A Highly Sensitive and Selective Fluorescent Sensor for Folic Acid Detection Based on D-penicillamine Stabilized Ag/Cu Alloy Nanoclusters.

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

Magnetic photoelectrochemical sensor array utilizing addressing sensing strategy for simultaneous detection of amyloid-ß 42 and microtubule-associated protein tau.

The accurate diagnosis of diseases can be improved by detecting multiple biomarkers simultaneously. This study presents the development of a magnetic photoelectrochemical (PEC) immunosensor array for the simultaneous detection of amyloid-ß 42 (Aß) and microtubule-associated protein (Tau), which are markers for neurodegenerative disorders. A metal-organic framework (MOF) derivative, Fe2O3@FeS2 magnetic composites with exceptional photoelectric and ferromagnetic properties was synthesized while preserving the original structure and advantages. Thus, the immunoassembly process of the sensor can be carried out in homogeneous solution and recovered by magnetic separation. For simultaneous detection, a chip is divided into multiple independent sensing sites, which have the same preparation and detection environment, allowing for the implementation of a self-calibration method. The sensor array demonstrates considerable detection ranges of 0.01-100 ng mL-1 for Aß and 0.05-100 ng mL-1 for Tau, with low detection limits of 2.1 pg mL-1 for Aß and 7.9 pg mL-1 for Tau. The PEC sensor array proposed in this study exhibits exceptional stability, selectivity, and reproducibility, providing a new method for detecting multiple markers.

Photocleavable DNA Nanotube-Based Dual-Amplified Resonance Rayleigh Scattering System for MicroRNA Detection Incorporating Molecular Computing-Cascaded Keypad Lock Functionality.

Cascade molecular events in complex systems are of vital importance for enhancing molecular diagnosis and information processing. However, the conversion of a cascaded biosensing system into a multilayer encrypted molecular keypad lock remains a significant challenge in the development of molecular logic devices. In this study, we present a photocleavable DNA nanotube-based dual-amplified resonance Rayleigh scattering (RRS) system for detecting microRNA-126 (miR-126). The cascading dual-amplification biosensing system provides a multilayer-encrypted prototype with the functionality of a molecular computing cascade keypad lock. RRS signals were greatly amplified by using photocleavable DNA nanotubes and enzyme-assisted strand displacement amplification (SDA). In the presence of miR-126, enzyme-assisted SDA produced numerous identical nucleotide fragments as the target, which were then specifically attached to magnetic beads through the DNA nanotube by using a Y-shaped DNA scaffold. Upon ultraviolet irradiation, the DNA nanotube was released into the solution, resulting in an increase in the intensity of the RRS signal. This strategy demonstrated a low limit of detection (0.16 fM) and a wide dynamic range (1 fM to 1 nM) for miR-126. Impressively, the enzyme-assisted SDA offers a molecular computing model for generating the target pool, which serves as the input element for unlocking the system. By cascading the molecular computing process, we successfully constructed a molecular keypad lock with a multilevel authentication technique. The proposed system holds great potential for applications in molecular diagnosis and information security, indicating significant value in integrating molecular circuits for intelligent sensing.

Oxygen vacancies-driven signal enhanced photoelectrochemical sensor for mercury ions detection.

Mercury ion (Hg2+) poses a serious threat to human health due to its high toxicity. In this study, a smartphone-based photoelectrochemical sensor based on oxygen vacancies (OVs) driven signal enhancement for mercury ion detection was designed. BiVO4-x/Bi2S3/AuNPs were combined with T-Hg2+-T recognition mode to construct a multi-sandwich photoelectrochemical sensor. On the one hand, the OVs can increase the adsorption of light by the materials and enhance the photocurrent response as well as the superconductivity of Au NPs to accelerate the charge transfer at the electrode interface. On the other hand, the multi-sandwich structure was exploited to increase the binding site of Hg2+, as well as the T-Hg2+-T structure for sensitive recognition of Hg2+ and signal amplification. The sensor showed good linearity for Hg2+ concentration in the range of 0.1 nM-1.0 µM with a detection limit of 4.8 pM (S/N = 3). Eventually the smartphone-based real-time detection sensor is expected to contribute to the future analysis of heavy metal ions.

Photocontrollable DNA Walker-Based Molecular Circuit for the Tunable Detection of MicroRNA-21 Using Metal-Organic Frameworks as Label-Free Fluorescence Tags.

Tunable detection of microRNA is crucial to meet the desired demand for sample species with varying concentrations in clinical settings. Herein, we present a DNA walker-based molecular circuit for the detection of miRNA-21 (miR-21) with tunable dynamic ranges and sensitivity levels ranging from fM to pM. The phosphate-activated fluorescence of UiO-66-NH2 metal-organic framework nanoparticles was used as label-free fluorescence tags due to their competitive coordination effect with the Zr atom, which significantly inhibited the ligand-to-metal charge transfer. To achieve a tunable detection performance for miR-21, the ultraviolet sensitive o-nitrobenzyl was induced as a photocleavable linker, which was inserted at various sites between the loop and the stem of the hairpin probe to regulate the DNA strand displacement reaction. The dynamic range can be precisely regulated from 700- to 67,000-fold with tunable limits of detection ranging from 2.5 fM to 36.7 pM. Impressively, a Boolean logic tree and complex molecular circuit were constructed for logic computation and cancer diagnosis in clinical blood samples. This intelligent biosensing method presents a powerful solution for converting complex biosensing systems into actionable healthcare decisions and will facilitate early disease diagnosis.

Magnetically Controlled and Addressable Photoelectrochemical Sensor Array with Self-Calibration for the Label-Free Detection of Amyloid ß-Proteins.

A label-free addressable photoelectric immunosensor array was designed for the detection of amyloid ß-proteins based on magnetic separation and self-calibration strategies. In this paper, Na2Ti6O13 with a flower-like morphology was prepared by the hydrothermal method; after continuously combining Fe3O4 and CdS, it was endowed with magnetism and better photoelectric activity. Subsequently, a series of reactions occurred in the solution, and the magnetic separation method was used to enrich the target. On the other hand, the ITO glass was separated into eight sites (2 × 4) using magnets, and a light shield was utilized to prevent light exposure, resulting in addressable and continuous detection. After the uniform preparation of magnetic photoelectric materials and precise control of testing conditions, the relative errors among different sites have been effectively reduced. Moreover, incorporating a self-calibration strategy has allowed the sensor array to achieve greater accuracy. The proposed photoelectrochemical biosensor exhibits a good relationship with amyloid ß-protein ranging from 0.01 to 100 ng mL-1 with a limit of detection of 1.1 pg mL-1 and exhibits excellent specificity, reproducibility, and stability.

DNA Tile and Invading Stacking Primer-Assisted CRISPR-Cas12a Multiple Amplification System for Entropy-Driven Electrochemical Detection of MicroRNA with Tunable Sensitivity.

Conventional electrochemical detection of microRNA (miRNA) encounters issues of poor sensitivity and fixed dynamic range. Here, we report a DNA tile and invading stacking primer-assisted CRISPR-Cas12a multiple amplification strategy to construct an entropy-controlled electrochemical biosensor for the detection of miRNA with tunable sensitivity and dynamic range. To amplify the signal, a cascade amplification of the CRISPR-Cas12a system along with invading stacking primer signal amplification (ISPSA) was designed to detect trace amounts of miRNA-31 (miR-31). The target miR-31 could activate ISPSA and produce numerous DNAs, triggering the cleavage of the single-stranded linker probe (LP) that connects a methylene blue-labeled DNA tile with a DNA tetrahedron to form a Y-shaped DNA scaffold on the electrode. Based on the decrease of current, miR-31 can be accurately and efficiently detected. Impressively, by changing the loop length of the LP, it is possible to finely tune the entropic contribution while keeping the enthalpic contribution constant. This strategy has shown a tunable limit of detection for miRNA from 0.31 fM to 0.56 pM, as well as a dynamic range from ∼2200-fold to ∼270,000-fold. Moreover, it demonstrated satisfactory results in identifying cancer cells with a high expression of miR-31. Our strategy broadens the application of conventional electrochemical biosensing and provides a tunable strategy for detecting miRNAs at varying concentrations.

d-Penicillamine@Ag/Cu Nanocluster-Based Fluorescent Nanoneuron for Logic Screening Phosphonate-Type Organophosphate Pesticides and Steganographically Encrypting Information.

Organophosphate pesticides are used in agriculture due to their high effectiveness and low persistence in eradicating insects and pests. However, conventional detection methods encounter the limitation of undesired detection specificity. Thus, screening phosphonate-type organophosphate pesticides (OOPs) from their analogues, phosphorothioate organophosphate pesticides (SOPs), remains a challenge. Here, we reported a d-penicillamine@Ag/Cu nanocluster (DPA@Ag/Cu NCs)-based fluorescence assay to screen OOPs from 21 kinds of organophosphate pesticides, which can be used for logic sensing and information encryption. Acetylthiocholine chloride was enzymatically split by acetylcholinesterase (AChE) to produce thiocholine, which reduced the fluorescence of DPA@Ag/Cu NCs due to the transmission of electrons from DPA@Ag/Cu NCs donor to the thiol group acceptor. Impressively, OOPs acted as an AChE inhibitor and retained the high fluorescence of DPA@Ag/Cu NCs due to the stronger positive electricity of the phosphorus atom. Conversely, SOPs possessed weak toxicity to AChE, which led to low fluorescence intensity. By setting 21 kinds of organophosphate pesticides as the inputs and the fluorescence of the resulting products as the outputs, DPA@Ag/Cu NCs could serve as a fluorescent nanoneuron to construct Boolean logic tree and complex logic circuit for molecular computing. As a proof of concept, by converting the selective response patterns of DPA@Ag/Cu NCs into binary strings, molecular crypto-steganography for encoding, storing, and concealing information was successfully achieved. This study is expected to advance the progress and practical application of nanoclusters in the area of logic detection and information security while also enhancing the relationship between molecular sensors and the world of information.

Enthalpy and entropy synergistic regulation-based programmable DNA motifs for biosensing and information encryption.

Deoxyribonucleic acid (DNA) provides a collection of intelligent tools for the development of information cryptography and biosensors. However, most conventional DNA regulation strategies rely solely on enthalpy regulation, which suffers from unpredictable stimuli-responsive performance and unsatisfactory accuracy due to relatively large energy fluctuations. Here, we report an enthalpy and entropy synergistic regulation-based pH-responsive A+/C DNA motif for programmable biosensing and information encryption. In the DNA motif, the variation in loop length alters entropic contribution, and the number of A+/C bases regulates enthalpy, which is verified through thermodynamic characterizations and analyses. On the basis of this straightforward strategy, the performances, such as pKa, of the DNA motif can be precisely and predictably tuned. The DNA motifs are finally successfully applied for glucose biosensing and crypto-steganography systems, highlighting their potential in the field of biosensing and information encryption.

Photoresponsive DNA-Modified Magnetic Bead-Assisted Rolling Circle Amplification-Driven Visual Photothermal Sensing of Escherichia coli.

The development of facile, reliable, and accurate assays for pathogenic bacteria is critical to environmental pollution surveillance, traceability analysis, prevention, and control. Here, we proposed a rolling circle amplification (RCA) strategy-driven visual photothermal smartphone-based biosensor for achieving highly sensitive monitoring of Escherichia coli (E. coli) in environmental media. In this design, E. coli could specifically bind with its recognition aptamer for initiating the RCA process on a magnetic bead (MB). Owing to the cleaving of UV irradiation toward photoresponsive DNA on MB, the RCA products were released to further hybridize with near-infrared excited CuxS-modified DNA probes. As a result, the photothermal signal was enhanced by RCA, while the background was decreased by UV irradiation and magnetic separation. The correspondingly generated photothermal signals were unambiguously recorded on a smartphone, allowing for an E. coli assay with a low detection limit of 1.8 CFU/mL among the broad linear range from 5.0 to 5.0 × 105 CFU/mL. Significantly, this proposed biosensor has been successfully applied to monitor the fouling levels of E. coli in spring water samples with acceptable results. This study holds great prospects by integrating a RCA-driven photothermal amplification strategy into a smartphone to develop accurate, reliable, and efficient analytical platforms against pathogenic bacteria pollutions for safeguarding environmental health.

Molecular Visual Sensing, Boolean Logic Computing, and Data Security Using a Droplet-Based Superwetting Paradigm.

Inspired by information processing and logic operations of life, many artificial biochemical systems have been designed for applications in molecular information processing. However, encoding the binary synergism between matter, energy, and information in a superwetting system remains challenging. Herein, a superwetting paradigm was proposed for multifunctional applications including molecular visual sensing and data security on a superhydrophobic surface. A Triton X-100-encapsulated gelatin (TeG) hydrogel was prepared and selectively decomposed by trypsin, releasing the surfactant to decrease the surface tension of a droplet. Integrating the droplet with the superhydrophobic surface, the superwetting behavior was utilized for visual detection and information encoding. Interestingly, the proposed TeG hydrogel can function as an artificial gelneuron for molecular-level logic computing, where the combination of matters (superhydrophobic surface, trypsin, and leupeptin) acts as inputs to interact with energy (liquid surface tension and solid surface energy) and information (binary character), resulting in superwettability transitions (droplet surface tension, contact angle, rolling angle, and bounce) as outputs. Impressively, the TeG gelneuron can be further developed as molecular-level double cryptographic steganography to encode, encrypt, and hide specific information (including the maze escape route and content of the classical literature) due to its programmability, stimuli responsive ability, and droplet concealment. This study will encourage the development of advanced molecular paradigms and their applications, such as superwetting visual sensing, molecular computing, interaction, and data security.

Bio-inspired Superwettable Surface for the Detection of Cancer Biomarker: A Mini Review.

Inspired by nature, superwettable material-based biosensors have aroused wide interests due to their potential in cancer biomarker detection. This mini review mainly summarized the superwettable materials as novel biosensing substrates for the development of evaporation-induced enrichment-based signal amplification and visual biosensing method. Biosensing applications based on the superhydrophobic surfaces, superwettable micropatterned surfaces, and slippery lubricant-infused porous surfaces for various cancer biomarker detections were described in detail. Finally, an insight of remaining challenges and perspectives of superwettable biosensor is proposed.

Label-Free Resonance Rayleigh Scattering Amplification for Lipopolysaccharide Detection and Logical Circuit by CRISPR/Cas12a-Driven Guanine Nanowire Assisted Non-Cross-Linking Hybridization Chain Reaction.

Although the CRISPR/Cas system has pioneered a new generation of analytical techniques, there remain many challenges in developing a label-free, accurate, and reliable CRISPR/Cas-based assay for reporting the levels of low abundance biomolecules in complex biological samples. Here, we reported a novel CRISPR-derived resonance Rayleigh scattering (RRS) amplification strategy and logical circuit based on a guanine nanowire (G-wire) assisted non-cross-linking hybridization chain reaction (GWancHCR) for label-free detection of lipopolysaccharide (LPS). In the presence of a target, the protospacer-adjacent motif-inserted aptamer is rationally designed to specifically combine with LPS rather than Cas12a, suppressing the trans-cleavage activity of CRISPR/Cas12a and retaining the reporter probes to trigger non-cross-linking aggregation. Owing to the automatic hybridization chain reaction (HCR), in the presence of Mg2+, the released G-quadruplex sequence aggregated to assemble the G-wire superstructure through non-cross-linking. As a result, a dramatically amplified RRS intensity is observed, allowing for reporting LPS levels in a low detection limit of 0.17 pg/mL and a wide linear range among 1.0-100.0 ng/mL. Moreover, this reaction event is capable of programming to perform classical Boolean logic tree analysis, including basic logic computing and complex integrated logic circuits. This study comprehensively analyzed with respect to information flow, matter (molecular events), and energy (RRS), revealing the potential promise in designing of molecular-level "Internet of Things", intelligent computing, and sensing systems.

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.

Superwettable Biosensor for Disease Biomarker Detection.

Bioinspired superwettable materials have aroused wide interests in recent years for their promising application fields from service life to industry. As one kind of emerging application, the superwettable surfaces used to fabricate biosensors for the detection of disease biomarkers, especially tumor biomarkers, have been extensively studied. In this mini review, we briefly summarized the sensing strategy for disease biomarker detection based on superwettable biosensors, including fluorescence, electrochemistry, surface-enhanced Raman scattering, and visual assays. Finally, the challenges and direction for future development of superwettable biosensors are also discussed.

Visual Detection of Adenosine Triphosphate by Taylor Rising: A Simple Point-of-Care Testing Method Based on Rolling Circle Amplification.

Rapid and sensitive point-of-care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP-dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor-rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 µL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user-friendly molecular diagnostics.

pH-Responsive DNA Motif: From Rational Design to Analytical Applications.

pH-responsive DNA motifs have attracted substantial attention attributed to their high designability and versatility of DNA chemistry. Such DNA motifs typically exploit DNA secondary structures that exhibit pH response properties because of the presence of specific protonation sites. In this review, we briefly summarized second structure-based pH-responsive DNA motifs, including triplex DNA, i-motif, and A+-C mismatch base pair-based DNA devices. Finally, the challenges and prospects of pH-responsive DNA motifs are also discussed.

Ultrasensitive photoelectrochemical platform with micro-emulsion-based p-type hollow silver iodide enabled by low solubility product (Ksp) for H2S sensing.

Since visible-light (VL) accounting for massive solar radiation energy, a large amount of attention has been paid to the development of highly efficient visible-light-driven (VLD) semiconductor materials. However, despite recent efforts to construct VL active material, hollow structure-based silver iodide (AgI) with appropriate band gap and a large surface area are limited because of lack of a proper synthesis method. Herein, hollow AgI with p-type semiconductor behavior is constructed on the basis of micro-emulsion strategy, which enables admirable cathode photoelectrochemical (PEC) response. The as-prepared hollow AgI is applied to fabricate the PEC sensing platform and reveals a low limit of detection of 0.04 fM and a wide dynamic range up to 5 orders of magnitude toward H2S. The PEC sensing mechanism is supposed to the 'signal-off' pattern on account of the ultralow solubility product (Ksp) of Ag2S, derived from the precipitation reaction due to the high affinity between sulfide ion and Ag+. Besides, the hollow structure of AgI provides sufficient surface area forin situproducing Ag2S that serves as recombination center of carrier, thus causing the efficient quenching of photocurrent signals. This work broadens the horizon of structuring VLD semiconductor nanomaterials andKsp-based H2S sensing.

Cu2+ enhanced fluorescent Ag nanoclusters with tunable emission from red to yellow and the application for Ag+ sensing.

In this work, the water-soluble fluorescent Ag nanoclusters (DPA@Ag NCs) were first prepared based on D-Penicillamine (DPA) as a stabilizer, however, the fluorescence quantum yield (QY) of DPA@Ag NCs was very low, then Cu2+ was employed to improve the fluorescence QY and the doped Ag nanoclusters with Cu2+ (DPA@Ag/Cu NCs) were obtained. The study showed that the QY increased fourfold and the emission of nanoclusters changed from red to yellow after addition of Cu2+. The reasonfor change of fluorescent properties wasattributed to the change of self-assembly structures caused by adding Cu2+ into reaction system, leading to the aggregation-induced emission enhancement (AIEE) effect and enhancing the band gap (Eg) between the HOMO and LUMO in nanoclusters. Subsequently, a fluorescent Ag+ sensor with high sensitivity and selectivity was established based on the DPA@Ag/Cu NCs as probes in aqueous solution. Experiments showed that the Ag+ could significantly quench the fluorescence of DPA@Ag/Cu NCs under experimental conditions, and there was a good linear relationship between the fluorescent intensity quenching value and Ag+ concentration in the range of 0.05-800 µM, and the limit of detection (LOD) was 0.03 µM (3σ/k). Meanwhile, most of common ions had no effect on the experimental results under the same conditions. In addition, the sensor was successfully applied on the detection of Ag+ in real water samples, and the recovery rate was 80.3-99.0%.