Multiscale Heterogeneities-Based Piezoresistive Interfaces with Ultralow Detection Limitation and Adaptively Switchable Pressure Detectability.

Mechanical compliance and electrical enhancement are crucial for pressure sensors to promote performances when perceiving external stimuli. Here we propose a bioinspired multiscale heterogeneity-based interface to adaptively regulate its structure layout and switch to desirable piezoresistive behaviors with ultralow detection limitation. In such a multiscale heterogeneities system, the micro-/nanoscale spiny Ag-MnO2 heterostructure contributes to an ultralow detection limitation of 0.008 Pa and can perceive minor pressure increments under preloads with high resolution (0.0083%). The macroscale heterogeneous orientation of the cellular backbone enables anisotropic deformation, allowing the sensor to switch to rational sensitivity and working range (e.g., 580 kPa-1 for 0-20 kPa/54 kPa-1 for 60-140 kPa) as required. The sensor's stepwise activation progresses from the micro-/nanoscale heterostructure to the macroscale heterogeneous orientation, which can adaptively match diverse sensing tasks in complex applications scenarios. This multiscale heterogeneous and switchable design holds immense potential in the development of intelligent electromechanical devices, including wearable sensors, soft robotics, and smart actuators.

Separable Microneedle for Integrated Hyperglycemia Sensing and Photothermal Responsive Metformin Release.

Microdevices that offer hyperglycemia monitoring and controllable drug delivery are urgently needed for daily diabetes management. Herein, a theranostic separable double-layer microneedle (DLMN) patch consisting of a swellable GelMA supporting base layer for glycemia sensing and a phase-change material (PCM) arrowhead layer for hyperglycemia regulation has been fabricated. The Cu-TCPP(Fe)/glucose oxidase composite and 3,3',5,5'-tetramethylbenzidine coembedded in the supporting base layer permit a visible color shift at the base surface in the presence of glucose via a cascade reaction, allowing for the in situ detection of glucose in interstitial fluid. The PCM arrowhead layer is encapsulated with water monodispersity melanin nanoparticles from Sepia officinalis and metformin that is imparted with a near-infrared ray photothermal response feature, which is beneficial to the controllable release of metformin for suppression of hyperglycemia. By applying the DLMN patch to the streptozotocin-induced type 2 diabetic Sprague-Dawley rat model, the results demonstrated that it can effectively extract dermal interstitial fluid, read out glucose levels, and regulate hyperglycemia. This DLMN-integrated portable colorimetric sensor and self-regulated glucose level hold great promise for daily diabetes management.

Colorimetric-photothermal-magnetic three-in-one lateral flow immunoassay for two formats of biogenic amines sensitive and reliable quantification.

Rapid, simple, sensitive and reliable approaches for biogenic amines quantification in various food samples are essential to food safety. Lateral flow immunoassay (LFIA) has been wildly utilized in point-of-care testing (POCT) owing to its advantage of flexibility and feasibility. Here, we reported a Fe3O4@Au nanoparticles (NPs) (Fe3O4@AuNPs) based multimodal readout LFIA for rapid putrescine (Put) and histamine (His) quantification with a LOD down to 10 and 10 ng/mL in naked eye mode, 2.31 and 4.39 ng/mL in photothermal mode, 0.17 and 0.31 ng/mL in magnetic mode, respectively. Such multi-mode assay has been successfully used to detect Biogenic amines (BAs) in raw aquatic foods, including fish, prawns, beef, and pork, with overall recoveries ranging from 93.68 to 109.34%. Meanwhile, it is easily expanded to detect other typical BAs with high sensitivity by simply replacing antibodies. In view of the multi-signal reading, two quantitative formats, and high sensitivity, it may greatly widen the application of lateral flow detection in food safety.

Metal-Organic Framework-Loaded Engineering DNAzyme for the Self-Powered Amplified Detection of MicroRNA.

DNAzyme shows great promise in designing a highly sensitive and specific sensing platform; however, the low cellular uptake efficiency, instability, and especially the insufficient cofactor supply inhibit the intracellular molecule sensor applications. Herein, we demonstrate a novel type of DNAzyme-based self-driven intracellular sensor for microRNA (miRNA) detection in living cells. The sensor consists of a metal-organic framework [zeolite imidazole framework (ZIF-8)] core loaded with a shell consisting of a rationally designed DNAzyme, where the substrate strand is modified with FAM and BHQ-1 nearby both the sides of the restriction site, respectively, while the enzyme strand consists of two separate strands with a complementary fragment to the substrate strand and the targeting miRNA, respectively. The ZIF-8 nanoparticles enable the efficient delivery of DNAzyme into the cell and protect the DNAzyme from degradation. The pH-responsive ZIF-8 degradation is accompanied with the release of the DNAzyme and Zn2+ cofactors, and the intracellular target miRNAs recognize and activate the DNAzyme driven by the Zn2+ cofactors to cleave the substrate strand, resulting in the release of the FAM-labeled shorter product strand and increased fluorescence for miRNA detection. The self-driven approach can be generally applied to various miRNAs' detection through DNAzyme engineering.

Mitochondria MicroRNA Spatial Imaging via pH-Responsive Exonuclease-Assisted AIE Nanoreporter.

Mitochondrial microRNAs (mitomiRs) critically orchestrate mitochondrial functions. Spatial imaging of mitomiRs is essential to understand its clinical value in diagnosis and prognosis. However, the direct monitoring of mitomiRs in living cells remains a key challenge. Herein, we report an AIE nanoreporter strategy for mitomiRs imaging in living cells through pH-controlled exonuclease (Exo)-assisted target cycle signal amplification. The AIE-labeled DNA detection probes are conjugated on Exo III encapsulated polymeric nanoparticles (NPs) via consecutive adenines (polyA). The amplified sensing functions are off during the cytoplasm delivery process, and it can be spatially switched from off to on when in the alkaline mitochondria (about pH 8) after triphenylphosphonium (TPP)-mediated mitochondrial targeting. Where the NPs degraded to release Exo III and cancer-specific mitomiRs hybridize with AIE-labeled DNA detection probes to expose the cleavage site of released Exo III, enabling spatially restricted mitomiRs imaging. The mitomiRs expression fluctuation was also realized. This study contributes to a facile strategy that could easily extend to a broad application for the understanding of mitomiRs-related pathological processes.

A fluorimetric test strip with suppressed "Coffee Ring Effect" for selective mercury ion analysis.

Nowadays, test strips are widely applied, but their use is mostly limited to the qualitative or half-quantitative analysis of targets. The main reason for their limited use is the "Coffee Ring Effect" (CRE) of probe materials, which leads to a heterogeneous probe distribution and poor testing reproducibility and sensitivity. In the present work, a fluorescent test strip was fabricated with a suppressed CRE of silver nanocluster (AgNC) probes coated by gelatin (Gel) under vacuum-aided fast lyophilization. Uniform and stable deposition of AgNC probes was achieved onto the test strips with a high loading capacity. The AgNCs displayed specific responses to Hg2+ ions, allowing sensitive and quantitative analysis in the linear concentration ranges from 0.20 to 50000 nM with a limit of detection of 0.10 nM. Given the advantages of rapid and facile preparation, CRE suppression, high biocompatibility, and cost-effectiveness, such a fabrication protocol may pave the way for the design of various test strips-based devices for point-of-care analytical applications in the fields of environmental monitoring, food quality analysis, and clinical diagnostics.

A Sample and Detection Microneedle Patch for Psoriasis MicroRNA Biomarker Analysis in Interstitial Fluid.

Skin interstitial fluid (ISF) containing a great variety of molecular biomarkers derived from cells and subcutaneous blood capillaries has recently emerged as a clinically potential component for early diagnosis of a wide range of diseases; however, the minimally invasive sampling and detection of cell-free biomarkers in ISF is still a key challenge. Herein, we developed microneedles (MNs) that consist of gelatin methacryloyl (GelMA) and graphene oxide (GO) for the enrichment and sensitive detection of multiple microRNA (miRNA) biomarkers from skin ISF. The GO-GelMA MNs exhibited robust mechanical properties, fast sampling kinetics, and large swelling capacity, which enabled collecting ISF volume high to 21.34 µL in 30 min, facilitating effective miRNA analysis. It preliminarily realized the sensitive detection of three types of psoriasis-related miRNAs biomarkers either on the patch itself or in solution after release from the hydrogel by combining catalytic hairpin assembly signal amplification reaction. The automated and minimally invasive ISF miRNA detection technology of GO-GelMA MNs has great potential to monitor cell-free clinically informative biomarkers for personalized diagnosis and prognosis.

Multiple amplified microRNAs monitoring in living cells based on fluorescence quenching of Mo2B and hybridization chain reaction.

Imaging intracellular microRNAs (miRNAs) demonstrated an essential role in exposing their biological and pathological functions. However, the detection of sequence-specific miRNAs in living cells remains a key challenge. Herein, a facile amplified multiple intracellular miRNAs imaging platform was constructed based on Mo2B nanosheets (NSs) fluorescence (FL) quenching and hybridization chain reaction (HCR). The Mo2B NSs demonstrated strong interaction with the hairpin probes (HPs), ssDNA loop, and excellent multiple FL dyes quenching performance, achieving ultralow background signal. After transfection, the HPs recognized specific targets miRNAs, the corresponding HCR was triggered to produce tremendous DNA-miRNA duplex helixes, which dissociated from the surface of the Mo2B NSs to produce strong FL for miRNAs detection. It realized to image multiple miRNAs biomarkers in different cells to discriminate cancer cells from normal cells owing to the excellent sensitivity, and the regulated expression change of miRNAs in cancer cells was also successfully monitored. The facile and versatile Mo2B-based FL quenching platform open an avenue to profile miRNAs expression pattern in living cells, and has great applications in miRNAs based biological and biomedical research.

Interstitial Fluid Biomarkers' Minimally Invasive Monitoring Using Microneedle Sensor Arrays.

Skin interstitial fluid (ISF) is a biofluid with information-rich biomarkers for disease diagnosis and prognosis. Microneedle (MN) integration of sampling and instant biomarker readout hold great potential in health status monitoring and point-of-care testing (POCT). The present work describes an attractive MN sensor array for minimally invasive monitoring of ISF microRNA (miRNA) and Cu2+. The MN array is made of methacrylated gelatin (GelMA) and methacrylated hyaluronic acid (MeHA), and a further divisionally encapsulated miRNA and Cu2+ detection system, and is cross-linked through blue-light irradiation. The MN patch displays good mechanical properties that enable withstanding more than 0.4 N per needle, and exhibits a high swelling ratio of 700% that facilitates timely extraction of sufficient ISF for biomarker analysis. For proof-of-concept, it realizes detection of miRNAs and Cu2+ efficiently and quantitatively in an agarose skin and fresh porcine cadaver skin model. Given the good sampling and in situ monitoring ability, the MN array holds great promise for skin ISF-based applications.

Bleomycin-Fe(II) agent with potentiality for treating drug-resistant H1N1 influenza virus: A study using electrochemical RNA beacons.

Rapid emergence of new strains of drug-resistant H1N1 influenza viruses calls for effective drugs for the controls prior to their outbreaks. In the present work, electrochemical H1N1 RNA beacons have been newly designed for exploring the potentiality of an anticancer agent of Bleomycin (BLM) with Fe (ΙΙ) ions (BLM-Fe(ΙΙ)) alternatively the treatment of drug-resistant H1N1 strains with H274Y gene mutation. Herein, biotinylated (-) ssRNA of H1N1 virus and its complementary (+) ssRNA were labeled with electrochemical signal probes of ferrocene and anthraquinone, respectively. The resultants were hybridized and conjugated with avidin-modified magnetic beads to create electrochemical RNA beacons. The electrochemical signal variation of the H1N1 RNA beacon treated with the RNA degradation agent of BLM-Fe(ΙΙ) were monitored. Results indicate that the BLM-Fe(ΙΙ) agent could effectively cleave both H1N1 dsRNAs and ssRNAs at selective cutting sites, as evidenced by the mass spectrometry analysis. This indicates that the BLM-Fe(II) agent could be utilized to block the viral-host infection process by curbing the host-cell viral RNA-mRNA transcription or inactivate the viruses through the cleavage of viral genomes. The efficiency of the BLM-Fe(ΙΙ) agent was verified with clinical seasonal H1N1 samples using real-time polymerase chain reaction. The therapeutic gene drug of BLM-Fe(ΙΙ) holds great potential for controlling new strains of H1N1 virus resistant to clinical antiviral drugs. More importantly, the so designed RNA beacons may provide a rapid, sensitive and cost-effective platform of drug screening by monitoring the drug-DNA/RNA interactions.

Recent progress in near-infrared photoacoustic imaging.

The emergence of the photoacoustic imaging (PAI) expands the application of biomolecules bioimaging in cells, various tissues, and living body to monitor multiple physiological processes in complex internal environments. The PAI possesses intriguing properties such as non-invasive, highly selective excitation, and weak signal attenuation. Especially, the near-infrared (NIR) PAI displays low optical absorption and scattering, good temporal or spatial resolution and deep penetration, holds great potential in biomedical applications. We briefly compare different imaging modalities to provide a comprehensive understanding of their characteristics and related applications, highlighting the feature of the PAI. The principle of PAI is then delineated and the emerging NIR-PAI is discussed. We then focus on elaboration of the recent achievement of typical NIR-PAI contrast and their biomedical applications, especially the strategies used to improve contrast rational design and PAI performance are summarized. The PAI-related multimodal imaging approaches for improving imaging accuracy are also covered in the review. Finally, the challenges and prospective are pointed out for attracting more researchers to accelerate the development of PAI.

V2C Nanosheets as Dual-Functional Antibacterial Agents.

Antibiotic-resistant bacterial strains have been continuously increasing and becoming a supreme threat to public health globally. The nanoparticle-based photothermal treatment has emerged as a powerful tool to combat toxic bacteria. Photothermal agents (PTAs) with cost-effective and high photothermal conversion efficiency are highly desirable. Herein, we unite the green process for delamination of V2AlC to produce a high yield mass of two-dimensional (2D) V2C nanosheets (NSs) by using algae extracts and demonstrate their high antibacterial efficiency. The resultant V2C NSs present decent structural reliability and intrinsic antibacterial ability. Powerful near-infrared (NIR) absorption and extraordinary photothermal conversion proficiency make it a good PTA for the photothermal treatment of bacteria. The antibacterial efficiency evaluation indicated that V2C NSs could effectively kill both Gram-positive S. aureus and Gram-negative E. coli. About 99.5% of both types of bacteria could be killed with low-dose of V2C NSs suspension (40 µg/mL) with 5 min NIR irradiation due to the intrinsic antibacterial ability and photothermal effect of V2C NSs, which is much higher than previous reports on Ta4C3, Ti3C2, MoSe2, and Nb2C. This work expands the application of MXene V2C NSs for rapid bacteria-killing and would gain promising attention for applications in the sterilization industry.

A Versatile Sunscreen with Minimal ROS Damage and Low Permeability.

Organic and inorganic ultraviolet (UV) filters possess themselves advantages, while they suffer from different limitations including photostability, penetration, and cytotoxicity. Integrating organic and inorganic UV filters in a single unit holds great potential for enhanced UV protection. Herein, the dendritic silicon dioxide microspheres (DSMs) are encapsulated with Bi2Ti2O7 nanocomposites (BTO-DSMs), an inorganic filter, and decorated with organic filters including sinapoyl malate (SM) and baicalin (BS/BTO-DSM) to enhance UV protection while significantly reducing ROS and skin permeability under UV exposure. The inorganic BTO-DSM component presents an expanded UV shield range and suppressed photocatalytic properties while preventing the organic filter SM direct contact with the epidermis and penetration behaviors. The baicalin efficiently scavenges the generated ROS from SM and reduces the transmittance of blue light. Notably, the results show that the proposed combined system significantly broadens the UV absorption region. Thus, the BS/BTO-DSM presents advanced in vitro anti-UV performance and in vivo UV protection against keratinocyte apoptosis and epidermal hyperplasia without long-term toxicity. The excellent anti-UV properties coupling with the suppressed photocatalytic capability and minimal epidermal penetration of BS/BTO-DSM make it promising for skin protection.

Polyhydric polymer-functionalized fluorescent probe with enhanced aqueous solubility and specific ion recognition: A test strips-based fluorimetric strategy for the rapid and visual detection of Fe3+ ions.

A polyhydric polymer-functionalized probe with enhanced aqueous solubility was designed initially by coupling 1-pyrenecarboxyaldehyde (Pyr) onto poly(vinyl alcohol) (PVA) via the one-step condensation reaction. Polyhydric PVA polymer chains could facilitate the Pyr fluorophore with largely improved aqueous solubility and especially strong cyan fluorescence. Importantly, the fluorescence of the PVA-Pyr probes could thereby be quenched specifically by Fe3+ ions through the strong PVA-Fe3+ interaction triggering the polymeric probe aggregation. Furthermore, a test strips-based fluorimetric method was developed with the stable and uniform probe distribution by taking advantage of the unique film-forming ability and the depression capacity of "coffee-stain" effects of PVA matrix. The as-developed test strips could allow for the rapid and visual detections of Fe3+ ions simply by a dipping way, showing a linear concentration range of 5.00-300µM, with the detection limit of 0.73µM. Moreover, the proposed method was applied to the evaluation of Fe3+ ions in natural water samples, showing the analysis performances better or comparable to those of current detection techniques. This test strips-based fluorimetric strategy promises the extensive applications for the rapid on-site monitoring of Fe3+ ions in environmental water and the outdoor finding of the potential iron mines.

Encapsulating chromogenic reaction substrates with porous hydrogel scaffolds onto arrayed capillary tubes toward a visual and high-throughput colorimetric strategy for rapid occult blood tests.

A porous hydrogel scaffold was fabricated for the first time to encapsulate chromogenic reaction substrates onto arrayed capillary tubes, resulting in a visual and high-throughput colorimetric method for rapid occult blood tests (OBTs) based on the hemoglobin (Hgb)-catalyzed chromogenic reactions. Gelatin (Gel), a biodegradable and biocompatible polymer, was introduced to couple with p-hydroxyphenyl-propionic acid (HPA) yielding the Gel-HPA hydrogel scaffold. Chromogenic reaction substrates of 3,3,5,5-tetramethylbenzidine and H2O2 were then encapsulated into the Gel-HPA matrix and further attached onto the amine-derivatized capillary tubes by forming porous chromogenic composites through the HPA-mediated bridging of Gel by the oxidization of H2O2. The developed Hgb catalysis-based OBT platform can facilitate the detection of Hgb with the level down to 0.125 µg mL-1 in human excreta (i.e., saliva, urine, and feces) through capillarity-enabled automatic sampling. This simple, sensitive, selective, and high-throughput colorimetric method may be promising for the bedside OBT for point-of-care monitoring and rapid diagnostics of clinical bleeding diseases.

A high-throughput fluorimetric microarray with enhanced fluorescence and suppressed "coffee-ring" effects for the detection of calcium ions in blood.

A rapid, ultrasensitive, and high-throughput fluorimetric microarray method has been developed using hydrophobic pattern as the microarray substrate and 3-aminopropyltriethoxysilane-coupled carboxylic acid calcium (APS-CCA) as the fluorescent probes for sensing Ca2+ ions in blood. The hydrophobic pattern of the developed Ca2+ analysis microarray could largely suppress the "coffee-ring" effects to facilitate the better distribution density of testing microspots toward the high-throughput detections, and especially prevent the cross-contamination of the multiple samples between adjacent microspots. Moreover, the use of APS matrix could endow the CCA probe the enhanced environmental stability and fluorescence intensity, which is about 2.3-fold higher than that of free CCA. The interactions between APS-CCA and Ca2+ ions were systematically characterized by UV-vis and fluorescence measurements including microscopy imaging. It was demonstrated that the fluorimetric microarray could display the strong capacity of specifically sensing Ca2+ ions with the minimal interferences from blood backgrounds. Such an APS-CCA-based fluorimetric microarray can allow for the analysis of Ca2+ ions down to 0.0050 mM in blood, promising a highly sensitive and selective detection candidate for Ca2+ ions to be applied in the clinical laboratory.

Fluorimetric Mercury Test Strips with Suppressed "Coffee Stains" by a Bio-inspired Fabrication Strategy.

A fluorimetric Hg2+ test strip has been developed using a lotus-inspired fabrication method for suppressing the "coffee stains" toward the uniform distribution of probe materials through creating a hydrophobic drying pattern for fast solvent evaporation. The test strips were first loaded with the model probes of fluorescent gold-silver nanoclusters and then dried in vacuum on the hydrophobic pattern. On the one hand, here, the hydrophobic constraining forces from the lotus surface-like pattern could control the exterior transport of dispersed nanoclusters on strips leading to the minimized "coffee stains". On the other hand, the vacuum-aided fast solvent evaporation could boost the interior Marangoni flow of probe materials on strips to expect the further improved probe distribution on strips. High aqueous stability and enhanced fluorescence of probes on test strips were realized by the hydrophilic treatment with amine-derivatized silicane. A test strips-based fluorimetry has thereby been developed for probing Hg2+ ions in wastewater, showing the detection performances comparable to the classic instrumental analysis ones. Such a facile and efficient fabrication route for the bio-inspired suppression of "coffee stains" on test strips may expand the scope of applications of test strips-based "point-of-care" analysis methods or detection devices in the biomedical and environmental fields.

Silver Nanoclusters with Specific Ion Recognition Modulated by Ligand Passivation toward Fluorimetric and Colorimetric Copper Analysis and Biological Imaging.

Silver nanoclusters were synthesized and passivated by glutathione (GSH) ligand, with high aqueous stability and powerful red fluorescence and UV-vis yellow colour. Importantly, the specific recognition of the AgNCs was modulated from Hg(2+) ions to Cu(2+) ions upon the GSH passivation, of which the unique GSH-Cu(2+) chelating reaction could conduct the fluorescence quenching of AgNCs. Strong UV-vis absorbance of GSH-passivated AgNCs could also be realized depending on the Cu(2+) levels. Moreover, the Cu(2+)-induced loss of fluorescence and UV-vis absorbance of GSH-passivated AgNCs could be well restored by using stronger Cu(2+) chelating agent. A simultaneous and reversible fluorimetric and colorimetric sensing method was thereby developed for probing Cu(2+) ions in blood with high sensitivity and selectivity. Subsequently, the fluorescence-trackable imaging for live tissues and cells was demonstrated towards the analysis Cu(2+) ions using GSH-passivated AgNCs as the fluorescent probes. This study indicates that the use of functional ligands like GSH could not only modulate the specific ion recognition of AgNCs, but also endow them the high aqueous stability and powerful red fluorescence towards the wide applications for ion sensing and biological imaging in the complicated media like blood.

A fluorometric microarray with ZnO substrate-enhanced fluorescence and suppressed "coffee-ring" effects for fluorescence immunoassays.

A glass slide was first patterned with hydrophobic hexadecyltrimethoxysilane (HDS) and then microspotted with hydrophilic ZnO nanoparticles in an aminopropyltriethoxysilane (APS) matrix. The resulting HDS-ZnO-APS microarray could present the capability of suppressing the undesirable "coffee-ring" effects through its hydrophobic pattern so as to allow the fabrication of ZnO-APS testing microspots with a highly dense and uniform distribution. The lotus-like "self-cleaning" function could also be expected to effectively curb the cross contamination of multiple sample droplets. More importantly, the introduction of ZnO nanoparticles could endow the testing microspots with substrate-enhanced fluorescence leading to signal-amplification microarray fluorometry. The practical application of the developed HDS-ZnO-APS microarray was investigated by the sandwiched fluorometric immunoassays of human IgG, showing a linear detection range from 0.010 to 10.0 ng mL(-1). Such a throughput-improved fluorometric microarray could be tailored for probing multiple biomarkers in complicated media like serum or blood.