Microliquid/Liquid Interfacial Sensors: Biomimetic Investigation of Transmembrane Mechanisms and Real-Time Determinations of Clemastine, Cyproheptadine, Epinastine, Cetirizine, and Desloratadine.

Antihistamines relieve allergic symptoms by inhibiting the action of histamine. Further understanding of antihistamine transmembrane mechanisms and optimizing the selectivity and real-time monitoring capabilities of drug sensors is necessary. In this study, a micrometer liquid/liquid (L/L) interfacial sensor has served as a biomimetic membrane to investigate the mechanism of interfacial transfer of five antihistamines, i.e., clemastine (CLE), cyproheptadine (CYP), epinastine (EPI), desloratadine (DSL), and cetirizine (CET), and realize the real-time determinations. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to uncover the electrochemical transfer behavior of the five antihistamines at the L/L interface. Additionally, finite element simulations (FEMs) have been employed to reveal the thermodynamics and kinetics of the process. Visualization of antihistamine partitioning in two phases at different pH values can be realized by ion partition diagrams (IPDs). The IPDs also reveal the transfer mechanism at the L/L interface and provide effective lipophilicity at different pH values. Real-time determinations of these antihistamines have been achieved through potentiostatic chronoamperometry (I-t), exhibiting good selectivity with the addition of nine common organic or inorganic compounds in living organisms and revealing the potential for in vivo pharmacokinetics. Besides providing a satisfactory surrogate for studying the transmembrane mechanism of antihistamines, this work also sheds light on micro- and nano L/L interfacial sensors for in vivo analysis of pharmacokinetics at a single-cell or single-organelle level.

A graphitic C3N4 nanocomposite-based fluorescence platform for label-free analysis of trace mercury ions.

In this study, a nanocomposite consisting of graphitic carbon nitride nanosheets loaded with graphitic carbon nitride quantum dots (CNQDs/CNNNs) was synthesized via a one-step pyrolysis method. This nanocomposite exhibited excellent thermal stability, photobleaching and salt resistance. Then a new fluorescence sensing platform based on CNQDs/CNNNs was constructed, which showed high sensitivity and selectivity towards trace mercury ions (Hg2+). By using X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectra and density functional theory, the fluorescence response mechanism was elucidated where Hg2+ could interact with CNQDs/CNNNs, causing a structural change in the nanocomposite, further affecting its bandgap structure, and finally leading to fluorescence quenching. The linear range for detecting Hg2+ was found to be 0.025-4.0 µmol L-1, with a detection limit of 7.82 nmol L-1. This strategy provided the advantages of a rapid response and a broad detection range, making it suitable for quantitative detection of Hg2+ in environmental water.

Near-infrared dye IRDye800CW-NHS coupled to Trastuzumab for near-infrared II fluorescence imaging in tumor xenograft models of HER-2-positive breast cancer.

Near-infrared II fluorescent probes targeting tumors for diagnostic purposes have received much attention in recent years. In this study, a fluorescent probe for the NIR-II was constructed by using IRDye800CW-NHS fluorescent dye with Trastuzumab, which was investigated for its ability to target HER-2-positive breast cancer in xenograft mice models. This probe was compared with Trastuzumab-ICG which was synthesized using a similar structure, ICG-NHS. The results demonstrated that the IRDye800CW-NHS had significantly stronger fluorescence in the NIR-I and NIR-II than ICG-NHS in the aqueous phase. And the different metabolic modes of IRDye800CW-NHS and ICG-NHS were revealed in bioimaging experiments. IRDye800CW-NHS was mainly metabolised by the kidneys, while ICG-NHS was mainly metabolised by the liver. After coupling with Trastuzumab, Trastuzumab-800CW (TMR = 5.35 ± 0.39) not only had a stronger tumor targeting ability than Trastuzumab-ICG (TMR = 4.42 ± 0.10) based on the calculated maximum tumor muscle ratio (TMR), but also had a comparatively lower hepatic uptake and faster metabolism. Histopathology analysis proved that both fluorescent probes were non-toxic to various organ tissues. These results reveal the excellent optical properties of IRDye800CW-NHS, and the great potential of coupling with antibodies to develop fluorescent probes that will hopefully be applied to intraoperative breast cancer navigation in humans.

A new ratiometric fluorescence nanosensor based on NaYF4:3%Er@NaYF4 upconversion nanoparticles for sensitive determination of Rose Bengal in water.

Rose Bengal (RB) is used as a sensitizer in ambient water due to its property of catalyzing the production of singlet oxygen (1O2). However, this property also brings phototoxicity and carcinogenicity. The NaYF4:3%Er@NaYF4 core-shell upconversion nanoparticles (UCNPs) with higher upconversion efficiency was synthesized to detect RB in ambient water. Due to fluorescence resonance energy transfer (FRET) between RB and UCNPs, the upconversion fluorescence at 538 nm emitted by UCNPs was quenched by the RB, while the emission at 566 nm of RB raised. In the best conditions, the ratiometric emission intensity F566/F538 was positively proportional to RB concentration and the linear range was 0.04-15.0 µg·mL-1 (R2 = 0.996). The detection limit (S/N = 3) of RB was 2.46 ng·mL-1. The recoveries ranged from 99.0% to 105.6% (relative standard deviation 0.97-3.24%, n = 3) in tap water and 100.3%-104.9% (relative standard deviation 0.66-1.94%, n = 3) in lake water. This proposed method exhibits lower detection limit and larger linear, which possesses practical application value to the detection of RB in water.

In situ reduction of gold nanoparticles-decorated MXenes-based electrochemical sensing platform for KRAS gene detection.

In this work, gold nanoparticles@Ti3C2 MXenes nanocomposites with excellent properties were combined with toehold-mediated DNA strand displacement reaction to construct an electrochemical circulating tumor DNA biosensor. The gold nanoparticles were synthesized in situ on the surface of Ti3C2 MXenes as a reducing and stabilizing agent. The good electrical conductivity of the gold nanoparticles@Ti3C2 MXenes composite and the nucleic acid amplification strategy of enzyme-free toehold-mediated DNA strand displacement reaction can be used to efficiently and specifically detect the non-small cell cancer biomarker circulating tumor DNA KRAS gene. The biosensor has a linear detection range of 10 fM -10 nM and a detection limit of 0.38 fM, and also efficiently distinguishes single base mismatched DNA sequences. The biosensor has been successfully used for the sensitive detection of KRAS gene G12D, which has excellent potential for clinical analysis and provides a new idea for the preparation of novel MXenes-based two-dimensional composites and their application in electrochemical DNA biosensors.

Monitoring Bipolar Electrochemistry and Hydrogen Evolution Reaction of a Single Gold Microparticle under Sub-Micropipette Confinement.

Herein, an approach to track the process of autorepeating bipolar reactions and hydrogen evolution reaction (HER) on a micro gold bipolar electrode (BPE) is established. Once blocking the channel of the sub-micropipette tip, the formed gold microparticle is polarized into the wireless BPE, which induces the dissolution of the gold at the anode and the HER at the cathode. The current response shows a periodic behavior with three regions: the bubble generation region (I), the bubble rupture/generation region (II), and the channel opening region (III). After a stable low baseline current of region I, a series of positive spike signals caused by single H2 nanobubbles rupture/generation are recorded standing for the beginning of region II. Meanwhile, the dissolution of the gold blocking at the orifice will create a new channel, increasing the baseline current for region III, where the synthesis of gold occurs again, resulting in another periodic response. Finite element simulations are applied to unveil the mechanism thermodynamically. In addition, the integral charge of the H2 nanobubbles in region II corresponds to the consumption of the anode gold. It simultaneously monitors autorepeating bipolar reactions of a single gold microparticle and HER of a single H2 nanobubble electrochemically, which reveals an insightful physicochemical mechanism in nanoscale confinement and makes the glass nanopore an ideal candidate to further reveal the heterogeneity of catalytic capability at the single particle level.

Galvani Potential-Dependent Single Collision/Fusion Impacts at Liquid/Liquid Interface: Faradic or Capacitive?

A new subtype of nano-impacts by emulsion droplets via reorganization of the electric double layer (EDL) at the liquid/liquid interface (LLI) is reported. This subtype shows anodic, bipolar, and cathodic transient currents with a potential of zero charge (PZC) dependence, revealing the non-faradic characteristic of single fusion impacts. In addition, the absolute integrated mean charge is proportional to the Galvani potential at the ITIES, indicating that the EDL at the LLI may obey the discrete Helmholtz model. The exact PZC point is interpolated from the fitting curve, and the droplet size distribution is estimated from the integrated charge distribution. Moreover, the different values of Epzc between single fusion impacts of MgCl2 droplets and pure water droplets is due to the specific absorption between Mg2+ and antagonistic anion in the organic phase. The influence of the concentration of the supporting electrolyte is also investigated. The above work gives physicochemical insights into the EDL at the micropipette-supported LLI and provides potential application to measure micro/nanoscale heterogeneous media without catalytic, reactive, or charge-transfer activity via impact experiments at LLI.

Confined Synthesis of Silver Wire at the Nanopipette-Liquid/Liquid Interface.

Herein, silver wire is synthesized electrochemically within a nanopipette using the nanopipette-liquid/liquid interface. The i-t curve characterizes the growth state of the silver wire. The higher rate of current increase indicates the faster electron transfer and the faster growth of the silver wire; conversely, when the current does not increase significantly with time, i.e., the rate of increase of the current is small, the growth rate of the silver wire is slow. The main driving force for the growth of silver into a linear structure is the theoretical current differential between the water and oil, caused by the concentration difference between the silver nitrate and ferrocene. The growth of the silver wire is also influenced by the shape of the nanopipette. If the diameter of the pipet increases quickly, silver wire tends to produce multibranched structures, while a smaller diameter makes it easier to obtain silver wire with fewer branches due to the confinement effect. This method is also applicable to the synthesis of gold within a nanopipette. The combination of nanopipette and metallic material using a liquid-liquid interface results in a broader application of nanopipettes for nanopore sensors, nanopore electrodes, bipolar electrodes, etc.

Variations in Surface Morphologies, Properties, and Electrochemical Responses to Nitro-Analyte by Controlled Electropolymerization of Thiophene Derivatives.

Herein, we reported the fabrication of conjugated microporous polymer (CMP) films based on three thiophene derivatives using a one-step templateless electropolymerization in dichloromethane without any surfactants. The formation of hydrophilic or hydrophobic films with specific morphology is a comprehensive result of the polymerization sites in each monomer, the polymerization rate, and the gas bubble produced in situ during the polymerization process, which can be easily controlled by the experimental conditions, such as electropolymerization method, electrolyte, and "trace water" existed in the organic solvent. Moreover, the electrochemical reduction of metronidazole as a prototypical nitro-analyte at CMP-modified glassy carbon (GC) electrode shows remarkably increased current response compared to nonmodified GC electrode. The process is demonstrated to be typical adsorption-controlled, and the hydrophobic surface of the electrode coating film is more favorable to the absorption and thus reduction of metronidazole. This work provides a new perspective and a breakthrough point for the application of CMPs in the electrochemical sensors.

Nanosized Difunctional Photo Responsive Magnetic Imprinting Polymer for Electrochemically Monitored Light-Driven Paracetamol Extraction.

Herein, a novel photoresponsive magnetic electrochemical imprinting sensor for the selective extraction of paracetamol from biological samples was designed. In particular, nanosized photoresponsive molecular imprinted polymers were prepared on the surface of magnetic Fe3O4 nanoparticles through living radical polymerization of azobenzene. The introduction of a magnetic-controlled glassy carbon electrode makes the immobilization and removal of nanosized photoresponsive molecular imprinted polymers on the magnetic-controlled glassy carbon electrode surface facilely operational. With the photoresponsive property, the sensor undergoes reversible release and uptake of paracetamol upon alternative irradiation at 365 and 440 nm basing on a configurational change of azobenzene monomer in the photoresponsive molecular imprinted polymers receptor sites. Simultaneously, these processes are monitored by the photoresponsive changes of electrochemical signal from paracetamol. Two linear ranges from 0.001 to 0.7 mmol L-1 (R2 = 0.96) and 0.7 to 7 mmol L-1 (R2 = 0.95) for paracetamol determination were obtained with a quantification limit of 0.000 86 mmol L-1 and a detection limit of 0.000 43 mmol L-1. The recoveries of paracetamol in the urine as determined by photoresponsive molecular imprinted polymers extraction were varied between 87.5% and 93.3%. As a consequence, combining photocontrolled selective extraction, interfacial stability from magnetic adsorption, and specifically electrochemical response, the photoresponsive molecular imprinted polymers sensor shows significant advantages for simultaneous separation, enrichment, and detection of trace paracetamol in biological samples.

Application of Coal in Electrochemical Sensing.

In this work, we first report a new application of coal as a novel modified electrode material in electrochemical sensing, achieving excellent electrochemical performance similar to graphene and making the utilization of coal become more multipurpose and more meaningful. Raw coal was first ball-milled, then centrifugated, and finally annealed, thus obtaining annealed coal that possesses lots of edge-plane-like defective sites, resulting in good electron-transfer efficiency and excellent electrocatalytic activity, which makes it promising when used as signal amplifier material and as a modified matrix in electrochemical sensing. And we also described an investigation into the electrochemical and spectroscopic properties of annealed coal samples and their application for the detection of electroactive redox molecules (rutin). Compared with other published carbon materials modified sensors, the annealed coal/chitosan/GCE sensor exhibited excellent electrocatalytic activity for the determination of rutin with good sensitivity, providing a wide linear detection range from 0.001 to 10 µmol dm-3 and a low detection limit of 0.2 nmol dm-3 (S/N = 3). Moreover, when the annealed coal/GCE sensor was applied for the determination of ascorbic acid, dopamine, uric acid, guanine, and adenine commonly contained in blood samples and urine samples, it also exhibited excellent detection performance with strong electrocatalytic activity. This research has opened up the application of coal in electroanalytical chemistry and held great promise for the sensing and biosensing application, which can be promising used as an alternative material of graphene.