Ultrasensitive Detection of SARS-CoV-2 Nucleocapsid Protein Based on Porphyrin-Based Metal-Organic Gels with Highly Efficient Electrochemiluminescence at Low Potential.

Metal-organic gels (MOGs) are a new type of intelligent soft material, which are bridged by metal ions and organic ligands through noncovalent interactions. In this paper, we prepared highly stable P-MOGs, using the classical organic electrochemiluminescence (ECL) luminescence meso-tetra(4-carboxyphenyl)porphine as the organic ligand and Fe3+ as the metal ion. Surprisingly, P-MOGs can stably output ECL signals at a low potential. We introduced P-MOGs into the ECL resonance energy transfer strategy (ECL-RET) and constructed a quenched ECL immunosensor for the detection of the SARS-CoV-2 nucleocapsid protein (SARS-CoV-2-N). In the ECL-RET system, P-MOGs were used as energy donors, and Au@Cu2O@Fe3O4 were selected as energy acceptors. The ultraviolet-visible spectrum of Au@Cu2O@Fe3O4 partially overlaps with the ECL spectrum of P-MOGs, which can effectively touch off the ECL-RET behavior between the donors and receptors. Under the ideal experimental situation, the linear detection range of the SARS-CoV-2-N concentration was 10 fg/mL to 100 ng/mL, and the limit of detection was 1.5 fg/mL. This work has broad application prospects for porphyrin-MOGs in ECL sensing.

Ternary electrochemiluminescence quenching effects of CuFe2O4@PDA-MB towards self-enhanced Ru(dcbpy)32+ functionalized 2D metal-organic layer and application in carcinoembryonic antigen immunosensing.

BACKGROUND: Carcinoembryonic antigen (CEA) is a significant glycosylated protein, and the unusual expression of CEA in human serum is used as a tumor marker in the clinical diagnosis of many cancers. Although scientists have reported many ways to detect CEA in recent years, such as electrochemistry, photoelectrochemistry, and fluorescence, their operation is complex and sensitivity is average. Therefore, finding a convenient method to accurately detect CEA is significance for the prevention of malignant tumors. With high sensitivity, quick reaction, and low background, electrochemiluminescence (ECL) has emerged as an essential method for the detection of tumor markers in blood. RESULTS: In this work, a "signal on-off" ECL immunosensor for sensitive analysis of CEA ground on the ternary extinction effects of CuFe2O4@PDA-MB towards a self-enhanced Ru(dcbpy)32+ functionalized metal-organic layer [(Hf)MOL-Ru-PEI-Pd] was prepared. The high ECL efficiency of (Hf)MOL-Ru-PEI-Pd originated from the dual intramolecular self-catalysis, including intramolecular co-reaction between polyethylenimine (PEI) and Ru(dcbpy)32+. At the same time, loading Pd NPs onto (Hf)MOL-Ru-PEI could not only improve the electron transfer ability of (Hf)MOL-Ru-PEI, but also provide more active sites for the reaction of Ru(dcbpy)32+ and PEI. In the presence of CEA, CuFe2O4@PDA-MB-Ab2 efficiently quenches the excited states of (Hf)MOL-Ru-PEI-Pd by PDA, Cu2+, and methylene blue (MB) via energy and electron transfer, leading to an ECL signal decrease. Under optimal conditions, the proposed CEA sensing strategy showed satisfactory properties ranging from 0.1 pg mL-1 to 100 ng mL-1 with a detection limit of 20 fg mL-1. SIGNIFICANCE: The (Hf)MOL-Ru-PEI-Pd and CuFe2O4@PDA-MB were prepared in this work might open up innovative directions to synthesize luminescence-functionalized MOLs and effective quencher. Besides, the ECL quenching mechanism of Ru(dcbpy)32+ by MB was successfully explained by the inner filter effect (ECL-IFE). At last, the proposed immunosensor exhibits excellent repeatability, stability, and selectivity, and may provide an attractive way for CEA and other disease markers determination.

Dual-Signal Integrated Aptasensor for Microcystin-LR Detection via In Situ Generation of Silver Nanoclusters Induced by Circular DNA Strand Displacement Reactions.

Inspired by the signal accumulation of circular DNA strand displacement reactions (CD-SDRs) and the in situ generation of silver nanoclusters (AgNCs) from signature template sequences, a dual-signal integrated aptasensor was designed for microcystin-LR (MC-LR) detection. The aptamer was programmed to be included in an enzyme-free CD-SDR, which utilized MC-LR as the primer and outputted the H1/H2 dsDNA in a continuous manner according to the ideal state. Ingeniously, H1/H2 dsDNA was enriched with signature template sequences, allowing in situ generation of AgNCs signal probes. To enhance the signal amplification performance, co-reaction acceleration strategies and CRISPR-Cas12a nucleases were invoked. The H1/H2 dsDNA could trigger the incidental cleavage performance of CRISPR-Cas12a nucleases: cis-cleavage reduced signature template sequences for the synthetic AgNCs, while trans-cleavage enabled fluorescence (FL) analysis. Meanwhile, AuPtAg was selected as the substrate material to facilitate the S2O82- reduction reaction for enhancing the electrochemiluminescence (ECL) basal signals. ECL and FL detection do not interfere with each other and have improved accuracy and sensitivity, with limits of detection of 0.011 and 0.023 pmol/L, respectively. This widens the path for designing dual-mode sensing strategies for signal amplification.

Hierarchically Structured and Highly Dispersible MOF Nanozymes Combining Self-Assembly and Biomineralization for Sensitive and Persistent Chemiluminescence Immunoassay.

Metal-organic frameworks (MOF) are promising candidates for the construction of artificial nanozymes and have found applications in many fields. However, the preparation of nanosized MOF materials with high performance and good dispersibility is still a big challenge and is in great demand as signal labels for immunoassays. In this work, hierarchically structured and highly dispersible MOF nanoparticles were facilely prepared in a one-pot method. Self-assembled micelles from PEGylated hematin were used as structured templates to mediate the formation of zeolitic imidazole framework-8 (ZIF-8) nanoparticles in aqueous solution. The encapsulation of micelles in ZIF-8 frameworks produces well-dispersed nanoparticles and generates dual-confinement effects for catalytic hematin. Owing to the hierarchical structures, the formed MOF nanozymes show enhanced peroxidase-like activity and enable persistent chemiluminescence behaviors for the luminol system. Sandwich-type chemiluminescence immunoassays for carcinoembryonic antigen (CEA) were proposed using MOF nanozymes as signal labels, and good analytical performances were achieved. The combination of self-assembly and biomineralization may open new avenues for the development of MOF nanomaterials.

Weak Capacitance Detection Circuit of Micro-Hemispherical Gyroscope Based on Common-Mode Feedback Fusion Modulation and Demodulation.

As an effective capacitance signal produced by a micro-hemisphere gyro is usually below the pF level, and the capacitance reading process is susceptible to parasitic capacitance and environmental noise, it is highly difficult to acquire an effective capacitance signal. Reducing and suppressing noise in the gyro capacitance detection circuit is a key means to improve the performance of detecting the weak capacitance generated by MEMS gyros. In this paper, we propose a novel capacitance detection circuit, where three different means are utilized to achieve noise reduction. Firstly, the input common-mode feedback is applied to the circuit to solve the input common-mode voltage drift caused by both parasitic capacitance and gain capacitance. Secondly, a low-noise, high-gain amplifier is used to reduce the equivalent input noise. Thirdly, the modulator-demodulator and filter are introduced to the proposed circuit to effectively mitigate the side effects of noise; thus, the accuracy of capacitance detection can be further improved. The experimental results show that with the input voltage of 6 V, the newly designed circuit produces an output dynamic range of 102 dB and the output voltage noise of 5.69 nV/√Hz, achieving a sensitivity of 12.53 V/pF.

Design and Optimization of Hemispherical Resonators Based on PSO-BP and NSGA-II.

Although one of the poster children of high-performance MEMS (Micro Electro Mechanical Systems) gyroscopes, the MEMS hemispherical resonator gyroscope (HRG) is faced with the barrier of technical and process limits, which makes it unable to form a resonator with the best structure. How to obtain the best resonator under specific technical and process limits is a significant topic for us. In this paper, the optimization of a MEMS polysilicon hemispherical resonator, designed by patterns based on PSO-BP and NSGA-II, was introduced. Firstly, the geometric parameters that significantly contribute to the performance of the resonator were determined via a thermoelastic model and process characteristics. Variety regulation between its performance parameters and geometric characteristics was discovered preliminarily using finite element simulation under a specified range. Then, the mapping between performance parameters and structure parameters was determined and stored in the BP neural network, which was optimized via PSO. Finally, the structure parameters in a specific numerical range corresponding to the best performance were obtained via the selection, heredity, and variation of NSGAII. Additionally, it was demonstrated using commercial finite element soft analysis that the output of the NSGAII, which corresponded to the Q factor of 42,454 and frequency difference of 8539, was a better structure for the resonator (generated by polysilicon under this process within a selected range) than the original. Instead of experimental processing, this study provides an effective and economical alternative for the design and optimization of high-performance HRGs under specific technical and process limits.

Dual Direct Z-Scheme Heterojunction with Stable Electron Supply to a Au/PANI Photocathode for Ultrasensitive Photoelectrochemical and Electrochromic Visualization Detection of Ofloxacin in a Microfluidic Sensing Platform.

A novel dual-mode microfluidic analytical device integrating self-powered photoelectrochemical (PEC) sensing with electrochromic visualization analysis was developed for ultrasensitive ofloxacin (OFL) detection. First, an advanced dual direct Z-scheme BiVO4@Ni-ZnIn2S4/Bi2S3 (BVZIS) heterojunction was designed as a photoanode matrix to steadily provide electrons. The dual Z-scheme structure formed in photoactive BVZIS composites greatly accelerated the migration of electrons. In addition, the doping of Ni in ZnIn2S4 markedly enhanced the optical absorption and promoted the separation of the photocarrier. Second, electrochromic material polyaniline-modified Au (Au/PANI) was first electrodeposited on the photocathode for immobilizing aptamers and realizing visualized readout. On the one hand, Au/PANI with excellent conductivity could receive electrons from the photoanode without external energy supply. On the other hand, PANI would be rapidly reduced by the received electrons and change its color from blue to green obviously. With the increase in OFL, the increased steric hindrance resulted in the significant decline in the PEC signal and RGBgreen value. Third, wide linear ranges of PEC (0.05 pg/mL to 150 ng/mL) and electrochromic technique (0.1 pg/mL to 100 ng/mL) as well as low detection limits of PEC (18 fg/mL) and electrochromic (30 fg/mL) sensors could achieve the ultrasensitive detection of OFL in milk and river water.

Fabrication of silk sericin-anthocyanin nanocoating for chelating and saturation-visualization detection of metal ions.

Silk sericin (SS) is a natural water-soluble protein with the potential to chelate metal ions via its polar groups. However, the difficulty of identifying the saturation of SS limits its application as filter films. One solution is to construct SS filter films with an indicator to reflect the degree of saturation of silk sericin. Hence, the nanocoating consisting of co-assembled SS protein and anthocyanin (C3G) nanoparticles is designed, constructed, and characterized to chelate metal ions with a saturation-visualization detection behavior. Here, metal ions Zn2+ and Al3+ are chosen as models to explore the chelating ability of SS and indicator behaviors of C3G, which could indicate the saturation degree of SS. Interestingly, after the saturation of SS in the solution and filter film situations, the visible color progressively shifts from pink to blue (Zn2+) or violet (Al3+), with the corresponding redshift of UV-Vis absorbance of C3G. Remarkable removal effectiveness of Zn2+ and Al3+, namely 93.16% and 53.97%, as well as an evident saturation-visualization detection, were identified by filter paper films with the nanocoating. Our research provides a fresh viewpoint for designing SS filter films that could effectively remove metal ions while enabling real-time viewing.

An orthogonal dual-regulation strategy for sensitive biosensing applications.

Biosensing systems based on controllable motion behaviors of droplets have attracted extensive attention, but still face challenges of insufficient sensitivity and uncontrollable dynamic range due to imprecise manipulation of droplet motion on the surfaces. Here, we report an orthogonal dual-regulation strategy for precise motion control of droplets and we demonstrate its utility as a sensitive sensing system with controllable dynamic ranges of sensing for adenosine triphosphate, miRNA, thrombin and kanamycin, as well as discrimination of five kinds of DNA. We endowed a DNA-contained bio-droplet sliding on a lubricant-infused structural surface with micro-grooves to separately adjust the resistance from liquid phase and solid phase. The resistance from liquid phase mainly depended on hydrophobic interaction between DNA and lubricant, which can be finely tuned by different DNA's average chain length. Meanwhile, the resistance from solid surface was determined by the energy barrier from the periodic micro-grooves, which can be adjusted by varying the droplet's sliding direction on the surface. The hydrophobic interaction is conformed to be orthogonal to the micro-grooves' anisotropic resistance by three different methods. This orthogonal dual-regulation strategy thus demonstrated its ability to precisely control bio-droplets' motion behaviors and sensitive detection with adjustable dynamic ranges for various bio-targets. The dual-regulation strategy will provide significant insights for super-wettable biosensors, visual inspection and beyond.

Feeding Alginate-Coated Liquid Metal Nanodroplets to Silkworms for Highly Stretchable Silk Fibers.

In this study, we fed the larval of Bombyx mori silkworms with nanodroplets of liquid metal (LM) coated with microgels of marine polysaccharides to obtain stretchable silk. Alginate-coated liquid metal nanodroplets (LM@NaAlg) were prepared with significant chemical stability and biocompatibility. This study demonstrates how the fed LM@NaAlg acts on the as-spun silk fiber. We also conducted a series of characterizations and steered molecular dynamics simulations, which showed that the LM@NaAlg additions impede the conformation transition of silk fibroins from the random coil and α-helix to the ß-sheet by the formation of hydrogen bonds between LM@NaAlg and the silk fibroins, thus enhancing the elongation at the breakpoints in addition to the tensile properties. The intrinsically highly stretchable silk showed outstanding mechanical properties compared with regular silk due to its 814 MPa breaking strength and a breaking elongation of up to 70%-the highest reported performance so far. We expect that the proposed method can expand the fabrication of multi-functional silks.