Cu Single-Atom Nanozyme-Mediated Electrochemiluminescence Biosensor for Highly Sensitive Detection of MicroRNA-622.

MicroRNA (miRNA) detection is a critical aspect of disease diagnosis, and recent studies indicate that miRNA-622 could be a potential target for lung cancer. Herein, Cu single atoms were anchored on graphitic carbon nitride (Cu SAs@CN) as a coreaction accelerator applied in luminol-H2O2 system, thereby establishing an efficient and sensitive electrochemiluminescence (ECL) biosensor for miRNA-622 detection. Cu SAs@CN was explored to possess excellent enzyme-like activities that promote the generation of abundant reactive oxygen species, which amplified ECL emission. Meanwhile, in order to improve the accuracy and sensitivity for miRNA-622 detection, the highly specific trans-cleavage ability of CRISPR/Cas12a was combined with a catalytic hairpin assembly strategy. Therefore, an ECL biosensor for miRNA-622 detection was systematically constructed as a proof of concept, achieving an ultralow limit of detection of 1.09 fM, and the feasibility was demonstrated in human serum samples. The findings of this research provide a promising strategy to enhance the ECL response using versatile single-atom catalysts, thus advancing the development of ECL biosensing applications.

Tetrahedral DNA Nanostructure-Engineered Paper-Based Sensor with an Enhanced Antifouling Ability for Photoelectrochemical Sensing.

Herein, a newly designed two-in-one tetrahedral DNA (TDN) nanostructure with an antifouling surface and backbone-rigidified interfacial tracks was developed for highly sensitive and selective detection of miRNA-182-5p. The well-regulated TDN tracks were assembled onto the surface of the TiO2/MIL-125-NH2-functionalized paper electrode, which efficiently avoided the obstacle of DNA strand tangling and decreased the probability of suspension during the walking process, thus greatly promoting the moving efficiency of DNA walkers. More interestingly, the TDN-modified sensing interfaces demonstrated incomparable antifouling ability against protein samples and interfering miRNAs due to the strong hydrophilic capacity and special molecular conformations, which addressed the dilemma of low sensitivity from traditional antifouling coating strategies. As a proof of concept, the designed bifunctional tetrahedron-modified paper-based photoelectrochemical sensor was successfully used to quantify miRNA-182-5p with a low detection limit of 0.09 fM and high specificity and was validated for monitoring of miRNA-182-5p in real samples. This TDN-engineered biointerface could be used as a universal platform for tracking various targets by substituting the biorecognition events, providing great promise for bioanalysis and clinical diagnosis.

Paper-Supported Photoelectrochemical Biosensor for Dual-Mode miRNA-106a Assay: Integration of Luminescence-Confined Upconversion-Actuated Fluorescent Resonance Energy Transfer and CRISPR/Cas13a-Powered Cascade DNA Circuits.

Near-infrared (NIR)-responsive bioassays based on upconversion nanoparticle (UCNP) incorporating high-performance semiconductors have been developed by researchers, but most lack satisfactory ultrasensitivity for exceedingly trace amounts of target. Herein, for the first time, the CRISPR/Cas13a system is combined with cascade DNA circuits, fluorescent resonance energy transfer (FRET) effect, and luminescence-confined UCNPs-bonded CuInS2/ZnO p-n heterostructures-functionalized paper-working electrode to construct dual-signal-on paper-supported NIR-irradiated photoelectrochemical (PEC) (NIR-PEC) and upconversion luminescence (UCL) bioassay for high-sensitive quantification of miRNA-106a (miR-106a). By constructing an ideal FAM-labeled aminating molecular beacon (FAM-H2) model, a relatively good FRET ratio between the UCNP and FAM (≈85.3%) can be achieved. In the existence of miR-106a, the hairpin-structure FAM-H2 was unwound, bringing about the distance increase of UCNP and FAM and the restraint of FRET. Accordingly, both the NIR-PEC signal and the UCL intensity gradually recovered distinctly. Unlike conventional single-mode PEC sensors, with NIR excitation, the designed dual-mode sensing system could implement minimized misdiagnose assay and quantitative miR-106a determination with low detection limits, that is, 76.54 and 51.36 aM for NIR-PEC and UCL detection, respectively. This work not only broadens the horizon of application of the CRISPR/Cas13a strategy toward biosensing but also constructs a new structure of the UCNP-semiconductor in the exploration of efficient NIR-responsive tools and inspires the construction of a no-misdiagnosed and novel biosensor for dual-mode liquid biopsy.

Photoelectrochemical Detection of Exosomal miRNAs by Combining Target-Programmed Controllable Signal Quenching Engineering.

MicroRNAs extracted from exosomes (exosomal miRNAs) have recently emerged as promising biomarkers for early prognosis and diagnosis. Thus, the development of an effective approach for exosomal miRNA monitoring has triggered extensive attention. Herein, a sensitive photoelectrochemical (PEC) biosensing platform is demonstrated for exosomal miRNA assay via the target miRNA-powered λ-exonuclease for the amplification strategy. The metal-organic framework (MOF)-decorated WO3 nanoflakes heterostructure is constructed and implemented as the photoelectrode. Also, a target exosomal miRNA-activatable programmed release nanocarrier was fabricated, which is responsible for signal control. Hemin that acted as the electron acceptor was prior entrapped into the programmed control release nanocarriers. Once the target exosomal miRNAs-21 was introduced, the as-prepared programmed release nanocarriers were initiated to trigger the release of hemin, which enabled the quenching of the photocurrent. Under the optimized conditions, the level of exosomal miRNAs-21 could be accurately tracked ranging from 1 fM to 0.1 µM with a low detection limit of 0.5 fM. The discoveries illustrate the possibility for the rapid and efficient diagnosis and prognosis prediction of diseases based on the detection of exosomal miRNAs-21 and would provide feasible approaches for the fabrication of an efficient platform for clinical applications.

Piezotronic Effect-Assisted Photoelectrochemical Exosomal MicroRNA Monitoring Based on an Electron Donor Self-Supplying Strategy.

Exosomal microRNAs (miRNAs) as newly emerging reliable and noninvasive biomarkers have demonstrated a significant function in early cancer diagnosis. Photoelectrochemical (PEC) biosensing has attracted unprecedented attention in exosomal miRNA monitoring due to its inherent advantages of both electrochemical and optical techniques; however, the severe charge carrier recombination greatly restricts the PEC assay performance. Herein, a high-sensitive PEC strategy assisted by the piezoelectric effect is designed based on Bi2WO6/Cu2S heterojunctions and implemented for the monitoring of exosomal miRNAs. The introduction of the piezoelectric effect enables promoted electron-hole transfer and separation, thereby improving the analytical sensitivity. In addition, a target reprogramming metal-organic framework-capped CaO2 (MOF@CaO2) hybrids is prepared, in which MOF@CaO2 being responsive to exosomal miRNAs induces exposure of the capped CaO2 to H2O and then triggers self-supplying of H2O2, which effectively suppresses the electron-hole recombination, giving rise to an amplified photocurrent and a decrease in the cost of the reaction. Benefiting from the coupled sensitization strategy, the as-fabricated PEC strategy exhibits high sensitivity, specificity, low cost, and ease of use for real-time analysis of exosomal miRNAs within the effectiveness linear range of 0.1 fM-1 µM. The present work demonstrates promising external field coupling-enhanced PEC bioassay and offers innovative thoughts for applying this strategy in other fields.

Dual-Engine Powered Paper Photoelectrochemical Platform Based on 3D DNA Nanomachine-Mediated CRISPR/Cas12a for Detection of Multiple miRNAs.

This work proposed a novel double-engine powered paper photoelectrochemical (PEC) biosensor based on an anode-cathode cooperative amplification strategy and various signal enhancement mechanisms, which realized the monitoring of multiple miRNAs (such as miRNA-141 and miRNA-21). Specifically, C3N4 quantum dots (QDs) sensitized ZnO nanostars and BiOI nanospheres simultaneously to construct a composite photoelectric layer that amplified the original photocurrent of the photoanode and photocathode, respectively. Through the independent design and partition of a flexible paper chip to functionalize injection holes and electrode areas, the bipolar combination completed the secondary upgrade of signals, which also provided biological reaction sites for multitarget detection. With the synergistic participation of a three-dimensional (3D) DNA nanomachine and programmable CRISPR/Cas12a shearing tool, C3N4 QDs lost their attachment away from the electrode surface to quench the signal. Moreover, electrode zoning significantly reduced the spatial cross talk of related substances for multitarget detection, while the universal trans-cleavage capability of CRISPR/Cas12a simplified the operation. The designed PEC biosensor revealed excellent linear ranges for detection of miRNA-141 and miRNA-21, for which the detection limits were 5.5 and 3.4 fM, respectively. With prominent selectivity and sensitivity, the platform established an effective approach for trace multitarget monitoring in clinical applications, and its numerous pioneering attempts owned favorable reference values.

A Target-Driven Self-Feedback Paper-Based Photoelectrochemical Sensing Platform for Ultrasensitive Detection of Ochratoxin A with an In2S3/WO3 Heterojunction Structure.

Currently, developing versatile, easy-to-operate, and effective signal amplification strategies hold great promise in photoelectrochemical (PEC) biosensing. Herein, an ultrasensitive polyvinylpyrrolidone-treated In2S3/WO3 (In2S3-P/WO3)-functionalized paper-based PEC sensor was established for sensing ochratoxin A (OTA) based on a target-driven self-feedback (TDSF) mechanism enabled by a dual cycling tactic of PEC chemical-chemical (PECCC) redox and exonuclease III (Exo III)-assisted complementary DNA. The In2S3-P/WO3 heterojunction structure with 3D open-structure and regulable topology was initially in situ grown on Au nanoparticle-functionalized cellulose paper, which was served as a universal signal transducer to directly record photocurrent signals without complicated electrode modification, endowing the paper chip with admirable anti-interference ability and unexceptionable photoelectric conversion efficiency. With the assistance of Exo III-assisted cycling process, a trace amount of OTA could trigger substantial signal reporter ascorbic acid (AA) generated by the enzymatic catalysis of alkaline phosphatase, which could effectively provoke the PECCC redox cycling among the tris(2-carboxyethyl)phosphine acid, AA, and ferrocenecarboxylic at the In2S3-P/WO3 photoelectrode, initiating TDSF signal amplification. Based on the TDSF process induced by the Exo III-assisted recycling and PECCC redox cycling strategy, the developed paper-based PEC biosensor realized ultrasensitive determination of OTA with persuasive selectivity, high stability, and excellent reproducibility. It is believed that the proposed paper-based PEC sensing platform exhibited enormous potential for the detection of other targets in bioanalysis and clinical diagnosis.

Laser ablative TiO2 and tremella-like CuInS2 nanocomposites for robust and ultrasensitive photoelectrochemical sensing of let-7a.

A photoelectrochemical (PEC) biosensor based on a multiple signal amplification strategy was established for highly sensitive detection of microRNA (miRNA). TiO2 was prepared on the surface of titanium sheet by laser etching to improve its stability and photoelectrical properties, and CuInS2-sensitized TiO2 was used to form a superior photoelectrical layer, which realized the initial signal amplification. The electron donor dopamine (DA) was modified to H2 as a signal regulator, which effectively increased the photocurrent signal. To further amplify the signal, an enzyme-free hybridization reaction was implemented. When target let-7a and fuel-DNA (F-DNA) were present, the base of H1 specifically recognized let-7a and forced dopamine@AuNPs-H2 away from the electrode surface. Subsequently, the end base of H1 specifically recognized F-DNA, and let-7a was replaced and recycled to participate in the next cycle. Enzyme-free circulation, as a multifunctional amplification method, ensured the recycling of target molecules. This PEC sensor for let-7a detection showed an excellent linear response from 0.5 to 1000 pM with a detection limit of 0.12 pM. The intra-batch RSD was 3.8% and the recovery was 87.74-108.1%. The sensor was further used for clinical biomolecular monitoring of miRNA, showing excellent quantitative detection capability.

Paper-Based Bipolar Electrode Electrochemiluminescence Platform for Detection of Multiple miRNAs.

This paper introduces a novel potential-resolved paper-based biosensor for simultaneous detection of multiple microRNAs (miRNAs) (taking miRNA-155 and miRNA-126 as examples) based on the bipolar electrode (BPE) electrochemiluminescence (ECL) strategy. The proposed multiple-channel paper-based sensing microfluidic platform was prepared by wax-printing technology, screen-printing method, and in situ Au nanoparticles (AuNPs) growth to form hydrophilic areas, hydrophobic boundaries, waterproof electronic bridge, driving electrode regions, and parallel bipolar electrode regions. CdTe quantum dots (QDs)-H2 and Au@g-C3N4 nanosheets (NSs)-DNA1 were used as dual electrochemiluminescence signal probes, and carboxylated Fe3O4 magnetic nanoparticles existed as carriers. CdTe QDs-H2/S2O82- and Au@g-C3N4 NSs-DNA1/S2O82- could exhibit two strong and stable ECL emissions at a drive voltage of 9 and 12 V, respectively, which can be used as effective potential-resolved signal tags. In addition, the proposed three-dimensional (3D) DNA nanomachine model and the target miRNA cycle strategy were used to achieve double amplification of electrochemiluminescence intensity. More importantly, the combination of the bipolar electrode system and the potential-resolved multitarget electrochemiluminescence method can greatly reduce the spatial interference between substances. The prepared ECL biosensor showed a favorable linear response for the detection of miRNA-155 and miRNA-126 with relatively low detection limits of 5.7 and 4.2 fM, respectively. With excellent sensitivity, the strategy may provide an efficient method for clinical application, especially in detection of trace multiple targets.

Ultrasensitive Microfluidic Paper-Based Electrochemical/Visual Analytical Device via Signal Amplification of Pd@Hollow Zn/Co Core-Shell ZIF67/ZIF8 Nanoparticles for Prostate-Specific Antigen Detection.

An effective signal amplification strategy is essential to enhance the analytical performance of microfluidic paper-based analytical devices (µPADs) for tracing biomarkers. Here, a simple but efficient approach with superior electrocatalytic performance of Pd@hollow Zn/Co core-shell ZIF67/ZIF8 nanoparticles for regulating the efficacious signal amplification process was utilized to realize the detection of prostate-specific antigen (PSA). By rationally designing the core-shell structure of ZIF67/ZIF8 with hollow characteristics on the nanoscale and introducing the noble metal element Pd into the cavity, the diffusion limitation and porous confinement reduction of the obtained nanomaterials with uniform morphology and satisfactory chemical stability could be realized, which endowed it with better catalytic performance than solid metal-organic frameworks (MOFs) and ensured effective signal amplification of H2O2 reduction for achieving enhanced electrochemical signals. Moreover, with the assistance of signal probes, the remaining H2O2 could flow to the color area to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine to form a colored product by changing the spatial configuration of the µPAD, thus realizing the visual detection of PSA. On the basis of this novel analytical device, dual-mode ultrasensitive detection of PSA could be achieved with a lower limit of detection of 0.78 pg/mL (S/N = 3) and a wider linear range from 5 pg/mL to 50 ng/mL. This work provided the opportunity of introducing the noble metal element Pd into the cavity of the MOF hollow structure to improve its electrocatalytic efficiency and construct a high-performance µPAD for clinical detection of other biomarkers.

3D DNA Walker-Assisted CRISPR/Cas12a Trans-Cleavage for Ultrasensitive Electrochemiluminescence Detection of miRNA-141.

In this study, a CRISPR/Cas12a (LbCpf1)-mediated electrochemiluminescence (ECL) paper-based platform on the basis of a three-dimensional (3D) DNA walker was proposed for the ultrasensitive detection of miRNA-141. Initially, 3D-rGO with a tremendous loading space was modified on the paper working electrode (PWE) to construct an excellent conductive substrate and facilitate the growth of AuPd nanoparticles (NPs). Afterward, the AuPd NPs were introduced as the coreaction emitter medium of the 3D-rGO/PWE to provide convenience for the transformation between S2O82- and SO42-, amplifying the ECL emission of g-C3N4 nanosheets (NSs). Meanwhile, with the help of Nt.BsmAI nicking endonuclease, a 3D DNA walker signal amplifier was designed to convert and magnify the target miRNA-141 into a particular trigger sequence, which could act as activator DNA to motivate the trans-acting deoxyribonuclease activity of CRISPR/Cas12a to further achieve efficient annihilation of the ECL signal. Furthermore, the proposed multimechanism-driven biosensor exhibited excellent sensitivity and specificity, with a relatively low detection limit at 0.331 fM (S/N = 3) in the concentration range between 1 fM and 10 nM. Consequently, the designed strategy not only extended the application scope of CRISPR/Cas12a but also devoted a new approach for the clinical diagnosis of modern medicine.

Near-Infrared Light-Initiated Photoelectrochemical Biosensor Based on Upconversion Nanorods for Immobilization-Free miRNA Detection with Double Signal Amplification.

Photoelectrochemical (PEC) sensors are relatively new sensing platforms with high detection sensitivity and low cost. However, the current PEC biosensors dependent on ultraviolet or visible light as the exciting resource cause injuries to biological samples and systems, which restrains the applications in complicated matrixes. Herein, a near-infrared light (NIR)-initiated PEC biosensor based on NaYF4:Yb,Tm@NaYF4@TiO2@CdS (csUCNRs@TiO2@CdS) was constructed for sensitive detection of acute myocardial infarction (AMI)-related miRNA-133a in an immobilization-free format coupled with a hybridization chain reaction and a redox circle signal amplification strategy. A low-energy 980 nm NIR incident laser was converted to 300-480 nm light to excite the adjacent TiO2@CdS photosensitive shell to generate photocurrent by NaYF4:Yb,Tm@NaYF4 upconversion nanorods. Also, magnetic beads were employed for the homogeneous determination of target miRNA-133a to reduce the recognition steric hindrance and improve the detection sensitivity. The photocurrent response was positively correlated with the level of ascorbic acid as the energy donor to consume photoacoustic holes produced on the surface of csUCNRs@TiO2@CdS, which was generated by alkaline phosphatase catalyzation and regenerated by tris(2-carboxyethyl) phosphine reduction upon the appearance of miRNA-133a. Exerting a NIR-light-driven and immobilization-free strategy, the as-constructed biosensor displayed linearly sensitive and selective determination of miRNA-133a with a detection limit of 36.12 aM. More significantly, the assay method provided a new concept of the PEC sensing strategy driven by NIR light to detect diverse biomarkers with pronounced sensitivity, light stability, and low photodamage.

Electrochemiluminescence biosensor based on molybdenum disulfide-graphene quantum dots nanocomposites and DNA walker signal amplification for DNA detection.

Based on the prominent electrochemiluminescence (ECL) performances of molybdenum disulfide-graphene quantum dots (MoS2-GQDs) nanocomposite and combined with enzyme-assisted recycling DNA walker signal amplification, an "on-off" switch ECL biosensor was proposed for sensitive assay of specific DNA sequences. Noticeably, MoS2 with two-dimensional nanosheet structure increased the loading capacity of GQDs to support abundant hairpin DNA (H). The composites of MoS2 and GQDs facilitated the charge transfer in ECL process, which significantly improved the ECL signal to achieve an "on" state. Then, the DNA walker cyclic amplification was performed by adding the target DNA and exonuclease III (Exo III). Finally, the DNA2-Fc-DNA1 was introduced into the system as ECL signal quencher, turning the ECL signal into an "off" state. The sensitive assay of ultra-low concentration specific DNA sequences was realized according to the variation of ECL signal strength before and after the existence of target DNA. The proposed ECL biosensor showed a good linear relationship ranging from 1 nM to 100 aM with a detection limit of 25.1 aM, providing a powerful strategy for biomedical research and clinical analysis.

Paper-Based Constant Potential Electrochemiluminescence Sensing Platform with Black Phosphorus as a Luminophore Enabled by a Perovskite Solar Cell.

Exploring efficient luminophores in the electrochemiluminescence (ECL) system is highly desired to pursue a sensitive ECL sensing platform. Herein, the black phosphorus nanosheets (BP NSs) with excellent ECL properties are investigated and serve as the luminophore with the coreactant of peroxydisulfate (S2O82-) solution. Moreover, owing to the overlapping of emission and absorbance spectra, effective resonance energy transfer (RET) is realized between the BP NSs and the introduced Au nanoparticles. In order to achieve the portable and miniaturized developing trends for the paper-based ECL sensing platform, a paper-based perovskite solar cell (PSC) device is designed to act as the power source to replace the commonly utilized expensive and cumbersome electrochemical workstation. Benefiting from that, a PSC driven paper-based constant potential ECL-RET sensing platform is constructed, thereby realizing sensitive microRNAs (miRNAs) detection. What's more, to attain the preferable analytical performance, the duplex-specific nuclease (DSN) is also introduced to assist the target recycling signal amplification strategy. Based on this, highly sensitive detection of miRNA-107 with a range from 0.1 pM to 15 nM is achieved by this designed sensing platform. Most importantly, this work not only pioneers a precedent for developing a high-sensitivity PSC triggered ECL sensing platform but also explores the application prospect of BP nanomaterial in the field of bioanalysis.

AgInSe2-Sensitized ZnO Nanoflower Wide-Spectrum Response Photoelectrochemical/Visual Sensing Platform via Au@Nanorod-Anchored CeO2 Octahedron Regulated Signal.

Herein an ultrasensitive photoelectrochemical (PEC)/visual biosensor coupled with a multiple signal amplification strategy was proposed for the detection of nucleic acids. The initial signal amplification was achieved via ternary AgInSe2 quantum dot (QD)-sensitized ZnO nanoflowers (ZnO NFs) to form an excellent photoelectric layer. A gold-modified nanorod-anchored CeO2 (Au@NR-CeO2) octahedron was introduced as a multifunctional signal regulator via the formation of triple helix molecules. The Au@NR-CeO2 octahedron could not only quench the photocurrent signal due to the competitive capture of photon energy and electron donors with the photoelectric layer but could also act like a peroxidase to catalyze the formation of mimetic enzymatic catalytic precipitation (MECP) on the surface of the photoelectric layer. Furthermore, the steric hindrance effect from the Au@NR-CeO2 octahedron further reduced the output of the photocurrent signal. After incubation with t-DNA, the triple helix conformation was disassembled and the Au@NR-CeO2 octahedron was released from the electrode surface, leading to the significant increase of photocurrent signal. Meanwhile, the released Au@NR-CeO2 octahedron could flow into the colorimetric area of the lab-on-paper device to catalyze the occurrence of the color reaction, achieving a visual detection for t-DNA. On the basis of the multiple signal amplification strategy, t-DNA was detected specifically with a lower limit of detection of 0.28 fM and a wider linear range from 0.5 fM to 50 nM. The proposed method has the potential utility to detect a variety of nucleic acids and biomarkers.

Paper-based electrochemiluminescence determination of streptavidin using reticular DNA-functionalized PtCu nanoframes and analyte-triggered DNA walker.

A paper-based electrochemiluminescence (ECL) biosensor characterized by the signal amplification of reticular DNA-functionalized PtCu nanoframes (DNA-PtCuTNFs) and analyte-triggered DNA walker was developed for sensitive streptavidin assay. Silver microflower functionalized paper-based sensing platform was prepared to fix the hairpin strand (S1). With addition of the streptavidin, plenty of DNA walkers consisting of the walking strands (S2) labeled with biotin and streptavidin were established, which protected S2 from digestion via the terminal protection mechanism. The sequential introduction of the DNA walker and capture probe initiated the hairpin structure opening of S1 and strand displacement reaction (SDR) happening, causing the S2 release. Subsequently, S1 hybridized with S3. The free S2 further hybridized with adjacent S1 to trigger the next cycle. After multiple cycles, the DNA-PtCuTNFs, the fire-new signal enhancer, with remarkable peroxidase activity, were successfully attached onto the paper electrode via metal-catalyst-free click chemistry. Based on the SDR of the DNA walker and the catalysis of DNA-PtCuTNFs, a significantly boosted ECL signal of luminol was obtained. Under the optimal conditions, the developed sensor for streptavidin assay exhibited a low detection limit of 33.4 fM with a linear range from 0.1 pM to 0.1 µM. Graphical abstract.

Low-Power and High-Performance Trimethylamine Gas Sensor Based on n-n Heterojunction Microbelts of Perylene Diimide/CdS.

In this work, low-power and high-performance gas sensors toward trimethylamine (TMA) are presented for the food quality control in the Internet of Things. An amphiphilic perylene diimide derivative (1,6,7,12-tetra-chlorinated perylene- N-(2-hydroxyethyl)- N'-hexylamine-3,4,9,10-tetracarboxylic bisimide, TC-PDI) is synthesized and further employed to construct the organic microrods of TC-PDI and organic/inorganic microbelts of TC-PDI/CdS by a phase transfer method. Due to the formation of n-n heterojunctions, the TC-PDI/CdS microbelts exhibit higher conductivity than the TC-PDI microrods alone, which present an efficient gas sensing platform for TMA determination at room operating temperature with high reproducibility and selectivity. Remarkably, the limit of detection, stability, and selectivity of the TC-PDI/CdS gas sensor are significantly improved, which ascribes to the efficient charge separation of n-n heterojunctions. More importantly, the fabricated gas sensor provides potential application of "on-site" and "on-line" TMA identification in real systems and suggests an efficient way to develop new hybrid n-n heterojunctions for a low-power and high-performance gas sensor.

Triggerable H2O2-Cleavable Switch of Paper-Based Biochips Endows Precision of Chemometer/Ratiometric Electrochemical Quantification of Analyte in High-Efficiency Point-of-Care Testing.

In this work, a triggerable H2O2-cleavable fluid switch mediated paper-based biochip, being amenable to multiplexing and quantitative analysis with the dual-response output of visual screening and ratiometric electrochemistry, was developed for sensitive detection of target on-site. By properly implanting hydrophobic Ag-H2O2 responsive material in specific zone to form a programmable fluid switch, the biochip could achieve different modes of blocking/connecting switching automatically. In order to improve the test performance, a ratiometric electrochemical signal readout was designed, which was enhanced by a secondary in situ growth method fabricating trepang-shaped Au modified paper working electrode. In virtue of hybridization chain reaction, classic competitive recognition interactions of aptamer and target, and ratiometric internally calibrated mechanisms, ultrasensitive detection of the target was realized. To acquire a more quantitative and straightforward naked eye visual screening, the hydrophobic Ag switch was triggered by stimulating instructions from H2O2, thus reconnecting the electrochemical and ratiometric units automatically and resulting in a "signal on" visual fluidic flow on the chemometer characterized by the accurate distance of color development as a detection motif. With MCF-7 and K562 cells as models, wider linear detection ranges from 150 to 1.0 × 107 and 220 to 7.0 × 106 cells mL-1 for MCF-7 and K562 cells, respectively, were achieved. Meanwhile, thanks to the paper fluid chemometer, an acceptable screening detection limit of 103 cells mL-1 was obtained in the quantitative colorimetric assays. The proposed paper-based biochips opened up new horizons for designing of integratable, easy-to-use, and precise point-of-care testing devices.

Visual distance readout to display the level of energy generation in paper-based biofuel cells: application to enzymatic sensing of glucose.

Biofuel cells (BFCs) based on anodic oxidation and cathodic oxygen reduction represent an attractive alternative to self-powered devices. A glucose/oxygen BFC is described for monitoring glucose. It is making use of a piece of paper carrying a glucose oxidase (GOx) based bioanode, and a bilirubin oxidase (BilOx) based biocathode. The performance of the BFC is affected by the generation of H2O2, a byproduct of enzymatic glucose oxidation. Therefore, the removal of H2O2 is a crucial step in terms of BFC performance and stability. In addition, direct, unambiguous visual read-out is an ideal way to provide quantitative information. The colorimetric readout system described here is based on the consumption of undesired H2O2 and to convert the extent of energy generation into recognizable variations in color. As the H2O2 travels along the hydrophilic channel by capillary action, the formation of red gold nanoparticles from AuCl4- leads to the appearance of a red bar that provides distance-based information that can be read visually. The multiply readable information (maximum power density of BFC or visible distance) provides further choices for quantification. It also enhances reliability. The self-powered system based on the BFC exhibits excellent performance. Glucose can be determined by this method in the 1 to 50 mM concentration range. Graphical abstract Schematic presentation of a paper-supported biofuel cell equipped with a visual distance readout to display the level of energy generation in biofuel cells, and its application in sensing of glucose.

Stackable Lab-on-Paper Device with All-in-One Au Electrode for High-Efficiency Photoelectrochemical Cyto-Sensing.

Highly conductive, robust, and multifunctional integrated paper-supported electrodes are requisite to fulfill the promise of paper-based analytical application. Herein, an all-in-one Au electrode comprising of detection zone, waterproof electronic bridge, and signal output contactor was engineered via combining the double-sided growth method with the secondary wax-printing. Benefiting from the strongly omnidirectional conductivity and desirably mechanical robustness of the as-prepared electrode, a stackable lab-on-paper cyto-device integrated with high-efficiency photoelectrochemical strategy was developed for the MCF-7 cells assay. Specifically, the detection zone of the electrode, serving as the signal generator, was functionalized with a low-toxic cosensitized structure composed of corn-like ZnO nanorods, graphene quantum dots (GQDs), and Ag2Se QDs. With the proximity control of DNA hairpin-based aptamer probe (DHAP), a strong photocurrent could be promoted by the activated cosensitization effect and collected on the signal output contactor via the electron transport of waterproof electronic bridge. Upon the MCF-7 cells recognition, the DHAP switched from closed to open state with the formation of DNA-cell bioconjugates and the spatial separation of Ag2Se QDs linked on the terminal of DHAP from the electrode surface. The photocurrent was noticeably decreased due to the double inhibition of steric hindrance effect and vanished cosensitization effect. Based on the target-triggered photocurrent attenuation, the sensitive detection of target cells was achieved. This work not only provided a unique method for paper-based electrode preparation but also offered a powerful platform for the highly sensitive photoelectrochemical bioanalysis.