Flexible liquid-diode microtubes from multimodal microfluidics.

Directional transport of liquids is of great importance in energy saving, chemical/biomedical engineering, and microfluidics applications. Despite considerable progress in engineering different open surfaces to achieve liquid manipulation, the realization of diode-like liquid transport in enclosed spaces is still challenging. Here, a flexible diode microtube is presented for directional liquid transport within confined spaces using pulsed microfluidics. The microtubes exhibit sophisticated microstructures on the inner wall, replicated from a precisely controlled flow configuration in the microfluidic channel. Under the effect of asymmetric pinning and unbalanced Laplace pressure, such microtubes enable directional liquid transport in closed channels. More importantly, by integrating in situ flow lithography with the microfluidic system, segmented liquid diodes are fabricated as assembly units for the construction of fluidic-electronic circuits that perform logic operations. These results demonstrate the capacity of the present liquid-diode microtubes for flexible, directional, and programmable liquid transport. We believe that it can open an avenue for designing advanced fluidic circuit-based devices toward versatile practical applications.

Cholesteric cellulose liquid crystal ink for three-dimensional structural coloration.

SignificanceWe propose a printable structural color ink composed of cholesteric cellulose liquid crystals together with gelatin and a thermal-responsive hydrogel. The ink is endowed with vivid structural colors and printability due to its constituents. Based on this, we print a series of graphics and three-dimensional (3D) objects with vivid color appearances. Moreover, the printed objects possess dual thermal responsiveness, which results in visible color change around body temperature. These performances, together with the biocompatibility of the constituents, indicate that the present ink represents a leap forward to the next-generation 3D printing and would unlock a wide range of real-life applications.

Scalable Production of Biomedical Microparticles via High-Throughput Microfluidic Step Emulsification.

Drug microcarriers are widely used in disease treatment, and microfluidics is well established in the preparation of microcarrier particles. A proper design of the microfluidic platform toward scalable production of drug microcarriers can extend its application values in wound healing, where large numbers of microcarriers are required. Here, a microfluidic step emulsification method for the preparation of monodisperse droplets is presented. The droplet size depends primarily on the microchannel depth rather than flow rate, making the system robust for high-throughput production of droplets and hydrogel microparticles. Based on this platform, basic fibroblast growth factor (bFGF) is uniformly encapsulated in the microparticles, and black phosphorus (BP) is incorporated for controllable release via near-infrared (NIR) stimulation. The microparticles serve as drug carriers to be applied to the wound site, inducing angiogenesis and collagen deposition, thereby accelerating wound repair. These results indicate that the step emulsification technique provides a promising solution to scalable production of drug microcarriers for wound healing as well as tissue regeneration.

Adhesive Composite Microspheres with Dual Antibacterial Strategies for Infected Wound Healing.

Skin damage and infection pose a severe challenge to human health. Construction of a novel versatile dressing with good anti-infection and healing-promoting abilities is greatly expected. In this paper, nature-source-based composite microspheres with dual antibacterial mechanisms and bioadhesive features by microfluidics electrospray for infected wound healing is developed. The microspheres enable sustained release of copper ions, which not only show long-term antibacterial properties, but also play important role in wound-healing-related angiogenesis. Additionally, the microspheres are coated with polydopamine via self-polymerization, which renders the microspheres adhesive to the wound surface, and further enhance the antibacterial ability through photothermal energy conversion. Based on the dual antibacterial strategies provided by copper ions and polydopamine as well as the bioadhesive property, the composite microspheres exhibit excellent anti-infection and wound healing performances in a rat wound model. These results, along with the nature-source-based composition and biocompatibility, indicate the great potential of the microspheres in clinical wound repair.

Microfluidics for Drug Development: From Synthesis to Evaluation.

Drug development is a long process whose main content includes drug synthesis, drug delivery, and drug evaluation. Compared with conventional drug development procedures, microfluidics has emerged as a revolutionary technology in that it offers a miniaturized and highly controllable environment for bio(chemical) reactions to take place. It is also compatible with analytical strategies to implement integrated and high-throughput screening and evaluations. In this review, we provide a comprehensive summary of the entire microfluidics-based drug development system, from drug synthesis to drug evaluation. The challenges in the current status and the prospects for future development are also discussed. We believe that this review will promote communications throughout diversified scientific and engineering communities that will continue contributing to this burgeoning field.

Spatial confinement toward creating artificial living systems.

Lifeforms are regulated by many physicochemical factors, and these factors could be controlled to play a role in the construction of artificial living systems. Among these factors, spatial confinement is an important one, which mediates biological behaviors at multiscale levels and participates in the biomanufacturing processes accordingly. This review describes how spatial confinement, as a fundamental biological phenomenon, provides cues for the construction of artificial living systems. Current knowledge about the role of spatial confinement in mediating individual cell behavior, collective cellular behavior, and tissue-level behavior are categorized. Endeavors on the synthesis of biomacromolecules, artificial cells, engineered tissues, and organoids in spatially confined bioreactors are then emphasized. After that, we discuss the cutting-edge applications of spatially confined artificial living systems in biomedical fields. Finally, we conclude by assessing the remaining challenges and future trends in the context of fundamental science, technical improvement, and practical applications.

Noninvasive Multiplexed Analysis of Bladder Cancer-Derived Urine Exosomes via Janus Magnetic Microspheres.

Bladder cancer greatly endangers human health, and its early diagnosis is of vital importance. Exosomes, which contain proteins and nucleic acids related to their source cells, are expected to be an emerging biomarker for bladder cancer detection. Here, we propose a novel system for multiplexed analysis of bladder cancer-derived urine exosomes based on Janus magnetic microspheres as barcoded microcarriers. The microcarriers are constructed by droplet-templated coassembly of colloidal silica nanoparticles and magnetic nanoparticles under a magnetic field. The microcarriers possess one hemisphere with structural color and the other hemisphere with magneto-responsiveness. Benefiting from the unique structure, these Janus microcarriers could serve as barcodes and could move controllably in a sample solution, thus realizing the multiplex detection of exosomes with high sensitivity. Notably, the present platform is noninvasive since a urine specimen, as an ideal source of bladder cancer-derived exosomes, is employed as the sample solution. This feature, together with the good sensitivity, specificity, low sample consumption, and easy operation, indicates the great potential of the platform for bladder cancer diagnosis in clinical applications.

Smart Film Actuators for Biomedical Applications.

Taking inspiration from the extremely flexible motion abilities in natural organisms, soft actuators have emerged in the past few decades. Particularly, smart film actuators (SFAs) demonstrate unique superiority in easy fabrication, tailorable geometric configurations, and programmable 3D deformations. Thus, they are promising in many biomedical applications, such as soft robotics, tissue engineering, delivery system, and organ-on-a-chip. In this review, the latest achievements of SFAs applied in biomedical fields are summarized. The authors start by introducing the fabrication techniques of SFAs, then shift to the topology design of SFAs, followed by their material selections and distinct actuating mechanisms. After that, their biomedical applications are categorized in practical aspects. The challenges and prospects of this field are finally discussed. The authors believe that this review can boost the development of soft robotics, biomimetics, and human healthcare.

Biomimic Trained Immunity-MSCs Delivery Microcarriers for Acute Liver Failure Regeneration.

Mesenchymal stem cells (MSCs) have a demonstrated value for acute liver failure (ALF) regeneration, while their delivery stratagems with long-term biological functions, low immune response, and high biocompatibility are still a challenge. Here, a lipopolysaccharide (LPS)-loaded photoresponsive cryogel porous microcarrier (CPM) for MSCs delivery and colonization is presented to promote defect liver regeneration. The CPMs are fabricated with graphene oxide, poly(N-isopropylacrylamide), and gelatin methacrylate (GelMA) via droplet microfluidic technology and a gradient-cooling procedure. Benefitting from the biocompatible GelMA component and the porous microstructure of the CPMs, MSCs can be nondestructively captured and abundantly delivered. Because the LPS can be released from the CPMs under NIR irradiation, the delivered MSCs are imparted with the feature of "trained immunity." Thus, when the MSCs-laden CPMs are tailored into the liver matched patches by bioprinting and applied in ALF rats, they display superior anti-inflammatory and more significant liver regeneration properties than the untrained MSCs. These features make the CPMs an excellent MSCs delivery system for clinical applications in tissue repair.

Programmable Knot Microfibers from Piezoelectric Microfluidics.

Microfibers have demonstrated significant application values in a large number of areas. Current efforts focus on developing new technologies to prepare microfibers with controllable morphological and structural features to enhance their functions. Here, a piezoelectric microfluidic platform is presented for consecutive spinning of functional microfibers with programmable spindle-knots. In this platform, a jet of a pregel-solution flowing in the channel can be subjected to a programmable piezoelectric signal and vibrates synchronously. Following a rapid polymerization of the wavy jet, microfibers with corresponding morphologies can be generated, including uniform, gradient, and symmetrical knots. Such a unique knot structure contributes to a water-collection mechanism. Thus, it has been observed that microfibers with programmed knots enable even more flexible droplet handling and active water transport. In addition, by constructing higher-order knot fiber networks, practical applications including spray reaction, lab-on-a-chip vapor detection, etc., can also be demonstrated. it is believed that this platform opens a new avenue for fiber spinning, and the programmable microfibers would be highly applicable in chemical, biomedical, and environmental areas.

Bio-inspired self-healing structural color hydrogel.

Biologically inspired self-healing structural color hydrogels were developed by adding a glucose oxidase (GOX)- and catalase (CAT)-filled glutaraldehyde cross-linked BSA hydrogel into methacrylated gelatin (GelMA) inverse opal scaffolds. The composite hydrogel materials with the polymerized GelMA scaffold could maintain the stability of an inverse opal structure and its resultant structural colors, whereas the protein hydrogel filler could impart self-healing capability through the reversible covalent attachment of glutaraldehyde to lysine residues of BSA and enzyme additives. A series of unprecedented structural color materials could be created by assembling and healing the elements of the composite hydrogel. In addition, as both the GelMA and the protein hydrogels were derived from organisms, the composite materials presented high biocompatibility and plasticity. These features of self-healing structural color hydrogels make them excellent functional materials for different applications.

Hollow Colloid Assembled Photonic Crystal Clusters as Suspension Barcodes for Multiplex Bioassays.

Barcode particles have a demonstrated value for multiplexed high-throughput bioassays. Here, a novel photonic crystal (PhC) barcode is presented that consists of hollow colloidal nanospheres assembled through microfluidic droplet templates. Due to their gas-filled core, the resultant barcode particles not only show increased refractive index contrast, but also remain in suspension by adjusting the overall density of the PhC to match that of a detection solution. In addition, magnetic nanoparticles can be integrated to give the barcodes a magnetically controllable motion ability. The encoding ability of the barcodes is demonstrated in microRNA detection with high specificity and sensitivity, and the excellent features of the barcodes make them potentially very useful for biomedical applications.

An Interfacial Layer Based on Polymers of Intrinsic Microporosity to Suppress Dendrite Growth on Li Metal Anodes.

The performance and safety of lithium (Li) metal batteries can be compromised owing to the formation of Li dendrites. Here, the use of a polymer of intrinsic microporosity (PIM) is reported as a feasible and robust interfacial layer that inhibits dendrite growth. The PIM demonstrates excellent film-forming ability, electrochemical stability, strong adhesion to a copper metal electrode, and outstanding mechanical flexibility so that it relieves the stress of structural changes produced by reversible lithiation. Importantly, the porous structure of the PIM, which guides Li flux to obtain uniform deposition, and its strong mechanical strength combine to suppress dendrite growth. Hence, the electrochemical performance of the anode is significantly enhanced, promising excellent performance and extended cycle lifetime for Li metal batteries.

Emerging Droplet Microfluidics.

Droplet microfluidics generates and manipulates discrete droplets through immiscible multiphase flows inside microchannels. Due to its remarkable advantages, droplet microfluidics bears significant value in an extremely wide range of area. In this review, we provide a comprehensive and in-depth insight into droplet microfluidics, covering fundamental research from microfluidic chip fabrication and droplet generation to the applications of droplets in bio(chemical) analysis and materials generation. The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development. We believe this review will promote communications among biology, chemistry, physics, and materials science.

Microfluidic Generation of Bioinspired Spindle-knotted Graphene Microfibers for Oil Absorption.

Graphene materials have a demonstrated value in water treatment. Efforts to promote these materials are focused on the generation of functional graphene adsorbents for effectively removing contaminants from water. Here, inspired by the conformation of spider silks, we present a novel graphene microfiber material with spindle-knotted microstructures by using a microfluidic emulsification and spinning collaborative technology. The size and spacing of the spindle-knots were highly controllable by adjusting the flow rates of microfluidics during the generation process of the microfibers. The generated microfibers could adsorb oil from a water-oil mixed environment due to their hydrophobic surface chemistry. Because of the surface energy curvature gradient and the difference in Laplace pressure, the collected oil tended to form droplets and move from joints between the spindle-knots to the knots. In addition, by encapsulating additional functional elements, such as magnetic nanoparticles, the graphene microfiber with the ability to control and facilitate the collection of oily contaminants can also be achieved. These features greatly prove the promising values of the spindle-knotted graphene microfibers in the protection of the environment.

Bioinspired Multifunctional Spindle-Knotted Microfibers from Microfluidics.

Heterostructured microfibers with spindle-knots and joints are developed using a novel microfluidic technology, which enables integrative microfiber joint spinning, fluid coating, and knot emulsification. The knots emulsification process can be precisely tunable by adjusting the flow rates. In this way, the size and spacing of the spindle-knots of the microfibers can be achieved with high controllability. More attractively, the construction process benefits from the broad availability of the coating fluids, which determines the compositions of the knots. Thus, the resultant microfibers are imparted with distinctive functions, such as humidity-responsive water capture, thermally triggered water convergence, induced colloidal crystal assembly, and cell microcarrier arrays. These features make such microfibers highly versatile for use in diverse applications.

Microfluidic Lithography of Bioinspired Helical Micromotors.

Considerable efforts have been devoted to developing artificial micro/nanomotors that can convert energy into movement. A flow lithography integrated microfluidic spinning and spiraling system is developed for the continuous generation of bioinspired helical micromotors. Because the generation processes could be precisely tuned by adjusting the flow rates and the illuminating frequency, the length, diameter, and pitch of the helical micromotors were highly controllable. Benefiting from the fast online gelation and polymerization, the resultant helical micromotors could be imparted with Janus, triplex, and core-shell cross-sectional structures that have never been achieved by other methods. Owing to the spatially controlled encapsulation of functional nanoparticles in the microstructures, the helical micromotors can perform locomotion not only by magnetically actuated rotation or corkscrew motion but also through chemically powered catalytic reaction.

Photonic Crystal Microbubbles as Suspension Barcodes.

A novel suspension array was developed that uses photonic crystal (PhC) microbubbles as barcode particles. The PhC microbubbles have an outer transparent polymeric shell, a middle PhC shell, and an inner bubble core, and they were achieved by extraction-derived self-assembly of colloidal nanoparticles in semipermeable solid microcapsules. The encoded elements of the microbubbles originated from their PhC structure with a coated shell, which not only improved the stability of the codes but also provided a flexible surface for bioassays. By using multicompartmental microcapsule templates, PhC microbubbles with substantial coding levels and controllable movement could also be achieved. In addition, as the size of the encapsulated bubbles could be tailored, the overall density of the PhC microbubbles could be adjusted to match the density of a detection solution and to remain in suspension. These remarkable properties make the PhC microbubbles excellent barcode particles.

Microfluidic synthesis of barcode particles for multiplex assays.

The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented.