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Multiplexed microRNA (miRNA) detection has proven valuable in disease diagnosis; yet, the development of advanced tools for their analysis remains a subject of broad interest. Here, we propose a novel single-particle method for multiplexed miRNA detection using self-directed hydrogel microspheres, which feature supersegmented compartments for loading analyte probes and an air-encapsulated region that grants the microsphere a unique preferred posture in aqueous solutions. By exploiting microfluidic technology, we can widely adjust the size of the microspheres and the number of compartments can be widely adjusted. The air-encapsulated region is located at the edge of the microsphere's symmetry axis, resulting in a spontaneous orientation that facilitates efficient multitarget signal readout in a standard manner without requiring active energy input. The microspheres exhibit excellent temperature stability, ensuring consistent performance under varying thermal conditions. Additionally, signal amplification strategies, such as hybridization chain reaction, are compatible with microspheres, enabling sensitive miRNA quantification. As a concept of proof, precise miRNA detection was demonstrated using these features. We hope that the proposed biocompatible microsphere tools will find broader application prospects in various clinical diagnostic settings.

Integrating structural colors and conductivity into aqueous inks has the potential to revolutionize wearable electronics, providing flexibility, sustainability, and artistic appeal to electronic components. This study aims to introduce bioinspired color engineering to conductive aqueous inks. Our self-assembly approach involves mixing poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with sulfonic acid-modified polystyrene (sPS) colloids to generate non-iridescent structural colors in the inks. This spontaneous structural coloration occurs because PEDOT:PSS and sPS colloids can self-assemble into core-shell structures and reversibly cluster into photonic aggregates of maximally random jammed packing within the aqueous environment, as demonstrated by small-angle X-ray scattering. Dissipative particle dynamics simulation confirms that the self-assembly aggregation of PEDOT:PSS chains and sPS colloids can be manipulated by the polymer-colloid interactions. Utilizing the finite-difference time-domain method, we demonstrate that the photonic aggregates of the core-shell colloids achieve close to maximum jammed packing, making them suitable for producing vivid structural colors. These versatile conductive inks offer adjustable color saturation and conductivity, with conductivity levels reaching 36 S cm -1 through the addition of polyethylene glycol oligomer, while enhanced water resistance and mechanical stability are achieved by doping with a cross-linker, poly(ethylene glycol) diglycidyl ether. With these unique features, the inks can create flexible, patterned circuits through processes like coating, writing, and dyeing on large areas, providing eco-friendly, visually appealing colors for customizable, stylish, comfortable, and wearable electronic devices.

Methyl iodide (CH 3 I) gas as a toxic gas causes great harm to organisms due to its high volatility and high reactivity with biological nucleophiles. Unfortunately, the sensing and detection of CH 3 I gas are challenging because of the diffusive nature of the gases and its low concentrations in the environment. Herein, we have developed a fast, green, and sensitive CH 3 I gas visual sensing method based on the capture technology of toxic gases by natural deep eutectic solvents (NADESs) coupled to the halide rapid exchange capability of perovskite nanocrystals (PNCs). In this strategy, NADESs are used as an absorption solution to adsorb gaseous CH 3 I, while simultaneously exposing I - through the action of the nucleophilic reagent; then, CsPbBr 3 PNCs were synthesized in NADESs and used as sensing material to achieve I - exchange. Benefiting from the capture and enrichment of CH 3 I gas, the sensitivity of the gas sensor was highly improved. The sensor exhibited the lowest detection limit (limits of detection) of 164.15 μmol/m 3 , below the minimum safe level for human inhalation, which is 200 μmol/m 3 . This breakthrough offers greater possibilities for the quantitative detection of CH 3 I gas.

Long nanowires offer an increased surface area for biomolecule immobilization, facilitating enhanced binding capacity and sensitivity in the detection of target analytes. However, robust long-nanowire fabrication remains a significant challenge. In this paper, we developed a novel construction of a micro chemical pen (MCP), called a clean-assisted micro chemical pen (CAMCP), for robust long-nanowire fabrication. CAMCP, based on localized hydrodynamic flow confinement, was conducted by incorporating a clean phase to effectively dissolve aggregated silver particles in the aspiration channel's shell, thereby enhancing the MCP's longevity by 60.84%, allowing for an 840 μm extension in nanowire patterning capability. A 4600-aspect ratio (length:1200 μm, width: 260 nm) nanowire was fabricated by CAMCP and utilized as a nanowire sensor, showing a 39.7% increase in IgA detection sensitivity compared to a 3000-aspect ratio sensor. Furthermore, the longer nanowire sensor exhibited enhanced signal responses, a higher signal-to-noise ratio, and a lower limit of detection (LOD). The preponderant bioassay performances of the longer nanowire sensor in bioassays, facilitated by CAMCP, open up its possibilities for chemical-synthesis nanowires (NWs) in ultrasensitive biodetection.

With the advantages of high-throughput manufacturing and customizability, on-microsphere construction of in vitro multicellular analytical systems has garnered significant attention. However, achieving a precise, biocompatible cell arrangement and spatial signal analysis in hydrogel microspheres remains challenging. In this work, a microfluidic method is reported for the biocompatible generation of addressable supersegmented multicompartmental microspheres. Additionally, these microspheres are developed as novel label-free multicellular systems. In the microfluidic approach, controllable microfluidics is used to finely tune the internal microstructure of the microspheres, and the gas ejector ensures the biocompatibility of the preparation process. As a proof of concept, six- and twenty-compartment microspheres were obtained without the addition of any biohazardous reagents. For microsphere decoding, the visualization of two basic compartments can provide clues for identifying label-free cells due to the structural regularity of the microspheres. Finally, by encapsulating cells of different types, these microspheres as multicellular systems were successfully used for cell coculture and drug testing. These biocompatible, scalable, and analyzable microspheres will open up new prospects for biomedical analysis.

The construction of isotypic high-nuclearity inorganic cages with identical pristine parent structure and increasing nuclearity is highly important for molecular growth and structure-property relationship study, yet it still remains a great challenge. Here, we provide an in situ growth approach for successfully synthesizing a series of new giant hollow polymolybdate dodecahedral cages, Mo 250 , Mo 260 -I , and Mo 260 -E , whose structures are growth based on giant polymolybdate cage Mo 240 . Remarkably, they show two pathways of nuclear growth based on Mo 240 , that is, the growth of 10 and 20 Mo centers on the inner and outer surfaces to afford Mo 250 and Mo 260 -I , respectively, and the growth of 10 Mo centers both on the inner and outer surfaces to give Mo 260 -E . To the best of our knowledge, this is the first study to display the internal and external nuclear growth of a giant hollow polyoxometalate cage. More importantly, regular variations in structure and nuclearity confer these polymolybdate cages with different optical properties, oxidative activities, and hydrogen atom transfer effect, thus allowing them to exhibit moderate to excellent photocatalytic performance in oxidative cross-coupling reactions between different unactivated alkanes and N-heteroarenes. In particular, Mo 240 and Mo 260 -E with better comprehensive abilities can offer the desired coupling product with yield up to 92% within 1 h.

Tin perovskite solar cells (TPSCs) were developed by adding the co-cations acetamidinium (AC) and rubidium (Rb) in varied proportions based on the FASnI 3 structure (E1). We found that adding 10% AC and 3% Rb can optimize the device (E1AC10Rb3) to attain an efficiency of power conversion of 14.5% with great shelf- and light-soaking stability. The films at varied AC and Rb proportions were characterized using XPS, SEM, AFM, GIWAXS, XRD, TOPAS, TOF-SIMS, UV-vis, PL, TCSPC, and femtosecond TAS techniques to show the excellent optoelectronic properties of the E1AC10Rb3 film in comparison to those of the other films. AC was found to have the effect of passivating the vacancy defects on the surface and near the bottom of the film, while Rb plays a pivotal role in passivating the bottom interface between perovskite and PEDOT:PSS. Therefore, the E1AC10Rb3 device with a band gap of 1.43 eV becomes a promising candidate as a narrow band gap device for tandem lead-free perovskite solar cell development.

Mitochondria (MT) and the endoplasmic reticulum (ER) maintain lipid and calcium homeostasis through membrane contacts, particularly MT-ER contacts (MERCs), spanning distances from 10 to 50 nm. However, the variation of different distance ranges and the metabolic factors influencing this variation remain poorly understood. This study employed microfluidic chip-based super-resolution microscopy in conjunction with a Moore-Neighbor tracing-incorporated organelle proximity analysis algorithm. This approach enabled precise three-dimensional localization of single-fluorescence protein molecules within narrow and irregular membrane proximities. It achieved lateral localization precision of less than 20 nm, resulting in a minimum MERC distance of approximately 8 nm in spatial and mean distances across multiple threshold ranges. Additionally, we demonstrated that the MERC distance variation was correlated with MT size rather than ER width. The proportion of each distance range varied significantly after the stimuli. Free cholesterol showed a negative correlation with various distances, while distances of 10-30 nm were associated with glucose, glutamine, and pyruvic acid. Furthermore, the 30-40 nm range was influenced by citric acid. These results underscore the role of advanced subcellular organelle analysis in elucidating the single-molecule behavior and organelle morphology in single-cell studies.

This study developed a class of novel structural antifungal hydrazylnaphthalimidols (HNs) with multitargeting broad-spectrum potential via multicomponent hybridization to confront increasingly severe fungal invasion. Some prepared HNs exhibited considerable antifungal potency; especially nitrofuryl HN 4a (MIC = 0.001 mM) exhibited a potent antifungal activity against Candida albicans , which is 13-fold higher than that of fluconazole. Furthermore, nitrofuryl HN 4a displayed low cytotoxicity, hemolysis and resistance, as well as a rapid fungicidal efficacy. Preliminary mechanistic investigations revealed that nitrofuryl HN 4a could inhibit lactate dehydrogenase to decrease metabolic activity and promote the accumulation of reactive oxygen species, leading to oxidative stress. Moreover, nitrofuryl HN 4a did not exhibit membrane-targeting ability; it could embed into DNA to block DNA replication but could not cleave DNA. These findings implied that HNs are promising as novel structural scaffolds of potential multitargeting broad-spectrum antifungal candidates for treating fungal infection.

Efficient and convenient delivery of exogenous molecules into cells is important for cell biology research. However, many intracellular delivery methods require carrier-mediated or physical field assistance, complicating the delivery process. Here, a general, simple, and effective method for in situ single-cell intracellular delivery is reported. A solution containing digitonin and cargo is precisely applied to single cells using a microfluidic probe. Digitonin binds to cholesterol in the plasma membrane to induce perforation, and the cargo enters the cell through the pore. By optimizing parameters, propidium iodide (0.67 kDa) and FITC-dextran (10, 40, and 150 kDa) can be successfully introduced into single cells within 3 min while maintaining cell viability. To prove the potential of this method for cell research, we delivered cytochrome C (13 kDa) and cyclophilin A (18 kDa) into cells by this method. The delivered cytochrome C successfully induces cell apoptosis by activating the caspase pathway, and cyclophilin A performs an antioxidant effect in the cells, which may enhance the drug resistance of glioma cells. It is believed that this method will be an attractive tool for single-cell intracellular delivery.

Due to incommensurability between initial thickness and interdomain distance, thermal annealing inevitably produces relief surface terraces (islands and holes) of various morphologies in thin films of block copolymers. We have demonstrated three kinds of surface terraces in blend films: polygrain terraces with diffuse edges, polygrain terraces with step edges, and pseudo-monograin terraces with island coarsening. The three morphologies were obtained by three different thermal histories, respectively. The thermal histories were imposed on blend films, which were prepared by mixing a homopolystyrene (hPS, 6.1 kg/mol) with a weakly segregated, symmetry polystyrene-block poly(methyl methacrylate) (PS- b -PMMA, 42 kg/mol) followed by spin coating. At a given weight-fraction ratio of PS- b -PMMA/hPS = 75/25, the interior of the blend films forms parallel cylinders. Nevertheless, the surface of the blend films is always dominated by a skin layer of perforations, which epitaxially grow on top of parallel cylinders. By oxygen plasma etching at various time intervals to probe interior nanodomains, the epitaxial relationship between surface perforations and parallel cylinders has been identified by a scanning electron microscope.

Understanding the relationship between the surface properties of a single plasmonic nanoparticle and its catalytic performance is critical for developing highly efficient nanocatalysts. In this study, a one-shot dual-detection-based single-molecule super-resolution imaging method in the evanescent field was developed to observe real-time spatiotemporal catalytic activity on a single plasmonic gold nanoparticle (AuNP) surface. The scattering intensity of AuNPs and the fluorescence of resorufin molecules produced on the AuNP surface were obtained simultaneously to investigate the relationship between nanoparticles and catalytic reactions at a single-molecule level. Chemisorbed adsorbates (i.e., catalytic product and resorufin) changed the electron density of individual AuNPs throughout the catalytic cycle, resulting in the fluctuation of the scattering intensity of individual AuNPs, which was attributed to the electron transfer between reactant resazurin molecules and AuNPs. The increase in the electron density of individual AuNPs affected the catalytic reaction rate. Furthermore, sequential mapping of individual catalytic events at the subdiffraction limit resolution was completed for real-time surface dynamics and spatiotemporal activity variations on the single AuNP surface. The developed method can aid in understanding surface-property-dependent catalytic kinetics and facilitate the development of nanoparticle-based heterogeneous catalysts at subdiffraction limit resolution.

The high-performance Y6-based nonfullerene acceptors (NFAs) feature a C-shaped A-DA'D-A-type molecular architecture with a central electron-deficient thiadiazole (Tz) A' unit. In this work, we designed and synthesized a new A-D-A-type NFA, termed CB16, having a C-shaped ortho -benzodipyrrole-based skeleton of Y6 but with the Tz unit eliminated. When processed with nonhalogenated xylene without using any additives, the binary PM6:CB16 devices display a remarkable power conversion efficiency (PCE) of 18.32% with a high open-circuit voltage ( V oc ) of 0.92 V, surpassing the performance of the corresponding Y6-based devices. In contrast, similarly synthesized SB16, featuring an S-shaped para -benzodipyrrole-based skeleton, yields a low PCE of 0.15% due to the strong side-chain aggregation of SB16. The C-shaped A-D N B N D-A skeleton in CB16 and the Y6-series NFAs constitutes the essential structural foundation for achieving exceptional device performance. The central Tz moiety or other A' units can be employed to finely adjust intermolecular interactions. The single-crystal X-ray structure reveals that ortho -benzodipyrrole-embedded A-D N B N D-A plays an important role in the formation of a 3D elliptical network packing for efficient charge transport. Solution structures of the PM6:NFAs detected by small- and wide-angle X-ray scattering (SWAXS) indicate that removing the Tz unit in the C-shaped skeleton could reduce the self-packing of CB16, thereby enhancing the complexing and networking with PM6 in the spin-coating solution and the subsequent device film. Elucidating the structure-property-performance relationships of A-DA'D-A-type NFAs in this work paves the way for the future development of structurally simplified A-D-A-type NFAs.

Precise sampling of undissolved chemical components from subcellular regions of living single cells is a prerequisite for their in-depth analysis, which could promote understanding of subtle early stage physiological or pathological processes. Here we report a microfluidic method to extract undissolved components from subcellular regions for MS analysis. The target single cell was isolated by the microchamber beneath the microfluidic probe and washed by the injected biocompatible isotonic glucose aqueous solution (IGAS). Then, the sampling solvent was injected to extract undissolved components from the expected subcellular region of the living single cell, where the position and size of the sampling region could be controlled. The components immobilized by undissolved cellular structures were proven to be successfully extracted. Since unextracted subcellular regions were protected by IGAS, the single cell could survive after a tiny part was extracted, providing the possibility of repetitive sampling of the same living cell. Phospholipids extracted from the subcellular regions were successfully identified. The results demonstrated the feasibility of our method for subcellular sampling and analysis.

Hyaluronidase (HAase) is a biomarker for cancer, and its detection is of great significance for early diagnosis. However, the requirement of sophisticated instruments, tedious operation procedures, and labeled molecules of conventional HAase biosensing methods hampers their widespread applications. Herein, we report a portable slippery viscosity-sensing platform with time readout for the first time and demonstrate HAase and tannic acid (TA, HAase inhibitor) detection as a model system. HAase specifically cleaves hyaluronic acid (HA) and decreases HA solution viscosity, thereby shortening the aqueous droplet's sliding time on a slippery surface. Thus, the HA solution viscosity alteration due to enzymatic hydrolysis is used to quantify the HAase concentration through the difference in the sliding time of the aqueous droplets on a slippery surface. The developed HAase sensing platform exhibits high sensitivity with a minimum detection limit of 0.23 U/mL and excellent specificity without the use of specialized instruments and labeled molecules. HAase detection in actual urine samples by a standard addition method is performed as well. Moreover, the quantitative detection of TA with an IC 50 value of 37.68 ± 1.38 μg/mL is achieved. As an equipment-free, label-free, and high-portability sensing platform, this method holds promise in developing a user-friendly and inexpensive point-of-care testing (POCT) device for HAase detection, and its use can be extended to analyze other analytes with different stimuli-responsive polymers for great universality and expansibility in biosensing applications.

This study has demonstrated how oxygen plasma etching carves surface structures for thin films of polystyrene- block -poly(methyl methacrylate)/homopolystyrene blends. By tuning the weight-fraction ratio, blend films form perforations and cylinders on the SiO x /Si substrate. Since perforations exist only on the free surface and substrate interface, short exposure to oxygen plasma to quickly etch the PMMA component produces distorted hexagonal arrays of nanodots on the free surface. The interior of the blend films forms polygrain micro-structures composed of parallel cylinders with an in-plane random orientation. Oxygen plasma etching imposed on the fractured surfaces results in five morphologies: (i) distorted hexagonal arrays of nanoholes, (ii) layer-by-layer stacks, (iii) zigzag-like arrays, (iv) intertwined rectangular arrays of nanodots and nanoholes, and (v) intertwined parallelogram arrays of nanodots and nanoholes. The morphologies suggest synergic effects of grain orientations, stresses, spatial confinement, local segregation of chains, and etching kinetics on the terraced films with oxygen plasma etching.

Plyfluoroalkyl substance (PFAS), featured with incredible persistence and chronic toxicity, poses an emerging ecological and environmental crisis. Although significant progress has been made in PFAS metabolism in vivo, the underlying mechanism of metabolically active organ interactions in PFAS bioaccumulation remains largely unknown. We developed a microfluidic-based assay to recreate the intestine-vessel-liver interface in three dimensions, allowing for high-resolution, real-time images and precise quantification of intestine-vessel-liver interactions in PFAS biotransformation. In contrast to the scattered arrangement of vascular endothelium on the traditional d-polylysine-modified two-dimensional (2D) plate, the microtubules in our three-dimensional (3D) platform formed a dense honeycomb network through the ECM, with longer tubular structures. Additionally, the slope culture of epithelial cells in our platform exhibited a closely arranged and thicker cell layer than the planar culture. To dynamically monitor the metabolic crosstalk in the intestinal-vascular endothelium-liver interaction under exposure to fluorotelomer alcohols (FTOHs), we combined the chip with a solid-phase extraction-mass spectrometry (SPE-MS) system. Our findings revealed that endothelial cells were involved in the metabolic process of FTOHs. The transformation of intestinal epithelial and hepatic epithelial cells produces toxic metabolite fluorotelomer carboxylic acids (FTCAs), which circulate to endothelial cells and affect angiogenesis. This system shows promise as an enhanced surrogate model and platform for studying pollutant exposure as well as for biomedical and pharmaceutical research.

Confinement of chemical species in a controllable micrometer-level (several to a dozen micrometers) space in an aqueous environment is essential for precisely manipulating chemical events in subcellular regions. However, rapid diffusion and hard-to-control micrometer-level fluids make it a tough challenge. Here, a versatile open microfluidic method based on an aqueous two-phase system (ATPS) is developed to restrict species inside an open space with micron-level width. Unequal standard chemical potentials of the chemical species in two phases and space-time correspondence in the microfluidic system prevent outward diffusion across the phase interface, retaining the target species inside its preferred phase flow and creating a sharp boundary with a dramatic concentration change. Then, the chemical flow (the preferred phase with target chemical species) is precisely manipulated by a microfluidic probe, which can be compressed to a micron-level width and aimed at an arbitrary position of the sample. As a demonstration of the feasibility and versatility of the strategy, chemical flow is successfully applied to subcellular regions of various kinds of living single cells. Subcellular regions are successfully labeled (cytomembrane and mitochondria) and damaged. Healing-regeneration behaviors of living single cells are triggered by subcellular damage and analyzed. The method is relatively general regarding the species of chemicals and biosamples, which could promote deeper cell research.

The development of liquid crystal (LC)-based sensors with superior performances such as high portability, excellent stability, great convenience, and remarkable sensitivity is highly demanded. This work proposes a new strategy for constructing the LC-based sensor using enzyme-linked dual-functional nucleic acid (d-FNA) on magnetic beads (MBs). The detection of kanamycin (KA) is demonstrated as a model. Acetylcholinesterase (AChE) is assembled onto the KA aptamer-modified MBs with a d-FNA strand that consists of an AChE aptamer and the complementary sequence of a KA aptamer. As the specific recognition of KA by its aptamer triggers the release of AChE from the MBs, the myristoylcholine (Myr) solution after incubation with the MBs causes the black image of the LCs due to the formation of the Myr monolayer at the aqueous/LC interface. Otherwise, in the absence of KA, AChE is still decorated on the MBs and causes the hydrolysis of Myr. Therefore, a bright image of LCs is obtained. The detection of KA is successfully achieved with a lower detection limit of 48.1 pg/mL. In addition, a thin polydimethylsiloxane (PDMS) layer-coated glass and a portable optical device are used to improve the stability and portability of the LC-based sensor to advance potential commercial applications. Furthermore, the detection of KA in milk with a portable device is demonstrated, showing the potential of the proposed enzyme-linked LC-based sensor.

A multifunctional platform that meets the demands of both bacterial detection and elimination is urgently needed because of their harm to human health. Herein, a "sense-and-treat" biosensor was developed by using immunomagnetic beads (IMBs) and AgPt nanoparticle-decorated PCN-223-Fe (AgPt/PCN-223-Fe, PCN stands for porous coordination network) metal-organic frameworks (MOFs). The synthesized AgPt/PCN-223-Fe not only exhibited excellent peroxidase-like activity but also could efficiently kill bacteria under near infrared (NIR) irradiation. This biosensor enabled the colorimetric detection of E. coli O157:H7 in the range of 10 3 -10 8 CFU/mL with a limit of detection of 276 CFU/mL, accompanied with high selectivity, good reproducibility, and wide applicability in diverse real samples. Furthermore, the biosensor possessed a highly effective antibacterial rate of 99.94% against E. coli O157:H7 under 808 nm light irradiation for 20 min. This strategy can provide a reference for the design of novel versatile biosensors for bacterial discrimination and antibacterial applications.

Early detection of foodborne bacteria is urgently needed to ensure food quality and to avoid the outbreak of foodborne bacterial diseases. Here, a kind of metal-organic framework (Zr-MOF) modified with Pt nanoparticles (Pt-PCN-224) was designed as a peroxidase-like signal amplifier for microfluidic biosensing of foodborne bacteria. Taking Escherichia coli ( E. coli ) O157:H7 as a model, a linear range from 2.93 × 10 2 to 2.93 × 10 8 CFU/mL and a limit of detection of 2 CFU/mL were obtained. The whole detection procedure was integrated into a single microfluidic chip. Water, milk, and cabbage samples were successfully detected, showing consistency with the results of the standard culture method. Recoveries were in the range from 90 to 110% in spiked testing. The proposed microfluidic biosensor realized the specific and sensitive detection of E. coli O157:H7 within 1 h, implying broad prospects of MOF with biomimetic enzyme activities for biosensing.

While the difference in catalytic reactivity between mono- and multimetallic sites is often attributed to more than just the number of active sites, still few catalyst model systems have been developed to explore more underlying causal factors. In this work, we have elaborately designed and constructed three stable calix[4]arene (C4A)-functionalized titanium-oxo compounds, Ti-C4A , Ti 4 -C4A , and Ti 16 -C4A , with well-defined crystal structures, increasing nuclearity, and tunable light absorption capacity and energy levels. Among them, Ti-C4A and Ti 16 -C4A can be taken as model catalysts to compare the differences in reactivity between mono- and multimetallic sites. Taking CO 2 photoreduction as the basic catalytic reaction, both compounds can achieve CO 2 -to-HCOO - conversion with high selectivity (close to 100%). Moreover, the catalytic activity of multimetallic Ti 16 -C4A is up to 2265.5 μmol g -1 h -1 , which is at least 12 times higher than that of monometallic Ti-C4A (180.0 μmol g -1 h -1 ), and is the best-performing crystalline cluster-based photocatalyst known to date. Catalytic characterization combined with density functional theory calculations shows that in addition to the advantage of having more metal active sites (for adsorption and activation of more CO 2 molecules), Ti 16 -C4A can effectively reduce the activation energy required for the CO 2 reduction reaction by completing the multiple electron-proton transfer process rapidly with synergistic metal-ligand catalysis, thus exhibiting superior catalytic performance to that of monometallic Ti-C4A . This work provides a crystalline catalyst model system to explore the potential factors underlying the difference in catalytic reactivity between mono- and multimetallic sites.

Developing advanced tools for multicomponent analysis is an open challenge in engineering and life science. Herein, multicompartmental hydrogel microspheres with multi-material compatibility and structural scalability are developed as a tool for multicomponent analysis at a single-particle level. Microfluidic technology endows particles with adjustable sizes and super-segmented layouts that can be used to load various analyte probes. In order to perform multicomponent analysis, these microspheres are structurally divided into identifier regions for indicating reading direction and analyte regions for detecting target molecules. The multiplex detection ability of these particles is demonstrated in microRNA bioassays with high specificity and sensitivity. The multi-target analysis is performed on a single-particle level, and the bioassay is free of conventional labeling interference. We expect these particles to reach their potential in clinical diagnostics.

Tumor-stroma interaction is the core process of tumor metastasis. Therefore, building a model of tumor-stromal cell communication is crucial for understanding the tumor metastasis process and curing cancer completely. In this research, a controllable three-dimensional (3D) tumor-stroma coculture microsphere model based on droplet microfluidic technology was developed to culture human lung cancer cells (A549 cell) and fibroblast cells (NIH-3T3 cell) using core-shell hydrogel microspheres to partition different kinds of cells. In our coculture model, tumor cells show a trend of epithelial-mesenchymal transition (EMT): a decrease in the number of surface E-cadherin and an increase in the number of N-cadherin. At the same time, fibroblasts are activated into cancer-associated fibroblasts (CAFs) as the level of interleukin-6 (IL-6) released is increased. In addition, an interesting phenomenon was discovered; in the absence of fibroblasts, the metabolism of the tumor cell culture alone leads to arginine depletion and citrulline accumulation, whereas a coculture can maintain the arginine-ornithine-citrulline cycle to reach equilibrium after 72 h, and the balance increases the stress resistance of tumor cells. This discovery may provide a new direction for understanding tumor resistance.

Rational design of crystalline catalysts with superior light absorption and charge transfer for efficient photoelectrocatalytic (PEC) reaction coupled with energy recovery remains a great challenge. In this work, we elaborately construct three stable titanium-oxo clusters (TOCs, Ti 10 Ac 6 , Ti 10 Fc 8 , and Ti 12 Fc 2 Ac 4 ) modified with a monofunctionalized ligand (9-anthracenecarboxylic acid (Ac) or ferrocenecarboxylic acid (Fc)) and bifunctionalized ligands (Ac and Fc). They have tunable light-harvesting and charge transfer capacities and thus can serve as outstanding crystalline catalysts to achieve efficient PEC overall reaction, that is, the integration of anodic organic pollutant 4-chlorophenol (4-CP) degradation and cathodic wastewater-to-H 2 conversion. These TOCs can all exhibit very high PEC activity and degradation efficiency of 4-CP. Especially, Ti 12 Fc 2 Ac 4 decorated with bifunctionalized ligands exhibits better PEC degradation efficiency (over 99%) and H 2 generation than Ti 10 Ac 6 and Ti 10 Fc 8 modified with a monofunctionalized ligand. The study of the 4-CP degradation pathway and mechanism revealed that such better PEC performance of Ti 12 Fc 2 Ac 4 is probably due to its stronger interactions with the 4-CP molecule and better • OH radical production. This work not only presents the effective combination of organic pollutant degradation and simultaneously H 2 evolution reaction using crystalline coordination clusters as both anodic and cathodic catalyst but also develops a new PEC application for crystalline coordination compounds.

Fabrication and application of novel anisotropic microparticles are of wide interest. Herein, a new method for producing novel crater-terrain hydrogel microparticles is presented using a concept of droplet-aerosol impact and regional polymerization. The surface pattern of microparticles is similar to the widespread "crater" texture on the lunar surface and can be regulated by the impact morphology of aerosols on the droplet surface. Methodological applicability was demonstrated by producing ionic-cross-linked (alginate) and photo-cross-linked (poly(ethylene glycol) diacrylate, PEGDA) microparticles. Additionally, the crater-terrain microparticles (CTMs) can induce nonspecific protein absorption on their surface to acquire cell affinity, and they were exploited as cell carriers to load living cells. Cells could adhere and proliferate, and a special cellular adhesion fingerprint was observed on the novel cell carrier. Therefore, the scalable manufacturing method and biological potential make the engineered microparticles promising to open a new avenue for exploring cell-biomaterial crosstalk.

Mass spectrometry (MS) is a powerful tool for exploring single-cell heterogeneity. However, due to the ultralow absolute content of most substances in a single cell, existing methods can only analyze high-content substances; conventional methods are incompetent for quantitative analysis of important trace-amount small-molecule metabolites such as ammonia and sulfide. Herein, a method integrating single-cell extraction, online derivatization, and MS for multifunctional and more accurate MS analysis is reported. For application, ammonia content in a single cell was analyzed, where the cellular heterogeneity in ammonia metabolism was revealed. First, the extraction room of a microfluidic probe was covered on the target single cell, and the extraction fluid was allowed to flow through a single cell and dissolve cellular ammonia. Then, the ammonia was mixed and reacted with the pretreatment reagent input from another inlet to achieve the derivatization and signal amplification, enhancing the analysis sensitivity on MS. Finally, the sample was sent to MS, and the ammonia content was successfully quantitatively evaluated by analyzing its derivative urotropine, demonstrating the potential of this method to advance single-cell mass spectrometry analysis to higher sensitivity.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is commonly applied to the identification of bacteria but rarely used for quantitative detection due to the inhomogeneous crystallization of the matrix leading to the unsatisfactory linear relationship between the sample amount and the mass spectrum signals. Herein, we proposed a noninterference ion addition (NIA) method by electrolysis to improve homogeneous crystallization during the evaporation progress of sample droplets on the target plates. The active metal wire was inserted in the droplet as the anode electrode, and metal ions were released through electrolysis. The directional migration of metal ions under the electric field can hinder the migration of matrix molecules to the boundary and homogenize the matrix crystals by forming spherical crystals. Simultaneously, trace cationic surfactant was added to the droplet for pinning the contact surface to define the circle crystallization region. The metal ions from the anode electrode wire were deposited on the surface of the target plates which served as the cathode. Therefore, ion addition has no interference effect on ionization during MALDI-MS detection. This NIA method benefits the homogeneous crystallization and so improves the quantitative analysis. NIA is suitable for biological samples with different matrices, and bacterial samples could be quantitatively analyzed.

This work presented an alternative approach for studying bacteria-cell interactions in three-dimensional (3D) hydrogel microspheres formed by the cross-linking reaction of alginate and calcium-ethylenediaminetetraacetic acid (EDTA-Ca) produced in a microfluidic chip. During the co-culture process of hepatocytes (HepG2) and Escherichia coli ( E. coli ) 25922, we concluded that the content change of tryptophan metabolites detected via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was related to the cell damage level and the change of interleukin (IL-22) detected by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) was related to the ways of co-cultivation. Compared to the two-dimensional (2D) adherent cell culture process in a Petri dish (2D), the co-culture process of HepG2 and E. coli 25922 in hydrogel microspheres indicated more information about metabolism such as the appearance of indole-3-propionic acid (IPA) and possibly IL-22. The method provides a new perspective to investigate the bacteria-cell interaction and it could be a promising tool in the study of gut microbiota and human health.

Human pancreatic lipase is a symbolic biomarker for the diagnosis of acute pancreatitis, which has profound significance for clinical detection and disease treatment. Herein, we first demonstrate a paper-based lipase sensor via a phase separation-induced viscosity change. Lipase catalyzes triolein to produce oleic acid and glycerol. Adding an excess of Ca 2+ produces calcium oleate. The remaining Ca 2+ binds with sodium alginate, triggering hydrogelation with an "egg-box" structure. The viscosity change of the aqueous solution induced by the phase separation process can be quantified by measuring the solution flow distance on a pH test paper. The paper-based lipase sensor has high sensitivity with a detection limit of 0.052 U/mL and also shows excellent specificity. Additionally, it is also utilized for quantitative lipase analysis in human serum samples to exhibit its potency in acute pancreatitis detection. This method overcomes the drawbacks of low sensitivity, slow response, and poor reproducibility caused by the nonuniform distribution of the highly viscous hydrogel on the sensing interface in existing approaches. In conclusion, thanks to the prominent characteristics of high portability, low cost, and easy operation, it is prospective for simple quantitative detection of lipase and has great potential for commercialization.

A portable microfluidic biosensor was developed for the detection of E. coli O157:H7 using finger actuation. The chip was assembled with three functional zones, immunomagnetic separation, nucleic acid extraction and purification, and signal detection. First, antibody-modified magnetic nanoparticles (MNPs) were used to separate the target bacteria from the sample. The captured bacteria were then lysed and silica-coated MNPs were used to absorb DNA, followed by washing and eluting to obtain purified DNA. The obtained DNA was subjected to amplification and fluorescence detection based on the recombinase polymerase amplification-clustered regularly interspaced short palindromic repeat-associated protein/Cas12a reaction. The fluorescence images were collected and analyzed using a smartphone app under a 3D-printed detection device. It could quantitatively detect E. coli O157:H7 from 10 2 to 10 8 CFU/mL in 2.5 h with a limit of detection (LOD) of 10 CFU/mL. The recovery rate ranged from 104 to 120%. Overall, the biosensor realizes "sample-in and answer-out" assay for E. coli O157:H7 and eliminates the need for external pumps and skilled personnel.

Discovering the fungus-infected or mycotoxin-contaminated biomarkers is significant for systems biology since the metabolites in biological samples have significant polarity differences in both stochastic gene expression and microenvironmental change. Here, we aim to establish a comprehensive method for a lipidome by ion mobility mass spectrometry (IMS) merged with chemometrics to accurately find out the more scientific markers of cell interference by mycotoxins and for pathogenesis exploration and drug development. The differences in the abundances of several small molecules found in these metabolites were explored through multivariate statistical analysis, including principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA), to further screen biomarkers. Good applicability and predictability were demonstrated by R 2 ( X ) and Q 2 ( R 2 = 0.959, Q 2 = 0.999). Five compounds with m / z values of 512.502 8, 540.5343, 722.525 8, 787.667 5, and 813.683 0 were selected as markers, and four of them were further confirmed by chemical standards (i.e., MSMS of m / z 813.683 0 covering m / z 86.0978, 125.0008, 184.0745, and 185.0781). In summary, we demonstrated the integration of UPLC-TOF-IMS and the chemometrics approach to elucidate identified biomarkers, which also provides a new way of thinking for covering lipid biomarkers or prognostic indicators for mycotoxins.

Microglia are the main immune cells in the brain playing a critical role in neuroinflammation, and numerous pieces of evidence have proved that energy metabolism is closely associated with inflammation in activated microglia. Salidroside (Sal) isolated from Tibetan medicine Rhodiola crenulate can inhibit microglial hypoxia inflammation (HI). However, whether the inhibition is due to the intervening energy metabolic process in microglia is not clear. In this work, the hypoxic microenvironment of BV2 microglial cells was simulated using deferoxamine (DFO) in vitro and the change of cell metabolites (lactate, succinate, malate, and fumarate) was real-time online investigated based on a cell microfluidic chip-mass spectrometry (CM-MS) system. Meanwhile, for confirming the metabolic mechanism of BV2 cells under hypoxia, the level of HI-related factors (LDH, ROS, HIF-1α, NF-κB p65, TNF-α, IL-1β, and IL-6) was detected by molecular biotechnology. Integration of the detected results revealed that DFO-induced BV2 cell HI was associated with the process of energy metabolism, in which cell energy metabolism changed from oxidative phosphorylation to glycolysis. Furthermore, administration of Sal treatment could effectively invert this change, and two metabolites of Sal were identified: tyrosol and 4-hydroxyphenylacetic acid. In general, we illustrated a new mechanism of Sal for reducing BV2 cell HI injury and presented a novel analysis strategy that opened a way for real-time online monitoring of the energy metabolic mechanism of the effect of drugs on cells and further provided a superior strategy to screen natural drug candidates for HI-related brain disease treatment.

Negative air ions (NAIs) produced by corona discharge is often used for indoor air purification; however, the specific aggregation of suspended particles caused by NAIs, especially fine particles (FPs), needs to be considered. Here, a nickel coated conductive sponge (NCCS) was used as the main adsorption interface for delaying the obstinate aggregation caused by NAIs on another surface. The specific aggregation of FPs is caused by the directional transfer of electric charge, and the oxidation characteristic of NAIs results in the surface reaction of FPs simultaneously. The conductivity and roughness of the adsorption interface determine the migration direction and enrichment number of FPs, respectively. Nickel coated conductive sponge with high conductivity and high specific surface area can effectively adsorb the FPs affected by NAIs and can effectively delay the specific aggregation on the surface of indoor objects., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Hyaluronidase (HAase) is implicated in inflammation, cancer development, and allergic reaction. The detection of HAase is significantly important in clinical diagnosis and medical treatment. Herein, we propose a new principle for the development of equipment-free and label-free paper-based flow sensors based on the enzymatic hydrolysis-induced viscosity change in a stimuli-responsive polymer solution, which increases the water flow distance on the pH indicator paper. The detection of HAase is demonstrated as an example. This facile and versatile method can overcome the potential drawbacks of traditional hydrogel-based sensors, including complex preparation steps, slow response time, or low sensitivity. Moreover, it can also avoid the use of specialized instruments, labeled molecules, or functionalized nanoparticles in the sensors developed using the polymer solutions. Using this strategy, the detection of HAase is achieved with a limit of detection as low as 0.2 U/mL. Also, it works well in human urine. Additionally, the detection of tannic acid, which is an inhibitor of HAase, is also fulfilled. Overall, a simple, efficient, high-throughput, and low-cost detection method is developed for the rapid and quantitative detection of HAase and its inhibitor without the use of labeled molecules, synthetic particles, and specialized instruments. As only minimal reagents of HAase, HA, and paper are used, it is very promising in the development of commercial kits for point-of-care testing.

Pathogen infections present a considerable threat to global health owing to the high morbidity and mortality, and usually multiple pathogens coexist in food and the environment. Consequently, it is in urgent need to develop some multiplexed and sensitive approaches for pathogen detection. Here, we presented a novel strategy using mass tag-mediated surface engineering for simultaneous detection of multiple bacteria by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Following aptamer binding, primer amplification, and DNA hybridization, bacteria were specifically labeled by their corresponding mass tags, which could be released and ionized after laser irradiation. This strategy converted the detection of bacteria to the analysis of mass tags, allowing simultaneous detection of multiple bacteria and avoiding the dependence of microbial mass spectra databases. In addition, this approach applied two rolling circle amplification (RCA) reactions to improve both the capture efficiency and detection sensitivity of the target bacteria. The specificity and the real sample detection were evaluated, and the results demonstrated a potential application of this approach in milk safety monitoring.

α-Amylase (AMS) in human serum is a critical biomarker for the early diagnosis of pancreatic damage. In addition, the inhibition of α-amylase has long been thought to decrease the occurrence of diabetes. Thus, it is critical to construct a facile and convenient method for the determination of AMS and its inhibitor. In this study, we demonstrate a novel amylase sensor based on translating the viscosity change of the aqueous solution into the difference of the water diffusion length on a pH paper strip. AMS can be quantitatively detected by measuring the viscosity change of the amylopectin solution in the presence of AMS with different concentrations. The paper-based AMS sensor has a very high sensitivity with a detection limit of 0.017 U/mL and also shows excellent specificity. In addition, the inhibitory effect of acarbose on AMS is demonstrated with the IC 50 value determined to be 21.66 ± 1.13 μg/mL. Furthermore, it is also evaluated for the detection of AMS in human serum samples of healthy people and acute pancreatitis patients. The difference in amylase levels between the two groups is unambiguously distinguished. Overall, this study provides a very simple, cost-effective, equipment-free, high-throughput, and label-free method for rapid and quantitative detection of α-amylase and may have significant applications in the diagnosis of acute pancreatitis and the screening of AMS inhibitors.

Composite adsorbents based on metal-organic frameworks (MOFs) are excellent candidates for solid-phase extraction (SPE) due to their diverse chemical functionality and multilevel porosity. MOF superstructures based on self-assembly at room temperature (RT) could have less energy consumption and easier manipulation due to the larger complex geometry. The π-π stacking of the benzene ring could not only enhance the interaction toward hydrophobic or plane-structured targets but also be expected to promote the formation of the MOF superstructure. In this work, in the established RT self-assembly synthesis system, several factors were investigated to see how to obtain functional MOF superstructures with a regular geometry, among which the number of benzene rings in the ligand was mainly tested for its impact on self-assembly and adsorption capacity. By means of adsorption experiments and computational fluid dynamics (CFD) simulation, the relationship between structure and activity (SARs) was further explored. Interestingly, the MOF unit with the lowest specific surface area performed the best in adsorption. Then, the selected functional MOF superstructure and ionic liquid were used to produce the composite paper membrane facilely applied in the SPE device. After optimization of the preparation conditions and operation parameters, the established SPE-HPLC-UV method could selectively analyze tetracycline-like antibiotics in the range of 16.6-833.3 ng/g (ppb) in a meat sample. This work provided an RT synthesis method to produce a microsize MOF superstructure, with experimental and theoretical insights into the SARs, which could be expanded in the design of other MOF-based SPE composite membranes toward one group of analogues.

Efficient capture of benzoylurea insecticide (BU) residue in food is a vital procedure for food safe monitoring. Herein, a core-shell structured magnetic fluorinated covalent organic framework with good magnetic responsiveness and abundant fluorine affinity sites was successfully synthesized, suitable for magnetic solid-phase extraction (MSPE) of BUs. Using a room-temperature synthesis strategy, the magnetic fluorinated covalent organic framework was fabricated by in situ polymerization of 1,3,5-tris(4-aminophenyl) triazine (TAPT) and 2,3,5,6-tetrafluoroterephthaldehyde (TFTA) on the surface of carboxylated Fe 3 O 4 nanoparticles. The competitive adsorption experiment and molecular simulation verified that this magnetic fluorinated covalent organic framework possesses favorable adsorption affinity for BUs. This magnetic fluorinated covalent organic framework could be easily regenerated and reused at least eight times with no reduction of enrichment performance. Combining this magnetic fluorinated covalent organic framework-based MSPE with high-performance liquid chromatography-tandem mass spectrometry, a novel sensitive method for the analysis of BUs was developed. In yellow wine and fruit juice samples, good linear correlations were obtained for BUs in the range of 10-2000 and 20-4000 ng·L -1 , respectively. The limit of quantitation of the BUs ranged from 1.4 to 13.3 ng·L -1 in the two beverage matrices. Desirable precision was achieved, with intraday and interday relative standard deviations lower than 11%.

The adhesion strength of a cancer cell is a valuable biophysical marker of its metastatic potential, tightly associated with various metastatic processes; for example, cancer cells escape from a primary tumor, and circulating tumor cells (CTCs) are anchored to the vessel wall. Although constriction-based microfluidics can realize the high-throughput characterization of single-cell deformability, due to the influence of cell size heterogeneity, accurately evaluating the adhesion strength of a cancer cell at high throughputs in constriction remains difficult. In this paper, we first proposed an approach for the assessment of adhesion strength of BGC-823 and SGC-7901 cell lines at high throughputs based on a friction coefficient using the constant velocity stage of cell transit in a long-channel constriction. Cell size was proven to be independent of adhesion strength by cell detachment assay; however, it has large effects on cell transit velocity in constriction. Therefore, the linear elasticity of a completely deformed cell in constriction is simplified as a compressed spring model, effectively reducing the influence of cell size heterogeneity. Theoretically, our proposed model can well offset the influence of cell size by cell transit velocity, while our experimental results indicate that the friction coefficient has a good linear relationship with the logarithm of the adhesion strength too. Therefore, our proposed approach can realize accurate characterization of cell adhesion strength at high throughputs using long-channel constriction-based microfluidics. Hence, this work might enrich the functions of constriction-based microfluidics and bring new insights into the characterization of mechanical phenotypes.

The level of circulating tumor cells (CTCs) in blood is a predictor of metastatic cancer progress, serving as an important biomarker for cancer diagnosis, prognosis, and therapy. Currently, there are mainly two conventional strategies to distinguish CTCs, including biological property-based affinity capture and physical property-based label-free isolation. Although great progress has been made in this field, the ability to distinguish CTCs still needs to be improved further due to the cell heterogeneity. Herein, a metabolism-based isolation approach was applied to identify tumor cells according to the "Warburg effect", and a bifunctional open-space platform with fluid walls was developed for real-time monitoring and in situ capture/analysis of tumor cells. A drop-on-demand inkjet printing technique was introduced to create a single cell-containing droplet array with high throughput and high encapsulation rate, and the homogeneous crystalline matrix spots ejected from the inkjet also provided high-quality and reproducible lipid profiling. This platform could combine both microscopic image and mass data, and it has been proven to be capable of isolating and identifying CTCs in complex blood samples, making it a promising tool for evaluating the efficacy of therapy and monitoring the disease progression.

Small-molecule drugs play an important role in the treatment of various diseases. The screening of enzyme inhibitors is one of the most important means in developing therapeutic drugs. Herein, we demonstrate a liquid crystal (LC)-based screening assay assisted with enzyme catalysis-induced aptamer release for screening xanthine oxidase (XOD) inhibitors. The oxidation of xanthine by XOD prevents the specific binding of xanthine and its aptamer, which induces a bright image of LCs. However, when XOD is inhibited, xanthine specifically binds to the aptamer. Correspondingly, LCs display a dark image. Three compounds are identified as potent XOD inhibitors by screening a small library of triazole derivatives using this method. Molecular docking verifies the occupation of the active site by the inhibitor, which also exhibits excellent biocompatibility to HEK293 cells and HeLa cells. This strategy takes advantages of the unique aptamer-target binding, specific enzymatic reaction, and simple LC-based screening assay, which allows high-throughput and label-free screening of inhibitors with high sensitivity and remarkable accuracy. Overall, this study provides a competent and promising approach to facilitate the screening of enzyme inhibitors using the LC-based assay assisted with the enzyme catalysis-induced aptamer release.

It is well known that cell can response to various chemical and mechanical stimuli. Therefore, flow pressure variation induced by sample loading and elution should be small enough to ignore the physical impact on cells when we use a Chip-SPE-MS system for cells. However, most existent Chip-SPE-MS systems ignored the pressure alternation because it is extremely difficult to develop a homogeneous-flow-pressure hyphenated module. Herein, we developed an interesting fluidic isolation-assisted homogeneous-flow-pressure Chip-SPE-MS system and demonstrated that it is adequate for online high-throughput determination and quantification of the 25-hydroxyvitamin D 3 (25(OH)D 3 ) biotransformation in different cells. Briefly, the homogeneous ambient flow pressure is achieved by fluidic isolation between the cell culture channel and the SPE column, and an automatic sampling probe could accomplish the sample loading and dispensing to fulfill online pretreatment of the sample. Through this new system, the expression levels of 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ) can be determined in real time with a detection limit of 2.54 nM. In addition, the results revealed that 25(OH)D 3 metabolic activity differed significantly between normal L-02 cells and cancerous HepG2 cells. Treatment of L-02 cells with a high dose of 25(OH)D 3 was found to increase significant formation of 24,25(OH) 2 D 3 , but this change was not apparent in HepG2 cells. The presented system promises to be a versatile tool for online accurate molecule biotransformation investigation and drug screening processes.

The pathological studies of cancer tissues and cell molecules could provide an early diagnosis for the treatment of cancer. In this work, we have designed a microfluidic surface extractor (MSE). The MSE has been coupled with electrospray mass spectrometry (extraction reagent, methanol; optimum flow rate, 0.5 mL/h) to analyze the phospholipid content of different tumor cells. Three types of cancer cell lines, including A549 cells, HepG2 cells, and U87 cells, were investigated, and the principle component analysis (PCA: linear discriminant analysis (LDA), PC1 97.2%; PC2, 2.8%) was carried out to analyze the difference in the lipid contents. The LDA revealed heterogeneity among the cancer cells. The designed MSE could have potential applications in the clinical analysis of cancer tissues.

This work focused on the chemisorption of volatile organic compounds (VOCs) on particulate matter of less than 2.5 μm (PM 2.5 ). The detection results illustrated that VOCs on PM 2.5 containing hydroxyl, carbonyl, and ester groups and C x H y on PM 2.5 were sequentially decreased as 70.02, 21.35, 6.42, and 2.21%, respectively. The chemisorption mechanism showed that the stronger the electronegativity of oxygen-containing functional groups of VOCs, the easier it is to adsorb them on the silicate PM 2.5 due to hydrogen bond formation. Strong electronegative oxygen-containing functional groups readily interacted through hydrogen bonds with silanol groups, which was the main component of PM 2.5 , resulting in VOC adsorption on PM 2.5 . Negative air ions (NAIs) can weaken the offset ability of the lone pair of electrons in oxygen-containing functional groups in VOCs, which could significantly weaken the possibility of forming hydrogen bonds with silanol groups. Therefore, NAIs can effectively inhibit the adsorption between VOCs and PM 2.5 , leading to a significant reduction in VOCs on the surface of PM 2.5 .

Multiplex detection of tumor markers in blood with high specificity and high sensitivity is critical to cancer diagnosis, treatment, and prognosis. Herein, we demonstrate a strategy for simultaneous detection of multiple tumor markers in blood by functional liquid crystal (LC) sensors assisted with target-induced dissociation (TID) of an aptamer for the first time. Magnetic beads (MBs) coated with an aptamer (apt1) are employed to specifically capture target proteins in blood. After incubation of the obtained protein-coated MBs with duplexes of another aptamer (apt2) and signal DNA, sandwich complexes of apt1/protein/apt2 are formed on the MBs due to specific recognition of target proteins by apt2, which induces release of signal DNA into the aqueous solution. Subsequently, signal DNA is specifically recognized by highly sensitive DNA-laden LC sensors. Using this strategy, a 3D printed optical cell was employed to enable simultaneous detection of multiple tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and prostate specific antigen (PSA) with high specificity and high sensitivity. Overall, this effective and low-cost multiplex approach takes advantage of the easy separation of MBs, high specificity of aptamer-based recognition, and high sensitivity of functional LC sensors. Plus, it offers a performance that is competitive to that of commercial ELISA kits without potential interference from hemolysis, which makes it very promising in multiplex detection of tumor markers in clinical applications.

In sprouting angiogenesis, a key process involved in the development and the intravasation of tumor tissues, the growth of vessel sprouts, is determined by migration of single endothelial cells (ECs). This paper presents an on-chip assaying method to investigate the migration of individual ECs by simulating vessel sprouts with microchannels. When chemical stimulus is present, ECs were observed to migrate individually toward the source of factors instead of migrating collectively. The validity of this method is shown by inducing EC migration with glioma cell coculture and culture media doped with vascular endothelial growth factor (VEGF) 165. A positive correlation between cell displacement and VEGF 165 concentration was observed. Difference in migrating ability among cells was reflected by tracking single cells, which could reveal cell heterogeneity in susceptibility to stimulus., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Tumor cells respond actively to the extracellular microenvironment via biomechanical and biochemical stimulation. Microchips provide a flexible platform to integrate multiple factors for cell research. In this work, we developed a subtle microfluidic chip that can generate a controllable stiffness gradient and orthogonal chemical stimulation to study the behaviors of glioma cells. Fibronectin-conjugated polyacrylamide (PAA) hydrogel with a longitudinal stiffness gradient ranging from about 1 kPa to 40 kPa is integrated within the cell culture chamber while lateral diffusion-based chemical stimulation is generated through circumambient microchannel arrays. The synergistic effect of epidermal growth factor (EGF) stimulation and hydrogel stiffness gradient on U87-MG cell migration was studied. By tracing cell migration, we discovered that hydrogel stiffness can promote cell chemotaxis, while the EGF gradient can accelerate cell migration. In addition, cell morphology showed typical cell spreading, increased aspect ratios, and decreased circularity in response to a stiffer substrate and plateaued at a certain stiffness level. Meanwhile, the content of intracellular reactive oxygen species (ROS) on the hydrogel soft end is enhanced by approximately 2 fold compared with that on the hydrogel stiff end. The enhancement of substrate stiffness on cell chemotaxis is very significant for in vitro model simulation and tissue engineering.

Three-dimensional (3D) hydrogel microspheres have aroused increasing attention as an in vitro cell culture model. Yet the preservation of cells' original biological properties has been overlooked during model construction. Here we present an integrated microfluidic device to accomplish the overall process including cell-laden microsphere generation, online extraction, and dynamic-culture. The method extends the noninvasive and nonsuppression capabilities of the droplet preparation system and provides a constant microenvironment, which reduces intracellular oxidative stress damage and the accumulation of mitochondria. Compared to the conventional preparation method, the coculture model of tumor-endothelial construction on an integrated platform displays high-level angiogenic protein expression. We believe that this versatile and biocompatible platform will provide a more reliable analysis tool for tissue engineering and cancer therapy.

Hydrogen peroxide (H 2 O 2 ) plays a persuasive role in the human cell physiology. Developing an efficient assay platform and a highly sensitive tracking and quantification of H 2 O 2 in a physiological system is crucial to understand the neoplastic changes and/or redox homeostasis of cells. In this study, a novel turn-on latent electrochemical redox probe coupled with electrocatalytic signal amplification strategy is proposed. A custom-made readily available turn-on latent electrochemical probe 4-methoxyphenylboronic acid pinacol ester (4-MPBP) have been designed for the selective detection of endogenous H 2 O 2 in live cells. The electrochemical probe composed of a latent electrochemical reporter (4-methoxy phenol, 4-MP) bearing a recognition unit (boronic acid pinacol ester) for H 2 O 2 sensing. The selective analyte-triggered chemical transformation releases free electrochemical reporter 4-MP. The amount of H 2 O 2 was evaluated electrochemically at glassy carbon electrode (GCE) with a broad detection range of 0.5 μM-1 mM. An amplified signal response of released 4-MP to build a highly sensitive assay tool has been achieved via replacing the GCE transducer electrode with polydopamine@carbonnanotube-molebtinumdisulfie hybrid modified GCE as it delivered an exceptional dynamic detection range of 0.01-100 μM. The innovative blend of electrochemical molecular probe strategy, with electrocatalytic signal amplification technique has delivered outstanding assay performance at trace level sensing of H 2 O 2 . Next, we set up a platform for real-time in vivo monitoring of the endogenously produced H 2 O 2 in Caco-2 and MCF-7 cells through spermine-polyamine analogue and phorbol 12-myristate 13-acetate induction in SSAT/PAO gene and protein kinase C, respectively. As expected, the 4-MPBP latent probe coupled with electrocatalytic signal amplification strategy delivered outstanding performance for in situ H 2 O 2 release and tracking over time.