Precision Phenotypic Profiling and Capture of Circulating Tumor Cells via a Vertical Laminar Flow-Stacked Microfluidic Chip.

The heterogeneity of circulating tumor cells has a significant impact on the diagnosis, treatment, and monitoring of cancer. Research on the subtypes of circulating tumor cells can bring better treatment outcomes for cancer patients. Here, we proposed a microfluidic chip for the magnetic capture of subtypes of circulating tumor cells from the whole blood and phenotypic profiling by stacking laminar flow vertically. Circulating tumor cells were sorted and captured by the three-dimensional regulation of both magnetic fields in the vertical direction and flow fields in the lateral direction. Using EpCAM-magnetic beads, we achieved sorting and sectional capture of target cells in whole blood and analyzed the surface expression levels of the captured cells, confirming the functionality of the microfluidic chip in sorting and capturing subtypes of circulating tumor cells. This microfluidic chip can also aid in the subsequent subtype analysis of other rare cells.

Status and developmental trends in recombinant collagen preparation technology.

Recombinant collagen is a pivotal topic in foundational biological research and epitomizes the application of critical bioengineering technologies. These technological advancements have profound implications across diverse areas such as regenerative medicine, organ replacement, tissue engineering, cosmetics and more. Thus, recombinant collagen and its preparation methodologies rooted in genetically engineered cells mark pivotal milestones in medical product research. This article provides a comprehensive overview of the current genetic engineering technologies and methods used in the production of recombinant collagen, as well as the conventional production process and quality control detection methods for this material. Furthermore, the discussion extends to foresee the strides in physical transfection and magnetic control sorting studies, envisioning an enhanced preparation of recombinant collagen-seeded cells to further fuel recombinant collagen production.

Rapid Fabrication of High-Resolution Flexible Electronics via Nanoparticle Self-Assembly and Transfer Printing.

Printed electronic technology serves as a key component in flexible electronics and wearable devices, yet achieving compatibility with both high resolution and high efficiency remains a significant challenge. Here, we propose a rapid fabrication method of high-resolution nanoparticle microelectronics via self-assembly and transfer printing. The tension gradient-electrostatic attraction composite-induced nanoparticle self-assembly strategy is constructed, which can significantly enhance the self-assembly efficiency, stability, and coverage by leveraging the meniscus Marangoni effect and the electric double-layer effect. The close-packed nanoparticle self-assembly layer can be rapidly formed on microstructure surfaces over a large area. Inspired by ink printing, a transfer printing strategy is further proposed to transform the self-assembly layer into conformal micropatterns. Large-area, high-resolution (2 µm), and ultrathin (1 µm) nanoparticle microelectronics can be stably fabricated, yielding a significant improvement over fluid printing methods. The unique deformability, recoverability, and scalability of nanoparticle microelectronics are revealed, providing promising opportunities for various academic and real applications.

Analysis of the Pattern Shapes Obtained By Micro/Nanospherical Lens Photolithography.

Micro/nanospherical lens photolithography (SLPL) constitutes an efficient and precise micro/nanofabrication methodology. It offers advantages over traditional nanolithography approaches, such as cost-effectiveness and ease of implementation. By using micrometer-sized microspheres, SLPL enables the preparation of subwavelength scale features. This technique has gained attention due to its potential applications. However, the SLPL process has a notable limitation in that it mostly produces simple pattern shapes, mainly consisting of circular arrays. There has been a lack of theoretical analysis regarding the possible shapes that can be created. In our experiments, we successfully prepared annular and ring-with-hole pattern shapes. To address this limitation, we applied the Mie scattering theory to systematically analyze and summarize the various patterns that can be obtained through the SLPL process. We also proposed methods to predict and obtain different patterns. This theoretical analysis enhances the understanding of SLPL and expands its potential applications, making it a valuable area for further research.

Near-Infrared Light Responsive Surface with Switchable Wettability in Microstructure and Surface Chemistry.

Intelligent surfaces with reversibly switchable wettability have recently drawn considerable attention. One typical strategy to obtain such a surface is to change the surface chemistry or the microstructure. Herein, we report a new smart surface for which the wettability was controlled by both the surface chemistry and microstructure. Various wetting states were reversibly and precisely controlled through heating, pressing, NIR irradiation, and oxygen plasma treatment. The excellent shape memory characteristics of shape memory polyurethane (SMPU) and the controlled release of hydrophobic/hydrophilic oxygen-containing functional groups contributed to this ability. Microcapsules were used to design these smart surfaces. They controlled the release of a fluorinated alkyl silane (FAS) through shell melting, changed the surface composition, and played a decisive role in protecting the FAS against hydrolysis and evaporation to ensure that the surface's wettability is recyclable. Controlling of the surface chemistry or microstructure was repeated for at least 19 or 16 cycles, respectively, which indicated excellent repeatability compared to other smart surfaces. Based on the excellent controllability, the surface exhibited multiple functions, such as liquid directional transport and coefficient of friction control. In addition, it maintained this extraordinary ability under harsh environments owing to the great stability of the SMPU and adequate protection of the FAS by the microcapsules. With switchable wettability based on the surface chemistry and microstructure, this work provides a new principle for designing smart surfaces with wettability controlled in two ways.

Progress and prospect of technical and regulatory challenges on tissue-engineered cartilage as therapeutic combination product.

Hyaline cartilage plays a critical role in maintaining joint function and pain. However, the lack of blood supply, nerves, and lymphatic vessels greatly limited the self-repair and regeneration of damaged cartilage, giving rise to various tricky issues in medicine. In the past 30 years, numerous treatment techniques and commercial products have been developed and practiced in the clinic for promoting defected cartilage repair and regeneration. Here, the current therapies and their relevant advantages and disadvantages will be summarized, particularly the tissue engineering strategies. Furthermore, the fabrication of tissue-engineered cartilage under research or in the clinic was discussed based on the traid of tissue engineering, that is the materials, seed cells, and bioactive factors. Finally, the commercialized cartilage repair products were listed and the regulatory issues and challenges of tissue-engineered cartilage repair products and clinical application would be reviewed.

High-Throughput and Efficient Intracellular Delivery Method via a Vibration-Assisted Nanoneedle/Microfluidic Composite System.

Intracellular delivery and genetic modification have brought a significant revolutionary to tumor immunotherapy, yet existing methods are still limited by low delivery efficiency, poor throughput, excessive cell damage, or unsuitability for suspension immune cells, specifically the natural killer cell, which is highly resistant to transfection. Here, we proposed a vibration-assisted nanoneedle/microfluidic composite system that uses large-area nanoneedles to rapidly puncture and detach the fast-moving suspension cells in the microchannel under vibration to achieve continuous high-throughput intracellular delivery. The nanoneedle arrays fabricated based on the large-area self-assembly technique and microchannels can maximize the delivery efficiency. Cas9 ribonucleoprotein complexes (Cas9/RNPs) can be delivered directly into cells due to the sufficient cellular membrane nanoperforation size; for difficult-to-transfect immune cells, the delivery efficiency can be up to 98%, while the cell viability remains at about 80%. Moreover, the throughput is demonstrated to maintain a mL/min level, which is significantly higher than that of conventional delivery techniques. Further, we prepared CD96 knockout NK-92 cells via this platform, and the gene-edited NK-92 cells possessed higher immunity by reversing exhaustion. The high-throughput, high-efficiency, and low-damage performance of our intracellular delivery strategy has great potential for cellular immunotherapy in clinical applications.

Effect of Doping SiO2 Nanoparticles and Phenylmethyl Silicone Oil on the Large-Scale Deicing Property of PDMS Coatings.

Recently, low interfacial toughness (LIT) materials have been developed to solve large-scale deicing problems. According to the theory of interfacial fracture, ice detachment is dominated by strength-controlled or toughness-controlled regimes, which are characterized by adhesive strength or constant shear force. Here, a new strategy is introduced to regulate the interfacial toughness of poly(dimethylsiloxane) (PDMS) coatings using silicon dioxide nanoparticles (SiO2 NPs) and phenylmethyl silicone oil (PMSO). By systematically adjusting the doping proportion of SiO2 NPs and PMSO, it is found that a lower interfacial toughness can be achieved with a lower constant shear force. The synergistic effect of the two dopants on the adhesive strength and interfacial toughness is analyzed. Meanwhile, finite element method (FEM) analysis of ice detachment is conducted to show the cracking process intuitively and explicate the mechanism of lowering the interfacial toughness of PDMS by doping SiO2 NPs and PMSO. It can be concluded that the cohesive zone material (CZM) model is effective for simulating the deicing process of PDMS coatings and provides a comprehensive understanding of the modulation of interfacial toughness.

Functionalization of biomedical materials using fusion peptides for tissue regeneration.

Tissue development deformity or tissue defect is a major clinical challenge. Tissue engineering technology provides a promising solution to these problems. Among them, functional biomaterials with regenerative abilities are one of the development trends. Polypeptide is a small molecule that can be used to modify tissue engineering materials. However, the function of a single polypeptide molecule is limited and insufficient to construct comprehensive microenvironment for tissue regeneration. Fusion peptides combining two or more polypeptide molecules with different functions were expected to achieve multiple efficaciesin vivo, providing a novel solution for clinical tissue regeneration engineering applications. This paper reviews the construction methods, degradation process, and biological activities of fusion peptides, and presents recent global research progress and prospects concerning fusion peptides. It provides a reference helping to guide the future exploration and development of fusion peptide-based functional biomaterials for tissue engineering.

Analysis of drug efficacy for inflammatory skin on an organ-chip system.

Bacterial skin infections cause a variety of common skin diseases that require drugs that are safer than antibiotics and have fewer side effects. However, for evaluating skin disease drugs, human skin tissue in vitro constructed traditionally on Transwell has inefficient screening ability because of its fragile barrier function. With mechanical forces and dynamic flow, the organ-on-a-chip system became an innovative, automatic, and modular way to construct pathological models and analyze effective pharmaceutical ingredients in vitro. In this research, we integrated skin extracellular matrix and skin cells into a microfluidic chip to construct a biomimetic "interface-controlled-skin-on-chip" system (IC-SoC), which constructed a stable air-liquid interface (ALI) and necessary mechanical signals for the development of human skin equivalents. The results demonstrated that in the microfluidic system with a flowing microenvironment and ALI, the skin tissue formed in vitro could differentiate into more mature tissue morphological structures and improve barrier function. Then, following exposing the skin surface on the IC-SoC to the stimulation of Propionibacterium acnes (P.acnes) and SLS (sodium lauryl sulfate), the barrier function decreased, as well as inflammatory factors such as IL-1α, IL-8, and PEG2 increased in the medium channel of the IC-SoC. After this pathological skin model was treated with dexamethasone and polyphyllin H, the results showed that polyphyllin H had a significant repair effect on the skin barrier and a significant inhibition effect on the release of inflammation-related cytokines, and the effects were more prominent than dexamethasone. This automated microfluidic system delivers an efficient tissue model for toxicological applications and drug evaluation for bacterial-infected damaged skin instead of animals.

A Highly Automated Mobile Laboratory for On-site Molecular Diagnostics in the COVID-19 Pandemic.

BACKGROUND: Infectious disease outbreaks such as the COVID-19 (coronavirus disease 2019) pandemic call for rapid response and complete screening of the suspected community population to identify potential carriers of pathogens. Central laboratories rely on time-consuming sample collection methods that are rarely available in resource-limited settings. METHODS: We present a highly automated and fully integrated mobile laboratory for fast deployment in response to infectious disease outbreaks. The mobile laboratory was equipped with a 6-axis robot arm for automated oropharyngeal swab specimen collection; virus in the collected specimen was inactivated rapidly using an infrared heating module. Nucleic acid extraction and nested isothermal amplification were performed by a "sample in, answer out" laboratory-on-a-chip system, and the result was automatically reported by the onboard information platform. Each module was evaluated using pseudovirus or clinical samples. RESULTS: The mobile laboratory was stand-alone and self-sustaining and capable of on-site specimen collection, inactivation, analysis, and reporting. The automated sampling robot arm achieved sampling efficiency comparable to manual collection. The collected samples were inactivated in as short as 12 min with efficiency comparable to a water bath without damage to nucleic acid integrity. The limit of detection of the integrated microfluidic nucleic acid analyzer reached 150 copies/mL within 45 min. Clinical evaluation of the onboard microfluidic nucleic acid analyzer demonstrated good consistency with reverse transcription quantitative PCR with a κ coefficient of 0.979. CONCLUSIONS: The mobile laboratory provides a promising solution for fast deployment of medical diagnostic resources at critical junctions of infectious disease outbreaks and facilitates local containment of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission.

Tension gradient-driven oil/water interface rapid particle self-assembly and its application in microdroplet motion control.

HYPOTHESIS: A binary mixture was used during injection with one water-miscible component and the other water-immiscible, which can help particles to migrate toward and then self-assemble at the interface. EXPERIMENTS: The ethanol-tetrachloromethane binary mixture was used to verify the self-assembly method, with the diameter of droplets being about 1 mm. As the ethanol diffused into the colloidal solution, the colloidal particles efficiently moved towards and self-assembled on the oil/water interface, while a colloidal particle film with high-coverage was able to rapidly form on the droplet surface even in an ultra-low concentration colloidal solution. The effects of ethanol concentration and particle concentration on self-assembly were investigated. FINDINGS: The driving force for self-assembly originated from the tension gradient generated by ethanol's concentration gradient at the particle/liquid interfaces, where the concentrations of ethanol and the colloidal solution had significant effects on self-assembly. The simulation and calculations results aligned well with experiments, providing the theoretical basis for this self-assembly method. Further, as-prepared magnetic particle-coated droplets transformed into a non-wetting soft solid, which had long lifetimes and could be precisely moved, coalesced, and transferred in various two-dimensional and three-dimensional liquid environments. Thus, wider applications are facilitated, such as droplet transfer, microreactor and other potential fields.

Simulation Study on the Dynamic Behaviors of Water-in-Oil Emulsified Droplets on Coalescing Fibers.

Although increasing superwetting membranes have been developed for separating oil-water emulsions based on the "size-sieving" mechanism, their pores are easily blocked and fouled by the intercepted emulsified droplets, which would result in a severe membrane fouling issue and a sharp decline in flux. Instead of droplet interception, a fiber-based coalescer separates oil/water emulsions by inducing the emulsified droplets to coalesce and transform into layered oil/water mixtures, exhibiting an ability to work continuously for a long time with high throughput, which makes it a promising technology for emulsion treatment. However, the underlying mechanism of the separation process is not well understood, which makes it difficult to further improve the separation performance. Hence, in this work, the dynamic behaviors of water-in-oil emulsified droplets on the surface of the coalescing fiber were numerically investigated based on the phase-field model. The attachment, transport, and detachment behaviors of droplets on fibers were directly observed, and the effects of fiber wettability, orientation, arrangement, and fluid speed were studied in detail. First, it was observed that the droplets will move downstream along the fiber surface under the effect of fluid shear, and the large droplets tend to coalesce with their downstream small droplets on the same fiber surface because they move faster compared to the small droplets. Second, it was found that the emulsified droplet will spontaneously transport to the intersection of two angled fibers under the drive of asymmetric Laplace pressure, which demonstrated that the emulsified droplets tend to gather at the intersection of fibers when permeating through a coalescing medium. Third, it was found that the detachment behaviors of droplets from the fiber surface are strongly affected by their size, fiber wettability, and fluid velocity. In addition, the results of our simulation show that the backside of two closely attached fibers can further inhibit the detachment of droplets. We truly believe that our research results are of significance to optimize the parameters of a fiber-based coalescer for separating oil-water emulsions and to develop novel oil/water separators.

Under-oil superhydrophilic salt particle filter for the efficient separation of water-in-oil emulsions.

In this study, a surfactant stabilized water-in-oil emulsion has been successfully separated by using only NaCl particles as a filter. This novel strategy is suitable for continuous filtration of a large quantity of water-in-oil emulsion with a volume of up to 1500 mL. Moreover, a filtration flux of up to 40 000 L m-2 h-1 is reported, which is around ten times higher than the conventional filtration methods.

Thickness-dependent Young's modulus of polycrystalline α-PbO nanosheets.

Litharge, in two dimensional (2D) nanostructure form, has recently ignited considerable theoretical interest due to its excellent photoelectric and magnetic properties. However, the lack of an efficient synthesis method hinders its development. Here, we provide an interfacial solvothermal strategy for controllably synthesizing ultrathin hexagonal polycrystalline α-PbO nanosheets in micrometer scale. This strategy can also be utilized for the synthesis of other 2D materials. Experimental atomic force microscope nanoindentation measurements reveal the relationship between the thickness of polycrystalline α-PbO nanosheets and the corresponding Young's modulus, expressed as E = E0 + Kt -1. First-principles calculation supports the result and ascribes the cause to interlayer sliding from particular weak interlayer interactions. Additionally, the enhanced mechanical strength of the polycrystalline structure compared to its single-crystal counterpart is attributed to the alternate arrangement of grain-boundaries effects. The summative formula may be extended to other 2D materials with weak interlayer interactions, which has the potential to provide guidance for constructing flexible devices.

Underoil Superhydrophilic Metal Felt Fabricated by Modifying Ultrathin Fumed Silica Coatings for the Separation of Water-in-Oil Emulsions.

Although various superhydrophobic/superoleophilic porous materials have been developed and successfully applied to separate water-in-oil emulsions through the size-sieving mechanism, the separation performance is restricted by their nanoscale pore size severely. In this study, the wettability of underoil water on fumed silica was experimentally observed, and the underlying mechanism was investigated by carrying out theoretical analysis and molecular dynamic (MD) simulations. Further, we present a novel, facile, and an inexpensive technique to fabricate an underoil superhydrophilic metal felt with microscale pores for the separation of water-in-oil emulsions using SiO2 nanoparticles (NPs) as building blocks. The as-prepared underoil superhydrophilic coating is closed-packed and ultrathin (the thickness is approximately hundreds of nanometers), as well as capable of being coated on a metal felt with complex structures without blocking its pores. The as-prepared metal felt could adsorb water droplets directly from oil, which endowed it with the ability to separate both surfactant-free and surfactant-stabilized water-in-oil emulsions with high separation efficiency up to 99.7% even though its pore size is larger than that of the emulsified droplet. The filtration flux for the separation of span 80-stabilized emulsion is up to ∼4000 L·m-2·h-1. Its separation performance is better than most of the other traditional membranes and superwettable materials used for the separation of water-in-oil emulsions. Moreover, the as-prepared metal felt retained outstanding separation performance even after 30 cycles of use, which demonstrated its excellent reusability and durability. Additionally, the distinctive wettability of underoil superhydrophilicity endued coated metal felt with superior antifouling properties toward crude oil. Overall, this study not only provides a new perspective on separating water-in-oil emulsions but also gives a universal approach to develop unique wettability surfaces.

Spontaneous propulsion of a water nanodroplet induced by a wettability gradient: a molecular dynamics simulation study.

The directional propulsion of liquid droplets at the nanoscale is quite an interesting topic of research in the fields of micro/nano-fluidics, water filtration, precision medicine, and cooling of electronics. In this study, the unidirectional spontaneous transport of a water nanodroplet on a solid surface with a multi-gradient surface (MGS) inspired by natural species is modeled and analyzed using molecular dynamics (MD) simulations. There are three different MGSs considered in this study containing different wedge angles of the hydrophilic region of the solid surface. The MGSs contain two regions: a hydrophilic wedge-shaped region with a constant surface energy parameter equal to 50 meV and a hydrophobic region with a tuned surface energy parameter. The energy parameter of the hydrophobic region is set equal to 1, 5, 10, 20, 30, and 40 meV in order to alter the intensity of the wettability gradient of the two surfaces and its effect on the propulsion of the water nanodroplet is analyzed. Furthermore, three different sizes of water droplets containing 6000, 8000, and 10 000 water molecules are also used in this study and their effect on the transport behavior of the water nanodroplet is also measured. Moreover, two different designs on a solid surface with a continuous wettability gradient are modelled and the impact of solid surface geometry on the transport of the water droplet is calculated by means of mean square displacement (MSD) and average velocity data. In addition, the wedge-shaped surface is found to be more superior to the parallel-shaped surface for the spontaneous propulsion of the water droplet.

Life-Like Motion of Oil Drops at the Air-Liquid Interface.

Generally, interactions of oil drops at the air-liquid interface mainly have two features, namely, attraction and repulsion. However, in our study, we find that the oil drops at the air-liquid interface have other interacting features, that is, the atomic-like motion and the "capture" motion. For the atomic-like motion, oil drops attract each other at a long distance, but repel when they are about to come into contact with each other. For the "capture" motion, a big oil drop can actively "capture" oil droplets like a zooplankton. In our research, we analyze interfacial forces among the oil drops. Based on the experiments and analyses, we demonstrate that the atomic-like motion of oil drops is mainly due to the lateral capillary force and the surface tension force, and the "capture" motion is mainly due to the unbalanced impact force of flow fluid around the drops. In addition, based on our results, we use the oil drops to perform many functions at the air-liquid interface. For example, the oil drops can drive an object with linear and rotational motion. When a carbon tetrachloride drop is suspended above the air-liquid interface, it can be used to control an oil droplet to pass through serpentine grooves and obstacles. In addition, the suspended carbon tetrachloride drops also can be used to rank multiple droplets with a special shape. Based on the results, our study makes it possible to use oil drops to transport materials, drive objects, and even collect droplets at the air-liquid interface.

Interactions of Oil Drops Induced by the Lateral Capillary Force and Surface Tension Gradients.

The interacting forces on the objects at the air-liquid interface are important for researching self-assembly of objects. Due to the interacting forces among objects, the objects self-assemble at the air-liquid interface and organize into ordered structures. In general, for the interacting of oil drops, they can attract coalescence or repel dispersion. However, according to our former research, we find that interactions of oil drops can be motion like interactions of gas atoms. The oil drops cannot coalesce to form a big oil drop or separate to form ordered structures. They attract at a long distance but repel when they almost contact. In this study, according to our simulation, we demonstrate that the atomic-like motion of oil drops is mainly caused by the surface tension gradient and the lateral capillary force. Based on the results, our research will facilitate the fundamental understanding about interactions among oil drops. Apart from giving detailed demonstration about the interacting forces among oil drops, our research may also put forward research about self-assembly, oil emulsification, and microfluidics.

Development of Durable, Fluorine-free, and Transparent Superhydrophobic Surfaces for Oil/Water Separation.

Although artificial superhydrophobic materials have extensive and significant applications in antifouling, self-cleaning, anti-icing, fluid transport, oil/water separation, and so forth, the poor robustness of these surfaces has always been a bottleneck for their development in practical industrial applications. Here, we report a facile, economical, efficient, and versatile strategy to prepare environmentally friendly, mechanically robust, and transparent superhydrophobic surfaces by combining adhesive and hydrophobic paint, which is applicable for both hard and soft substrates. The coated substrates exhibit excellent superhydrophobic property and ultralow adhesion with water (contact angle ≈ 160° and sliding angle <2°). Additionally, the coated surface maintained its superhydrophobicity even after 325 sandpaper abrasion cycles, showing remarkable mechanical robustness. Furthermore, the coated surfaces were applied to separate oil/water mixtures because of their unique characteristics of being simultaneously superhydrophobic and superoleophilic. In addition, it is believed that this fabrication method is significant, promising, and feasible for mass production of superhydrophobic surfaces for industrial applications.