Nucleic acid-based wearable and implantable electrochemical sensors.

The rapid advancements in nucleic acid-based electrochemical sensors for implantable and wearable applications have marked a significant leap forward in the domain of personal healthcare over the last decade. This technology promises to revolutionize personalized healthcare by facilitating the early diagnosis of diseases, monitoring of disease progression, and tailoring of individual treatment plans. This review navigates through the latest developments in this field, focusing on the strategies for nucleic acid sensing that enable real-time and continuous biomarker analysis directly in various biofluids, such as blood, interstitial fluid, sweat, and saliva. The review delves into various nucleic acid sensing strategies, emphasizing the innovative designs of biorecognition elements and signal transduction mechanisms that enable implantable and wearable applications. Special perspective is given to enhance nucleic acid-based sensor selectivity and sensitivity, which are crucial for the accurate detection of low-level biomarkers. The integration of such sensors into implantable and wearable platforms, including microneedle arrays and flexible electronic systems, actualizes their use in on-body devices for health monitoring. We also tackle the technical challenges encountered in the development of these sensors, such as ensuring long-term stability, managing the complexity of biofluid dynamics, and fulfilling the need for real-time, continuous, and reagentless detection. In conclusion, the review highlights the importance of these sensors in the future of medical engineering, offering insights into design considerations and future research directions to overcome existing limitations and fully realize the potential of nucleic acid-based electrochemical sensors for healthcare applications.

Silver nanowires/waterborne polyurethane composite film based piezoresistive pressure sensor for ultrasensitive human motion monitoring.

Flexible piezoresistive pressure sensors are gaining significant attention, particularly in the realm of flexible wearable electronic skin. Here, a flexible piezoresistive pressure sensor was developed with a broad sensing range and high sensitivity. We achieved this by curing polydimethylsiloxane (PDMS) on sandpaper, creating a PDMS film as the template with a micro-protrusion structure. The core sensing layer was formed using a composite of silver nanowires (AgNWs) and waterborne polyurethane (WPU) with a similar micro-protrusion structure. The sensor stands out with its exceptional sensitivity, showing a value of 1.04 × 106kPa-1with a wide linear range from 0 to 27 kPa. It also boasts a swift response and recovery time of 160 ms, coupled with a low detection threshold of 17 Pa. Even after undergoing more than 1000 cycles, the sensor continues to deliver stable performance. The flexible piezoresistive pressure sensor based on AgNWs/WPU composite film (AWCF) can detect small pressure changes such as pulse, swallowing, etc, which indicates that the sensor has great application potential in monitoring human movement and flexible wearable electronic skin.

Role of maternally expressed 8 small nucleolar RNA (MEG8) in osteogenic differentiation of periodontal ligament stem cells.

OBJECTIVES: Periodontal ligament stem cells (PDLSCs) are essential for the treatment of bone diseases because of its great potential to differentiate into osteoblasts. Remarkably, increasing long-non-coding RNAs (lncRNAs) have been reported to be involved in the osteogenic differentiation of PDLSCs. Maternally expressed 8, small nucleolar RNA host gene (MEG8) is implicated in multiple diseases. This study intended to unearth the potential role of MEG8 and unveil the mechanism in PDLSCs undergoing osteoblastic differentiation. MATERIALS AND METHODS: MEG8 expression was measured by quantitative real-time PCR (RT-qPCR) during osteogenic differentiation of PDLSCs into bone cells. Functional assays were used to uncover the biological function of MEG8. Besides, RNA pulldown, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assays were used to explore the molecular mechanism of MEG8. RESULTS: MEG8 was apparently overexpressed in osteogenically differentiated PDLSCs. Moreover, MEG8 deficiency suppressed the osteoblastic differentiation of PDLSCs. Furthermore, MEG8 modulated the expression of transcription factor 4 (TCF4) by scavenging microRNA-495-3p (miR-495-3p) and microRNA-485-3p (miR-485-3p) through the competing endogenous RNA (ceRNA) mechanism, further stimulating the Wnt/ß-catenin pathway. CONCLUSION: MEG8 stimulates the capacity of PDLSCs for osteogenic differentiation through a ceRNA mode.

N-Doping Coupled with Co-Vacancies Activating Sulfur Atoms and Narrowing Bandgap for CoS Toward Synergistically Accelerating Hydrogen Evolution.

The combination of hetero-elemental doping and vacancy engineering will be developed as one of the most efficient strategies to design excellent electrocatalysts for hydrogen evolution reaction (HER). Herein, a novel strategy for N-doping coupled with Co-vacancies is demonstrated to precisely activate inert S atoms adjacent to Co-vacancies and significantly improve charge transfer for CoS toward accelerating HER. In this strategy, N-doping favors the presence of Co-vacancies, due to greatly decreasing their formation energy. The as-developed strategy realizes the upshift of S 3p orbitals followed by more overlapping between S 3py and H 1s orbitals, which results in the favorable hydrogen atom adsorption free energy change (ΔGH ) to activate inert S atoms as newborn catalytical sites. Besides, this strategy synergistically decreases the bandgap of CoS, thereby achieving satisfactory electrical conductivity and low charge-transfer resistance for the as-obtained electrocatalysts. With an excellent HER activity of -89.0 mV at 10.0 mA cm-2 in alkaline environments, this work provides a new approach to unlocking inert sites and significantly improving charge transfer toward cobalt-based materials for highly efficient HER.

Engineering Rich Active Sites and Efficient Water Dissociation for Ni-Doped MoS2/CoS2 Hierarchical Structures toward Excellent Alkaline Hydrogen Evolution.

Besides improving charge transfer, there are two key factors, such as increasing active sites and promoting water dissociation, to be deeply investigated to realize high-performance MoS2-based electrocatalysts in alkaline hydrogen evolution reaction (HER). Herein, we have demonstrated the synergistic engineering to realize rich unsaturated sulfur atoms and activated O-H bonds toward the water for Ni-doped MoS2/CoS2 hierarchical structures by an approach to Ni doping coupled with in situ sulfurizing for excellent alkaline HER. In this work, the Ni-doped atoms are evolved into Ni(OH)2 during alkaline HER. Interestingly, the extra unsaturated sulfur atoms will be modulated into MoS2 nanosheets by breaking Ni-S bonds during the formation of Ni(OH)2. On the other hand, the higher the mass of the Ni precursor (mNi) for the fabrication of our samples, the more Ni(OH)2 is evolved, indicating a stronger ability for water dissociation of our samples during alkaline HER. Our results further reveal that regulating mNi is crucial to the HER activity of the as-synthesized samples. By regulating mNi to 0.300 g, a balance between increasing active sites and promoting water dissociation is achieved for the Ni-doped MoS2/CoS2 samples to boost alkaline HER. Consequently, the optimal samples present the highest HER activity among all counterparts, accompanied by reliable long-term stability. This work will promise important applications in the field of electrocatalytic hydrogen evolution in alkaline environments.

Morphological and Compositional Analysis on Thermal Deposition of Supercritical Aviation Kerosene in Micro Channels.

The integration of active cooling systems in super or hypersonic aircraft using endothermic hydrocarbon fuels is considered an effective way to relieve the thermal management issues caused by overheating. When the temperature of aviation kerosene exceeds 150 °C, the oxidation reaction of fuel is accelerated, forming insoluble deposits that could cause safety hazards. This work investigates the deposition characteristic as well as the morphology of the deposits formed by thermal-stressed Chinese RP-3 aviation kerosene. A microchannel heat transfer simulation device is used to simulate the heat transfer process of aviation kerosene under various conditions. The temperature distribution of the reaction tube was monitored by an infrared thermal camera. The properties and morphology of the deposition were analyzed by scanning electron microscopy and Raman spectroscopy. The mass of the deposits was measured using the temperature-programmed oxidation method. It is observed that the deposition of RP-3 is highly related to dissolved oxygen content (DOC) and temperature. When the outlet temperature increased to 527 °C, the fuel underwent violent cracking reactions, and the structure and morphology of deposition were significantly different from those caused by oxidation. Specifically, this study reveals that the structure of the deposits caused by short-to-medium term oxidation are dense, which is different from long-term oxidative deposits.

Cu3(PO4)2/BiVO4 photoelectrochemical sensor for sensitive and selective determination of synthetic antioxidant propyl gallate.

Propyl gallate (PG) as one of the most important additives has been widely used to prevent or slow the oxidation of foods in the food industry. In this work, Cu3(PO4)2/BiVO4 composite is synthesized through two hydrothermal processes. With visible light irradiation, the Cu3(PO4)2/BiVO4 composites modified PEC platform displays a superior anode photocurrent signal. The PEC sensor showed a wide linear range from 1 × 10-10 to 1 × 10-3 mol L-1 with a detection limit as low as 0.05 × 10-10 mol L-1. The Cu3(PO4)2/BiVO4 photoelectrochemical (PEC) sensor is designed and characterized by electrochemical impedance. Compared with GCE/BiVO4 and GCE/Cu3(PO4)2, the GCE/Cu3(PO4)2/BiVO4 has a higher photocurrent response. In addition, the sensor is highly selective for samples containing other antioxidants. Furthermore, the sensor can be used to detect PG in edible oil samples with satisfactory results. The recoveries of propyl gallate in edible oil ranged from 95.5 to 101.8%. The results show that Cu3(PO4)2/BiVO4 composites can be used to analyze PG in different edible oil samples, which are beneficial for food quality monitoring and reduce the risk of PG overuse in food.

CdS/Ti3C2 heterostructure-based photoelectrochemical platform for sensitive and selective detection of trace amount of Cu2.

Photoelectrochemical (PEC) detection as a potential development strategy for Cu2+ ion sensor has arisen extensive attention. Herein, CdS/Ti3C2 heterostructure was synthesized by electrostatically driven assembly and hydrothermal method. On the basis of a CdS/Ti3C2 heterostructure, a novel anodic PEC sensing platform was constructed for highly sensitive detection of trace amount of Cu2+. Carrier transport at the interface of CdS/Ti3C2 heterostructure was tremendously improved, due to the generation of effective Schottky junctions. Under visible light irradiation, the CdS/Ti3C2 heterostructure-modified PEC platform exhibits great anode photocurrent signal, and the formation of CuxS reduces the PEC response with the presence of Cu2+ as a representative analyte. Thus, the linear response of Cu2+ ranges from 0.1 nM to 10 µM and the limits of detection (LOD, 0.05 nM) are obtained, which is lower than that of WHO's Guidelines for Drinking-water Quality (30 µM). This idea of component reconstitution provides a new paradigm for the design of advanced PEC sensors.

Ultrathin Covalent Organic Framework Nanosheets/Ti3C2Tx-Based Photoelectrochemical Biosensor for Efficient Detection of Prostate-Specific Antigen.

Designable and ultrathin covalent organic framework nanosheets (CONs) with good photoelectric activity are promising candidates for the construction of photoelectrochemical (PEC) biosensors for the detection of low-abundance biological substrates. However, achieving highly sensitive PEC properties by using emerging covalent organic framework nanosheets (CONs) remains a great challenge due to the polymeric nature and poor photoelectric activity of CONs. Herein, we report for the first time the preparation of novel composites and their PEC sensing properties by electrostatic self-assembly of ultrathin CONs (called TTPA-CONs) with Ti3C2Tx. The prepared TTPA-CONs/Ti3C2Tx composites can be used as photocathodes for PEC detection of prostate-specific antigen (PSA) with high sensitivity, low detection limit, and good stability. This work not only expands the application of CONs but also opens new avenues for the development of efficient PEC sensing platforms.

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.

A highly sensitive strain sensor with a sandwich structure composed of two silver nanoparticles layers and one silver nanowires layer for human motion detection.

The fabrication of strain sensors with high sensitivity, large sensing range and excellent stability is highly desirable because of their promising applications in human motion detection, human-machine interface and electric skin, etc. Herein, by introducing a highly conductive silver nanowire (AgNW) layer between two serried silver nanoparticle (AgNP) layers, forming a sandwich structure, a strain sensor with high sensitivity (a large gauge factor of 2.8 × 105), large sensing range (up to 80% strain) and excellent stability (over 1000 cycles) can be achieved. A combination of experimental and mechanism studies shows that the high performance of the obtained strain sensor is ascribed to the synergy of the highly conductive AgNW layer, astatic AgNP layers and the presence of large cracks in stretching. As a proof-of-concept application, the obtained strain sensor can be used for highly effective human motion detection ranging from large scale motions, i.e. kneel bending and wrist flexion, to subtle scale motions, i.e. pulse and swallowing.

Enhanced stability of silver nanowire transparent conductive films against ultraviolet light illumination.

Silver nanowires are susceptible to degradation under ultraviolet (UV) light illumination. Encapsulating silver nanowire transparent conductive films (AgNW TCFs) with UV shielding materials usually result in the increasing of the sheet resistance or the decrease of the visible light transparency. Herein, we combine a reducing species (FeSO4) and a thin layer (overcoating) of UV shielding material to solve the stability and the optical performance issues simultaneously. The AgNW TCFs show excellent stability under continuous UV light illumination for 14 h, and their sheet resistance varies only 6%. The dramatic enhancement of the stability against UV light illumination for as-obtained TCFs will make them viable for real-world applications in touch panels and displays.

Evodiamine alleviates lipopolysaccharide-induced pulmonary inflammation and fibrosis by activating apelin pathway.

Inflammation can cause a series of inflammatory lung disease, which seriously endangers human health. Pulmonary fibrosis is a kind of inflammatory disease with end-stage lung pathological changes. It has complicated and unknown pathogenesis and is still lack of effective therapeutic drugs. LPS-induced inflammation is a common feature of many infectious inflammations such as pneumonia, bacteremia, glomerulonephritis, etc. Evodiamine, one of the main components of Evodia rutaecarpa, is an alkaloid with excellent antiinflammatory effects. In this study, we evaluated the protective capacities of evodiamine on LPS-induced inflammatory damages in vitro and in vivo. MTT method, flow cytometry, immunofluorescence, and other methods were used for in vitro study to determine the protective capacities of evodiamine. The results suggest that evodiamine can protect murine macrophages from the LPS-nigericin-induced damages by (a) inhibiting cellular apoptosis, (b) inhibiting inflammatory cytokines releasing, and (c) activating the apelin pathway. We also used the exogenous apelin-13 peptide co-cultured with LPS-nigericin in RAW264.7 cells and found that apelin-13 contributes to protecting the effects of evodiamine. In vivo, the ELISA method and immunohistochemistry were used to examine inflammatory cytokines, apelin, and histological changes. BALB/c mice were exposed to LPS and subsequent administration of evodiamine （p.o.）for some time, the results of the alveolar lavage fluid and the tissue slices showed that evodiamine treatment alleviated the pulmonary inflammation and fibrosis, stimulated apelin expression and inhibited the inflammatory cytokines. These results provide a basis for the protective effect and mechanism of evodiamine in LPS-induced inflammation and suggest that it might be potential therapeutics in human pulmonary infections.

Measurement Method to Determine the Difference in Tear Trough and Palpebromalar Groove Distribution After Transconjunctival Fat Reposition.

PURPOSE: This study designed an efficient measurement method to evaluate the outcome of transconjunctival fat reposition in the tear trough and palpebromalar groove. METHODS AND TECHNIQUES: A total of 41 patients (82 eyes) who underwent transconjunctival fat reposition surgery between January 2016 and March 2019 were retrospectively analyzed. Preoperative and postoperative (at least six months) standardized digital images were taken from the patients. A satisfaction survey was conducted on all patients. Their images were analyzed by using the Adobe Photoshop CS5 software. Ratios of the tear trough and palpebromalar groove were calculated. These data were analyzed by SPSS 20.0. RESULTS: The overall satisfaction rate was 90.2%. With a partition in the infraorbital region, a line graph showed that the location of the tear trough and palpebromalar groove moved to the upper squares postoperatively. The number of patients whose end points of the tear trough and palpebromalar groove located outside the midline of the pupil decreased by 30.5%. When we processed all the parameters of the preoperative and postoperative groups by profile analysis, a significant difference in the tear trough and palpebromalar groove before and after surgery was observed (right: F = 79.844, P = 0.000 < 0.01; left: F = 161.799, P = 0.000 < 0.01). CONCLUSIONS: Digital image analysis is feasible and useful in investigating the improvement of the tear trough and palpebromalar groove. The tear trough and palpebromalar groove shifted up and became shortened, which provided a more reliable evidence for lower eyelid rejuvenation.

Enhanced photoelectrochemical sensing based on novel synthesized Bi2S3@Bi2O3 nanosheet heterostructure for ultrasensitive determination of L-cysteine.

The design of a low-cost and highly efficient photoactive heterojunction material for sensing is still a challenging issue. On the basis of the formation of sheet-like Bi2O3 via coating Bi2S3, a novel Bi2O3@Bi2S3 heterostructure is controllably synthesized via a facile water bath approach. The prepared Bi2O3@Bi2S3 nanosheets show a superior photoelectrochemical (PEC) performance for the detection of L-cysteine (L-Cys), and the photocurrent signal is three and four times higher than those of Bi2S3 and Bi2O3 under visible irradiation, respectively. Also, the heterostructure presents an outstanding linear range for the detection of L-Cys: 0.1-10,000 µM. In addition, the mechanism of improved PEC response of Bi2O3@Bi2S3 nanosheets is investigated according to the estimated energy band positions. Thus, the integration of the novel heterostructure and the photoelectrochemical technique demonstrates a rapid photocurrent response, showing a great effect on the performance of the sensing system and a new PEC method for highly selective and sensitive chemical detection. Graphical abstract.

Visual detection of the prostate specific antigen via a sandwich immunoassay and by using a superwettable chip coated with pH-responsive silica nanoparticles.

A pH-responsive superwettable chip is described whose surface can switch between superhydrophobic and superhydrophilic. It can be used for the visual detection of the prostate specific antigen (PSA) based on contact angle readout. Magnetic beads were modified with primary antibody against PSA. After immunobinding, gold nanoparticles loaded with secondary antibody labeled with glucose oxidase is added. On addition of glucose, gluconic acid is formed which causes a drop in the local pH value. This results in a wettability switch of the pH-responsive superwettable chip from hydrophobic to hydrophilic. Under the optimized conditions, PSA can be quantified with a 3.2 pg mL-1 limit of detection by analyzing the contact angle and the related color that changes from blue via orange to red. The method is applicable to PSA detection in serum samples and for visual classification by cancer patients and healthy persons. It is also suitable for color-blind and color-weak individuals. Conceivably, this kind of assay can be transferred to the determination of various kinds of other bioanalytes including nucleotide, proteins, and even of ions and small organic molecules, and thus is has a wide scope. Graphical abstract Schematic presentation of a pH-responsive superwettable chip coated with silica nanoparticles for the visual detection of prostate specific antigen (PSA) by reading the contact angle. The superwettable chip achieves reliable clinical detection of serum PSA from prostate cancer patients.

A novel "signal-on" photoelectrochemical sensor for ultrasensitive detection of alkaline phosphatase activity based on a TiO2/g-C3N4 heterojunction.

The use of alkaline phosphatase (ALP) as a biomarker in some diseases including hepatitis, obstructive jaundice, osteoblastic bone cancer, and osteomalacia is important in clinical diagnosis. Furthermore, ALP activity detection is an essential hot topic in environmental monitoring, biomedical research, and other research fields. In this study, a novel "signal-on" photoelectrochemical (PEC) biosensor based on the ALP-catalyzed phosphorylation reaction was designed to sensitively detect ALP activity. In this design, ascorbic acid-an electron donor-was catalytically produced by ALP from l-ascorbic acid 2-phosphate trisodium salt in situ, which results in an increased photocurrent response signal. For immobilizing the ALP on the electrode surface, poly diallyl dimethyl ammonium chloride was used for the conjugation of ALP, and titanium dioxide (TiO2)-a photoactive material-and graphite-like carbon nitride (g-C3N4) nanocomposites were prepared and characterized. TiO2 attached on g-C3N4 plays an important role for the biosensing purpose due to their good biocompatibility and chemical/thermal stability, while g-C3N4 provides the PEC response signal. Furthermore, the prepared TiO2/g-C3N4 nanocomposites can effectively suppress electron-hole recombinations, improve the excitation conversion efficiency, and make the best use of solar energy. The PEC biosensor for ALP activity detection displays a detection limit of 0.03 U L-1 (S/N = 3), which offers a new route for the ALP activity assay in human serum samples.

Nanosized Metal Phosphides Embedded in Nitrogen-Doped Porous Carbon Nanofibers for Enhanced Hydrogen Evolution at All pH Values.

Transition-metal phosphides (TMPs) have emerged as promising catalyst candidates for the hydrogen evolution reaction (HER). Although numerous methods have been investigated to obtain TMPs, most rely on traditional synthetic methods that produce materials that are inherently deficient with respect to electrical conductivity. An electrospinning-based reduction approach is presented, which generates nickel phosphide nanoparticles in N-doped porous carbon nanofibers (Ni2 P@NPCNFs) in situ. Ni2 P nanoparticles are protected from irreversible fusion and aggregation in subsequent high-temperature pyrolysis. The resistivity of Ni2 P@NPCNFs (5.34â€…Ω cm) is greatly decreased by 104 times compared to Ni2 P (>104 â€…Ω cm) because N-doped carbon NFs are incorporated. As an electrocatalyst for HER, Ni2 P@NPCNFs reveal remarkable performance compared to other previously reported catalysts in acidic media. Additionally, it offers excellent catalytic ability and durability in both neutral and basic media. Encouraged by the excellent electrocatalytic performance of Ni2 P@NPCNFs, a series of pea-like Mx P@NPCNFs, including Fe2 P@NPCNFs, Co2 P@NPCNFs, and Cu3 P@NPCNFs, were synthesized by the same method. Detailed characterization suggests that the newly developed method could render combinations of ultrafine metal phosphides with porous carbon accessible; thereby, extending opportunities in electrocatalytic applications.

Label-Free Photoelectrochemical "Off-On" Platform Coupled with G-Wire-Enhanced Strategy for Highly Sensitive MicroRNA Sensing in Cancer Cells.

MicroRNA (miRNAs) quantification, especially at low abundance, is vital for disease diagnosis, prognosis, and therapy. Herein we develop a distinctive label-free "off-on" configuration for photoelectrochemical (PEC) sensing platform fabrication, coupled with DNA four-way junction (4J) architecture as well as G-wire superstructure for signal amplification. In addition, ultrathin copper phosphate nanosheets (CuPi NSs) coating Au nanoparticles (Au-CuPi NSs) serve as a highly efficient photocathode substrate. To improve the sensitivity, and avoid the false positive signals, the quencher, gold nanoparticles (GNPs), is utilized to switch off the PEC signal because of the commendable surface plasmon resonance (SPR) absorption. Subsequently, ingenious DNA 4J architecture is applied to export proportional c-myc regions for target quantification. Assisted with the G-wire superstructure formation, the enhancer 5,10,15,20-tetra(4-sulfophenyl)-21H,23H-porphyrin (TSPP) is coupled on the substrate to switch on the PEC signal, thus realizing the miRNA assay with persuasive accuracy, high sensitivity, and low detection limit. In addition, we execute the miRNA detection in prostate carcinoma cell line 22Rv1, and acquire desirable quantitative capability. Remarkably, the prepared PEC sensing platform not only realizes the highly efficient miRNAs quantification, but also uncovers a marvelous horizon for sensing platform fabrication.

Ligating Dopamine as Signal Trigger onto the Substrate via Metal-Catalyst-Free Click Chemistry for "Signal-On" Photoelectrochemical Sensing of Ultralow MicroRNA Levels.

The efficiency of photon-to-electron conversion is extremely restricted by the electron-hole recombinant. Here, a new photoelectrochemical (PEC) sensing platform has been established based on the signal amplification of click chemistry (CC) via hybridization chain reaction (HCR) for highly sensitive microRNA (miRNA) assay. In this proposal, a preferred electron donor dopamine (DA) was first assembled with designed ligation probe (probe-N3) via amidation reaction to achieve DA-coordinated signal probe (PDA-N3). The PDA-N3 served as a flexible trigger to signal amplification through efficiently suppressing the electron-hole recombinant. Specifically, the PDA-N3 can be successfully ligated into the trapped hairpins (H1 and H2) via the superior ligation method of metal-catalyst-free CC, in which the electron donor DA was introduced into the assay system. Moreover, the enzyme-free HCR, employed as a versatile amplification way, ensures that lots of PDA-N3 can be attached to the substrate. This PEC sensing for miRNA-141 detection illustrated the outstanding linear response to a concentration variation from 0.1 fM to 0.5 nM and a detection limit down to 27 aM, without additional electron donors. The sensor is further employed to monitor miRNA-141 from prostate carcinoma cell (22Rv1), showing good quantitative detection capability. This strategy exquisitely influences the analytical performance and offers a new PEC route to highly selective and sensitive detection of biological molecules.