Machine-Learning-Assisted Procoagulant Extracellular Vesicle Barcode Assay toward High-Performance Evaluation of Thrombosis-Induced Death Risk in Cancer Patients.

Venous thromboembolism (VTE) is the most fatal complication in cancer patients. Unfortunately, the frequent misdiagnosis of VTE owing to the lack of accurate and efficient evaluation approaches may cause belated medical intervention and even sudden death. Herein, we present a rapid, easily operable, highly specific, and highly sensitive procoagulant extracellular vesicle barcode (PEVB) assay composed of TiO2 nanoflower (TiNFs) for visually evaluating VTE risk in cancer patients. TiNFs demonstrate rapid label-free EV capture capability by the synergetic effect of TiO2-phospholipids molecular interactions and topological interactions between TiNFs and EVs. From ordinary plasma samples, the PEVB assay can evaluate potential VTE risk by integrating TiNFs-based EV capture and in situ EV procoagulant ability test with machine-learning-assisted clinical data analysis. We demonstrate the feasibility of this PEVB assay in VTE risk evaluation by screening 167 cancer patients, as well as the high specificity (97.1%) and high sensitivity (96.8%), fully exceeding the nonspecific and posterior traditional VTE test. Together, we proposed a TiNFs platform allowing for highly accurate and timely diagnosis of VTE in cancer patients.

Recent advances in bio-inspired ionic liquid-based interfacial materials from preparation to application.

Natural creatures always display unique and charming functions, such as the adhesion of mussels and the lubrication of Nepenthes, to maintain their life activities. Bio-inspired interfacial materials infused with liquid, especially for ionic liquids (ILs), have been designed and prepared to meet the emerging and rising needs of human beings. In this review, we first summarize the recent development of bio-inspired IL-based interfacial materials (BILIMs), ranging from the synthesis strategy to the design principle. Then, we discuss the advanced applications of BILIMs from anti-adhesive aspects (e.g., anti-biofouling, anti-liquid fouling, and anti-solid fouling) to adhesive aspects (e.g., biological sensor, adhesive tape, and wound dressing). Finally, the current limitations and future prospects of BILIMs are provided to feed the actual needs.

Water Spider-Inspired Nanofiber Coating with Sustainable Scale Repellency via Air-Replenishing Strategy.

To survive underwater even in severely hypoxic water for a long period, the water spider has to periodically collect and replenish air into the diving bell. Inspired by this natural air-replenishing strategy, a water spider-inspired nanofiber (WSN) coating with underwater superaerophilicity displaying excellent and sustainable scalephobic capability is prepared. Air film on the WSN coating can be well-kept and further employed as the barrier layer for scale repellence. Significantly, scalephobic capability of the WSN coating mainly originates from two aspects: inhibiting interfacial nucleation and reducing interfacial adhesion of scale. Compared with previous studies, this WSN coating achieves excellent and sustainable scale repellence (≈ 98% reduction in scale deposition) even after a one-month dynamic scaling test. Thus, this air-replenishing strategy may raise a new avenue for advanced long-term scalephobic materials.

Sustainable scale resistance on a bioinspired synergistic microspine coating with a collectible liquid barrier.

Scale deposition, especially in the petroleum industry, has always been a serious issue because of its potential safety hazards and huge economic cost. However, conventional scale-resistant strategies based on mechanical descaling and chemical detergents can't feed the urgent demand for energy saving and environmental protection. Herein, we report a bioinspired long-term oil collectible mask (BLOCK)-a microspine coating with the synergistic effect of anti-adhesion and oil collection, displaying sustainable scale resistance towards oilfield-produced water. Inspired by pitcher plants, the oil layer as a liquid barrier inhibits scale deposition by changing the underwater scaling micro-environment from liquid/solid/solid to a liquid/solid/liquid triphase system. Oil droplets are collected by cacti-inspired microspines to enhance oil layer stability. Compared with stainless steel, the BLOCK coating shows ca. 98% reduction even after 35 days in artificial produced water. This strategy could be utilized to design integrated functional materials for conquering complex environments such as oil recovery and transportation.

Nacre-inspired underwater superoleophobic films with high transparency and mechanical robustness.

Underwater superoleophobic materials have attracted increasing attention because of their remarkable potential applications, especially antifouling, self-cleaning and oil-water separation. A limitation of most superoleophobic materials is that they are non-transparent and have limited mechanical stability underwater. Here, we report a protocol for preparing a transparent and robust superoleophobic film that can be used underwater. It is formed by a hydrogel layer prepared by the superspreading of chitosan solution on a superhydrophilic substrate and biomimetic mineralization of this layer. In contrast to conventional hydrogel-based materials, this film exhibits significantly improved mechanical properties because of the combination of high-energy, ordered, inorganic aragonite (one crystalline polymorph of calcium carbonate) and homogeneous external hierarchical micro/nano structures, leading to robust underwater superoleophobicity and ultralow oil adhesion. Moreover, the mineralized film is suitable for neutral and alkaline environments and for containing organic solvent underwater and can be coated on different transparent materials, which has promising applications in underwater optics, miniature reactors and microfluidic devices. In this protocol, the time for the whole biomimetic mineralization process is only ~6 h, which is significantly shorter than that of traditional methods, such as gas diffusion and the Kitano method. The protocol can be completed in ~2 weeks and is suitable for researchers with intermediate expertise in organic chemistry and inorganic chemistry.

Evaporation-Induced rGO Coatings for Highly Sensitive and Non-Invasive Diagnosis of Prostate Cancer in the PSA Gray Zone.

The prostate-specific antigen (PSA) has been widely used for the early diagnosis of prostate cancer during routine check-ups. However, the low sensitivity of regular PSA tests in the PSA gray zone often means that patients are required to undergo further invasive needle biopsy for the diagnosis of prostate cancer, which may lead to potential overdiagnosis and overtreatment. In this study, a circulating tumor cell (CTC)-chip based on an evaporation-induced reduced graphene oxide (rGO) coating is presented, which enables a highly specific and non-invasive diagnosis of prostate cancer in the PSA gray zone. During the evaporation process of the rGO dispersion, the Marangoni effect induces the self-assembly of a hierarchical micro/nanowrinkled rGO coating, which can capture CTCs after subsequent surface modification of capture agents. Compared to the low diagnostic sensitivity (58.3%) of regular PSA tests, a combination of CTC detection and PSA-based hematological tests via machine-learning analysis can greatly upgrade the diagnostic sensitivity of this disease to 91.7% in clinical trial. Therefore, this study provides a non-invasive alternative with high sensitivity for the diagnosis of prostate cancer in the PSA gray zone.

Advanced Nanotechnologies for Extracellular Vesicle-Based Liquid Biopsy.

Extracellular vesicles (EVs) are emerging as a new source of biomarkers in liquid biopsy because of their wide presence in most body fluids and their ability to load cargoes from disease-related cells. Owing to the crucial role of EVs in disease diagnosis and treatment, significant efforts have been made to isolate, detect, and analyze EVs with high efficiency. A recent overview of advanced EV detection nanotechnologies is discussed here. First, several key challenges in EV-based liquid biopsies are introduced. Then, the related pivotal advances in nanotechnologies for EV isolation based on physical features, chemical affinity, and the combination of nanostructures and chemical affinity are summarized. Next, a summary of high-sensitivity sensors for EV detection and advanced approaches for single EV detection are provided. Later, EV analysis is introduced in practical clinical scenarios, and the application of machine learning in this field is highlighted. Finally, future opportunities for the development of next-generation nanotechnologies for EV detection are presented.

Nickel-Catcher-Doped Zwitterionic Hydrogel Coating on Nickel-Titanium Alloy Toward Capture and Detection of Nickel Ions.

Nickel-titanium (NiTi) alloys show broad applicability in biomedical fields. However, the unexpected aggregation of bacteria and the corrosion of body fluid on NiTi-based medical devices often lead to the leakage of nickel ions, resulting in inevitable allergic and cytotoxic activities. Therefore, the capture and detection of nickel ions are important to avoid serious adverse reactions caused by NiTi-based medical devices. Herein, we presented a nickel ion capture strategy by the combination of zwitterionic hydrogels as anti-bacteria layers and carbon disulfide (CS2) components as nickel-catchers (Ni-catchers). On the one hand, the hydration layer of zwitterionic hydrogel can efficiently inhibit bacteria adhesion and reduce nickel ions leakage from NiTi corrosion. On the other hand, Ni-catchers can capture leaked nickel ions from NiTi alloy actively by chelation reaction. Therefore, this strategy shows great capabilities in resisting bacteria adhesion and capturing nickel ions, providing the potential possibility for the detection of nickel ion leakage for implantable biomedical materials and devices.

Recent Progress of Bioinspired Scalephobic Surfaces with Specific Barrier Layers.

Bioinspired superwettable surfaces have been widely harnessed in diverse applications such as self-cleaning, oil/water separation, and liquid transport. So far, only a little work is focused on scalephobic capability of those superwettable surfaces. However, the troublesome scale deposition will inevitably be observed in our daily production and life, greatly reducing heat transfer efficiency and inhibiting the liquid transport. To address this annoying problem, as the emerging strategy, specific barrier layers are introduced onto superwettable surfaces to reduce or even avoid the direct contact between scale and the surfaces. In this feature article, we first provide the basic concept of bioinspired scalephobic surfaces with specific barrier layers. Then, we briefly introduce the typical fabrication methods of scalephobic surfaces. Later, we summarize recent progress of bioinspired scalephobic surfaces with specific barrier layers. Furthermore, we point out the guiding theory and criteria for the stability of barrier layers. Finally, we put forward the forecast on the existing problems and future direction in bioinspired scalephobic surfaces.

How to Prevent Bubbles in Microfluidic Channels.

Microfluidic technology has aroused wide applications, including analytical science, diagnostic technology, and micro-/nanofabrication. However, bubbles in microfluidic channels always bring out adverse impacts such as cell damage and device malfunction. To prevent bubble formation, numerical simulation and experiments were integrated to reveal the effect of the factors including the internal structure of the channel, internal wettability, and liquid flow rate. On one hand, the simulation results reveal that bubble formation can be prevented by these mentioned factors, the weight of which can be provided by a logistic regression model. In addition, the raised equilibrium equations can efficiently explain the influence of these factors on bubble prevention. On the other hand, the validity of the simulation was further verified by the prevention of bubbles in the water-flowing microchannels. Therefore, this work provides a promising strategy to prevent bubble formation in microchannels, which has wide applications in microfluidic systems.

Nacre-Inspired Mineralized Films with High Transparency and Mechanically Robust Underwater Superoleophobicity.

Underwater superoleophobic materials have shown promising applications in various fields, especially in the highly frequent oil-spill accidents. However, the transparency and mechanical properties of existing underwater superoleophobic materials are generally mutually exclusive. In this work, a transparent and mechanically robust underwater superoleophobic film is presented by combining superspreading and biomineralization. Unlike the conventional hydrogel-based materials, the transparent mineralized film exhibits significantly improved mechanical properties, which lead to a robust underwater superoleophobicity and an ultralow oil adhesion. Such a bioinspired mineralized film can be coated on various transparent supporting materials such as glass, polystyrene (PS), poly(ethylene terephthalate) (PET), and polypropylene (PP), showing promising applications in various fields, such as goggles, underwater cameras, and submarines.

Photo-Irresponsive Molecule-Amplified Cell Release on Photoresponsive Nanostructured Surfaces.

Cell manipulation has raised extensive concern owing to its underlying applications in numerous biological situations such as cell-matrix interaction, tissue engineering, and cell-based diagnosis. Generally, light is considered as a superior candidate for manipulating cells (e.g., cell release) due to their high spatiotemporal precision and non-invasion. However, it remains a big challenge to release cells with high efficiency due to their potential limitation of the light-triggered wettability transition on photoresponsive surfaces. In this study, we report a photoresponsive spiropyran-coated nanostructured surface that enables highly efficient release of cancer cells, amplified by the introduction of a photo-irresponsive molecule. On one hand, structural recognition stems from topological interaction between nanofractal surfaces and the protrusions of cancer cells. On the other, molecular recognition can be amplified by a photo-irresponsive and hydrophilic molecule by reducing the steric hindrance of photoresponsive components and resisting nonspecific cell adhesion. Therefore, this study may afford a novel avenue for developing advanced smart materials for high-quality biological analysis and clinical diagnosis.

Bioinspired Microfluidic Device by Integrating a Porous Membrane and Heterostructured Nanoporous Particles for Biomolecule Cleaning.

Mimicking the structures and functions of biological systems is considered as a promising approach to construct artificial materials, which have great potential in energy, the environment, and health. Here, we demonstrate a conceptually distinct design by synergistically combining a kidney-inspired porous membrane and natural sponge-inspired heterostructured nanoporous particles to fabricate a bioinspired biomolecule cleaning device, achieving highly efficient biomolecule cleaning spanning from small molecules to macromolecules. The bioinspired biomolecule cleaning device is a two-layer microfluidic device that integrates a polyamide porous membrane and heterostructured nanoporous poly(acrylic acid)-poly(styrene divinylbenzene) particles. The former as a filtration membrane isolates the upper sample liquid and the latter fixed onto the bottom of the underlying channel acts as an active sorbent, particularly enhancing the clearance of macromolecules. As a proof-of-concept, we demonstrate that typical molecules, including urea, creatinine, lysozyme, and ß2-microglobulin, can be efficiently cleaned from simulant liquid and even whole blood. This study provides a method to fabricate a bioinspired biomolecule cleaning device for highly efficient biomolecule cleaning. We believe that our bioinspired synergistic design may expand to other fields for the fabrication of integrated functional devices, creating opportunities in a wide variety of applications.

Topography-Induced Cell Self-Organization from Simple to Complex Aggregates.

Self-organization is a fundamental and indispensable process in a living system. To understand cell behavior in vivo such as tumorigenesis, 3D cellular aggregates, instead of 2D cellular sheets, have been employed as a vivid in vitro model for self-organization. However, most focus on the macroscale wetting and fusion of cellular aggregates. In this study, it is reported that self-organization of cells from simple to complex aggregates can be induced by multiscale topography through confined templates at the macroscale and cell interactions at the nanoscale. On the one hand, macroscale templates are beneficial for the organization of individual cells into simple and complex cellular aggregates with various shapes. On the other hand, the realization of these macro-organizations also depends on cell interactions at the nanoscale, as demonstrated by the intimate contact between nanoscale pseudopodia stretched by adjacent frontier cells, much like holding hands and by the variation in the intermolecular interactions based on E-cadherin. Therefore, these findings may be very meaningful for clarifying the organizational mechanism of tumor development, tissue engineering and regenerative medicine.

Polyoxometalate-based microcrystal arrays patterned on air-grid superwettable surface.

Surface patterning of polyoxometalates (POMs) is an important step to gain functional materials and devices. However, some special requirements such as complex operation steps or strict synthesis environment greatly limit their further applications. Herein, we have employed a simple and universal strategy for patterning POM-based microcrystal arrays on air-grid superwettable surfaces. The size and distribution of POM crystals were precisely adjusted by varying the pillar parameter of superwettable surface and concentration of POM mother liquid. We envision that this POM patterning method may bring valuable insights for designing POM-based functional materials and devices.

Bio-Inspired Underwater Super Oil-Repellent Coatings for Anti-Oil Pollution.

Underwater superoleophobic surfaces have attracted great attention due to their broad applications such as anti-oil adhesion, oil capture and transportation, and oil/water separation. However, it is often fairly complex and time-consuming, involved in the construction of micro/nanostructures and the regulation of chemical compositions; there is an urgent need to develop new strategies to conquer these problems. Inspired by the strong anchoring capability and easy accessibility of plant polyphenols, we can readily and rapidly fabricate tannic acid (TA) coated copper surfaces with the excellent underwater super oil-repellent property. To achieve the optimal condition for TA modification, the influence of immersion time, TA concentration, and pH value on underwater-oil wettability and adhesion has been systematically explored. Furthermore, the underwater super oil-repellent feature can be widely achieved for different oils and on various metal sheets, suggesting the potential applications for plenty of fields such as anti-oil pollution.

Electrochemical Responsive Superhydrophilic Surfaces of Polythiophene Derivatives towards Cell Capture and Release.

Highly efficient cell capture and release with low background are urgently required for early diagnosis of diseases such as cancer. Herein, we report an electrochemical responsive superhydrophilic surface exhibiting specific cell capture and release with high yields and extremely low nonspecific adhesion. Through electrochemical deposition, 3-substituted thiophene derivatives are deposited onto indium tin oxide (ITO) nanowire arrays with 4-n-nonylbenzeneboronic acid (BA) as dopant, fabricating the electrochemical responsive superhydrophilic surfaces. The molecular recognition between sialic acids over-expressed on the cell membrane and doped BAs endows the electrochemical responsive surfaces with the ability to capture and release targeted cancer cells. By adjusting the substituent group of thiophene derivatives, the surface wettability can be readily regulated and further utilized for reducing nonspecific cell adhesion. Significantly, the released cells still maintain a high proliferation ability, which indicates that the applied potential does not significantly harm the cells. Therefore, these results may provide a new strategy to achieve advanced functions of biomedical materials, such as low nonspecific adhesion.

Protein-mediated anti-adhesion surface against oral bacteria.

Biomedical materials, such as orthopedic biomaterials, have a great impact on improving life quality and self-esteem of human beings. However, the usage of fixed appliances during dental treatment often increases the difficulty of oral cleaning and enlarges the adhesion opportunity of oral bacteria. Furthermore, the existing anti-adhesion coatings, such as polyethylene glycol derivatives and zwitterionic polymers, have not been universally accepted in the oral environment due to their intrinsic problems. Herein, inspired by the anti-adhesion capability of bovine serum albumin, we report a facile protein-based anti-bacterial surface, showing excellent anti-adhesion performance toward oral bacteria. This protein-mediated anti-adhesion strategy may provide a promising clue for developing new anti-bacterial biomaterials, such as dental fixed appliances, restorative materials and medical mouthwashes.