tested and it is found that this process is governed by a combination of electrostatic interactions between the mucosal surface and the h‐μPs as well as hygroscopic effects. Thus, this approach can help to optimize inhalable drug carriers to increase the efficiency of pulmonary drug administration via the respiratory pathway. [ABSTRACT FROM AUTHOR]

• A new microfluidic in-vitro endothelial cell culture system (ECCS) was proposed. • Blood pressure, shear stress, and circumferential strain were accurately reproduced. • The coupling relationship among the above signals was accurately reproduced. • The area for cell study in this system had uniform stress and strain distribution. • The system had better biological properties and potential in mechanobiology study. Microfluidics has been an effective technology to reconstruct the in-vivo physiological hemodynamic microenvironment, which is significantly important for preventing and curing circulatory system-related diseases. However, these existing microfluidic systems have failed to accurately reproduce the arterial blood pressure, shear stress, circumferential strain, as well as their coupling relationship, and have not taken into account whether the cells at various locations in the culture chamber are subjected to consistent mechanical stimulation. To solve the above shortcomings, this study developed an in-vitro endothelial cell culture system (ECCS) containing a microfluidic chip and afterload components based on the hemodynamic principles to reappear the desired hemodynamic signals and their coupling relationship accurately, while a relatively uniform area of stress and strain distribution was selected in the microfluidic chip for a more reliable cell mechanobiology study. The sensitivity of global hemodynamic behaviors of the ECCS was analyzed, and numerical simulation and in-vitro experiments were implemented to verify the performance of the proposed ECCS. Finally, the cellular hemodynamic response was tested using human umbilical vein endothelial cells, demonstrating that the proposed in-vitro ECCS has better biological effectiveness. In general, the proposed ECCS in this study provided a more accurate and reliable tool for reproducing the in-vivo hemodynamic microenvironment and showed good potential in the mechanobiology study. [ABSTRACT FROM AUTHOR]

Phenols are well-known noxious compounds, that are often found in various water sources. In this research, a new method was used to determine the total phenol by using microfluidic paper-based (µPAD), with a smartphone Sensor. It is portable, inexpensive, and environmentally friendly. The paper was prepared using filter paper by the cutting method. The reagent was dried on the paper. The color sensor of the smartphone device was used as the color intensity sensor of the samples through the images captured by the smartphone through software downloaded to the phone. The focus of the samples is measured from the RGB value of the images taken from the (iPhone 14) device, where each image represents a specific focus. The calibration curve for this method was in the range of M (0.00016–0.5), the correlation coefficient (R2) was equal to (0.9753), the limit of detection was in the amount of (0.000032) M, and the relative standard deviation (RSD%) for the concentration was (0.02) M, for which the examination was repeated (10) times and its value was (0 %), and the recovery value (Recovery%) was equal to (100 %). The method was successfully applied for the determination of total phenols in wastewater. [ABSTRACT FROM AUTHOR]

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Microbial fuel cells (MFCs) represent a promising avenue for sustainable energy production by harnessing the metabolic activity of microorganisms. In this study, a novel design of MFC—a Microfluidic Benthic Microbial Fuel Cell (MBMFC)—was developed, fabricated, and tested to evaluate its electrical energy generation. The design focused on balancing microfluidic architecture and wiring procedures with microbial community dynamics to maximize power output and allow for upscaling and thus practical implementation. The testing phase involved experimentation to evaluate the performance of the MBMFC. Microbial feedstock was varied to assess its impact on power generation. The designed MBMFC represents a promising advancement in the field of bioenergy generation. By integrating innovative design principles with advanced fabrication techniques, this study demonstrates a systematic approach to optimizing MFC performance for sustainable and clean energy production. [ABSTRACT FROM AUTHOR]

We introduce a novel approach for highly parallel droplet dispensing with precise control over the droplet parameters such as droplet volume, droplet velocity, etc. This approach facilitates the fabrication of homogeneous and precise thin layers with uniform coverage on defined small areas (e.g., a specific area of 1 × 1.4 mm2 in microfluidic channels or microwells). The presented approach ensures layer uniformity and high precision in X/Y extent and edge resolution, making it well suited for achieving precise and controlled coating for a variety of applications such as homogeneous coatings for lateral flow tests, ELISA plates, and biosensors for continuous glucose monitoring (CGM) devices. Our approach is based on direct liquid displacement employing a piston that is in direct contact with the liquid and an array of nozzles. Considering a variety of nozzle chip designs (i.e., varying nozzle diameter and pitch), we evaluated a multitude of parameters to derive general design rules for the nozzle chip design. Thus, we achieved a tunable droplet volume from 200 to 800 pL and droplet velocities from 0.5 to 2.5 m/s, applying a nozzle diameter of 50 μm and a nozzle pitch of 165 μm. The presented results showcase the versatility of the approach, offering precise dispensing capabilities. [ABSTRACT FROM AUTHOR]