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The power-law fluid flow in tree-like self-similar branching networks is prevalent throughout the natural world and also finds numerous applications in technology such as oil recovery and microfluidic devices. We investigate analysis of optimal power-law fluid flow conditions and the optimal structures within tree-like branching networks, focusing on maximizing flow conductance under the constraint of the network tube's volume and the surface area. The study considered fully developed laminar power-law fluid flow regimes without considering any losses in the network system. A key observation was the sensitivity of the dimensionless effective flow conductance to the network's geometrical parameters. We found that the maximum flow conductance occurs when a dimensionless radius ratio β ∗ satisfies the equation β ∗ = N − 1 / 3 and β ∗ = N − (n + 1) / (3 n + 2) under constrained tube-volume and surface-area, respectively. Here, N represents the bifurcation number of branches splitting at each junction, and n is the fluid power-law index. We further find that this optimal condition occurs when pressure drops are equipartition across each branching level. We validated our results with various experimental results and theories under limiting conditions. Further, Hess–Murray's law is justified and extended for the shear-thinning and shear-thickening fluid flows for an arbitrary number of branches N. Further, in this study, we also derive the relationships between the geometrical and flow characteristics of the parent and daughter tubes as well as the generalized scaling laws at the optimal conditions for the other essential parameters such as tube-wall stresses, length ratios, mean velocities, tube-volume, and surface-area of the tube distributing within the networks. We find that the fluid power-law index n does not influence the constrained tube-volume scaling at the optimal conditions; however, the scaling laws vary with n under the constrained tube's surface area. These findings offer valuable design principles for developing efficient transport and flow systems. [ABSTRACT FROM AUTHOR]

3D printing techniques allow for the precise placement of living cells, biological substances, and biochemical components, establishing themselves as a promising approach in bioengineering. Recently, 3D printing has been applied to develop human-relevant in vitro cancer models with highly controlled complexity and as a potential method for drug screening and disease modeling. Compared to 2D culture, 3D-printed in vitro cancer models more closely replicate the in vivo microenvironment. Additionally, they offer a reduction in the complexity and ethical issues associated with using in vivo animal models. This focused review discusses the relevance of 3D printing technologies and the applied cells and materials used in cutting-edge in vitro cancer models and microfluidic device systems. Future prospective solutions were discussed to establish 3D-printed in vitro models as reliable tools for drug screening and understanding cancer disease mechanisms. [ABSTRACT FROM AUTHOR]

Accurate rotation of microparticles is of great significance in micro-rotors, multi-angle microscopic observation, microbial three-dimensional phenotyping, and microsystem assembly. However, most methods can only rotate a single object, thus limiting the throughput. In this study, we realized the simultaneous rotation of many trapped and aligned subwavelength glass cylinders inside an evanescent wave field excited by a resonant phononic crystal plate. The unique feature of the rotation lies in its periodic distribution as well as the rotation axis being perpendicular to the acoustic axis. The rotary power originates from viscous torque generated by the evanescent wave-induced near-boundary acoustic streaming's asymmetry distribution on the trapped cylinder. Furthermore, the three-dimensional topographies of rotated cylinders can be reconstructed from the microscopic images under different rotating angles. Our findings can pave the way toward developing simple, disposable, and scalable microfluidic devices for massive subwavelength acoustic rotation by carefully designing acoustic metamaterials. [ABSTRACT FROM AUTHOR]

A significant challenge in the treatment of central nervous system (CNS) disorders is represented by the presence of the blood--brain barrier (BBB), a highly selective membrane that regulates molecular transport and restricts the passage of pathogens and therapeutic compounds. Traditional in vivo models are constrained by high costs, lengthy experimental timelines, ethical concerns, and interspecies variations. In vitro models, particularly microfluidic BBB-on-a-chip devices, have been developed to address these limitations. These advanced models aim to more accurately replicate human BBB conditions by incorporating human cells and physiological flow dynamics. In this framework, here we developed an innovative microfluidic system that integrates thin-film electrodes for non-invasive, real-time monitoring of BBB integrity using electrochemical impedance spectroscopy (EIS). EIS measurements showed frequencydependent impedance changes, indicating BBB integrity and distinguishing well-formed from non-mature barriers. The data from EIS monitoring was confirmed by permeability assays performed with a fluorescence tracer. The model incorporates human endothelial cells in a vessel-like arrangement to mimic the vascular component and three-dimensional cell distribution of human astrocytes and microglia to simulate the parenchymal compartment. By modeling the BBB-on-a-chip with an equivalent circuit, a more accurate trans-endothelial electrical resistance (TEER) value was extracted. The device demonstrated successful BBB formation and maturation, confirmed through live/dead assays, immunofluorescence and permeability assays. Computational fluid dynamics (CFD) simulations confirmed that the device mimics in vivo shear stress conditions. Drug crossing assessment was performed with two chemotherapy drugs: doxorubicin, with a known poor BBB penetration, and temozolomide, conversely a specific drug for CNS disorders and able to cross the BBB, to validate the model predictive capability for drug crossing behavior. The proposed sensorized microfluidic device represents a significant advancement in BBB modeling, offering a versatile platform for CNS drug development, disease modeling, and personalized medicine. [ABSTRACT FROM AUTHOR]

Electrode fabrication in microfluidic devices is often avoided due to the smaller footprint of the platform, associated complexity in the process, and absence of a well-established method. In this article a glass microchip with chemically modified and vapor deposited gold internal electrode was fabricated and used for biomolecule immobilization and electrochemical applications. The silanol (-OH) on glass surface of the microdevice was modified with (3-mercaptopropyl)trimethoxysilane prior to gold deposition to achieve a strong attachment of the metal film using the gold-thiol binding. The practical utility of the microdevice with gold surface was demonstrated by performing quantitative enzyme linked immunosorbent assay (ELISA) of human interferon gamma (IFN-γ) antigen, yielding a limit of detection (LOD) of 0.15 pg/mL compared to 4 pg/mL in the microplate assay. Additionally, the functionality of the internal electrode was established by performing cyclic voltammetry (CV) and linear sweep voltammetry (LSV) of potassium ferricyanide (III) in potassium chloride (KCl) solution using the proposed gold patterned electrode in the microchip, offering limits of detection of 0.14 and 0.11 mM for CV and LSV respectively. Both the ELISA and electrochemical assays were validated by generating calibration curves and using a control sample for the electroanalytical sensing applications. The measurements yielded experimental results that agreed with control concentration with 7% relative standard deviation (RSD). The promising reproducibility of the electrode in fabrication with no/minimum failure rate and its outstanding performance in immunosensor applications as well as an electron exchange surface makes our technique of gold electrode fabrication in microchips a state of the art. [ABSTRACT FROM AUTHOR]

The importance of microfluidics research is growing, especially in the fields of chemistry, biology or medicine. This is coupled with a growing demand for specialized capillary equipment that allows advanced research at the microscale. Conventional methods of manufacturing such devices are expensive, time-consuming and do not guarantee good results. An alternative to these methods is the use of 3D printing technology. Despite the existence of numerous works presenting the possibilities of 3D printing in the context of creating microfluidic devices, there is a lack of comprehensive works presenting qualitative analysis of printed objects. This paper presents a method of producing microcapillary structures for microfluidics research with the help of 3D printing using stereolithography technology. The quality requirements that the printed objects should meet are defined and all stages of production are characterized. A qualitative analysis of the obtained objects was carried out, taking into account both the influence of individual printing parameters and print processing methods. The results of microfluidic tests using printed objects are also presented. This work is aimed at providing specific knowledge that allows the manufacture of precision devices for microfluidics purposes at low cost. [ABSTRACT FROM AUTHOR]

The "Lab on a Chip" journal, published by The Royal Society of Chemistry, features various papers on micro- and nanoscale devices and applications. The current issue includes topics such as surface modification of paper-based microfluidic devices, reversible bonding in thermoplastic elastomer microfluidic platforms, and multiplexed ultrasensitive detection of cancer biomarkers. Other papers cover areas like neuroplasticity investigations, miRNA detection in skin interstitial fluid, and artificial intelligence performance in testing microfluidics for point-of-care applications. The journal also explores topics such as magnetophoresis in millifluidic systems, dynamic sampling from ex vivo adipose tissue, and inertial co-focusing of heterogeneous particles in hybrid microfluidic channels. [Extracted from the article]

Pathologies in adipose (fat) tissue function are linked with human diseases such as diabetes, obesity, metabolic syndrome, and cancer. Dynamic, rapid release of metabolites has been observed in adipocyte cells and tissue, yet higher temporal resolution is needed to adequately study this process. In this work, a microfluidic device with precise and regular valve-automated droplet sampling, termed a microfluidic analog-to-digital converter (μADC), was used to sample secretions from ∼0.75 mm diameter adipose explants from mice, and on-chip salt water electrodes were used to merge sampled droplets with reagent droplets from two different fluorometric coupled enzyme assays. By integrating sampling and assays on-chip, either glycerol or non-esterified fatty acids (NEFA), or both, were quantified optically within merged 12 nanoliter droplets using a fluorescence microscope with as high as 20 second temporal resolution. Limits of detection were 6 μM for glycerol (70 fmol) and 0.9 μM for NEFA (10 fmol). Multiple ex vivo adipose tissue explants were analyzed with this system, all showing clear increases in lipolytic function after switching from feeding to fasting conditions. Enabled by high temporal resolution, lipolytic oscillations of both glycerol and NEFA were observed for the first time in the range of 0.2 to 1.6 min−1. Continuous wavelet transform (CWT) spectrograms and burst analyses (0.1 to 4.0 pmol bursts) revealed complex dynamics, with multiplexed assays (duplex for glycerol and NEFA) from the same explants showing mostly discordant bursts. These data support separate mechanisms of NEFA and glycerol release, although the connection to intracellular metabolic oscillations remains unknown. Overall, this device allowed automated and highly precise temporal sampling of tissue explants at high resolution and programmable downstream merging with multiple assay reagents, revealing unique biological information. Such device features should be applicable to various other tissue or spheroid types and to other assay formats. [ABSTRACT FROM AUTHOR]

We report on the use of a microfluidic antisolvent crystallization method to investigate the effect of solution volume on the chiral symmetry breaking (CSB) phenomena of enantiomeric sodium chlorate crystals. The utilization of a microfluidic device is capable of periodically producing emulsion droplets of uniform size and facilitates the quantitative analysis and visualization of crystallization phenomena occurring within the individual emulsions immersed in an oil continuous medium (i.e., dodecane). To promote nucleation and crystallization, a small amount of an antisolvent (i.e., ethanol) is introduced into the continuous phase. We observe that 100% CSB occurs within a certain critical emulsion volume. Beyond this critical volume, the probability of forming two different enantiomeric crystal particles increases. This solution volume-dependent CSB phenomenon can be attributed to the rapid depletion of surrounding molecules by spontaneous crystal growth after the formation of the initial nucleus within the critical volume, thereby suppressing further primary nucleation. [ABSTRACT FROM AUTHOR]

Transplantable ready-made microvessels have therapeutic potential for tissue regeneration and cell replacement therapy. Inspired by the natural rapid angiogenic sprouting of microvessels in vivo, engineered injectable 3D microvessel networks are created using thermoplastic elastomer (TPE) microfluidic devices. The TPE material used here is flexible, optically transparent, and can be robustly yet reversibly bonded to a variety of plastic substrates, making it a versatile choice for microfluidic device fabrication because it overcomes the weak self-adhesion properties and limited manufacturing options of poly(dimethylsiloxane) (PDMS). By leveraging the reversible bonding characteristics of TPE material templates, we present their utility as an organ-on-a-chip platform for forming and handling microvessel networks, and demonstrate their potential for animal-free tissue generation and transplantation in clinical applications. We first show that TPE-based devices have nearly 6-fold higher bonding strength during the cell culture step compared to PDMS-based devices while simultaneously maintaining a full reversible bond to (PS) culture plates, which are widely used for biological cell studies. We also demonstrate the successful generation of perfusable and interconnected 3D microvessel networks using TPE–PS microfluidic devices on both single and multi-vessel loading platforms. Importantly, after removing the TPE slab, microvessel networks remain intact on the PS substrate without any structural damage and can be effectively harvested following gel digestion. The TPE-based organ-on-a-chip platform offers substantial advantages by facilitating the harvesting procedure and maintaining the integrity of microfluidic-engineered microvessels for transplant. To the best of our knowledge, our TPE-based reversible bonding approach marks the first confirmation of successful retrieval of organ-specific vessel segments from the reversibly-bonded TPE microfluidic platform. We anticipate that the method will find applications in organ-on-a-chip and microphysiological system research, particularly in tissue analysis and vessel engraftment, where flexible and reversible bonding can be utilized. [ABSTRACT FROM AUTHOR]

Paper-based microfluidic devices offer an ideal platform for biological and environmental detection because they are low-cost, small, disposable, and fill by natural capillary action. In this tutorial review, we discuss the surface modification of paper-based microfluidic devices with functional polymers using the initiated chemical vapor deposition (iCVD) process. The iCVD process is solventless and therefore ideal for coating cellulose paper because there are no surface tension effects or solvent compatibility issues. The process can also be scaled up for roll-to-roll manufacturing. The chemical functionality of the iCVD coating can be tuned by varying the monomer and the structure of the coating can be tuned by varying the processing parameters. [ABSTRACT FROM AUTHOR]

Digital nucleic acid quantification has emerged as an exceptionally valuable technique in molecular diagnosis, capturing significant attention in the biomedical field. This study introduces a novel multi‐volume digital loop‐mediated isothermal amplification (dLAMP) chip that offers an extensive detection range and user‐friendly operation. The chip consists of 1024 large chambers with the volume of 7.2 nL and 6400 small chambers with the volume of 0.064 nL. The ingenious combination of chambers with volume difference beyond a 100‐fold on the single chip enables a broad dynamic range exceeding 105 for nucleic acid quantification. Furthermore, this chip incorporates an automated strategy, enabling the rapid loading and partitioning of the reaction mixture into subvolumes within 4 min. In order to evaluate the quantitative capability of the multi‐volume dLAMP chip, a 10‐fold serial dilution of the β‐actin DNA template is measured. Additionally, the chip is tested for β‐actin DNA concentration in plasma samples from colorectal cancer patients and healthy individuals. By providing enhanced automation, wide dynamic range, and improved accuracy, this chip paves the way for broader applications and the advancement of biomedical research fields. [ABSTRACT FROM AUTHOR]

Unidirectional liquid transport, a special self‐propelled wetting phenomenon observed in natural structures like the Nepenthes pitcher plant peristome, Araucaria leaves, and Crassula muscosa shoots, has inspired scientists to develop various novel microfluidic devices for liquid collection, physical/chemical reactions, and irrigation. Recently, the concept of capillary transistors is proposed to enable a programmable transport area and a significant increase in unidirectional capillary height, which is expected to greatly expand the applications of conventional microfluidic chips. In this work, using black resin as the three‐dimensional (3D) printing material, we construct microfluidic chips with capillary transistors for photothermal‐responsive unidirectional liquid transport. The transistors consist of asymmetric overhanging structures with connected overhangs, allowing for fast, long‐distance, and large‐area unidirectional liquid transport, with a unidirectional capillary height exceeding 90.0 mm—more than double the values reported in most previous studies. Furthermore, smart control of capillary height is achieved by applying external photothermal stimuli to the capillary transistors, demonstrating their potential applications in photothermal‐responsive unidirectional liquid transport and mixing in 3D space. It is envisioned that additional functions such as liquid patterning, desalination, and biochemical microreactions would be developed by engineering capillary transistors and their responsiveness. [ABSTRACT FROM AUTHOR]

An incompressible boundary‐layer third‐grade nanomaterial stagnated flow confined by stretchy regime is formulated. The laminar magnetized thermal and solutal flow features the aspects of Brownian diffusion, generalized thermal‐flux, thermophoresis, and generalized solutal‐flux. The dimensionalized third‐grade steady‐state model is obtained by implementing appropriate variables. The subsequent nonlinear mathematical model is analytically computed by utilizing homotopy algorithm. The graphics demonstration of nondimensional fields (i.e., velocity, concentration, and temperature) for distinct physical variables is exhibited. The outcomes for the skin‐friction coefficient are calculated and confirmed to be precise. The analysis reveals that augmented values of material parameters escalate nanomaterial velocity while the Hartman number exhibits lower velocity. The temperature field displays a decaying trend for Prandtl number and thermal relaxation variable while contrary effects for nanoscale parameters (i.e., thermophoresis diffusive and Brownian diffusive) are reported. Besides, the nanomaterial concentration shows a decreasing trend with respect to the Schmidt number, Brownian motion, and solutal‐relaxation variable while thermophoresis parameter exhibits opposite effects. Furthermore, this study could be valuable for the design of various lab‐on‐a‐chip and thermal microfluidic devices in the field of biomedicine. Besides contributing to the creation of new devices, they may also be advantageous for performing genetic testing and developing innovative tools. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can a functional in vitro model, containing the main cellular components of the uterine wall, be generated from cells derived from patient tissues? SUMMARY ANSWER We present a three-dimensional (3D) physiologically relevant, organ-on-a-chip model of the uterine wall containing primary endometrial and myometrial cellular participants, generated from human uterine tissue. WHAT IS KNOWN ALREADY As a highly dynamic reproductive organ, the human uterus plays fundamental physiological roles in menstruation and childbirth. The endometrial–myometrial junction (EMJ) defines the interface between the inner mucosal layer (endometrium) and outer smooth muscle zone (myometrium) that comprises the uterine wall. The EMJ is implicit in several uterine pathologies of unknown aetiology, including adenomyosis and abnormally invasive placenta; however, despite this, no patient-derived in vitro models of the uterine wall containing all EMJ participants currently exist. STUDY DESIGN, SIZE, DURATION We employed microfluidic technology to characterize multiple miniaturized models of the uterine wall. Protocols were tested that included variations in the seeding order of endometrial and myometrial fractions, and the addition of a low viscosity extracellular matrix to influence cell behaviour. Ultimately, functional hormone responses of patient-derived uterine wall models were assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS Endometrial (n = 9) and myometrial biopsies (n = 4) were enzymatically dissociated to create epithelial, stromal and myometrial cellular fractions. Cell suspensions were seeded into non-adhesive poly(dimethylsiloxane) microfluidic devices containing 5 × 5 microwell arrays. The fate of individual cell types was monitored in real-time using fluorescent tracers, and cell phenotype was characterized by immunocytochemistry. Model functionality was assessed by measuring Ca2+ responses to agonist stimulation, and both insulin-like growth factor binding protein 1 (IGFBP-1) and osteopontin secretion in response to hormone stimulation. MAIN RESULTS AND THE ROLE OF CHANCE When subjected to microfluidic culture in isolation, endometrial stromal cells and smooth muscle myocytes formed compact spheroids, whilst epithelial cells produced diffuse aggregates. Tri-cultures were established by sequential seeding of individual or combined cell fractions at various ratios. Regardless of the protocol, epithelial cells localized to the outer periphery of tri-culture spheroids, which varied in morphology across the protocols. Incorporation of 5% [v/v] Matrigel® improved the reproducibility of 3D aggregates which exhibited robust self-assembly of a stromal/smooth muscle core encased in epithelium. Exposure of tri-cultures to oestradiol, medroxyprogesterone acetate and cyclic adenosine monophosphate (cAMP) increased secretion of IGFBP-1, which indicates stromal decidualization, and enhanced epithelial cell osteopontin secretion. Stimulation with endothelin-1 induced Ca2+ signalling in myocytes. LIMITATIONS, REASONS FOR CAUTION Endometrial and myometrial tissue was collected from relatively few donors. Myometrial tissue was collected from pregnant donors, which may have influenced the myocyte phenotype. Furthermore, endometrial tissue sampling was from women not having a hysterectomy, thus may not include the deeper basalis region, which may limit the physiological mimicry of the final models. WIDER IMPLICATIONS OF THE FINDINGS Our novel approach to modelling the uterine wall in 3D captures all of the main cell types in a medium-throughput system, enabling the screening of hundreds of cultures in parallel from a single biopsy. This system shows great promise for examining the cellular interplay between physiological cues and EMJ pathologies, such as the impact of uterine peristalsis and cyclical hormones on the pathogenesis of adenomyosis. STUDY FUNDING/COMPETING INTEREST(S) C.B. was supported by an Organ-on-a-Chip Technologies Network Pump Priming Project grant. C.J.H. was supported by a Wellbeing of Women project grant (RG2137), SRI/Bayer and Wellcome Trust IFFS3. D.K.H. was supported by a Wellbeing of Women project grant (RG2137) and MRC clinical research training fellowship (MR/V007238/1). M.Z. is Director and Co-Founder of ScreenIn3D Limited. The other authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Microfluidic devices have been the subject of considerable attention in recent years. The development of novel microfluidic devices, their evaluation, and their validation requires simulations. While common methods based on Computational Fluid Dynamics (CFD) can be time-consuming, 1D simulation provides an appealing alternative that leads to efficient results with reasonable quality. Current 1D simulation tools cover specific microfluidic applications; however, these tools are still rare and not widely adopted. There is a need for a more versatile and adaptable tool that covers novel applications, like mixing and the addition of membranes, and allows easy extension, resulting in one comprehensive 1D simulation tool for microfluidic devices. In this work, we present an open-source, modular, and extendable 1D simulation approach for microfluidic devices, which is available as an open-source software package at https://github.com/cda-tum/mmft-modular-1D-simulator. To this end, we propose an implementation that consists of a base module (providing the core functionality) that can be extended with dedicated application-specific modules (providing dedicated support for common microfluidic applications such as mixing, droplets, membranes, etc.). Case studies show that this indeed allows to efficiently simulate a broad spectrum of microfluidic applications in a quality that matches previous results or even fabricated devices. [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]

The aim of this research is to validate a new prototyping method for microfluidic devices which could compete with the widely used polydimethylsiloxane soft lithography. This alternative methodology uses laser‐etched glass and pre‐cured silicone as main materials. A dual approach is chosen for validation, testing prototypes of a mixing device well known in the scientific literature. Specifically the focus is to evaluate the mixing efficiency (ME) of two fluids flowing through the device. After fine‐tuning the fabrication process, the ME is experimentally evaluated, and the results are compared with a 3D computational fluid dynamic analysis. [ABSTRACT FROM AUTHOR]

The present study explores the application of X-ray scattering, using synchrotron radiation, to assess the diffusive transport of nanomedicines in tumor on a chip devices fabricated by 3D stereolithography using a resin with high optical and X-ray transmittance. Unlike conventional methods that require fluorescent labeling of nanoparticles, potentially altering their in vitro and in vivo behavior, this approach enables the investigation of the transport properties for unlabeled nanoparticles. In particular, the results presented confirm the influence of the porosity of the extracellular matrix-like microenvironment, specifically Matrigel, on the diffusive transport of oligonucleotide-functionalized gold nanoparticles. The analysis of the scattering patterns allows to create 2D maps showing the nanoparticle distribution with high spatial resolution. The proposed approach demonstrates the potential for studying other factors involved in nanoparticle diffusion processes. By implementing X-ray scattering to track unmodified nanomedicines within extracellular matrix-like microenvironments, increasingly accurate models for evaluating and predicting therapeutics transport behaviors can be developed. [ABSTRACT FROM AUTHOR]

Nanocarriers are essential for targeted and enhanced drug delivery. However, the use of toxic solvent and the complex of chemical functionalization have seriously limited their clinical translation. Here, a one‐step strategy is developed to direct the self‐assembly of biocompatible core‐shell nanocapsules with tunable surface functionality by microfluidics. Upon rapid mixing and solvent exchange of ethanol with water in a microfluidic device, drug, oil, polymer, and polymer‐PEG‐function co‐precipitate and self‐assemble into core‐shell nanocapsules with desired surface functionality as driven by energy minimization. The prepared PCL‐PEG‐FA core‐shell nanocapsules demonstrate a high encapsulation efficiency and loading capacity and exhibit excellent tumor‐targeting drug delivery performances both in vitro and in vivo via the binding of functional group on the nanocapsule surface with corresponding receptor on the tumor cell membrane. The immune activation in the tumor microenvironment is investigated in detail by flow cytometry and multiplex immunohistochemistry staining to reveal the underlying mechanism for enhanced anti‐tumor performances. The developed strategy is green, facile, versatile, scalable and offers a promising platform for the design of advanced nanocarriers with hierarchical structure and desired function for enhanced drug delivery. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons (MNs), and despite progress, there is no effective treatment. A large body of evidence shows that astrocytes expressing ALS-linked mutant proteins cause non-cell autonomous toxicity of MNs. Although MNs innervate muscle fibers and ALS is characterized by the early disruption of the neuromuscular junction (NMJ) and axon degeneration, there are controversies about whether muscle contributes to non-cell-autonomous toxicity to MNs. In this study, we generated primary skeletal myotubes from myoblasts derived from ALS mice expressing human mutant SOD1G93A (termed hereafter mutSOD1). Characterization revealed that mutSOD1 skeletal myotubes display intrinsic phenotypic and functional differences compared to control myotubes generated from non-transgenic (NTg) littermates. Next, we analyzed whether ALS myotubes exert non-cell-autonomous toxicity to MNs. We report that conditioned media from mutSOD1 myotubes (mutSOD1-MCM), but not from control myotubes (NTg-MCM), induced robust death of primary MNs in mixed spinal cord cultures and compartmentalized microfluidic chambers. Our study further revealed that applying mutSOD1-MCM to the MN axonal side in microfluidic devices rapidly reduces mitochondrial axonal transport while increasing Ca2 + transients and reactive oxygen species (i.e., H2O2). These results indicate that soluble factor(s) released by mutSOD1 myotubes cause MN axonopathy that leads to lethal pathogenic changes. [ABSTRACT FROM AUTHOR]

Currently, despite the vast amounts of time and money invested in cancer treatment, cancer remains one of the primary threats to human life. The primary factor contributing to the low treatment efficacy is cancer heterogeneity. The unclear molecular mechanisms underlying tumorigenesis, coupled with the complexity of human physiology, and the inability of animal models to accurately replicate the human tumor microenvironment, pose significant hurdles in the development of novel cancer therapies. Tumor-microenvironment-on-chip (TMOC) represents a research platform that integrates three-dimensional cell culture with microfluidic systems, simulating the essential components and physiological traits of the in vivo tumor microenvironment. It offers a dynamic setting within the chip system to study tumor progression, potentially heralding a breakthrough in cancer research. In this review, we will summarize the current advancements in this platform, encompassing various types of TMOCs and their applications in different types of cancer. From our perspective, the TMOC platform necessitates enhanced integration with tissue engineering techniques and microphysiological environments before it can evolve into a more refined preclinical model for cancer research. [ABSTRACT FROM AUTHOR]

AbstractRestoring cartilage to healthy state is challenging due to low cell density and hence low regenerative capacity. The current platforms are not compatible with clinical translation and require dedicated handling of trained personnel. However, by engineering and implanting cell microaggregates in higher concentrations, efficient formation of new cartilage can be achieved, even in the absence of exogenous growth factors. Therefore, one-step surgeries are preferable for novel treatments and we need cell laden microgels allowing the formation of microaggregaets in vivo. Injectability is a key parameter for in situ forming the shape and minimally invasive clinical applications. Hydrogels as bioinks can restore damaged tissues to their primary shape. Chitosan is a polysaccharide derived from chitin with abundant usage in tissue engineering. This review highlights the use of chitosan as an injectable hydrogel for osteochondral defects. Several studies focused on encapsulating mesenchymal stem cells within chitosan hydrogels have been categorized and incorporating microfluidic devices has been identified in the forefront to form microgels. Additionally, the printability is another convenience of chitosan for using in 3D printing for cartilage tissue engineering which is described in this review. [ABSTRACT FROM AUTHOR]

Sperm capture techniques that immobilize sperm to halt their motility are essential for the long-term analysis of individual sperm. These techniques are beneficial in assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) by allowing selective screening of sperm. However, there is a notable lack of high-throughput and non-destructive sperm capture methods that allow the flagellum to beat freely, which is crucial for accurately reflecting the behavior of unfettered, freely swimming sperm. To bridge this gap, we introduce a novel microfluidic device specifically engineered to capture sperm without restricting flagellar motion. The design utilizes sperm's innate boundary-following behavior in both 3D and 2D environments to direct them into a capture zone. Once captured, the sperm head is restrained while the flagellum remains free to exhibit natural beating patterns. Utilizing this device, we explore the effects of hyperactivating agents, temperature, and their combined influence on the dynamics of bovine sperm flagella. The unrestricted flagellar motion offered by our device yields two prominent advantages: it mirrors the flagellar behavior of free-swimming sperm, ensuring research findings are consistent with natural sperm activity, and it prevents imaging overlap between the flagellum and the capture structures, simplifying the automation of flagellar tracking and analysis. This technological advancement facilitates the collection of waveform parameters along the entire flagellum, addressing inconsistencies that have arisen in previous research due to differing measurement sites, and enabling precise extraction of sperm behavioral properties. [ABSTRACT FROM AUTHOR]

Fluorescence polarization (FP) assays are widely used to quantify biomolecules, and their combination with microfluidic devices has the potential for application in onsite analysis. However, the hydrophobic surface of polydimethylsiloxane (PDMS)-based microfluidic devices and the amphiphilicity of the blocking agents can cause the nonspecific adsorption of biomolecules, which in turn reduces the sensitivity of the FP assay. To address this, we demonstrated an FP assay with improved sensitivity in microfluidic devices using a polyethylene glycol-based surface modification to avoid the use of blocking agents. We evaluated the effectiveness of the modification in inhibiting nonspecific protein adsorption and demonstrated the improved sensitivity of the FP immunoassay (FPIA). Our study addressed the lack of sensitivity of FP assays in microfluidic devices, particularly for the quantification of low-abundance analytes. [ABSTRACT FROM AUTHOR]

The glycocalyx is a complex layer of carbohydrate and protein molecules that surrounds the cell membrane of many types of mammalian cells. It serves several important functions, including cell adhesion and communication, and maintain cell shape and stability, especially in the case of erythrocytes. Alteration of glycocalyx composition represents a cardiovascular health threatening. For example, in diabetes mellitus glycocalyx of erythrocytes and of endothelial cells is known to be impaired, a potential source of blood occlusion in microcirculation, which may lead to blindness, and renal failure of patients. The impact of glycocalyx impairment on erythrocyte aggregation remains a largely unexplored research area. We conduct here in vitro-experiments in microfluidic devices in order to investigate erythrocytes aggregation incubated with amylase, an enzyme that partially breaks down glycocalyx molecules. It is found that incubation of erythrocytes by amylase leads to a dramatic increase of their aggregation and stability and alters the aggregates morphologies. Confocal microscopy analysis reveals a significant degradation of the glycocalyx layer, correlated with enhanced erythrocytes aggregation. An increased erythrocyte aggregation in vivo should affect oxygen and other metabolites delivery to organs and tissues. This study brings new elements about elucidation of microscopic origins of erythrocyte aggregation and their potential impact on cardiovascular pathologies. [ABSTRACT FROM AUTHOR]

The peristaltic flow with applications of electro-osmotic phenomenon finds novel applications in microfluidic devices, biotechnology, environmental engineering, micro-reactor, and various medical devices. Owing to such motivations in mind, the objective of this analysis is to present the applications of electro-osmotic phenomenon in transport of Prandtl hybrid nanofluid due to non-uniform duct. The characteristics of hybrid nanofluid have been justified by using the single-walled carbon nanotubes (SWCNT) as well as multiple-walled carbon nanotubes (MWCNT) uniformly decomposed to engine oil base liquid. The novel aspects of viscous dissipation and Joule heating effects are attributed. The thermal problem is further influenced by electro-osmotic force. The electric field effects are attributed with the help of Poisson–Boltzmann and Nernst–Planck expressions. The simplification of electric field expressions is done via Debye–Heckle linearization. The problem is modeled under certain constraints of creeping transport and lubrication theory. The novel numerical treatment is performed with the help of Keller Box method. Physical visualization of results is performed for assisting as well as opposing electro-kinetic pumping constraints. It is claimed that the velocity profile increases in the central line of duct with variation of electro-osmotic coefficient. The heat transfer reduces due to potential ratio parameter electro-osmotic constant. Furthermore, the enhancement of Prandtl fluid parameter leads to decrement of axial pressure. [ABSTRACT FROM AUTHOR]

The nematode Caenorhabditis elegans is widely employed as a model organism to study basic biological mechanisms. However, transgenic C. elegans are generated by manual injection, which remains low-throughput and labor-intensive, limiting the scope of approaches benefitting from large-scale transgenesis. Here, we report a robotic microinjection system, integrating a microfluidic device capable of reliable worm immobilization, transfer, and rotation, for high-speed injection of C. elegans. The robotic system provides an injection speed 2-3 times faster than that of experts with 7–22 years of experience while maintaining comparable injection quality and only limited trials needed by users to become proficient. We further employ our system in a large-scale reverse genetic screen using multiplexed alternative splicing reporters, and find that the TDP-1 RNA-binding protein regulates alternative splicing of zoo-1 mRNA, which encodes variants of the zonula occludens tight junction proteins. With its high speed, high accuracy, and high efficiency in worm injection, this robotic system shows great potential for high-throughput transgenic studies of C. elegans. Manual injection, which remains low-throughput and labor-intensive, is a technical bottleneck for large-scale genetic studies of C. elegans. Here, the authors report a robotic microinjection system which facilitates injection speed while maintaining injection quality which is comparable to experienced experts. [ABSTRACT FROM AUTHOR]

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

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

Bonding is the key step in the fabrication of microfluidic devices. In the conventional approaches for the fabrication of polymer-based microfluidics, the substrate and cover plate were fabricated and then bonded to enclose the micro channels. Various methods have been invented for bonding polymer-based microfluidics, e.g. adhesive bonding, solvent bonding, thermal fusion, etc., materials with the same or different materials were bonded. The bonding quality of the polymer-based microfluidics is critical during use, leakage or even detachment is not allowed. The bonding quality of polymer-based microfluidic devices has been evaluated in different ways, some of the typical methods include the tensile test, shear test, and burst opening test, and each method has its own strengths and weaknesses. The standard procedure for bonding strength test hasn't been established yet. In this study, different evaluation methods for bonding quality were discussed and compared in detail, the application scenarios for each method are also discussed. An outlook for the future standardization trend of bonding test methods for microfluidic device is also provided in this study. [ABSTRACT FROM AUTHOR]

The constant improvement of stereolithography (SL) in terms of achievable resolution and printing time has sparked high expectations that SL will enable the rapid prototyping of truly microfluidic chips with features below 100 µm. However, most commercial high‐resolution stereolithography devices are based on Digital Light Processing (DLP) and thus sacrifice lateral printing size for resolution. Consequently, even 10 years after the advent of microstereolithography there is no commercialized 3D printing system that can effectively fulfill all the demands to replace soft lithography for microfluidic prototyping. In this work, for the first time, This study demonstrates that a commercial laser‐based stereolithography device is capable of manufacturing microfluidic chips with embedded channels smaller than 100 µm with a footprint of 7.24 × 0.3 cm2. A chip fabricated in poly(ethylene glycol) diacrylate (PEGDA) that can readily be used for fluid mixing, is presented in this study. This research shows that the accessibility of high‐resolution chips with footprints of several cm2, using laser‐based stereolithography, enables the manufacturing of truly microfluidic systems with high impact on prototyping and manufacturing. [ABSTRACT FROM AUTHOR]

The gut is a vital organ that is central to the absorption and metabolic processing of orally administered drugs. While there have been many models developed with the goal of studying the absorption of drugs in the gut, these models fail to adequately recapitulate the diverse, complex gastrointestinal microenvironment. The recent emergence of microfluidic organ-on-a-chip technologies has provided a novel means of modeling the gut, yielding radical new insights into the structure of the gut and the mechanisms through which it shapes disease, with key implications for biomedical developmental efforts. Such organ-on-a-chip technologies have been demonstrated to exhibit greater cost-effectiveness, fewer ethical concerns, and a better ability to address inter-species differences in traditional animal models in the context of drug development. The present review offers an overview of recent developments in the reconstruction of gut structure and function in vitro using microfluidic gut-on-a-chip (GOC) systems, together with a discussion of the potential applications of these platforms in the context of drug development and the challenges and future prospects associated with this technology. This paper outlines the characteristics of the different cell types most frequently used to construct microfluidic gut-on-a-chip models and the microfluidic devices employed for the study of drug absorption. And the applications of gut-related multichip coupling and disease modelling in the context of drug development is systematically reviewed. With the detailed summarization of microfluidic chip-based gut models and discussion of the prospective directions for practical application, this review will provide insights to the innovative design and application of microfluidic gut-on-a-chip for drug development. [Display omitted] [ABSTRACT FROM AUTHOR]

In the quest for miniaturization across technical disciplines, microscale ceramic blocks emerge as pivotal components, with performance critically dependent on precise scales and intricate shapes. Sharp-edged ceramic microparticles, applied from micromachining to microelectronics, require innovative fabrication techniques for high-throughput production while maintaining structural complexity and mechanical integrity. This study introduces a "one-pot microfluidic fabrication" system incorporating two device fabrication strategies, "groove & tongue" and sliding assembling, achieving an unprecedented array of microparticles with diverse, complex shapes and refined precision, outperforming traditional methods in production rate and quality. Optimally designed sintering profiles based on derivative thermogravimetry enhance microparticles' shape retention and structural strength. Compression and scratch tests validate the superiority of microparticles, suggesting their practicability for diverse applications, such as precise micromachining, sophisticated microrobotics and delicate microsurgical tools. This advancement marks a shift in microscale manufacturing, offering a scalable solution to meet the demanding specifications of miniaturized technology components. Drawing from historical tradition, "groove & tongue" sliding assembled devices were created in a one-pot microfluidic fabrication system, enabling the production of complex-shaped microparticles with high precision. [ABSTRACT FROM AUTHOR]

As interest in deep space travel grows exponentially, understanding human adaptation in becoming an interplanetary species is crucial. This includes the prospect of reproduction. This review summarizes recent updates and innovations in assisted reproductive technologies (ART) on Earth, while also discussing current challenges and areas for improvement in adapting ART studies to the space environment. We discuss the critical components of ART - gamete handling and preparation, fertilization, embryo culture, and cryopreservation - from the daily practice perspective of clinical embryologists and reproductive endocrinologists and lay out the complicated path ahead. In vitro embryo development in low Earth orbit and beyond remains questionable due to synergetic effects of microgravity and radiation-induced damage observed in simulated and actual in-space mammalian studies. Cryopreservation and long-term storage of frozen samples face substantial obstacles - temperature limitations, lack of trained personnel, and absence of adapted cosmic engineering options. We touch on recent innovations, which may offer potential solutions, such as microfluidic devices and automated systems. Lastly, we stress the necessity for intensive studies and the importance of an interdisciplinary approach to address numerous practical challenges in advancing reproductive medicine in space, with possible implications for both space exploration and terrestrial fertility treatments. [ABSTRACT FROM AUTHOR]

Stem cell‐derived cardiac spheroids are promising models for cardiac research and drug testing. However, generating contracting cardiac spheroids remains challenging because of the laborious experimental procedure. Here, we present a microfluidic hanging‐heart chip (HH‐chip) that uses a microchannel and flow‐driven system to facilitate cell loading and culture medium replacement operations to reduce the laborious manual handling involved in the generation of a large quantity of cardiac spheroids. The effectiveness of the HH‐chip was demonstrated by simultaneously forming 50 mouse embryonic stem cell‐derived embryonic bodies, which sequentially differentiated into 90% beating cardiac spheroids within 15 days of culture on the chip. A comparison of our HH‐chip method with traditional hanging‐drop and low‐attachment plate methods revealed that the HH‐chip could generate higher contracting proportions of cardiac spheroids with higher expression of cardiac markers. Additionally, we verified that the contraction frequencies of the cardiac spheroids generated from the HH‐chip were sensitive to cardiotoxic drugs. Overall, our results suggest that the microfluidic hanging drop chip‐based approach is a high‐throughput and highly efficient method for generating contracting mouse embryonic stem cell‐derived cardiac spheroids for cardiac toxicity and drug testing applications. [ABSTRACT FROM AUTHOR]

The document is a contents list for the journal "Lab on a Chip," which focuses on devices and applications at the micro- and nanoscale. It includes various articles and papers on topics such as microfluidics, robotics, bioprinting, and drug release. The journal aims to connect the world with the chemical sciences and is published by The Royal Society of Chemistry. [Extracted from the article]

Stereolithography (SLA) and other photopolymerization-based additive manufacturing approaches are becoming popular for the fabrication of microfluidic devices and cell-infused platforms, but many of the resins employed in these techniques are cytotoxic to cells or do not have the appropriate mechanical properties for microfluidic components. Here, using a commercially available resin, we demonstrate that biocompatibility and a range of mechanical properties can be achieved through post-print optimization involving baking, soaking, network swelling, and UV exposure. We show that UV-vis spectrophotometry can be used to detect methacrylate monomer/oligomer, and utilizing this method, we found that baking at 120 °C for 24 hours was the optimal method for removing cytotoxic chemical species and creating nontoxic cell culture platforms, though UV exposure and soaking in 100% ethanol also can substantially reduce cytotoxicity. Furthermore, we show that the mechanical properties can be modified, including up to 50% for the Young's modulus and an order of magnitude for the flexural modulus, through the post-processing approach employed. Based on the study results, users can choose post-processing approaches to achieve needed cytotoxicity and mechanical profiles, simultaneously. [ABSTRACT FROM AUTHOR]

Snap-through is a buckling instability that allows slender objects, including those in plant and biological systems, to generate rapid motion that would be impossible if they were to use their internal forces exclusively. In microfluidic devices, such as micromechanical switches and pumps, this phenomenon has practical applications for manipulating fluids at small scales. The onset of this elastic instability often drives the surrounding fluid into motion – a process known as snap-induced flow. To analyse the complex dynamics resulting from the interaction between a sheet and a fluid, we develop a prototypical model of a thin sheet that is compressed between the two sides of a closed channel filled with an inviscid fluid. At first, the sheet bends towards the upstream direction and the system is at rest. However, once the pressure difference in the channel exceeds a critical value, the sheet snaps to the opposite side and drives the fluid dynamics. We formulate an analytical model that combines the elasticity of thin sheets with the hydrodynamics of inviscid fluids to explore how external pressure differences, material properties and geometric factors influence the system's behaviour. To analyse the early stages of the evolution, we perform a linear stability analysis and obtain the growth rate and the critical pressure difference for the onset of the instability. A weakly nonlinear analysis suggests that the system can exhibit a pressure spike in the vicinity of the inverted configuration. [ABSTRACT FROM AUTHOR]

A three-dimensional spectral boundary element method has been employed to compute for the dynamics of the droplet motion driven by shear flow near a single solid substrate with a rough surface. The droplet size is comparable with the surface features of the substrate. This is a problem that has barely been explored but with applications in biomedical research and heat management. This work numerically investigated the influences of surface roughness features, such as the roughness amplitude and wavelength, on the droplet deformation and velocities. We observe that a greater amplitude or wavelength leads to larger variations in droplet velocity perpendicular to the substrate. The droplet velocity along the substrate increases when the amplitude is reduced or when the wavelength increases. The effects of capillary number and viscosity ratios have also been studied. The droplet deformation and its velocity increases as we increase the capillary number, while the viscosity ratio shows a non-monotonic influence on the droplet behavior. The predicted droplet behaviors, including deformation, velocities, and trajectories, can provide physical insight, help to understand the droplet behavior in microfluidic devices without a perfectly smooth surface, and contribute in the design and operation of those devices. [ABSTRACT FROM AUTHOR]

Continuous-wave lasers generated bubbles in microfluidic channels are proposed for applications such as needle-free jet injection due to their small size and affordable price of these lasers. However, water is transparent in the visible and near-IR regime, where the affordable diode lasers operate. Therefore, a dye is required for absorption, which is often unwanted in thermocavitation applications, such as vaccines or cosmetics. In this work, we explore a different mechanism of the absorption of optical energy. The microfluidic channel wall is partially covered with a thin gold layer, which absorbs light from a blue laser diode. This surface absorption is compared with the conventional volumetric absorption by a red dye. The results show that this surface absorption can be used to generate bubbles without the requirement of a dye. However, the generated bubbles are smaller and grow slower when compared to the dye-generated bubbles. Furthermore, heat dissipation in the glass channel walls affects the overall efficiency. Finally, degradation of the gold layer over time reduces the reproducibility and limits its lifetime. Further experiments and simulations are proposed to potentially solve these problems and optimize the bubble formation. Our findings can inform the design and operation of microfluidic devices used in phase transition experiments and other cavitation phenomena, such as jet injectors or liquid dispensing for bio-engineering. [ABSTRACT FROM AUTHOR]

The performance of single‐chain polymeric nanoparticles (SCPNs) in biomedical applications highly depends on their conformational stability in cellular environments. Until now, such stability studies are limited to 2D cell culture models, which do not recapitulate the 3D tumor microenvironment well. Here, a microfluidic tumor‐on‐a‐chip model is introduced that recreates the tumor milieu and allows in‐depth insights into the diffusion, cellular uptake, and stability of SCPNs. The chip contains Matrigel/collagen‐hyaluronic acid as extracellular matrix (ECM) models and is seeded with cancer cell MCF7 spheroids. With this 3D platform, it is assessed how the polymer's microstructure affects the SCPN's behavior when crossing the ECM, and evaluates SCPN internalization in 3D cancer cells. A library of SCPNs varying in microstructure is prepared. All SCPNs show efficient ECM penetration but their cellular uptake/stability behavior depends on the microstructure. Glucose‐based nanoparticles display the highest spheroid uptake, followed by charged nanoparticles. Charged nanoparticles possess an open conformation while nanoparticles stabilized by internal hydrogen bonding retain a folded structure inside the tumor spheroids. The 3D microfluidic tumor‐on‐a‐chip platform is an efficient tool to elucidate the interplay between polymer microstructure and SCPN's stability, a key factor for the rational design of nanoparticles for targeted biological applications. [ABSTRACT FROM AUTHOR]

Lab-on-chips supported by hydrogel matrices are excellent solutions for cell culture; thus, this literature review presents examples of scientific research in this area. Several works are presenting the properties of biocompatible hydrogels that mimic the cellular environment published recently. Hydrogels can also be treated as cell transporters or as a structural component of microfluidic devices. The rapidly growing scientific sector of hydrogel additive manufacturing is also described herein, with attention paid to the appropriate mechanical and biological properties of the inks used to extrude the material, specifically for biomedical purposes. The paper focuses on protocols employed for additive manufacturing, e.g., 3D printing parameters, calibration, ink preparation, crosslinking processes, etc. The authors also mention potential problems concerning manufacturing processes and offer example solutions. As the novel trend for hydrogels enriched with several biocompatible additives has recently risen, the article presents examples of the use of high-quality carbon nanotubes in hydrogel research enhancing biocompatibility, mechanical stability, and cell viability. Moving forward, the article points out the high applicability of the hydrogel-assisted microfluidic platforms used for cancer research, especially for photodynamic therapy (PDT). This innovative treatment strategy can be investigated directly on the chip, which was first proposed by Jędrych E. et al. in 2011. Summarizing, this literature review highlights recent developments in the additive manufacturing of microfluidic devices supported by hydrogels, toward reliable cell culture experiments with a view to PDT research. This paper gathers the current knowledge in these intriguing and fast-growing research paths. [ABSTRACT FROM AUTHOR]

A wearable potentiometric device is reported based on an innovative butterfly-like paper-based microfluidic system, allowing for continuous monitoring of pH and Na+ levels in sweat during physical activity. Specifically, the use of the butterfly-like configuration avoids evaporation phenomena and memory effects, enabling precise and timely biomarker determination in sweat. Two ad hoc modified screen-printed electrodes were embedded in the butterfly-like paper-based microfluidics, and the sensing device was further integrated with a portable and miniaturized potentiostat, leveraging Bluetooth technology for efficient data transmission. First, the paper-based microfluidic configuration was tested for optimal fluidic management to obtain optimized performance of the device. Subsequently, the two electrodes were individually tested to detect the two biomarkers, namely pH and Na+. The results demonstrated highly promising near-Nernstian (0.056 ± 0.002 V/dec) and super-Nernstian (− 0.080 ± 0.003 V/pH) responses, for Na+ and pH detection, respectively. Additionally, several important parameters such as storage stability, interferents, and memory effect by hysteresis study were also investigated. Finally, the butterfly-like paper-based microfluidic wearable device was tested for Na+ and pH monitoring during the physical activity of three volunteers engaged in different exercises, obtaining a good correlation between Na+ increase and dehydration phenomena. Furthermore, one volunteer was tested through a cardiopulmonary test, demonstrating a correlation between sodium Na+ increase and the energetic effort by the volunteer. Our wearable device highlights the high potential to enable early evaluation of dehydration and open up new opportunities in sports activity monitoring. [ABSTRACT FROM AUTHOR]

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

Inertial microfluidics is essential for separating particles and cells, enabling numerous biomedical applications. Despite the simplicity of spiral microchannels, the lack of predictive models hampers real‐world applications, highlighting the need for cost‐effective computational tools. In this study, four novel data fitting models are developed using linear and power regression analyses to investigate how flow conditions influence particle behaviors within spiral microchannels. These models are rigorously tested under two different flow rates, focusing on a smaller particle representing Salmonella Typhimurium and a larger particle representing bacterial aggregates, aiming for effective separation and detection. A critical parameter, the sheath‐to‐sample flow rate ratio, is either interpolated or extrapolated using the microchannel's aspect ratios to predict particle separation. The models show strong agreement with experimental data, underscoring their predictability and efficiency. These insights suggest that further refinement of these models can significantly reduce research and development costs for advanced inertial microfluidic devices in biomedical applications. This work represents a crucial step towards establishing a robust computational framework, advancing inertial microfluidics towards practical biomedical applications. [ABSTRACT FROM AUTHOR]

Tetrafluoroethylene (TFE) terpolymers have emerged as advantageous substitutes for polytetrafluoroethylene (PTFE). Therefore, they are being considered as alternatives to PTFE in many application areas. The advantages of TFE terpolymers include their facile processability at elevated temperatures, their solubility in some polar organic solvents, their inertness against aqueous acids, aqueous bases and a large number of mostly nonpolar organic solvents, their low dielectric constant, their low refractive index as well as useful electro‐ and thermochemical properties. This review on TFE terpolymers focuses on their processing including shaping and surface modification as well as on selected properties including wettability, dielectric properties, mechanical response behavior, chemical stability, and degradability. Applications including their use as elastomeric sealing material, liner and cladding layer as well as their use as material for membranes, microfluidic devices, photonics, photovoltaics, energy storage, energy harvesting, sensors, and nanothermitic composites will be discussed. The review concludes with a discussion of the future potential of TFE terpolymers and scientific challenges to be addressed by future research on TFE terpolymers. [ABSTRACT FROM AUTHOR]

Background: Spores are highly resistant dormant cells, adapted for survival and dispersal, that can withstand unfavourable environmental conditions for extended periods of time and later reactivate. Understanding the germination process of microbial spores is important in numerous areas including agriculture, food safety and health, and other sectors of biotechnology. Microfluidics combined with high-resolution microscopy allows to study spore germination at the single-cell level, revealing behaviours that would be hidden in standard population-level studies. Methods: Here, we present a microfluidic platform – the so-called four-conditions microfluidic chemostat (4CMC) – for germination studies where spores are confined to monolayers inside microchambers, allowing the testing of four growth conditions in parallel. This platform can be used with multiple species, including non-model organisms, and is compatible with existing image analysis software. Results: In this study, we focused on three soil dwellers, two bacteria and one fungus, and revealed new insights into their germination. We studied endospores of the model bacterium Bacillus subtilis and demonstrated a correlation between spore density and germination in rich media. We then investigated the germination of the obligate-oxalotrophic environmental bacterium Ammoniphilus oxalaticus in a concentration gradient of potassium oxalate, showing that lower concentrations result in more spores germinating compared to higher concentrations. We also used this microfluidic platform to study the soil beneficial filamentous fungus Trichoderma rossicum, showing for the first time that the size of the spores and hyphae increase in response to increased nutrient availability, while germination times remain the same. Discussion: Our platform allows to better understand microbial behaviour at the single-cell level, under a variety of controlled conditions. While we used it to decipher the responsiveness of soil dwellers' spores, it would also be suitable for other spores from bacteria or filamentous fungi, but also vegetative cells and yeast, and even microbial communities. [ABSTRACT FROM AUTHOR]

This work has the purpose to elucidate in deeper detail the conjugated physical phenomena at the interface between two immiscible fluids in microfluidic devices. The two typical regimes—dripping and jetting—emerging in flow-focusing devices are considered for the analysis. Dynamic (time-dependent analysis of fixed or Lagrangian-tracked points) and local (lines along the interface, at a fixed time instance) analyses have been conducted from a parallel numerical simulation on a fine numerical grid. The results comprise various pressures and tangential stresses and their balance during the droplet formation process with special attention paid to the moments and locations of the droplet release. It was found that the dripping regime is characterized by the local balance of the pressure drop due to surface tension Δ p σ and the Laplace pressure Δ p Lapl across the interface. Only at the last moments before the droplet pinch-off does the former pressure dominate. In contrast, in the jetting regime, there is a clear domination of the pressure due to tension during the whole process of droplet formation. Shear stresses, presented by the von Mises criterion, are several times (jetting regime) or even an order of magnitude (dripping regime) lower than the surface tension pressure and the Laplace pressure. In both regimes, when the interface curvature κ changes locally its sign, the pressure at the centerline axis shows a clear local maximum. For the jetting regime, the downstream derivative of this centerline pressure is the first parameter that changes along the jet axis—thus indicating the onset of instabilities for this regime—and it is then followed by a wavelike change of the radius of the jet. [ABSTRACT FROM AUTHOR]