Yuanhua Shao

A novel type of coaxial Pt-disk-microelectrode@micropipette probe was designed and fabricated, which comprises an internal Pt ultramicroelectrode (UME) wrapped with an Ag/AgCl wire on its glass shield and an external micropipette. This new probe can integrate the advantages of scanning electrochemical microscopy (SECM) and scanning electrochemical cell microscopy (SECCM) and overcome the disadvantages of both methods. Optical microscopy and SECM-SECCM measurements confirmed that the device with a stable, renewable nanoliter-scale electrochemical droplet cell exhibited excellent electrochemical performances. Crucially, the probe achieved long-term and large-area imaging of the conductivity and morphology on diverse dry surfaces. Moreover, confining the reaction within the droplet significantly enhances tip-collection efficiency, thereby substantially improving spatial resolution and sensitivity in the substrate-generation/tip-collection mode. Significantly, leveraging the renewable droplet cell to minimize multisample heterogeneity errors, the probe was applied to high-throughput detection of alkaline phosphatase activity in an authentic blood fingerprint at different storage periods and established a high-precision time since deposition estimation with unprecedented accuracy of ∼97%. In all, this flexible design construction of the probe can combine SECM and SECCM advantages in various applications with high sensitivity, high-resolution, high-throughput, and high-accuracy detection.

For valuable ammonia synthesis and green nitrogen recycling, electrocatalytic nitrate reduction reaction (NO ₃ RR) presents a sustainable alternative to the conventional Haber–Bosch process. The NO ₃ RR involves intricate, multi-step proton-coupled electron transfers (PCET) featuring multiple nitrogen-oxygen intermediates and reaction branches. Unveiling this complex reaction library is crucial for rational tailoring of NO ₃ RR for improved practical application, yet it remains a formidable challenge. Herein we present an in situ ultramicroelectrode-hyphenated mass spectrometry technique to systematically investigate the dynamic electrocatalytic NO ₃ RR, using a cobalt-based molecular catalyst as a model system, and to decipher its mechanistic library under complex reaction environments (potential- and pH-dependent). Several key short-lived CoNO _x H _y intermediates were directly tracked and identified, experimentally revealing that the overall catalytic pathway of NO ₃ RR proceeds through the intermediary [LCo-NO ₃ ]→[LCo-NO ₃ H] ⁺ →[LCo-NO ₂ ] ⁺ → [LCo-NO ₂ H] ⁺ → [LCo-NO] ⁺ → [LCo-NHOH] ⁺ → [LCo-NH] ⁺ to produce NH ₃ , which were further validated by isotopic ¹⁵ N-labeling and collision-induced dissociation experiments. Combining theoretical simulations, a complete PCET-based mechanistic pathway was elucidated and distinguished from competing hydrogenation–deoxygenation mechanisms. Notably, a systematically interconnected electrochemical mechanistic library for NO ₃ RR, visualized through heat maps, was constructed to illustrate intermediate selectivity across a broad potential-pH space. This platform underscores the promising potential of navigating the pathway prediction and regulation of complex reaction environments, thereby advancing the mechanistic understanding of NO ₃ RR and other complicated electrocatalytic processes.

Electrochemical liquid-phase transmission electron microscopy (EC-LP-TEM) offers an unprecedented view of the dynamic solid-liquid interfaces that regulate electrochemical processes. Although mainstream planar or microfluidic EC-LP-TEM cells have uncovered important nanoscale transformations, there is a spatial discrepancy between the imaging area and the detected electrochemical signal. Recent advances in nanopipette-based structures─inspired by ultramicroelectrode electrochemistry─allow for the colocalization of imaging and electrochemical regions within highly confined geometries, attaining both nanometer-scale visualization and picoampere-to-nanoampere current detectability. In this perspective, we follow the development of EC-LP-TEM from conventional designs to emerging nanopipette-based setups, examine the conceptual shift toward interface-resolved imaging, and outline major technical challenges in geometry optimization, signal synchronization, and multimodal data correlative analysis. We also emphasize the potential of nanopipette-enabled EC-LP-TEM to directly observe electric double layer dynamics and nanoscale reaction heterogeneity─revolutionizing our ability to investigate electrochemical interfaces from ensemble averages to spatiotemporally resolved events.

Distinct from most electrochemiluminescence sensors that rely on elaborate materials, this study develops an immunosensor using simple materials for low-cost and highly sensitive biological analysis. We elucidated the mechanism of paradoxical amplification of gold nanoparticles (AuNPs), designed strategies of bidirectional catalysis, and expanded the application for multibiomarker detection. First, a new understanding of AuNPs' catalytic role was established through investigating the inhibitory effects of five phenolic compounds on the luminol-H₂O₂ ECL system, and an AuNP-induced "paradoxical amplification" of phenolic electrochemiluminescence (ECL) inhibition was first identified. Contrary to the common view that AuNPs always enhance ECL, here, AuNPs amplified the inhibitory effect of phenolics, thereby reducing the ECL signal. Such a mechanism was validated via electrochemistry-mass spectrometry. Second, a methodological innovation is presented: a switch-type immunosensor with bidirectional catalytic amplification via dynamic conversion. Specifically, the same catalyst flexibly switches between enhancement and inhibition: horseradish peroxidase (HRP) and AuNPs first act synergistically to enhance the initial ECL signal of the luminol-H₂O₂ system; then, alkaline phosphatase serves as a "switch" and introduces phenolic compounds, triggering HRP and AuNPs to automatically convert into signal-inhibiting catalysts. This induces multiple signal attenuation via ECL energy resonance transfer, radical quenching, and mass transfer hindrance, leading to a rapid decrease in ECL response. Finally, a highly sensitive coupled enzyme-linked attenuated ECL immunoassay involving AuNPs was constructed and successfully applied to the specific detection of cardiac troponin I and erythropoietin with a wide linear range (from fg/mL to ng/mL), and a detection limit as low as fg/mL.

Chronic kidney disease (CKD) is a global public health issue, with high prevalence and mortality. As cystatin C is a biomarker for the early diagnosis of CKD, there is an urgent need to develop a simple and inexpensive method for the detection of Cys C in human plasma. Herein, a sensitive method with flexible electrochemical aptamer-based (E-AB) sensing interfaces has been established using poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)-treated paper-based electrodes. Introduction of MoS₂ quantum dots increased the specific surface area and realized effective immobilization of the thiolated Cys C aptamer (Cys C Apt) modified with methylene blue through the formation of disulfide bonds. The E-AB sensing interfaces were successfully applied to the quantification of Cys C in human venous whole blood and plasma samples based on the binding-induced conformational change mechanism of Cys C Apt by employing square wave voltammetry. The flexible E-AB sensing interfaces show significant potential to be developed into wearable patches for in vivo detection of Cys C, which will pave the way for early diagnosis and long-term monitoring of CKD.

The mechanisms of electrochemical/chemical oxygen reduction catalyzed by an iron porphyrin were studied by in situ EC-MS/CR-MS assisted by electrochemical characterization and stopped-flow UV-vis spectroscopy.