Stretchable Electrochemical Sensor for Real‐Time Monitoring of Cells and Tissues

Stretchable electrochemical sensors are conceivably a powerful technique that provides important chemical information to unravel elastic and curvilinear living body. However, no breakthrough was made in stretchable electrochemical device for biological detection. Herein, we synthesized Au nanotubes (NTs) with large aspect ratio to construct an effective stretchable electrochemical sensor. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allows for the first time, real‐time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching‐free and stretching states as well as sensing of the inner lining of blood vessels. The results demonstrate the great potential of this sensor in electrochemical detection of living body, opening a new window for stretchable electrochemical sensor in biological exploration.     

光致清洁电极可见光在线更新与细胞实时监测

电化学传感器在用于细胞实时监测过程中,电极界面污染严重影响其检测性能.通过将纳米光催化剂与电化学传感材料复合,构建光致清洁电化学传感器,为电极界面的高效及无损更新提供了新思路.然而光催化产生的活性氧自由基导致细胞损伤,限制了细胞培养及检测过程中电极界面的实时更新.为此,我们在PEDOT@CdS/TiO₂/ITO可见光致更新电极表面旋涂明胶薄层,在保持电极良好的光致清洁和电化学传感性能同时,利用明胶薄层阻碍光催化产生的活性氧自由基扩散至细胞表面,显著降低了细胞损伤.此外,明胶优良的生物相容性有利于细胞的黏附及增殖.利用该电极,我们实现了人脐静脉内皮细胞（HUVECs）培养过程中,电极的在线更新以及细胞释放一氧化氮的实时监测.     

Real‐Time Monitoring of Auxin Vesicular Exocytotic Efflux from Single Plant Protoplasts by Amperometry at Microelectrodes Decorated with Nanowires

Recent biochemical results suggest that auxin (IAA) efflux is mediated by a vesicular cycling mechanism, but no direct detection of vesicular IAA release from single plant cells in real‐time has been possible up to now. A TiC@C/Pt‐QANFA micro‐electrochemical sensor has been developed with high sensitivity in detection of IAA, and it allows real‐time monitoring and quantification of the quantal release of auxin from single plant protoplast by exocytosis.     

Fabrication of Gold‐Directed Conducting Polymer Nanoarrays for High‐Performance Gas Sensor

Gold‐directed polypyrrole (PPy) nanoarrays are fabricated by hydrogel‐assisted nanotransfer edge printing (HnTEP) and electrochemical polymerization. Gold nanoarrays are fabricated through the HnTEP method, which involves metal deposition, hydrogel etching, and nanotransfer edge printing. By utilizing the well‐positioned gold nanostructures, PPy nanoarrays with smooth morphology and controllable dimensions are fabricated through in situ electrochemical polymerization, the results of which are characterized by scanning electron microscopy and atomic force microscopy. A gas sensor based on PPy nanoarrays results in excellent sensing capabilities towards NH₃ detection, especially the sensitivity and fast response. This method appears to be general and may aid in the future design and implementation of other active materials which can also be manipulated by the same procedure and serve as functional components for chemical sensing, optoelectronics, biodetection, and other applications.     

Real‐Time Monitoring of Phosphorylation Kinetics with Self‐Assembled Nano‐oscillators

Phosphorylation is a post‐translational modification that is involved in many basic cellular processes and diseases, but is difficult to detect in real time with existing technologies. A label‐free detection of phosphorylation is reported in real time with self‐assembled nano‐oscillators. Each nano‐oscillator consists of a gold nanoparticle tethered to a gold surface with a molecular linker. When the nanoparticle is charged, the nano‐oscillator can be driven into oscillation with an electric field and detected with a plasmonic imaging approach. The nano‐oscillators measure charge change associated with phosphorylation of peptides attached onto a single nanoparticle, allowing us to study the dynamic process of phosphorylation in real time without antibodies down to a few molecules, from which Michaelis and catalytic rate constants are determined.     

A Chemiluminescent Probe for HNO Quantification and Real‐Time Monitoring in Living Cells

Azanone (HNO) is a reactive nitrogen species with pronounced biological activity and high therapeutic potential for cardiovascular dysfunction. A critical barrier to understanding the biology of HNO and furthering clinical development is the quantification and real‐time monitoring of its delivery in living systems. Herein, we describe the design and synthesis of the first chemiluminescent probe for HNO, HNOCL‐1 , which can detect HNO generated from concentrations of Angeli's salt as low as 138 nm with high selectivity based on the reaction with a phosphine group to form a self‐cleavable azaylide intermediate. We have capitalized on this high sensitivity to develop a generalizable kinetics‐based approach, which provides real‐time quantitative measurements of HNO concentration at the picomolar level. HNOCL‐1 can monitor dynamics of HNO delivery in living cells and tissues, demonstrating the versatility of this method for tracking HNO in living systems.     

A Freezing‐Induced Turn‐On Imaging Modality for Real‐Time Monitoring of Cancer Cells in Cryosurgery

Cryosurgery has attracted much attention for the treatment of tumors owing to its clear advantages. However, determining the volume of frozen tissues in real‐time remains a challenge, which greatly lowers the therapeutic efficacy of cryosurgery and hinders its broad application for the treatment of cancers. Herein, we report a freezing‐induced turn‐on strategy for the selective real‐time imaging of frozen cancer cells. As a type of aggregation‐induced emission (AIE) fluorogen, TABD‐Py molecules interact specifically with ice crystals and form aggregates at the ice/water interface. Consequently, bright fluorescent emission appears upon freezing. TABD‐Py molecules are enriched mostly in the cancer cells and exhibit high biocompatibility as well as low cytotoxicity; therefore, a freezing‐induced turn‐on imaging modality for cryosurgery is developed, which will certainly maximize the therapeutic efficacy of cryosurgery in treating tumors.     

Turn‐On Luminescent Probes for the Real‐Time Monitoring of Endogenous Hydroxyl Radicals in Living Cells

The utilization of semiconductor quantum dots (QDs) as optical labels for biosensing and biorecognition has made substantial progress. However, the development of a suitable QD‐based luminescent probe that is capable of detecting individual reactive oxygen species (ROS) represents a great challenge, mainly because the fluorescence of QDs is quenched by a wide variety of ROS. To overcome this limitation, a novel QD‐based turn‐on luminescent probe for the specific detection of ^.OH has been designed, and its application in monitoring the endogenous release of ^.OH species in living cells is demonstrated. Metal citrate complexes on the surfaces of the QDs can act as electron donors, injecting electrons into the LUMO of the QDs, while ^.OH can inject holes into the HOMO of the QDs. Accordingly, electron–hole pairs are produced, which could emit strong luminescence by electron–hole recombination. Importantly, this luminescent probe does not respond to other ROS.     

An Electrochemophysiological Microarray for Real‐Time Monitoring and Quantification of Multiple Ions in the Brain of a Freely Moving Rat

Herein, we present an electrochemophysiological microarray (ECPM) for real‐time mapping and simultaneous quantification of chemical signals for multiple ions in the deep brain of a freely moving rat, in which microelectrode arrays were developed for direct determination of multiple ions using open‐circuit potentiometry. Specific recognition ionophores were synthesized and optimized for determination of K⁺, Ca²⁺, Na⁺ and pH. A reference electrode was also developed to avoid interferences in the brain. The microarrays were successfully applied in real‐time monitoring and quantification of ions in a live brain. The extra current‐free potentiometry allowed mapping and biosensing of chemical signals, together with recording of electrical signals in the whole brain without cross‐talk, for the first time. Furthermore, the ECPM provided a platform for real‐time monitoring of the dynamic changes of multiple ions in the deep brain of freely moving rat during a seizure.     

A Highly Sensitive and Recyclable Ln‐MOF Luminescent Sensor for the Efficient Detection of Fe3+ and CrVI Anions

Two new three‐dimensional (3D) Ln^III metal‐organic frameworks (MOFs) were designed and successfully obtained via a solvothermal reaction between lanthanide(III) nitrates and a semi‐flexible carbazole tetracarboxylate acid linker as a high‐performance chromophore. 1 and 2 possess porous 3D networks with channels along the a axis, and more importantly, they show a highly sensitive and selective fluorescence quenching response to Fe³⁺ and Cr^VI anions. The sensing mechanism investigation revealed that the weak interactions of Fe³⁺ with nitrogen atoms of carbazole and deprotonated carboxylic acids protruding into the pores of MOFs quenched the luminescence of 1 and 2 effectively. In addition, the competition absorption also played an important role in the luminescence quenching detection of Fe³⁺ based on 1 , and Cr^VI anions based on 1 and 2 . Therefore, 1 and 2 represent an alternative example of regenerable luminescence based sensors for the quantitative detection of Fe³⁺ and Cr^VI anions.     

Direct Real‐Time Monitoring of Prodrug Activation by Chemiluminescence

The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal‐to‐noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β‐galactosidase. The activation of the prodrug in the presence of β‐galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses β‐galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in β‐galactosidase‐overexpressing tumor‐bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment.     

Real‐Time Monitoring of Nanoparticle Formation by FRET Imaging

Understanding the formation process of nanoparticles is of the utmost importance to improve their design and production. This especially holds true for self‐assembled nanoparticles whose formation processes have been largely overlooked. Herein, we present a new technology that integrates a microfluidic‐based nanoparticle synthesis method and Förster resonance energy transfer (FRET) microscopy imaging to visualize nanoparticle self‐assembly in real time. Applied to different nanoparticle systems, for example, nanoemulsions, drug‐loaded block‐copolymer micelles, and nanocrystal‐core reconstituted high‐density lipoproteins, we have shown the approach's unique ability to investigate key parameters affecting nanoparticle formation.     

A Highly Selective and Sensitive Chemiluminescent Probe for Real‐Time Monitoring of Hydrogen Peroxide in Cells and Animals

Selective and sensitive molecular probes for hydrogen peroxide (H₂O₂), which plays diverse roles in oxidative stress and redox signaling, are urgently needed to investigate the physiological and pathological effects of H₂O₂. A lack of reliable tools for in vivo imaging has hampered the development of H₂O₂ mediated therapeutics. By combining a specific tandem Payne/Dakin reaction with a chemiluminescent scaffold, H₂O₂‐CL‐510 was developed as a highly selective and sensitive probe for detection of H₂O₂ both in vitro and in vivo. A rapid 430‐fold enhancement of chemiluminescence was triggered directly by H₂O₂ without any laser excitation. Arsenic trioxide induced oxidative damage in leukemia was successfully detected. In particular, cerebral ischemia‐reperfusion injury‐induced H₂O₂ fluxes were visualized in rat brains using H₂O₂‐CL‐510 , providing a new chemical tool for real‐time monitoring of H₂O₂ dynamics in living animals.     

Nanostructured Gold Microelectrodes for Non‐enzymatic Glucose Sensor

A novel, highly stable, selective, and sensitive non‐enzymatic glucose sensor was developed by simple and effective modification procedure. The modification of gold microelectrodes by electrochemically deposited gold nanoparticles resulted in increase of surface area up to 37 %. The nanostructured surfaces of the gold microelectrodes obtained by different modifications were studied by confocal microscopy, atomic force microscopy, and scanning electron microscopy. The gold nanoclusters exhibit great electrocatalytic properties toward glucose with a wide linear range from 0.5 to 50 mM, with a limit of detection 218 μM, and sensitivity of 185.2 mA mM^?1cm^?2. Moreover, the modified microelectrodes display good reproducibility, stability, and selectivity in the presence of poisoning compounds. Due to the small dimensions of gold microelectrodes and a very small volume of the sample, the microelectrodes make a contribution to miniaturisation of the system.     

Semi‐Interpenetrated Hydrogels‐Microfibers Electroactive Assemblies for Release and Real‐Time Monitoring of Drugs

Simultaneous drug release and monitoring using a single polymeric platform represents a significant advance in the utilization of biomaterials for therapeutic use. Tracking drug release by real‐time electrochemical detection using the same platform is a simple way to guide the dosage of the drug, improve the desired therapeutic effect, and reduce the adverse side effects. The platform developed in this work takes advantage of the flexibility and loading capacity of hydrogels, the mechanical strength of microfibers, and the capacity of conducting polymers to detect the redox properties of drugs. The engineered platform is prepared by assembling two spin‐coated layers of poly‐γ‐glutamic acid hydrogel, loaded with poly(3,4‐ethylenedioxythiophene) (PEDOT) microparticles, and separated by a electrospun layer of poly‐ε‐caprolactone microfibers. Loaded PEDOT microparticles are used as reaction nuclei for the polymerization of poly(hydroxymethyl‐3,4‐ethylenedioxythiophene) (PHMeDOT), that semi‐interpenetrate the whole three layered system while forming a dense network of electrical conduction paths. After demonstrating its properties, the platform is loaded with levofloxacin and its release monitored externally by UV–vis spectroscopy and in situ by using the PHMeDOT network. In situ real‐time electrochemical monitoring of the drug release from the engineered platform holds great promise for the development of multi‐functional devices for advanced biomedical applications.     

Enhanced Electrochemical Capacitive Properties of Nickel‐Cobalt Oxide Nano‐flakes Materials

Nickel‐cobalt oxide nano‐flakes materials are successfully synthesized by a facile chemical co‐precipitation method followed by a simple calcination process. The studies show that the as‐prepared nickel‐cobalt oxides with different Ni/Co ratio are composed of NiO and Co₃O₄ compounds. The Co_0.56Ni_0.44 oxide material, which exhibits a mesoporous structure with a narrow distribution of pore size from 2 to 7 nm, possesses markedly enhanced charge‐discharge properties at high current density compared with the pure NiO and pure Co₃O₄. The Co_0.56Ni_0.44 oxide electrode shows a specific capacitance value of 1227 F/g at 5 mA/cm², which is nearly three times greater than that of the pure NiO electrode at the same current density.     

Real‐time Monitoring of Discrete Synaptic Release Events and Excitatory Potentials within Self‐reconstructed Neuromuscular Junctions

Chemical synaptic transmission is central to the brain functions. In this regard, real‐time monitoring of chemical synaptic transmission during neuronal communication remains a great challenge. In this work, in vivo‐like oriented neural networks between superior cervical ganglion (SCG) neurons and their effector smooth muscle cells (SMC) were assembled in a microfluidic device. This allowed amperometric detection of individual neurotransmitter release events inside functional SCG‐SMC synapse with carbon fiber nanoelectrodes as well as recording of postsynaptic potential using glass nanopipette electrodes. The high vesicular release activities essentially involved complex events arising from flickering fusion pores as quantitatively established based on simulations. This work allowed for the first time monitoring in situ chemical synaptic transmission under conditions close to those found in vivo, which may yield important and new insights into the nature of neuronal communications.     

Fluorescence Turn‐On Detection of Nitric Oxide in Aqueous Solution Using Cationic Conjugated Polyelectrolytes

A fluorescent turn‐on detection for nitric oxide in aqueous solution is developed using cationic conjugated polymers. The assay benefits from the sensitivity of optical signals from conjugated polymers and the simplicity of fluorescence measurement techniques. The assay contains three elements: a cationic conjugated polymer that contains imidazole moieties, Cu²⁺ ions, and the target nitric oxide. The highly fluorescent conjugated polymer coordinates to Cu²⁺ ions through weak N · · · Cu interactions, and its fluorescence is efficiently quenched by a photo‐induced electron transfer process (‘off’ state). In the presence of nitric oxide, the transformation of the paramagnetic Cu²⁺ ion into a diamagnetic Cu¹⁺ ion inhibits the quenching and, therefore, the fluorescence of the conjugate polymer is recovered (‘on’ state). Other biologically relevant reactive nitrogen species, such as NOBF₄, NaNO₂, and NaNO₃ don't exhibit the fluorescence recovery of the conjugated polymer under the same conditions as nitric oxide. The cationic conjugated polymer/Cu²⁺ complex can thus be used as a platform to detect nitric oxide in aqueous solution with high sensitivity and selectivity.