Cascading CRISPR/Cas and Nanozyme for Enhanced Organic Photoelectrochemical Transistor Detection with Triple Signal Amplification.

Innovative signal amplification and transduction play pivotal roles in bioanalysis. Herein, cascading CRISPR/Cas and the nanozyme are integrated with electronic amplification in an organic photoelectrochemical transistor (OPECT) to enable triple signal amplification, which is exemplified by the miRNA-triggered CRISPR/Cas13a system and polyoxometalate nanozyme for OPECT detection of miRNA-21. The CRISPR/Cas13a-enabled release of glucose oxidase could synergize with peroxidase-like SiW12 to induce catalytic precipitation on the photogate, inhibiting the interfacial mass transfer and thus the significant suppression of the channel current. The as-developed OPECT sensor demonstrates good sensitivity and selectivity for miRNA-21 detection, with a linear range from 1 fM to 10 nM and an ultralow detection limit of 0.53 fM. This study features the integration of bio- and nanoenzyme cascade and electronic triple signal amplification for OPECT detection.

Photoresponsive Hydrogen-Bonded Organic Frameworks-Enabled Organic Photoelectrochemical Transistors for Sensitive Bioanalysis.

A facile route for exponential magnification of transconductance (gm) in an organic photoelectrochemical transistor (OPECT) is still lacking. Herein, photoresponsive hydrogen-bonded organic frameworks (PR-HOFs) have been shown to be efficient for gm magnification in a typical poly(ethylene dioxythiophene):poly(styrenesulfonate) OPECT. Specifically, 450 nm light stimulation of 1,3,6,8-tetrakis (p-benzoic acid) pyrene (H4TBAPy)-based HOF could efficiently modulate the device characteristics, leading to the considerable gm magnification over 78 times from 0.114 to 8.96 mS at zero Vg. In linkage with a DNA nanomachine-assisted steric hindrance amplification strategy, the system was then interfaced with the microRNA-triggered structural DNA evolution toward the sensitive detection of a model target microRNA down to 0.1 fM. This study first reveals HOFs-enabled efficient gm magnification in organic electronics and its application for sensitive biomolecular detection.

Molecule Engineering Metal-Organic Framework-Based Organic Photoelectrochemical Transistor Sensor for Ultrasensitive Bilirubin Detection.

The functionalization of metal-organic frameworks (MOFs) with organic small molecules by in situ postsynthetic modification has garnered considerable attention. However, the precise engineering of recognition sites using this method remains rarely explored in optically controlled bioelectronics. Herein, employing the Schiff base reaction to embed the small molecule (THBA) into a Zr-MOF, we fabricated a hydroxyl-rich MOF on the surface of titanium dioxide nanorod arrays (U6H@TiO2 NRs) to develop light-sensitive gate electrodes with tailored recognition capabilities. The U6H@TiO2 NR gate electrodes were integrated into organic photoelectrochemical transistor (OPECT) sensing systems to tailor a sensitive device for bilirubin (I-Bil) detection. In the presence of I-Bil, coordination effects, hydrogen bonding, and π-π interactions facilitated strong binding between U6H@TiO2 NRs and the target I-Bil. The electron-donating property of I-Bil influenced the gate voltage, enabling precise control of the channel status and modulation of the channel current. The OPECT device exhibited exceptional analytical performance toward I-Bil with wide linearity ranging from 1 × 10-16 to 1 × 10-9 M and a low limit detection of 0.022 fM. Leveraging the versatility of small molecules for boosting the functionalization of materials, this work demonstrates the great potential of the small molecule family for OPECT bioanalysis and holds promise for the advancement of OPECT sensors.

Reticular Heterojunction for Organic Photoelectrochemical Transistor Detection of Neuron-Specific Enolase.

Reticular heterojunctions on the basis of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) have sparked considerable interest in recent research endeavors, which nevertheless have seldom been studied in optoelectronic biosensing. In this work, its utilization for organic photoelectrochemical transistor (OPECT) detection of the important cancer biomarker of neuron-specific enolase (NSE) is reported. A MOF@COF@CdS quantum dots (QDs) heterojunction is rationally designed to serve as the photogating module against the polymeric channel. Linking with a sandwich complexing event, target-dependent alternation of the photogate is achieved, leading to the changed photoelectric conversion efficiency as indicated by the amplified OPECT signals. The proposed assay demonstrates good analytical performance in detecting NSE, featuring a linear detection range from 0.1 pg mL-1 to 100 ng mL-1, with a detection limit of 0.033 pg mL-1.

Visible light driven photoredox/nickel-catalyzed stereoselective synthesis of Z- or E-vinyl thioethers from thiosilane and terminal alkynes.

A new method for the synthesis of anti-Markovnikov Z- or E-vinyl thioethers from thiosilane and terminal alkynes under visible-light-induced photoredox/nickel dual catalysis conditions is described. With a judicious choice of a simple nickel catalyst and a ligand, this strategy enables efficient and divergent access to both Z- or E-vinyl thioethers from the same set of simple starting materials. Notably, the approach is free of odorous thiol and has excellent compatibility with functional groups and substrate scope.

Biological Transformation of AgI on MOF-on-MOF-Derived Heterostructures: Toward Polarity-Switchable Photoelectrochemical Biosensors for Neuron-Specific Enolase.

The sensitive detection of neuron-specific enolase (NSE) as a biomarker for lung cancer at an early stage is critical but has long been a challenge. The emergence of polarity-switchable photoelectrochemical (PEC) bioanalysis has opened up new avenues for developing highly sensitive NSE sensors. In this study, we present such a biosensor depending on the bioinduced AgI transition on MOF-on-MOF-derived semiconductor heterojunctions. Specifically, treatment of ZnO@In2O3@AgI by bioproduced H2S can in situ generate the ZnO@In2O3@In2S3@Ag2S heterojunction, with the photocurrent switching from the cathodic to anodic one due to the changes in the carrier transfer pathway. Linking an NSE-targeted sandwich immunorecognition with labeled alkaline phosphatase (ALP) catalyzed generation of H2S, such a phenomenon was correlated to NSE concentration with good performance in terms of selectivity and sensitivity and a low detection limit of 0.58 pg/mL. This study offered a new perspective on the use of MOF-on-MOF-derived heterostructures for advanced polarity-switchable PEC bioanalysis.

Oxygen Vacancy-Mediated CuWO4/CuBi2O4 Samples with Efficient Charge Transfer for Enhanced Catalytic Activity toward Photodegradation of Pharmacologically Active Compounds.

Photocatalytic degradation is a promising method for controlling the increasing contamination of the water environment due to pharmacologically active compounds (PHACs). Herein, oxygen vacancy (OV)-modulated Z-scheme CuWO4/CuBi2O4 hybrid systems were fabricated via thermal treatment by loading of CuWO4 nanoparticles with OVs on CuBi2O4 surfaces. The synthesized CuWO4/CuBi2O4 hybrid samples exhibited an enhanced photodegradation ability to remove PHACs under visible-light irradiation. More importantly, an optimized sample (10 wt % CuWO4/CuBi2O4) exhibited superior catalytic activity and excellent recycling stability for PHAC photodegradation. In addition, possible degradation paths for PHAC removal over the CuWO4/CuBi2O4 hybrid systems were proposed. The enhanced photocatalytic performance could be attributed to the efficient separation and transfer of photoformed charge pairs via the Z-scheme mechanism. This Z-scheme mechanism was systematically analyzed using trapping experiments of active species, ultraviolet photoelectron spectroscopy, electron spin resonance, and the photodepositions of noble metals. The findings of this study can pave the way for developing highly efficient Z-scheme photocatalytic systems for PHAC photodegradation.

A well-fabricated Ru@C material derived from Ru/Zn-MOF with high activity and stability in the hydrogenation of 4-chloronitrobenzene.

4-Chloroaniline (4-CAN) plays an important role in chemical and industrial production. However, it remains a challenge to avoid the hydrogenation of the C-Cl bond in the synthesis process to improve selectivity under high activity conditions. In this study, we in situ fabricated ruthenium nanoparticles (Ru NPs) containing vacancies inserted into porous carbon (Ru@C-2) as a highly efficient catalyst for the catalytic hydrogenation of 4-chloronitrobenzene (4-CNB) with remarkable conversion (99.9%), selectivity (99.9%), and stability. Experiments and theoretical calculations indicate that the appropriate Ru vacancies affect the charge distribution of the Ru@C-2 catalyst, promote the electron transfer between the Ru metal and support, and increase the active sites of the Ru metal, thus facilitating the adsorption of 4-CNB and the desorption of 4-CAN to improve the activity and stability of the catalyst. This study can provide some enlightenment for the development of new 4-CNB hydrogenation catalysts.

Ultrasensitive and Label-Free Detection of Multiple DNA Methyltransferases by Asymmetric Nanopore Biosensor.

DNA methylation is catalyzed by a family of DNA methyltransferases that play crucial roles in various biological processes. Therefore, an ultrasensitive methyltransferase assay is highly desirable in biomedical research and clinical diagnosis. However, conventional assays for the detection of DNA methyltransferase activity often involve radioactive labeling, costly equipment, and laborious operation. In this study, an ultrasensitive and label-free method for detecting DNA adenine methyltransferase (Dam) and CpG methyltransferase (M.SssI) was developed using the nanopore technique coupled with DNA cascade signal amplification reactions. A hairpin DNA (HD) comprising of the methylation-responsive sequences was skillfully designed. In the presence of Dam methyltransferase, the corresponding recognition site of hairpin HD was methylated and specifically cleaved by DpnI endonuclease, thus forming a DNA fragment that induces the catalytic hairpin assembly and hybridization chain reaction (CHA-HCR). The generated products could be absorbed onto the Zr4+-coated nanopore, resulting in an ion current rectification signal change. Considering the high sensitivity of the nanopore and excellent specificity toward the recognition of methyltransferase/endonuclease, our developed method could detect both Dam and M.SssI methyltransferases in the same sensing platform. Furthermore, the designed nanopore sensor could realize the multiplex detection of Dam and M.SssI methyltransferases after integration with the cascaded INHIBIT-AND logic gate. This ultrasensitive methyltransferase assay holds great promise in the field of cancer diagnosis.

Engineering of Portable Smartphone Integrated with Liposome-Encapsulated Curcumin for Onsite Visual Ratiometric Fluorescence Imaging of Hypochlorite.

Precisely onsite monitoring of hypochlorite (ClO- ) is of great significance to guide its rational use, reducing/avoiding its potential threat toward food safety and human health. Considering ClO- could quench fluorescence of curcumin (CCM) by oxidizing the o-methoxyphenol of CCM into benzoquinone, a portable ratiometric fluorescence sensor integrated with smartphone was designed for realizing the visual point-of-care testing (POCT) of ClO- . The amphiphilic phospholipid polymer was used as carrier to wrap curcumin, forming a novel liposome-encapsulated CCM, which provided a scaffold to bind with [Ru(bpy)3 ]2+ through electrostatic interaction, thus assembling [Ru(bpy)3 ]2+ -functionalized liposome-encapsulated CCM ([Ru(bpy)3 ]2+ @CCM-NPs). Further integrated with smartphone, visual imaging of [Ru(bpy)3 ]2+ @CCM-NPs could be achieved and the accurate onsite detection of ClO- could be realized with a detection limit of 66.31 nM and a linear range of 0.2210 to 80.0 µM. In addition, the sensor could monitor ClO- in real samples with an onsite detection time of ∼154.0 s.

Rational Utilization of Photoelectrochemistry of Photosystem II for Self-Powered Photocathodic Detection of MicroRNA in Cells.

The photoanode, photosystem II (PSII)/hierarchical inverse opal (IO) TiO2, is coupled to the complementary photocathode, PbS quantum dots (QDs)/DNA probes, which is then integrated into a two-compartment photoelectrochemical (PEC) cell to achieve a self-powered system to enable photocathodic detection of microRNA-10b from HeLa cells. In such a system, all of the PSII catalytic products, i.e., electrons, protons, and O2, were rationally utilized and could overcome the general issue of varied O2 levels in photocathodic detection. The correlation between the target-triggered formation of the DNA complexes and the catalytic reduction of the dissolved O2 makes possible the steady microRNA-10b detection with good sensitivity and selectivity. This work has unveiled the ability of PSII to construct self-powered detecting devices and shed light on its application in new arenas.

Target-Dependent Gating of Nanopores Integrated with H-Cell: Toward A General Platform for Photoelectrochemical Bioanalysis.

Herein we present a proof-of-concept study of target-dependent gating of nanopores for general photoelectrochemical (PEC) bioanalysis in an H-cell. The model system was constructed upon a left chamber containing ascorbic acid (AA), the antibody modified porous anodic alumina (AAO) membrane separator, and a right chamber placed with the three-electrode system. The sandwich immunocomplexation and the associated enzymatic generation of biocatalytic precipitation (BCP) in the AAO nanopores would regulate the diffusion of AA from the left cell to the right cell, leading to a varied photocurrent response of the ZnInS nanoflakes photoelectrode. Exemplified by fatty-acid-banding protein (FABP) as the target, the as-developed protocol achieved good performance in terms of sensitivity, selectivity, reproducibility, as well as efficient reutilization of the working electrode. On the basis of an H-cell, this work features a new protocol of target-dependent gating-based PEC bioanalysis, which can serve as a general PEC analytical platform for various other targets of interest.

Twin Nanopipettes for Real-Time Electrochemical Monitoring of Cytoplasmic Microviscosity at a Single-Cell Level.

Cytoplasmic microviscosity (CPMV) plays essential roles in governing the diffusion-mediated cellular processes and has been recognized as a reliable indicator of the cellular response of many diseases and malfunctions. Current CPMV studies are exclusively established by probe-assisted optical methods, which nevertheless necessitate the complicated synthesis and delivery of optical probes into cells and thus the issues of biocompatibility and bio-orthogonality. Using twin nanopipettes integrated with a patch-clamp system, a practical electrochemical single-cell measurement is presented, which is capable of real-time and long-term CPMV detection without cell disruption. Specifically, upon the operation of the twin nanopipettes, the cellular CPMV status, which is correlated to cytoplasmic ionic mobility, could be sensibly transduced via the ionic current passing through the nanosystem. The average CPMV value of HeLa cells was detected as ca. 86 cP. Notably, the correlation between chemotherapy and CPMV alterations makes this approach possible for the real-time and long-term assessment of the evolution of external stimuli, as exemplified by the two natural products taxol and colchicine. Integrated with the patch-clamp setup, this study features the first use of twin nanopipettes for electrochemical CPMV monitoring of single living cells, and it is expected to inspire more interest in the exploitation of dual- and multiple nanopipettes for advanced single-cell analysis.

Liposome-Assisted Enzymatic Modulation of Plasmonic Photoelectrochemistry for Immunoassay.

Recently emerged liposomal photoelectrochemical (PEC) bioanalysis has brought new opportunities for biosensor development. This work presents the new concept of liposome-assisted enzymatic modulation of plasmonic photoelectrochemistry for PEC bioanalysis, which was exemplified by an Au nanoclusters (NCs)-sensitized nanoporous TiO2 nanotubes (Au NC@TiO2 NT) photoelectrode and an alkaline phosphatase (ALP)-loaded liposomal immunoassay of heart-type fatty acid binding protein in a 96-well plate. After sandwich immunorecognition and subsequent lysis treatment, enzymatically generated ascorbic acid by the released ALP was directed to reduce Au3+ into Au nanoparticles using the Au NCs as seeds, leading to the in situ change of the photoelectrochemistry of the electrode and corresponding reduction of the photocurrent. The depressed signal could be correlated with the target concentration with good analytical performance in terms of sensitivity and selectivity. This work features the liposome-assisted enzymatic modulation of plasmonic photoelectrochemistry, which provides a new protocol for general PEC bioanalysis development.

Fabrication of a Biomimetic Nanochannel Logic Platform and Its Applications in the Intelligent Detection of miRNA Related to Liver Cancer.

Nanochannel-based analytical techniques have great potential applications for nucleic acid sequencing and high sensitivity detection of biological molecules. However, the sensitivity of conventional solid-state nanochannel sensors is hampered by a lack of effective signal amplification strategies, which has limited its utility in the field of analytical chemistry. Here we selected a solid-state nanochannnel modified with polyethylenimine and Zr4+ in combination with graphene oxide as the sensing platform. The high-performance sensor is based upon the change of the surface charge of the nanochannel, which is resulted from DNA cascade signal amplification in solution. The target miRNA (miR-122) can be indirectly quantitated with a detection limit of 97.2 aM with an excellent selectivity. Depending on the nucleic acid's hybridization and configuration transform, the designed nanochannel sensing systems can realize the intelligent detection of multiple liver cancer-related miRNA (miR-122 and miR Let-7a) integrating with cascaded INHIBIT-OR logic gate to provide theoretical guidance and technical support for clinical diagnosis and therapeutic evaluation of liver cancer.

Self-Assembled Peptide Nanostructures for Photoelectrochemical Bioanalysis Application: A Proof-of-Concept Study.

Currently, one of important research directions of photoelectrochemical (PEC) bioanalysis is to exploit innovative photoactive species and their elegant implementations for selective detection and signal transduction. Different from existing candidates for photoelectrode development, this study, exemplified by the cationic dipeptide nanoparticles (CDNPs), reports the first demonstration of self-assembled peptide nanostructures (SAPNs) for the PEC bioanalysis. Specifically, the CDNPs were prepared as representative materials and then immobilized onto the indium tin oxide (ITO) electrode for the PEC differentiation of several commonly involved biomolecules such as ascorbic acid (AA) and l-cysteine. Significantly, the experimental results disclosed that the CDNPs possessed unique photocathodic responses and good analytical performance toward AA detection in terms of rapid response, high stability, and excellent selectivity. This work demonstrates the great potential of the large SAPN family for the future PEC bioanalysis development and has not been reported to our knowledge.

Liposome-Mediated in Situ Formation of AgI/Ag/BiOI Z-Scheme Heterojunction on Foamed Nickel Electrode: A Proof-of-Concept Study for Cathodic Liposomal Photoelectrochemical Bioanalysis.

This work reports the liposome-mediated in situ formation of the AgI/Ag/BiOI Z-scheme heterojunction on foamed nickel electrode for signal-on cathodic photoelectrochemical (PEC) bioanalysis. Specifically, in a proof-of-concept study, Ag nanoparticle-encapsulated liposomes were initially confined via the sandwich immunobinding and then processed to release numerous Ag+ ions, which were then directed to react with the BiOI/Ni electrode, resulting in the in situ generation of a AgI/Ag/BiOI Z-scheme heterojunction on the electrode. The enhanced cathodic signal could be correlated to the target concentration, which thus underlays a novel signal-on cathodic liposomal PEC bioanalysis strategy. Different from previous anodic liposomal PEC bioanalysis, this work features the first cathodic liposomal PEC bioanalysis on the basis of the in situ formation of a Z-scheme heterojunction. More generally, integrated with various biorecognition events, this protocol could serve as a common basis for addressing numerous targets of interest.

Sodium Triethylborohydride-Catalyzed Controlled Reduction of Unactivated Amides to Secondary or Tertiary Amines.

The first transition-metal-free catalytic protocol for controlled reduction of amide functions using cheap and bench-stable hydrosilanes as reducing agents has been established. By altering the hydrosilane and solvent, the new method enables the selective cleavage of unactivated C-O bonds in amides and allows the C-N bonds to selectively break via the deacylated cleavage. Overall, this novel process may offer a versatile alternative to current methodologies employing stoichiometric metal systems for the controlled reduction of carboxamides.

An Additive-Free, Base-Catalyzed Protodesilylation of Organosilanes.

We report an additive-free, base-catalyzed C-, N-, O-, and S-Si bond cleavage of various organosilanes in mild conditions. The novel catalyst system exhibits high efficiency and good functional group compatibility, providing the corresponding products in good to excellent yields with low catalyst loadings. Overall, this transition-metal-free process may offer a convenient and general alternative to current employing excess bases, strong acids, or metal-catalyzed systems for the protodesilylation of organosilanes.

A tri-site fluorescent probe for simultaneous sensing of hydrogen sulfide and glutathione and its bioimaging applications.

Hydrogen sulfide (H2S) and biothiol molecules, such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy), play an important role in biology. However, understanding the complicated relationship between H2S and biothiols remains an enormous challenge owing to the difficulty in sensing H2S and biothiols simultaneously. Therefore, the development of probes for detecting H2S and biothiols is of great importance in biological science. In this work, we reported a novel fluorescent probe for the sensitive and selective detection of H2S and glutathione (GSH) simultaneously in different buffer solutions. The key design principle is based on a coumarin as the fluorophore structuring a fluorescent probe with three potential sites which could react with H2S and biothiols. This probe displays a rapid response with highly sensitive and selective detection of H2S and GSH (the detection limit of 75 nM and 280 nM, respectively). Moreover, with the assistance of a confocal fluorescence microscope, we demonstrated that the probe can be successfully applied for imaging H2S and GSH in MCF-7 cells.