Multifunctional DNA Tetrahedron for Alzheimer's Disease Mitochondria-Targeted Therapy by MicroRNA Regulation.

The principal hallmark of Alzheimer's disease (AD) is neuron mitochondrial dysfunction, whereas mitochondrial miRNAs potentially play important roles. Nevertheless, efficacious mitochondria organelle therapeutic agents for treatment and management of AD are highly advisable. Herein, we report a multifunctional DNA tetrahedron-based mitochondria-targeted therapeutic platform, termed tetrahedral DNA framework-based nanoparticles (TDFNs), which was modified with triphenylphosphine (TPP) for mitochondria-targeting, cholesterol (Chol) for crossing the central nervous system, and functional antisense oligonucleotide (ASO) for both AD diagnosis and gene silencing therapy. After injecting intravenously through the tail vein of 3 × Tg-AD model mice, TDFNs can both easily cross the blood brain barrier and accurately arrive at the mitochondria. The functional ASO could not only be detected via the fluorescence signal for diagnosis but also mediate the apoptosis pathway through knocking miRNA-34a down, leading to recovery of the neuron cells. The superior performance of TDFNs suggests the great potential in mitochondria organelle therapeutics.

Ultrasensitive Hybridization Chain Reaction-Assisted Multisite Exonuclease III Amplification Strategy Combined with a Direct Quantitative Fluorescence Lateral Flow Technique for Multiple Bacterial 16S rRNA Detection.

Accurate and in-time detection of bacteria conduces to preventing their rapid spread around the environment, while a nucleic acid test (NAT) is a powerful tool for early diagnosis of pathogens. Herein, we propose a hybridization chain reaction (HCR)-mediated multisite exonuclease III (Exo-III) amplification strategy (HCR/Exo-III amplifier) to achieve the one-pot and ultrasensitive isothermal amplification of bacterial 16S rRNA and a portable fluorescence detection device (PFD) to directly read signals in a lateral flow assay (LFA). In detail, the target-initiated HCR products present multiple binding sites for triggering the Exo-III amplifier that produces numerous target amplicons. Following that, the target amplicons travel up on the strip and bridge between the DNA-CdTe/CdS probes and the capture DNA to form a positive fluorescence line. After that, the strip is inserted into the PFD to accomplish the fluorescence signal reading. The constructed HCR/Exo-III amplifier-based PFD-LFA implemented the simultaneous and specific detection of three bacteria with a detection limit of a few tenths of fM for synthetic 16S rRNA fragments and dozens of CFU/mL for Staphylococcus aureus, Listeria monocytogenes, and Salmonella typhimurium in pure cultures. The sensing platform features isothermal amplification, convenient operation, and good economy, displaying great potential for on-site testing toward multiple nucleic acid analytes.

A paper-based microfluidic sensor array combining molecular imprinting technology and carbon quantum dots for the discrimination of nitrophenol isomers.

Paper-based microfluidic analytical devices (µPADs) have recently attracted attention as a rapid test kit owing to their low cost and nonrequirement for external driving pump. However, low accuracy and poor anti-interference ability of µPADs under complex detection condition limit their practical applications. Here, we present a facile way to prepare a novel fluorescence sensor-array µPAD for multi-analyte discrimination based on molecular imprinting technology, and its sensing behavior was studied by using three nitrophenol (NP) isomers (2-, 3-, and 4-NP) as the testing models. Carbon quantum dots (CQDs) emitting blue light were grafted on glass-fiber paper, followed by in-situ modification of three types of molecularly imprinted polymers (MIPs) with 2-, 3-, and 4-NP as template. Each sensing unit on the array showed differential yet cross-reactive binding affinity to NP isomers, resulting in distinct fluorescence quenching efficiency. Thus, precise distinguishment of the three NPs was realized with the MIPs/CQDs/paper-based sensor array. Furthermore, the discrimination ability of the platform was evaluated in mixtures of the NP isomers. Practicability of this apparatus was validated by identification of blind samples and 100% accuracy was achieved. The µPAD has proven to be highly sensitive and accurate, which will serve as an ideal analytical tool in the fields of environment monitoring, disease prognosis, food safety and so on.

Hydrogel-Involved Colorimetric Platforms Based on Layered Double Oxide Nanozymes for Point-of-Care Detection of Liver-Related Biomarkers.

Monitoring the liver status in a convenient and low-cost way is significant for obtaining a warning about drug-indued liver diseases promptly. Herein, we designed a novel colorimetric point-of-care (POC) platform for the determination of three liver-related biomarkers─aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP). This platform integrated agarose hydrogels into a portable device, where hydrogels were loaded with nanozymes and different reaction substances for triggering specific reactions and generating colorimetric signals. Typically, Au-decorated CoAl-layered double oxide (Au/LDO) was for the first time developed as the nanozyme with peroxidase (POD) mimic activity, which can accelerate the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxTMB with the coexistence of hydrogen peroxide (H2O2). The detection mechanism of AST and ALT is based on the fact that they can cause individual cascade reactions to generate H2O2, and H2O2 further activates the Au/LDO nanozyme to catalyze the chromogenic reaction of TMB. As for ALP, it can catalytically hydrolyze l-ascorbic acid-2-phosphate to ascorbic acid. The latter then discolored the oxTMB that was produced with the assistance of Au/LDO. Teaming up with a smartphone, the color information of hydrogels can be converted to hue values, which allow quantitative analysis of ALT, AST, and ALP with detection limits of 15, 10, and 5 U/L, respectively. Moreover, the simple and cost-effective platform was successfully applied for the simultaneous determination of the three analytes in human plasma. Additionally, since the hydrogel is disposable and can be replaced by new ones loaded with different reaction regents, the platform is expected to serve the POC testing of various chem/bio targets.

Hand-Held and Integrated Tubular Tip-like Sensing Platform Series: Point-of-care Device for Semi-automated Multiplexed Assay.

Currently, most of the electrochemical sensors were prepared based on the planar electrode (PE) and utilized in open circumstance. The accompanying issues include fixed and limited sensing area of PE, insufficient usage of the testing sample, tedious operation, and susceptibility to external environment. Herein, a novel tubular tip-like sensor (TTLS) platform was proposed, where a small tip accommodates all electrodes with a curved surface and also acts as a closed detection chamber. Teaming up with a commercial pipette and potentiostat, the TTLS is able to accomplish the whole assay procedure including sampling, detection, rinsing, and regeneration with a single hand. The electrochemical interface area can be easily tuned to adapting for different scenarios with varied sensitivity request. Moreover, two TTLS-based array systems were derived: one integrates multiple working electrodes in one tip for multicomponent quantification and the other assembles eight independent TTLSs for high-throughput analysis. The admirable sensing performance of the TTLS was fully proved by detecting several liver-related biomarkers in 5 µL of the serum sample. The proposed tubular sensor platform is superior to the traditional electrochemical sensor in the aspects of unique sensing surface, fast and simple operation, good portability, and great compatibility. The TTLS could be used as an ideal analytical tool in point-of-care testing and other fields.

Dual-Mode Sensing Platform for Electrochemiluminescence and Colorimetry Detection Based on a Closed Bipolar Electrode.

Development of sensors uniting different sensing principles is in line with the concept of reliable, comprehensive, and diversified equipment construction. However, the current exploration in this field is obstructed by compromise of reaction conditions and inevitable mutual interference arising from different sensing modes. This work reported a closed bipolar electrode (c-BPE) strategy for dual-modality detection or dual-target detection. To this end, a c-BPE sensing platform installed in physically separated anode and cathode compartments was well designed and carefully optimized. If luminol was present in the anode section and Prussian blue (PB) was at the cathode part, single stimulation could realize electrochemiluminescence (ECL) from luminol at the anode and conversion of PB to Prussian white (PW) at the cathode. The latter reaction helped elevate the ECL signal and also prepared for colorimetric detection as color change from PW to PB under the trigger of oxidant (like H2O2) was used to track the content of the oxidant. Thus, dual signals were obtained for dual-modality detection of single target or the detection of different targets was realized at different poles. Detection of glucose was carried out to validate the application for dual-modality detection, while VLDL/AChE and NADH/H2O2 assays illustrated the potential of dual-target detection. The proposed platform possesses outstanding sensing performance including selectivity, repeatability, long-term stability, accuracy, and so forth. This work implements a breakthrough in designing dual-mode sensors and is expected to present a rational basis for development of a diversified sensing platform.

Electrochemical sensor based on dual-template molecularly imprinted polymer and nanoporous gold leaf modified electrode for simultaneous determination of dopamine and uric acid.

A novel electrochemical sensor based on dual-template molecularly imprinted polymer (MIP) with nanoporous gold leaf (NPGL) was established for the simultaneous determination of dopamine (DA) and uric acid (UA). NPGL acts as an enlarged loading platform to enhance sensing capacity, and the MIP layer was synthesized in situ in the presence of monomer and dual templates (DA and UA) to provide specific recognition. Under the optimal conditions, the sensor shows a good linear range of 2.0~180 µM for DA at a working potential of 0.15 V (vs. Ag/AgCl) and 5.0~160 µM for UA at 0.35 V (vs. Ag/AgCl), with the respective detection limit of 0.3 µM and 0.4 µM (S/N = 3). Good selectivity of the sensor to its dual templates was confirmed as the sensing signals are significantly different between templates and interfering species. The responses maintained higher than 96% of the initial values after 30-day storage, and the day-to-day relative standard deviation is less than 3.0%. Real sample simultaneous determination of DA and UA was conducted with bovine serum, and the results were in good agreement with those from high-performance liquid chromatography. It can be concluded that this work offers a reliable, facile, fast, and cost-effective method of simultaneous quantification of two or more chem-/bio-molecules. Graphical abstract.

The microscale Weissenberg effect for high-viscosity solution pumping at the picoliter level.

Transportation of highly viscous solutions at the picoliter level with a rapid dynamic response is paramount for micro/nano-fabrication. With the advantages of a higher length-wall (thickness) ratio and a more stable free surface compared to those of the traditional Weissenberg effect (TWE), the microscale Weissenberg effect (MWE) can continuously and controllably pump high-viscosity solutions at the picoliter scale. Some typical characteristics and behaviors of MWE are investigated as the rotation rod diameter decreases to the microscale of ∼100 µm. The pumped minimum solution volume can reach 167.5 pL per second, and the minimum response time of solution pumping is 0.3 s, which is much shorter than that of pressure driven pumping. Then, a new direct writing with an adjustable jet diameter based on the MWE is proposed to write microstructures on a substrate from a solution with a viscosity of approximately 130.1 Pa s. The stability of the as-spun jet and the deposited structures is improved when a high voltage is applied. To fully demonstrate the advantages of MWE, MWE-based direct writing is performed to successfully fabricate microfluidic channels with variable diameters. Thus, the system can overcome the problems of high transport resistance to the pumping of a high-viscosity solution.

Direct write micro/nano optical fibers by near-field melt electrospinning.

A simple fabrication method of micro/nano-optical fibers (MNOFs) based on near-field melt electrospinning (NMES) is proposed in this Letter. Single fibers with diameters ranging from 500 nm to 6 µm were directly written by near-field electrospinning of molten poly(methyl methacrylate) (PMMA). The morphology and transmission characteristics of single PMMA MNOFs were experimentally measured. The results showed that PMMA MNOFs have the advantages of smooth surfaces, uniform diameters, and low loss. As an example of one-step fabrication for MNOF devices, a planar helical MNOF structure was directly written and optically characterized. To demonstrate the versatility of the NMES process, in combination with the microfluidic technique, a liquid refractive index-sensing chip was fabricated and tested. Our results demonstrate that the proposed fabrication method has strong potential in the direct writing of patterned optical devices and heterogeneous integrated devices.