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This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (<1000 cells), transparent, and genetically tractable. Despite its simplicity, the worm exhibits complex phenotypes associated with multicellularity: the worm has differentiated cells and organs, it ages and has a well-defined lifespan, and it is capable of learning and remembering. This Review argues that the balance between simplicity and complexity in the worm will make it a useful tool in determining the relationship between molecular-scale phenomena and organism-level phenomena, such as aging, behavior, cognition, and disease. Following an introduction to worm biology, the Review provides examples of current research with C. elegans that is chemically relevant. It also describes tools-biological, chemical, and physical-that are available to researchers studying the worm., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Surface-attached micro- and nanobubbles are known for their resistance to external forces. This study experimentally and theoretically investigates their response to strong ultrasonic fields. Surface-attached micro- and nanobubbles with contact radii from 2 μm to 20 μm are generated in a microchannel and exposed to ultrasound through a vibrating glass substrate. At a driving frequency over 200 kHz up to 2 MHz tested, no significant response from the micro- and nanobubbles is observed. By contrast, at 100 kHz–200 kHz, ultrasonic cavitation bubbles appear in the microchannel and migrate toward the surface micro- and nanobubbles. Then the surface micro- and nanobubbles merge with the ultrasonic cavitation bubbles, detach from the substrate, and become free gaseous nuclei susceptible to further cavitation. Notably, the removal process leaves no observable residue. Theoretical analysis suggests that the directional migration of cavitation bubbles is driven by mutual acoustic radiation forces. This work demonstrates that ultrasonic fields can effectively remove surface micro- and nanobubbles, transforming them into free gaseous cavitation nuclei.

Abstract Osteoarthritis has been regarded as a complex and serious degenerative disease. Attempts in this area are focused on improving the curative effect of stem cell‐based therapies. In this work, we present a novel inverse opal microcarriers‐based cytokines delivery system to induce autologous stem cell homing for osteoarthritis treatment. Considering their important role in stem cell recruitment and chondrogenic differentiation respectively, platelet‐derived growth factor BB (PDGF‐BB) and transforming growth factor β3 (TGF‐β3) are loaded into inverse opal microcarriers as model cytokines. Since cytokine release induces the corresponding variations in characteristic reflection spectra and structural colors, the inverse opal microcarriers possess the optical self‐reporting capacity to monitor the release process. In vitro cell experiments reveal that inverse opal microcarriers could successfully recruit the gathering of mesenchymal stem cells through the release of loaded cytokines. Based on these features, we have demonstrated the enhanced therapeutic effect of PDGF‐BB and TGF‐β3 loaded inverse opal microcarriers in the treatment of rat osteoarthritis models. These results indicate that the multifunctional inverse opal microcarriers‐based cytokines delivery system would find broad prospects in osteoarthritis treatment and other biomedical fields.

Abstract Reactive oxygen species (ROS) have certain effect in cancer treatment, thus many studies have been focused on developing functional systems to generate ROS in tumor. Here, inspired by the multi‐enzyme biocatalysis in organisms, novel ultrasound‐triggered temporospatial catalytic cascades systems are presented based on barium titanate (BTO) and platinum (Pt) co‐loaded multi‐component microparticles (Pt/BTO@MCMPs) to successively achieve oxygen and ROS production for tumor sonodynamic therapy. By using a customized capillary microfluidic device, the Pt/BTO@MCMPs are fabricated with Pt nanoparticles located in their core part and BTO nanocubes located in their peripheral part, alternating with blank porous hydrogel components for increasing interaction areas between the encapsulated nanomaterials and the ambient substrates. In the microparticles, the Pt can catalyze hydrogen peroxide from the tumor microenvironment to generate O2 and H2O serving as substrates for piezoelectric catalytic reactions, contributing to additional generation of ROS under US activation. Based on the system, it is demonstrated that the Pt/BTO@MCMPs are featured with excellent biocompatibility under normal biological conditions and show desired tumor eradication properties under ultrasound irradiation in mice carrying pancreatic tumors. These results indicate that the proposed ultrasound‐triggered temporospatial catalytic cascades systems are promising for clinic anti‐tumor applications.

Abstract Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required. MXene is a promising candidate owning these advantages, yet pristine MXene faces dilemmas including insufficient utility of surface site as well as limited processibility. Here, we develop MXene‐encapsulated porous microcapsules via microfluidics. The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core, by which the microcapsules are endowed with high MXene dosage and remarkable biosafety. Additionally, the MXene nanoflakes assemble into a three‐dimensional network via metal ion‐induced gelation, thereby avoiding restacking and significantly improving surface utilization. Moreover, a freeze‐pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell, which can facilitate the diffusion of the target molecules. These features, combined with additional magneto‐responsiveness rendered by the incorporation of magnetic nanoparticles, contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine, urea, and uric acid. Thus, it is anticipated that the MXene‐encapsulated microcapsules will be promising adsorbents in dialysis‐related applications, and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions.

Semi-transparent platinum electrodes were designed and optimized to implement photoluminescence (PL) and electrochemiluminescence (ECL) in microchannels under flow conditions. The luminescence properties of tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy)32+) were used to map steady-state emitted light through semi-transparent microchannel electrodes. Several diffusive-convective regimes were thus imposed in order to experimentally highlight the operating conditions of the electrodes, in particular the active zones at their upstream edges contributing to the Faradaic current. PL and ECL profiles were established on the electrode surfaces as a function of flow rate. The PL profiles confirmed the control of the process by mass transport. The data were validated by numerical simulations within the limits of experimental accuracy. ECL emission in presence of the co-reactant tri-n-propylamine (TPA) was also limited by mass transport. However, in comparison the characteristics of the ECL profiles demonstrated the complexity of the underlying mechanism involving Ru(bpy)32+ regeneration and TPA consumption.

This study introduces the Theokane number (Tk) as a groundbreaking dimensionless number in Electrochemistry. Tk enables the determination of the operating state of an electrochemical (EC) system—indicating whether it is in a transient state (characteristic of cyclic voltammetry) or a steady state (typical of linear sweep voltammetry)—based on a given combination of potential scan rate and residence time. It aims to bridge the gap between various voltamperometric methods. Tk uniquely compares the duration of the potential scan applied to an EC system to the residence time of the reaction mixture at the electrode. This comparison is pertinent in environments ranging from microfluidic setups to macroscale reactors, including stirred vessels.Tk is particularly crucial for understanding the ‘continuous answer’ of an EC system subjected to voltamperometric polarization across a spectrum of potential scan and stirring rates. Voltammograms recorded in a micro-reactor under varying conditions highlight the influence of operating parameters on EC responses. The approach introduced in this study accomplish three key objectives: i) it validates the Tk number through the comparison of experimental and simulation data, ii) it proposes a range for its applicability; and iii) it opens a new mode for analyzing EC responses. It is important to note that Tk is applicable to both quasi-reversible and irreversible systems.

The development of highly selective separation processes is a focus of current research. In 2016, the German Science Foundation funded a priority program SPP 2045 “MehrDimPart—highly specific multidimensional fractionation of fine particles with technical relevance” that aims to develop new or enhance existing approaches for the separation of nano- and micrometer-sized particles. Dielectrophoretic separators achieve highly selective separations of (bio-)particles in microfluidic devices or can handle large quantities when non-selective separation is sufficient. Recently, separator designs were developed that aim to combine a high throughput and high selectivity. Here, we summarize the development from a microfluidic fast chromatographic separation via frequency modulated dielectrophoretic particle chromatography (DPC) toward a macrofluidic high throughput separation. Further, we provide a starting point for future work by providing new experimental data demonstrating for the first time the trapping of 200 nm polystyrene particles in a dielectrophoretic high-throughput separator that uses printed circuit boards as alternatives for expensive electrode arrays.

The combination of micro- or nanofluidics and strong light–matter coupling has gained much interest in the past decade, which has led to the development of advanced systems and devices with numerous potential applications in different fields, such as chemistry, biosensing, and material science. Strong light–matter coupling is achieved by placing a dipole (e.g., an atom or a molecule) into a confined electromagnetic field, with molecular transitions being in resonance with the field and the coupling strength exceeding the average dissipation rate. Despite intense research and encouraging results in this field, some challenges still need to be overcome, related to the fabrication of nano- and microscale optical cavities, stability, scaling up and production, sensitivity, signal-to-noise ratio, and real-time control and monitoring. The goal of this paper is to summarize recent developments in micro- and nanofluidic systems employing strong light–matter coupling. An overview of various methods and techniques used to achieve strong light–matter coupling in micro- or nanofluidic systems is presented, preceded by a brief outline of the fundamentals of strong light–matter coupling and optofluidics operating in the strong coupling regime. The potential applications of these integrated systems in sensing, optofluidics, and quantum technologies are explored. The challenges and prospects in this rapidly developing field are discussed.

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

Abstract Colloidal crystals are materials self‐assembled from the colloidal nanoparticles. Due to the ordered microstructure, they exhibit significant optical properties and have shown huge potential in the field of biosensing. Besides, the unique macroscopic shapes can also play a critical role in the sensing process. Here, we present a comprehensive discussion on the colloidal crystal‐based biosensors with different topological shapes, including the development strategies of currently reported colloidal crystal particles, films, and fibers, and their recent progress in biosensing. In addition, the faced challenges and the possible solutions are also concluded and discussed. We expect this review can enrich the knowledge and encourage the communication of interdisciplinary researchers, thus promoting the further development and practical applications of colloidal crystal‐based biosensors.

Abstract Messenger RNA (mRNA) therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins. Developing strategies for local mRNA delivery is still required where direct intra‐articular injections are inappropriate for targeting a specific tissue. The mRNA delivery efficiency depends on protecting nucleic acids against nuclease‐mediated degradation and safe site‐specific intracellular delivery. Herein, novel mRNA‐releasing matrices based on RGD‐moiety‐rich gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffolds are reported. GelMA concentration in aerogel‐based microgels (µgels) produced through a microfluidic process, MAP stiffnesses, and microporosity are crucial parameters for cell adhesion, spreading, and proliferation. After being loaded with mRNA complexes, MAP scaffolds composed of 10% GelMA µgels display excellent cell viability with increasing cell infiltration, adhesion, proliferation, and gene transfer. The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA‐releasing scaffolds. These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes, making them promising mRNA‐releasing biomaterials for tissue engineering.

Abstract Organoids have emerged as a powerful platform for studying complex biological processes and diseases in vitro. However, most studies have focused on individual organoids, overlooking the inter‐organ interactions in vivo and limiting the physiological relevance of the models. To address this limitation, the development of a multi‐organoid system has gained considerable attention. This system aims to recapitulate inter‐organ communication and enable the study of complex physiological processes. This review provides a comprehensive overview of the recent advancements in organoid engineering and the emerging strategies for constructing a multi‐organoid system. First, we highlight the critical mechanical, structural, and biochemical factors involved in designing suitable materials for the growth of different organoids. Additionally, we discuss the incorporation of dynamic culture environments to enhance organoid culture and enable inter‐organoid communication. Furthermore, we explore techniques for manipulating organoid morphogenesis and spatial positioning of organoids to establish effective inter‐organoid communication networks. We summarize the achievements in utilizing organoids to recapitulate inter‐organ communication in vitro, including assembloids and microfluidic multi‐organoid platforms. Lastly, we discuss the existing challenges and opportunities in developing a multi‐organoid system from its technical bottlenecks in scalability to its applications toward complex human diseases.

With the development of microfluidics, there are increasing reports of syntheses using not only conventional laminar flow at the microscale, but also the dissociation and aggregation of microdroplets. It is known, to some extent, that the microfluidics scale differs from normal scales in terms of the specific surface area, mass diffusion, and heat conduction; these are opposite to those in scale-up in-plant chemical engineering. However, it is not easy to determine what changes when the microdroplet flows through the channel. In this context, the author would like to clarify how the behavior of chemical species, which is expected to appear unique at the nanoscale, contributes to chemical reactions. What do we need in order to develop a completely new theory of chemical reactions? The characteristics of chemical reactions on the nanoscale are clarified via the encountering of solutions by the microfluidic device itself, or the chemical reaction of nanoscale droplets generated by the microfluidic device. Specifically, in recent years, experimental reports have accumulated that are expected to develop a fluidic device that can stably generate nanodroplets, and complex reactions of different reactivity are expected to occur that are specific to the nanoscale. In this short article, microfluidic devices, nanoscale droplets, experimental synthetic examples, and findings that may provide solutions are described.

Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are not without their own drawbacks; namely, these hydrogels are rapidly degraded in vivo, and cells delivered via microtissues are quickly expelled from the area of action. Here, we report the development of an easily customized protocol for creating a protective, biocompatible hydrogel barrier around microtissues. We show that calcium carbonate nanoparticles embedded within an ECM-based microtissue diffuse outwards and, when then exposed to a solution of alginate, can be used to generate a coated layer around the tissue. We further show that this technique can be fine-tuned by adjusting numerous parameters, granting us full control over the thickness of the hydrogel coating layer. The microtissues’ protective hydrogel functioned as hypothesized in both in vitro and in vivo testing by preventing the cells inside the tissue from escaping and protecting the microdroplets against external degradation. This technology may provide microtissues with customized properties for use as sources of regenerative therapies.

The vascular system maintains cellular homeostasis by transporting oxygen, nutrients, and metabolic waste products. The vascular system is involved in a variety of fundamental physiological phenomena and is closely associated with human vascular diseases. Additionally, the stability of drugs in the vasculature affects their efficacy. Therefore, researchers have used vascular models to study vascular diseases, assess drug stability, and screen drugs. However, there are many shortcomings in the animal models and in vitro two-dimensional vascular models that have been extensively developed. In this paper, we specifically review the construction methods of in vitro vascular models and classify the specific methods into photolithography, soft lithography, self-assembly, template, 3D bioprinting, and laser degradation/cavitation. The first two are microfluidics-based methods and the last three are non-microfluidics-based methods. The vascular model construction methods reviewed in this paper overcome the shortcomings of traditional models—which cannot accurately reproduce the human vascular microenvironment—and can assist in the construction of in vitro 3D vascular models and tissue engineering vascularization. These models can be reused by perfusion devices, and the cells within the channels reside on biocompatible materials that are used to simulate the microenvironment and 3D cellular organization of the vasculature in vivo. In addition, these models are reproducible in shape and length, allowing experiments to be repeated, which is difficult to do with natural vessels. In vitro vascular models are widely used in research and drug screening for diseases associated with endothelial dysfunction, cancer, and other vascular abnormalities.

In the context of advanced nanomaterials research, nanogels (NGs) have recently gained broad attention for their versatility and promising biomedical applications. To date, a significant number of NGs have been developed to meet the growing demands in various fields of biomedical research. Summarizing preparation methods, physicochemical and biological properties, and recent applications of NGs may be useful to help explore new directions for their development. This article presents a comprehensive overview of the latest NG synthesis methodologies, highlighting advances in formulation with different types of hydrophilic or amphiphilic polymers. It also underlines recent biomedical applications of NGs in drug delivery and imaging, with a short section dedicated to biosafety considerations of these innovative nanomaterials. In conclusion, this article summarizes recent innovations in NG synthesis and their numerous applications, highlighting their considerable potential in the biomedical field.

The paper presents the results of a systematic microfluidic study of the application of nanosuspensions for enhanced oil recovery. For the first time, approximately a dozen nanosuspensions prepared by the dilution of silica sols as displacement fluids were considered. The concentration of nanoparticles in the suspensions varied from 0.125 to 2 wt%, and their size ranged from 10 to 35 nm. Furthermore, the silica sols under consideration differed in their compositions of functional groups and pH. The effects of concentration, nanoparticle size, fluid flow rate, and the viscosity of the displaced oil were investigated using microfluidic technology. The microfluidic experiments demonstrated that the application of nanosuspensions for water flooding has significant potential. The efficiency of oil displacement by nanosuspensions was found to increase significantly (up to 30%) with the increasing concentration and decreasing average size of nanoparticles. The application of nanosuspensions for the enhancement of oil recovery is most appropriate for reservoirs with highly viscous oil.

Measuring the viscosity of pharmaceutical dosage forms is a crucial process. Viscosity provides information about the stability of the composition, the release rate of the drug, bioavailability, and, in the case of injectable drug formulations, even the force required for injection. However, measuring viscosity is a complex task with numerous challenges, especially for non-Newtonian materials, which include most pharmaceutical formulations, such as gels. Selecting the appropriate shear rate is critical. Since viscosity in many systems is highly temperature-dependent, stable temperature control is necessary during the measurement. Using microfluidics technology, it is now possible to perform rheological characterization and conduct fast and accurate measurements. Small sample volumes (even below 500 µL) are required, and viscosity determination can be carried out over a wide range of shear rates. Nevertheless, the pharmaceutical application of viscometers operating on the principle of microfluidics is not yet widespread. In our work, we compare the results of measurements taken with a microfluidic chip-based viscometer on different pharmaceutical forms (gels, solution) with those obtained using a traditional rotational viscometer, evaluating the relative advantages and disadvantages of the different methods. The microfluidics-based method enables time- and sample-efficient viscosity analysis of the examined pharmaceutical forms.

Today, microfluidics has become a revolutionary interdisciplinary topic with considerable attention in a wide range of biotechnology applications. In this research work, a numerical investigation of a microfluidic micromixer is carried out using a hybrid actuation approach with different micropillar shapes and gaps. For this purpose, COMSOL Multiphysics v.5.2. is used with three different physics, such as thermoviscous acoustic physics to solve acoustic governing equations, laminar physics to solve fluid flow governing equations, and diluted transport species to solve mixing governing equations. The simulations were carried out at different Reynolds numbers such as 2, 4, 6, 8, 10, and 12 with an oscillation frequency of 15 kHz. The results were in the form of acoustic characteristics such as acoustic pressure, acoustic velocity, acoustic stream, mixing index, and fluid flow behaviour at various Reynolds numbers. The results revealed that the inclusion of micropillars improved the mixing performance and strength of the acoustic field, resulting in an improvement of the mixing performance compared to the case without micropillars. In addition, the mixing performance is also investigated at different Reynolds numbers, and a higher mixing index is investigated at lower Reynolds numbers. Moreover, it was also investigated that blade-shaped micropillars with 0.150 mm gaps deliver the best results compared to the other cases, and the maximum and minimum values of the mixing index are 0.97 and 0.72, respectively, at Reynolds number 2. The main reason behind this larger mixing index at low Reynolds numbers is due to the inclusion of micropillars that enhance the diffusion rate and contact area, leading to the homogenisation of the heterogeneous fluids in the microchamber. The obtained results can be extremely helpful for the design and modifications of a hybrid microfluidics micromixer.

Recent developments in the field of additive manufacturing processes have led to tremendous technological progress and opened directions for the field of microfluidics. For instance, new flexible materials for 3D printing allow the substitution of polydimethylsiloxane (PDMS) in microfluidic prototype development. Three-dimensional-printed microfluidic components open new horizons, in particular for the automated handling of biological cells (e.g., eukaryotic cells or bacteria). Here, we demonstrate how passive mixing and passive separation processes of biological cells can be realized using 3D printing concepts for rapid prototyping. This technique facilitates low-cost experimental setups that are easy to modify and adopt for specific detection and diagnostic purposes. In particular, printing technologies based on fused deposition modeling and stereolithography are used and their realization is discussed. Additive technologies enable the fabrication of multiplication mixers, which overcome shortcomings of current pillar or curve-based techniques and enable efficient mixing, also of biological cells without affecting viability. Using standard microfluidic components and state-of-the art 3D printing technologies, we realize a separation system based on Dean flow fragmentation without the use of PDMS. In particular, we describe the use of a 3D-printed helix for winding a capillary for particle flow and a new chip design for particle separation at the outlet. We demonstrate the functionality of the system by successful isolation of ~12 µm-sized particles from a particle mixture containing large (~12 µm, typical size of eukaryotic cells) and small (~2 µm, typical size of bacteria or small yeasts) particles. Using this setup to separate eukaryotic cells from bacteria, we could prove that cell viability is not affected by passage through the microfluidic systems.

Abstract Three‐dimensional (3D) printing is an emerging technique that has shown promising success in engineering human tissues in recent years. Further development of vat‐photopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and components. Similarly, the development of microfluidic chip systems is an emerging research sector with promising medical applications. This work demonstrates the coupling of a digital light processing (DLP) printing procedure with a microfluidic chip system to produce size‐tunable, 3D‐printable porosities with narrow pore size distributions within a gelatin methacryloyl (GelMA) hydrogel matrix. It is found that the generation of size‐tunable gas bubbles trapped within an aqueous GelMA hydrogel‐precursor can be controlled with high precision. Furthermore, the porosities are printed in two‐dimensional (2D) as well as in 3D using the DLP printer. In addition, the cytocompatibility of the printed porous scaffolds is investigated using fibroblasts, where high cell viabilities as well as cell proliferation, spreading, and migration are confirmed. It is anticipated that the strategy is widely applicable in a range of application areas such as tissue engineering and regenerative medicine, among others.

Sensing technology is receiving increasing attention and improvements every day, making it a suggested component of personalized healthcare management. This is due to the capabilities of organometallic compounds supported by bioengineering. Organometallic compounds have abundant biological activity and many industrial and material science applications. Due to their unique biological targetability, they possess potential applications in drug development, diagnosis, and treatment. Organometallic compounds are emerging as promising candidates for the advancement in sensor technology as they are engineered to address some of the limitations encountered by their traditional counterparts. These compounds have distinctive characteristics that render them exceptionally responsive to alterations in their surroundings, hence enabling their use as sensors for the detection of diverse chemicals or circumstances. In addition, the adaptability of organometallic compounds allows for their incorporation into various sensor platforms, rendering them appropriate for a diverse array of applications such as environmental surveillance, medical analysis, and industrial assurance of quality. This review presents an overview of the recent progress made in the field of organometallic compounds’ design and production, specifically focusing on their potential uses as sensors. In addition, the structural modifications, functionalization procedures, integration of microfluidics, and the consequent effects on the sensing capacities of the materials are recalled. These bio-based approaches will align with sustainability objectives and make sensing more affordable, applicable, and successful.

Microfluidics, also known as lab-on-a-chip or micro total analysis systems, can precisely regulate and manipulate micro-sized fluids. They have great potential in biology, chemistry, and medicine, as well as other fields of science. By definition, microfluidic devices operate with small-volume samples and small reactant quantities, which renders them both efficient and affordable. However, such small objects have very demanding requirements for the utilized optical detection system. Due to the specifics of those devices, monitoring the results of experiments is carried out with commercial inverted optical microscopes. Unfortunately, that type of optical device is still expensive. In this article, we present a truly functional, inexpensive, standalone, three-dimensionally printed, and inverted microscope, including the design, engineering, and manufacturing process and some of the experiments that have been conducted with it. Finally, we summarize the advantages of this three-dimensionally printed microscope (including the total fabrication costs) and the future improvements that will be introduced to it.

Sepsis, a life-threatening condition resulting from a failing host response to infection, causes millions of deaths annually, necessitating rapid and simple prognostic assessments. A variety of genomic and proteomic biomarkers have been developed for sepsis. For example, it has been shown that the level of plasma cell-free DNA (cfDNA) and circulating histones increases considerably during sepsis, and they are linked with sepsis severity and mortality. Developing a diagnostic tool that is capable of assessing such diverse biomarkers is challenging as the detection methodology is quite different for each. Here, a fully integrated microfluidic device capable of detecting a genomic biomarker (cfDNA) and a proteomic biomarker (total circulating histones) using a common detection platform has been demonstrated. The microfluidic device utilizes dehydrated agarose gates loaded with pH-specific agarose to electrophoretically trap cfDNA and histones at their respective isoelectric points. It also incorporates fluorescent dyes within the device, eliminating the need for off-chip sample preparation and allowing the direct testing of plasma samples without the need for labeling DNA and histones with fluorescent dyes beforehand. Xurography, which is a low-cost and rapid method for fabrication of microfluidics, is used in all the fabrication steps. Experimental results demonstrate the effective accumulation and separation of cfDNA and histones in the agarose gates in a total processing time of 20 min, employing 10 and 30 Volts for cfDNA and histone accumulation and detection, respectively. The device can potentially be used to distinguish between the survivors and non-survivors of sepsis. The integration of the detection of both biomarkers into a single device and dye immobilization enhances its clinical utility for rapid point-of-care assessment of sepsis prognosis.

It is well established that the chemistry in microdroplets has been found to be radically different from reactions in bulk, particularly in the case of water. It has also been established that there is a threshold size for microdroplets to behave differently than droplets near the 10 µm diameter range. We present a three-dimensional electrostatic treatment in the spirit of the Gouy–Chapman model for double layers at interfaces. Our treatment predicts a strong concentration of charged molecules toward the surface of the droplet. As the droplet size deceases, the majority of the volume of the liquid experiences a large DC electric field. Such electric fields are highly unusual in a conducting fluid such as water. We believe that this unique environment helps to explain the reaction rate acceleration and new chemistry that have been observed in microdroplets compared to bulk phase. [ABSTRACT FROM AUTHOR]

Developing effective strategies for the flexible control of fluid is vital for microfluidic electrochemical biosensing. In this study, a gigahertz (GHz) acoustic streaming (AS) based sonoelectrochemical system was developed to realize an on-chip surface modification and sensitive hydrogen peroxide (H2O2) detection from living cells. The flexible and controlled fluid surrounding the electrochemical chip was optimized theoretically and applied in the sonoelectrochemical deposition of Au nanoparticles (AuNPs) first. Under the steady and fast flow stimulus of AS, AuNPs could be synthesized with a smaller and evener size distribution than the normal condition, allowing AuNPs to show an excellent peroxidase-like activity. Moreover, the AS also accelerated the mass transport of target molecules and improved the catalytic rate, leading to the enhancement of H2O2 detection, with an extremely low detection limit of 32 nM and a high sensitivity of 4.34 μA/ (mM·mm2). Finally, this system was successfully applied in tracking H2O2 release from different cell lines to distinguish the cancer cells from normal cells. This study innovatively integrated the surface modification and molecules detection process on a chip, and also proposed a simple but sensitive platform for microfluidic biosensing application.

High‐strength and high‐toughness bio‐based fibers attract broad interest in biomechanical applications. Herein, strong and tough organic–inorganic regenerated silk fibroin/hydroxyapatite (RSF/HAP) hybrid fibers are prepared using a single‐channel microfluidic device. Calcium phosphate oligomers (CPOs) dispersed in the RSF matrix first grow into spherical amorphous calcium phosphates (ACPs), which then crystallize into needle‐like HAPs under a humidity condition, mimicking the biomineralization in collagen bundles. HAPs are better aligned along the RSF/HAP fiber direction after poststretching, forming a highly ordered and densely packed microstructure within the fiber and thus facilitating highly dense noncovalent interactions between rigid inorganic HAP nanocrystals and flexible organic RSF matrix. The highly dense noncovalent interactions endow the organic–inorganic hybrid fibers with superior mechanical properties and twisted RSF/HAP fiber bundles demonstrate a remarkable tensile strength of 778 MPa, a high Young's modulus of 17.8 GPa, a large tensile strain of 19.9%, and an excellent toughness of 121 MJ m−3 after proper twisting treatments. RSF/HAP hybrid fibers also show good performances against static loading, dynamic impact, and extreme cold condition and they can maintain their mechanical properties down to −50 °C. Therefore, the fibers are strong and tough and the strategy is facile and efficient.

Abstract Functional polymer microspheres have broad application prospects in various fields, such as metal ion detection, adsorption, separation, and controlled drug release. However, integrating different functions in a single microsphere system is a significant challenge in this field. In this work, we prepared multicompartmental emulsion droplets utilizing microfluidic technology. Fe3O4 magnetic nanoparticles were added to one of the compartments of the emulsion droplets as functional particles, and Janus microspheres were obtained after curing. Fluorescent probes enter the two compartments of the Janus microspheres by diffusion. The fluorescence changes of the microspheres were observed in situ and captured through a fluorescence microscope. The images are processed by image recognition software and a Python program. The “fingerprint” of the detected metal ions is obtained by dimensionality reduction of the data through Principal Component Analysis. We employ different algorithms to build Machine Learning models for predicting the metal ion species and concentration. The variation of fluorescence intensity of the three fluorescent probes and the corresponding R, G, and B channel values and time are used as descriptors. The results show that the Random Forest, K‐neighborhood (KNN), and Neural Network models demonstrated a better predicted effect with a variance (R2) greater than 0.9 and a smaller root mean square error; among them, the KNN model predicted the most accurate results.

Understanding the effects of inflammation and cirrhosis on the regulation of drug metabolism during the progression of hepatocellular carcinoma (HCC) is critical for developing patient‐specific treatment strategies. Herein, novel 3D vascularized HCC on chips (HCCoCs), composed of HCC, endothelial, stellate, and Kupffer cells tuned to mimic normal or cirrhotic liver stiffness, are created. HCC inflammation is controlled by tuning Kupffer macrophage numbers, and the impact of cytochrome P450‐3A4 (CYP3A4) is investigated by culturing HepG2 HCC cells transfected with CYP3A4 to upregulate expression from baseline. This model allows for the simulation of chemotherapeutic delivery methods such as intravenous injection and transcatheter arterial chemoembolization (TACE). It is shown that upregulation of metabolic activity, incorporation of cirrhosis and inflammation, increases vascular permeability due to upregulated inflammatory cytokines leading to significant variability in chemotherapeutic treatment efficacy. Specifically, it is shown that further modulation of CYP3A4 activity of HCC cells by TACE delivery of doxorubicin provides an additional improvement to treatment response and reduces chemotherapy‐associated endothelial porosity increase. The HCCoCs are shown to have utility in uncovering the impact of the tumor microenvironment during cancer progression on vascular properties, tumor response to therapeutics, and drug delivery strategies.

Manipulation of micro-objects have been playing an essential role in biochemical analysis or clinical diagnostics. Among the diverse technologies for micromanipulation, acoustic methods show the advantages of good biocompatibility, wide tunability, a label-free and contactless manner. Thus, acoustic micromanipulations have been widely exploited in micro-analysis systems. In this article, we reviewed the acoustic micromanipulation systems that were actuated by sub-MHz acoustic waves. In contrast to the high-frequency range, the acoustic microsystems operating at sub-MHz acoustic frequency are more accessible, whose acoustic sources are at low cost and even available from daily acoustic devices (e.g. buzzers, speakers, piezoelectric plates). The broad availability, with the addition of the advantages of acoustic micromanipulation, make sub-MHz microsystems promising for a variety of biomedical applications. Here, we review recent progresses in sub-MHz acoustic micromanipulation technologies, focusing on their applications in biomedical fields. These technologies are based on the basic acoustic phenomenon, such as cavitation, acoustic radiation force, and acoustic streaming. And categorized by their applications, we introduce these systems for mixing, pumping and droplet generation, separation and enrichment, patterning, rotation, propulsion and actuation. The diverse applications of these systems hold great promise for a wide range of enhancements in biomedicines and attract increasing interest for further investigation.

Effective filling materials, typically bone cements, are essential for providing mechanical support during bone fracture treatment. A current challenge with bone cement lies in achieving continuous drug release and forming porous structures that facilitate cell migration and enhance osteoconductivity. We report a droplet microfluidics-based method for synthesizing uniform-sized gelatin hydrogel beads. A high hydrogel concentration and increased crosslinking levels were found to enhance drug loading as well as release performance. Consequently, the droplet microfluidic device was optimized in its design and fabrication to enable the stable generation of uniform-sized droplets from high-viscosity gelatin solutions. The size of the generated beads can be selectively controlled from 50 to 300 μm, featuring a high antibiotic loading capacity of up to 43% dry weight. They achieve continuous drug release lasting more than 300 h, ensuring sustained microbial inhibition with minimal cytotoxicity. Furthermore, the hydrogel beads are well suited for integration with calcium phosphate cement, maintaining structural integrity to form porous matrices and improve continuous drug release performance. The uniform size distribution of the beads, achieved through droplet microfluidic synthesis, ensures predictable drug release dynamics and a measurable impact on the mechanical properties of bone cements, positioning this technology as a promising enhancement to bone cement materials.

Aqueous phase pH is a critical metric with significant importance in understanding reactive transport processes in porous media. At the microscale, however, traditional pH detection methods face challenges in capturing dynamic pH due to limited sample volume and sensing time. To overcome these limitations, we leveraged micro/nanofabrication techniques to create a microfluidic porous medium coated with polyaniline (PAni) on its surface. Using this innovative microfluidic design, we achieved colorimetric delineation of pH spatial distribution with fast response and robustness in porous media. By conducting coinjection tests with hydrochloric acid (pH = 2) and DI water (pH ≈ 5.8, equilibrated with air) at various flow rates and relative flow rate ratios in a sandstone-patterned microfluidic device, we observed dynamic pH changes in porous media and obtained a comprehensive understanding of the acid advection-diffusion dynamics. The results highlighted the capability of PAni to enable microscale pH sensing. This research contributes to the development of advanced porous media microfluidics and applications, particularly in mass transfer limits during reactive transport of carbon dioxide sequestration and geological hydrogen storage.

Magnetic fluids were historically the first active nano-dispersion material. Despite over half a century of research, interest in these nano-objects continues to grow every year. This is due to the impressive development of nanotechnology, the synthesis of nanoscale structures, and surface-active systems. The unique combination of fluidity and magnetic response allows magnetic fluids to be used in engineering devices and biomedical applications. In this review, experimental results and fundamental theoretical approaches are systematized to predict the micro- and macroscopic behavior of magnetic fluid systems under different external influences. The article serves as working material for both experienced scientists in the field of magnetic fluids and novice specialists who are just beginning to investigate this topic.

We demonstrated resonance-based detection of magnetic nanoparticles employing novel designs based upon planar (on-chip) microresonators that may serve as alternatives to conventional magnetoresistive magnetic nanoparticle detectors. We detected 130 nm sized magnetic nanoparticle clusters immobilized on sensor surfaces after flowing through PDMS microfluidic channels molded using a 3D printed mold. Two detection schemes were investigated: (i) indirect detection incorporating ferromagnetic antidot nanostructures within microresonators, and (ii) direct detection of nanoparticles without an antidot lattice. Using scheme (i), magnetic nanoparticles noticeably downshifted the resonance fields of an antidot nanostructure by up to 207 G. In a similar antidot device in which nanoparticles were introduced via droplets rather than a microfluidic channel, the largest shift was only 44 G with a sensitivity of 7.57 G/ng. This indicated that introduction of the nanoparticles via microfluidics results in stronger responses from the ferromagnetic resonances. The results for both devices demonstrated that ferromagnetic antidot nanostructures incorporated within planar microresonators can detect nanoparticles captured from dispersions. Using detection scheme (ii), without the antidot array, we observed a strong resonance within the nanoparticles. The resonance’s strength suggests that direct detection is more sensitive to magnetic nanoparticles than indirect detection using a nanostructure, in addition to being much simpler.

Microfluidic methods for the synthesis of nanomaterials allow the generation of high-quality products with outstanding structural, electronic and optical properties. At a fundamental level, this is engendered by the ability to control both heat and mass transfer in a rapid and precise manner, but also by the facile integration of in-line characterization tools and machine learning algorithms. Such integrated platforms provide for exquisite control over material properties during synthesis, accelerate the optimization of electronic and optical properties and bestow new insights into the optoelectronic properties of nanomaterials. Herein, we present a brief perspective on the role that microfluidic technologies can play in nanomaterial synthesis, with a particular focus on recent studies that incorporate in-line optical characterization and machine learning. We also consider the importance and challenges associated with integrating additional functional components within experimental workflows and the upscaling of microfluidic platforms for production of industrial-scale quantities of nanomaterials.

The popularity of microflow chemistry has skyrocketed in the last 20 years, more and more chemists are switching from macro-batch reactors to miniaturized flow devices. As a result, microfluidics is paving its way into the future by consolidating its position in organic chemistry not only as a trend but as a new, effective, and sustainable way of conducting chemistry, that clearly will continue to grow and evolve. This perspective highlights the most relevant examples of innovative enhancing technologies applied to microflow reactors aimed to improve and intensify chemical processes. The extensive applicability of microflow chemistry is further illustrated by briefly discussing examples of complex integrated microsystems and scale-up technologies, demonstrating ultimately that microflow chemistry has the potential to become the ideal technology for the future.

Acoustic streaming (AS) is the steady time-averaged flow generated by acoustic field, which has been widely used in enhancing mixing and particle manipulation. Current researches on acoustic streaming mainly focus on Newtonian fluids, while many biological and chemical solutions exhibit non-Newtonian properties. The acoustic streaming in viscoelastic fluids has been studied experimentally for the first time in this paper. We found that the addition of polyethylene oxide (PEO) polymer to the Newtonian fluid significantly altered the flow characteristics in the microchannel. The resulting acousto-elastic flow showed two modes: positive mode and negative mode. Specifically, the viscoelastic fluids under acousto-elastic flow exhibit mixing hysteresis features at low flow rates, and degeneration of flow pattern at high flow rates. Through quantitative analysis, the degeneration of flow pattern is further summarized as time fluctuation and spatial disturbance range reduction. The positive mode in acousto-elastic flow can be used for the mixing enhancement of viscoelastic fluids in the micromixer, while the negative mode provides a potential method for particle/cell manipulation in viscoelastic body fluids such as saliva by suppressing unstable flow.

Gelatin methacryloyl (GelMA) is widely used for the formulation of hydrogels in diverse biotechnological applications. After the derivatization of raw gelatin, the degree of functionalization (DoF) is an attribute of particular interest as the functional residues are necessary for crosslinking. Despite progress in the optimization of the process found in the literature, a comparison of the effect of raw gelatin on the functionalization is challenging as various approaches are employed. In this work, the modification of gelatin was performed at room temperature (RT), and eight different gelatin products were employed. The DoF proved to be affected by the bloom strength and by the species of gelatin at an equal reactant ratio. Furthermore, batch-to-batch variability of the same gelatin source had an effect on the produced GelMA. Moreover, the elasticity of GelMA hydrogels depended on the DoF of the protein as well as on bloom strength and source of the raw material. Additionally, GelMA solutions were used for the microfluidic production of droplets and subsequent crosslinking to hydrogel. This process was developed as a single pipeline at RT using protein concentrations up to 20% (w/v). Droplet size was controlled by the ratio of the continuous to dispersed phase. The swelling behavior of hydrogel particles depended on the GelMA concentration.

Monodispersed polyethylene glycol diacrylate (PEGDA)/acrylic acid (AA) microgels with a tuneable negative charge and macroporous internal structure have been produced using a Lego-inspired droplet microfluidic device. The surface charge of microgels was controlled by changing the content of AA in the monomer mixture from zero (for noncharged PEGDA beads) to 4 wt%. The macroporosity of the polymer matrix was introduced by adding 20 wt% of 600-MW polyethylene glycol (PEG) as a porogen material into the monomer mixture. The porogen was successfully leached out with acetone after UV-crosslinking, which resulted in micron-sized cylindrical pores with crater-like morphology, uniformly arranged on the microgel surface. Negatively charged PEGDA/AA beads showed improved adsorption capacity towards positively charged organic dyes (methylene blue and rhodamine B) compared to neutral PEGDA beads and high repulsion of negatively charged dye molecules (methyl orange and congo red). Macroporous microgels showed better adsorption properties than nonporous beads, with a maximum adsorption capacity towards methylene blue of 45 mg/g for macroporous PEGDA/AA microgels at pH 8.6, as compared to 23 mg/g for nonporous PEGDA/AA microgels at the same pH. More than 98% of Cu(II) ions were removed from 50 ppm solution at pH 6.7 using 2.7 mg/mL of macroporous PEGDA/AA microgel. The adsorption of cationic species was significantly improved when pH was increased from 3 to 9 due to a higher degree of ionization of AA monomeric units in the polymer network. The synthesized copolymer beads can be used in drug delivery to achieve improved loading capacity of positively charged therapeutic agents and in tissue engineering, where a negative charge of scaffolds coupled with porous structure can help to achieve improved permeability of high-molecular-weight metabolites and nutrients, and anti-fouling activity against negatively charged species.

This study proposes a redesign of asymmetric single-chamber microbial fuel cells (a-SCMFCs) with the goal of optimizing energy production. In the present work, the new approach is based on the introduction of a novel intermediate microfluidic septum (IMS) inside the electrolyte chamber. This IMS was designed as a relatively simple and inexpensive method to optimize both electrolyte flow and species transfer inside the devices. a-SCMFCs, featuring the IMS, are compared to control cells (IMS-less), when operated with sodium acetate as the carbon energy source. Performances of cells are evaluated in terms both of maximum output potential achieved, and energy recovery (Erec) as the ratio between the energy yield and the inner electrolyte volume. The a-SCMFCs with the novel IMS are demonstrated to enhance the energy recovery compared to control cells exhibiting Erec values of (37 ± 1) J/m3, which is one order of magnitude higher than that achieved by control cells (3.0 ± 0.3) J/m3. Concerning the maximum output potential, IMS cells achieve (2.8 ± 0.2) mV, compared to control cells at (0.68 ± 0.07) mV. Furthermore, by varying the sodium acetate concentration, the Erec and maximum potential output values change accordingly. By monitoring the activity of a-SCMFCs for over one year, the beneficial impact of the IMS on both the initial inoculation phase and the long-term stability of electrical performance are observed. These improvements support the effectiveness of IMS to allow the development of efficient biofilms, likely due to the reduction in oxygen cross-over towards the anode. Electrochemical characterizations confirm that the presence of the IMS impacts the diffusion processes inside the electrolytic chamber, supporting the hypothesis of a beneficial effect on oxygen cross-over.

Hydrogel droplets are biodegradable and biocompatible materials with promising applications in tissue engineering, cell encapsulation, and clinical treatments. They represent a well-controlled microstructure to bridge the spatial divide between two-dimensional cell cultures and three-dimensional tissues, toward the recreation of entire organs. The applications of hydrogel droplets in regenerative medicine require a thorough understanding of microfluidic techniques, the biocompatibility of hydrogel materials, and droplet production and manipulation mechanisms. Although hydrogel droplets were well studied, several emerging advances promise to extend current applications to tissue engineering and beyond. Hydrogel droplets can be designed with high surface-to-volume ratios and a variety of matrix microstructures. Microfluidics provides precise control of the flow patterns required for droplet generation, leading to tight distributions of particle size, shape, matrix, and mechanical properties in the resultant microparticles. This review focuses on recent advances in microfluidic hydrogel droplet generation. First, the theoretical principles of microfluidics, materials used in fabrication, and new 3D fabrication techniques were discussed. Then, the hydrogels used in droplet generation and their cell and tissue engineering applications were reviewed. Finally, droplet generation mechanisms were addressed, such as droplet production, droplet manipulation, and surfactants used to prevent coalescence. Lastly, we propose that microfluidic hydrogel droplets can enable novel shear-related tissue engineering and regeneration studies.

A significant growth of research on digital microfluidics has been achieved over the past several decades, and the field is still attracting increasing attention for fulfilling relevant mechanisms and potential applications. Numerous studies have been devoted to actively manipulating droplets in a variety of fundamental and applicational scenarios. In this work, the deformation of ferromagnetic fluid droplets is studied under an external uniform magnetic field. The droplets are precisely dispersed on the bottom surface of a container assembled with polymer methacrylate (PMMA) plates. Mineral oil is applied instead of air as the surrounding medium for easy stretching and preventing water solvent evaporation in ferrofluid. The design and processing of the container are firstly carried out to observe the shape and characterize the wettability of the droplets in the immiscible mineral oil medium. Furthermore, the droplets’ deformation and the working mechanism are given under the action of the horizontal uniform magnetic field. At different magnetic field intensities, the droplet is stretched in the horizontal direction parallel to the applied field. Due to volume conservation, the dimension in the height reduces correspondingly. With the coupling effect of magnetic force, viscous force and interfacial tension, the contact angle first increases with the magnetic field and then basically remains unchanged upon magnetization saturation. Consistent with the experimental results, the numerical method clearly reveals the field coupling mechanism and the nonlinear deformation of the sessile droplet.

Abstract Organ‐on‐a‐chip (OOC) platforms recapitulate human in vivo‐like conditions more realistically compared to many animal models and conventional two‐dimensional cell cultures. OOC setups benefit from continuous perfusion of cell cultures through microfluidic channels, which promotes cell viability and activities. Moreover, microfluidic chips allow the integration of biosensors for real‐time monitoring and analysis of cell interactions and responses to administered drugs. Three‐dimensional (3D) bioprinting enables the fabrication of multicell OOC platforms with sophisticated 3D structures that more closely mimic human tissues. 3D‐bioprinted OOC platforms are promising tools for understanding the functions of organs, disruptive influences of diseases on organ functionality, and screening the efficacy as well as toxicity of drugs on organs. Here, common 3D bioprinting techniques, advantages, and limitations of each method are reviewed. Additionally, recent advances, applications, and potentials of 3D‐bioprinted OOC platforms for emulating various human organs are presented. Last, current challenges and future perspectives of OOC platforms are discussed.

Abstract Drugs are metabolized within the liver (pH 7.4) by phase I and phase II metabolism. During the process, reactive metabolites can be formed that react covalently with biomolecules and induce toxicity. Identifying and detecting reactive metabolites is an important part of drug development. Preclinical and clinical investigations are conducted to assess the toxicity and safety of a new drug candidate. Electrochemistry coupled to mass spectrometry is an ideal complementary technique to the current preclinical studies, a pure instrumental approach without any purification steps and tedious protocols. The combination of microfluidics with electrochemistry towards the mimicry of drug metabolism offers portability, low volume of reagents and faster reaction times. This review explores the development of microfluidic electrochemical cells for mimicking drug metabolism.

Abstract The aim of our work was to develop a low-cost, portable device for the fast and easy determination of total protein content by using PDMS-based lab-in-a-syringe technology with removal of 3D-printed channels. We proposed two designs with a one-step PDMS curing and a two-step PDMS-curing fabrication procedure. The one-step PDMS microdevices were found to be the best in the view of preparation, repeatability, and stability of the reagent. This design was then applied for the determination of total protein content in biomedical products using the Bradford assay.

The microfluidics of magnetic fluids is gaining popularity due to the possibility of the non-contact control of liquid composite systems using a magnetic field. The dynamics of non-magnetic droplets and gas bubbles in magnetic fluids were investigated for various configurations of magnetic fields, coatings, and channel geometries, as well as the rate of component supply and their physical properties. Optimal regimes for forming droplet and bubble flows were determined. The mechanism for non-contact control of the size of droplets and bubbles using a magnetic field is proposed in this article. The dependences of the sizes of non-magnetic inclusions in magnetic liquids on the continuous phase flow rate and the displacement of magnets were obtained. The obtained dependences of the volume of non-magnetic inclusions on the flow rate of the continuous phase follow the classic dependences. Changing the size of air bubbles can be achieved by shifting the magnet from −5 mm to +2 mm. The ratio of the maximum and minimum breakaway inclusion varies from 5 to 2 depending on the flow rates of the continuous phase. The range of changing the size of oil droplets with the displacement of magnets is from 1.1 to 1.51. These studies show how, with the help of various mechanisms of influence on microfluidic flows, it is possible to control the size of bubbles and droplets forming in microchannels. The obtained data can be applied for controlled microfluidic dosing and counting devices.

Innovative materials are needed to produce scaffolds for various tissue engineering and regenerative medicine (TERM) applications, including tissue models. Materials derived from natural sources that offer low production costs, easy availability, and high bioactivity are highly preferred. Chicken egg white (EW) is an overlooked protein-based material. Whilst its combination with the biopolymer gelatin has been investigated in the food technology industry, mixed hydrocolloids of EW and gelatin have not been reported in TERM. This paper investigates these hydrocolloids as a suitable platform for hydrogel-based tissue engineering, including 2D coating films, miniaturized 3D hydrogels in microfluidic devices, and 3D hydrogel scaffolds. Rheological assessment of the hydrocolloid solutions suggested that temperature and EW concentration can be used to fine-tune the viscosity of the ensuing gels. Fabricated thin 2D hydrocolloid films presented globular nano-topography and in vitro cell work showed that the mixed hydrocolloids had increased cell growth compared with EW films. Results showed that hydrocolloids of EW and gelatin can be used for creating a 3D hydrogel environment for cell studies inside microfluidic devices. Finally, 3D hydrogel scaffolds were fabricated by sequential temperature-dependent gelation followed by chemical cross-linking of the polymeric network of the hydrogel for added mechanical strength and stability. These 3D hydrogel scaffolds displayed pores, lamellae, globular nano-topography, tunable mechanical properties, high affinity for water, and cell proliferation and penetration properties. In conclusion, the large range of properties and characteristics of these materials provide a strong potential for a large variety of TERM applications, including cancer models, organoid growth, compatibility with bioprinting, or implantable devices.