Recent Developments and Challenges in Solid-Contact Ion-Selective Electrodes.

Solid-contact ion-selective electrodes (SC-ISEs) have the advantages of easy miniaturization, even chip integration, easy carrying, strong stability, and more favorable detection in complex environments. They have been widely used in conjunction with portable, wearable, and intelligent detection devices, as well as in on-site analysis and timely monitoring in the fields of environment, industry, and medicine. This article provides a comprehensive review of the composition of sensors based on redox capacitive and double-layer capacitive SC-ISEs, as well as the ion-electron transduction mechanisms in the solid-contact (SC) layer, particularly focusing on strategies proposed in the past three years (since 2021) for optimizing the performance of SC-ISEs. These strategies include the construction of ion-selective membranes, SC layer, and conductive substrates. Finally, the future research direction and possibilities in this field are discussed and prospected.

Cathodic electrochemiluminescence of boron and nitrogen-codoped carbon dots for the detection of dissolved oxygen in seawater.

Electrochemiluminescence (ECL) is widely used in various fields due to its high sensitivity and controllable characteristics. Carbon dots (CDs) have emerged as promising ECL emitters due to their simple synthesis, low toxicity, and excellent biocompatibility. However, the practical application of many CDs emitters is hindered by their limited luminous efficiency, often necessitating additional coreactants to enhance the ECL signal intensity. In this study, we synthesized boron and nitrogen-codoped carbon dots (BN-CDs) as ECL emitters, utilizing dissolved oxygen (DO) as the coreactant. The BN-CDs/DO system exhibited a strong cathodic ECL signal. We proposed a reaction mechanism for the BN-CDs/DO ECL system. Additionally, we developed an ECL sensor for DO detection based on this system, showing a linear correlation between ECL peak intensity and DO concentration from 0.5 to 19.8 mg/L, with a detection limit of 0.12 mg/L. It was proven reliable for DO analysis in seawater and freshwater environments. This study provides insights into the synthesis and utilization of BN-CDs, highlighting the potential of DO as an intrinsic coreactant in CDs ECL systems. Furthermore, it provides new perspectives on the detection of DO in seawater and the design of innovative DO sensors.

Engineering nanoparticles-enabled tumor-associated macrophages repolarization and phagocytosis restoration for enhanced cancer immunotherapy.

Tumor-associated macrophages (TAMs) are pivotal within the immunosuppressive tumor microenvironment (TME), and recently, have attracted intensive attention for cancer treatment. However, concurrently to promote TAMs repolarization and phagocytosis of cancer cells remains challenging. Here, a TAMs-targeted albumin nanoparticles-based delivery system (M@SINPs) was constructed for the co-delivery of photosensitizer IR820 and SHP2 inhibitor SHP099 to potentiate macrophage-mediated cancer immunotherapy. M@SINPs under laser irradiation can generate the intracellular reactive oxygen species (ROS) and facilitate M2-TAMs to an M1 phenotype. Meanwhile, inhibition of SHP2 could block the CD47-SIRPa pathway to restore M1 macrophage phagocytic activity. M@SINPs-mediated TAMs remodeling resulted in the immunostimulatory TME by repolarizing TAMs to an M1 phenotype, restoring its phagocytic function and facilitating intratumoral CTLs infiltration, which significantly inhibited tumor growth. Furthermore, M@SINPs in combination with anti-PD-1 antibody could also improve the treatment outcomes of PD-1 blockade and exert the synergistic anticancer effects. Thus, the macrophage repolarization/phagocytosis restoration combination through M@SINPs holds promise as a strategy to concurrently remodel TAMs in TME for improving the antitumor efficiency of immune checkpoint block and conventional therapy.

Research Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) stands as the prevailing form of primary liver cancer, characterized by a poor prognosis and high mortality rate. A pivotal factor in HCC tumorigenesis is epigenetics, specifically the regulation of gene expression through methylation. This process relies significantly on the action of proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These proteins are crucial regulators, orchestrating the methylation process by regulating enzymes and their corresponding binding proteins. This orchestration facilitates the reading, binding, detection, and catalysis of gene methylation sites. Methylation ences the development, prolisignificantly influferation, invasion, and prognosis of HCC. Furthermore, methylation modification and its regulatory mechanisms activate distinct biological characteristics in HCC cancer stem cells, such as inducing cancer-like differentiation of stem cells. They also influence the tumor microenvironment (TME) in HCC, modulate immune responses, affect chemotherapy resistance in HCC patients, and contribute to HCC progression through signaling pathway feedback. Given the essential role of methylation in genetic information, it holds promise as a potential tool for the early detection of HCC and as a target to improve drug resistance and promote apoptosis in HCC cells.

Research progress in the metabolic reprogramming of hepatocellular carcinoma (Review).

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and its morbidity is increasing worldwide due to increasing prevalence. Metabolic reprogramming has been recognized as a hallmark of cancer and serves a role in cancer progression. Glucose, lipids and amino acids are three major components whose altered metabolism can directly affect the energy production of cells, including liver cancer cells. Nutrients and energy are indispensable for the growth and proliferation of cancer cells, thus altering the metabolism of hepatoma cells can inhibit the progression of HCC. The present review summarizes recent studies on tumour regulatory molecules, including numerous noncoding RNAs, oncogenes and tumour suppressors, which regulate the metabolic activities of glucose, lipids and amino acids by targeting key enzymes, signalling pathways or interactions between the two. These regulatory molecules can regulate the rapid proliferation of cancer cells, tumour progression and treatment resistance. It is thought that these tumour regulatory factors may serve as therapeutic targets or valuable biomarkers for HCC, with the potential to mitigate HCC drug resistance. Furthermore, the advantages and disadvantages of metabolic inhibitors as a treatment approach for HCC, as well as possible solutions are discussed, providing insights for developing more effective treatment strategies for HCC.

Pharmacological inhibition of ICOS attenuates the protective effect of exercise on cardiac fibrosis induced by isoproterenol.

AIMS: To investigate the cardioprotective mechanism of exercise or exercise combined with inducible costimulatory molecules (ICOS) monoclonal antibody (mAb) therapy against isoproterenol (ISO)-induced cardiac remodeling. MAIN METHODS: Totally 24 male C57BL/6J mice were randomly divided into four groups: the control group (normal saline treatment), ISO group (subcutaneous injection of isoproterenol, 10 mg/kg/day, once daily for 5 consecutive days), the exercise with subcutaneous ISO injection group (EPI), and the exercise with injected with ISO and ICOS mAb group (EPII). The mice in EPI and EPII group were trained on a small animal treadmill for 4 weeks (13 m/min, 0% grade, 60min/day). KEY FINDINGS: Exercise significantly attenuated CD45+, Mac-2 inflammatory cell infiltration, cardiac fibrosis and inhibited the RIPK1/RIPK3/MLKL/CaMKII and cardiomyocyte pyroptosis pathways to counter ISO-induced severe cardiac injury. The administration of the ICOS mAb may inhibit the cardioprotection of exercise against ISO-induced heart damage. Compared to those in EPI, our data showed that the increasing levels of myocardial fibrosis, the leukocyte infiltration of cardiac tissue and proteins expression of cardiac myocyte necrosis and pyroptosis signaling pathways in the EPII group. SIGNIFICANCE: Our results demonstrated that exercise decreased leukocyte infiltration in heart, inhibited the cardiomyocyte pyroptosis and necroptosis signaling pathways, and attenuated inflammatory responses to alleviate ISO-induced cardiac fibrosis. However, the antifibrotic effects of combined treatment with exercise and ICOS mAb intervention did not exhibit synergistic enhancement.

A novel and efficient electrochemiluminescence sensing strategy for the determination of trimethylamine oxide in seafood.

A novel and efficient electrochemiluminescence (ECL) sensing strategy and a solid-state ECL sensor was proposed to detect trimethylamine oxide (TMAO), which is widely presented in marine species and has important physiological functions. TMAO was reduced by Fe(II)-EDTA complex to trimethylamine, acting as coreactant, to amplify the ECL response of the Ru (bpy)32+ system. To improve the detection sensitivity and efficiency, a robust solid-state ECL probe was prepared and a flow injection ECL detection system was established with a specially designed flow ECL unit, under the excitation of stepping pulse potentials. Under optimized experimental conditions, the developed ECL sensor worked well for TMAO detection in a wide linear range of 10.00 µM to 1.00 mM with a limit of detection of 3.41 µM. It was successfully applied to determine TMAO in various species of seafood samples. This work provides a promising strategy for TMAO detection.

Rational Design of Electrochemiluminescent Devices.

Electrochemiluminescence (ECL) is a light-emitting process which combines the intriguing merits of both electrochemical and chemiluminescent methods. It is an extensively used method especially in clinical analysis and biological research due to its high sensitivity, wide dynamic range, and good reliability. ECL devices are critical for the development and applications of ECL. Much effort has been expended to improve the sensitivity, portability, affordability, and throughput of new ECL devices, which allow ECL to adapt broad usage scenarios.In this Account, we summarize our efforts on the recent development of ECL devices including new electrodes, ECL devices based on a wireless power transfer (WPT) technique, and novel bipolar electrochemistry. As the essential components in the ECL devices, electrodes play an important role in ECL detection. We have significantly improved the sensitivity of luminol ECL detection of H2O2 by using a stainless steel electrode. By using semiconductor materials (e.g., silicon and BiVO4), we have exploited photoinduced ECL to generate intense emission at much lower potentials upon illumination. For convenience, portability, and disposability, ECL devices based on cheap WPT devices have been designed. A small diode has been employed to rectify alternating current into direct current to dramatically enhance ECL intensity, enabling sensitive ECL detection using a smart phone as a detector. Finally, we have developed several ECL devices based on bipolar electrochemistry in view of the convenience of multiplex ECL sensing using a bipolar electrode (BPE). On the basis of the wireless feature of BPE, we have employed movable BPEs (e.g., BPE swimmers and magnetic rotating BPE) for deep exploration of the motional and ECL properties of dynamic BPE systems. To make full use of the ECL solution, we have dispersed numerous micro-/nano-BPEs in solution to produce intense 3D ECL in the entire solution, instead of 2D ECL in conventional ECL devices. In addition, the interference of ECL noise from driving electrodes was minimized by introducing the stainless steel with a passivation layer as the driving electrode. To eliminate the need for the fabrication of electrode arrays and the interference from the driving electrode and to decrease the applied voltage, we develop a new-type BPE device consisting of a single-electrode electrochemical system (SEES) based on a resistance-induced potential difference. The SEES is fabricated easily by attaching a multiperforated plate to a single film electrode. It enables the simultaneous detection of many samples and analytes using only a single film electrode (e.g., screen-printed electrode) instead of electrode arrays. It is of great potential in clinical analysis especially for multiple-biomarker detection, drug screening, and biological studies. Looking forward, we believe that more ECL devices and related ECL materials and detection methods will be developed for a wide range of applications, such as in vitro diagnosis, point-of-care testing, high-throughput analysis, drug screening, biological study, and mechanism investigation.

Detection of ascorbic acid based on its quenching effect on luminol-artemisinin chemiluminescence.

We find that luminol can react with artemisinin (ART) to produce chemiluminescence (CL) in the absence of a catalyst and ascorbic acid (AA) can quench luminol-ART CL. Based on its efficient inhibition effect on luminol-ART CL, a new AA detection method is established. The calibration curve for the determination of AA is in the linear range of 5 × 10-7 M to 1 × 10-4 M with a detection limit of 50 nM, which is more sensitive than many other reported methods. This CL approach was utilized to detect AA in vitamin C tablets by applying the standard addition method, and the recoveries of 104.0%, 96.8% and 103.4% were obtained, respectively, at concentrations of 1 µM, 5 µM and 10 µM with a RSD value of less than 3.6%. This developed method for AA assay is distinguished by its fastness, reproducibility, easy operation and good selectivity.

Emulsion Doping of Ionophores and Ion-Exchangers into Ion-Selective Electrode Membranes.

Ion-selective electrodes (ISEs) are widely used analytical devices to selectively measure ionic species. Despite significant advances in recent years, ion-selective membranes are still mostly prepared in the same manner, by preloading the selective components into a solvent that is subsequently cast into a membrane or film. This paper describes an alternative method to prepare ISE membranes by mass transfer of the sensing components from an emulsion phase. Specifically, blank (undoped) plasticized poly(vinyl chloride) (PVC) membranes mounted into an electrode body are immersed into an aqueous solution containing analyte ions and an appropriate emulsion of the desired sensing components to allow their transfer into the membrane. The concept is demonstrated with conventional membrane electrodes containing an inner solution as well as all-solid-state electrodes. It is shown to be universally useful for the realization of ISEs for K+, Na+, Ca2+, and NO3-.

Direct Potentiometric Sensing of Anion Concentration (Not Activity).

Potentiometric probes used in direct potentiometry are attractive sensing tools. They give information on ion activities, which is often uniquely useful. If, instead, concentrations are desired as sensor output, the ionic strength of the sample must be precisely known, which is often not possible. Here, for the first time, direct potentiometry can be made to report concentrations, rather than activities. It is demonstrated for the detection of monovalent anionic species by using a self-referencing Ag/AgI pulstrode as the reference element instead of a traditional reference electrode. This reference pulstrode releases a discrete quantity of iodide ions from the electrode and the resulting reference potential varies with the activity coefficient of iodide. The effects of activity coefficient on the indicator and reference electrode are therefore compensated and the observed cell potential may now be described in a Nernstian manner against anion concentration, rather than activity. Theoretical simulations and experimental results support the validity of this approach. For most monovalent anions of practical relevance, the potential difference between this approach and from a traditional activity coefficient calculation is less than 0.5 mV. The concept is validated with an all-solid-state nitrate sensor as well as a commercial fluoride-selective electrode, giving Nernstian responses in different ionic strength backgrounds against concentration without the need for correcting activity coefficients or liquid junction potentials.

A Solid-State Reference Electrode Based on a Self-Referencing Pulstrode.

The design of solid-state reference electrodes without a liquid junction is important to allow miniature and cost-effective electrochemical sensors. To address this, a pulse control is proposed using an Ag/AgI element as reliable solid-state reference electrode. It involves the local release of iodide by a cathodic current that is immediately followed by an electromotive force (EMF) measurement that serves as the reference potential. The recapture of iodide ions is achieved by potentiostatic control. This results in intermittent potential values that are reproducible to less than one millivolt (SD=0.27 mV, n=50). The ionic strength is shown to influence the activity coefficient of released iodide in accordance with the extended Debye-Hückel equation, resulting in a predictable change of the potential reading. The principle is applied to potentiometric potassium detection with a valinomycin-based ion-selective electrode (ISE), demonstrating a completely solid-state sensor configuration.

Artesunate-luminol chemiluminescence system for the detection of hemin.

Fabricating simple, accurate and user-friendly diagnostic device for "point of care testing" (POCT) applications is one of the most challenging objectives in the analytical field. Hemin detection is important for drugs monitoring, diagnosis, and forensic latent bloodstain imaging. Herein is developed, luminol chemiluminescence biosensor for hemin detection using artesunate as coreactant. A possible mechanism to account for the chemiluminescence reaction is discussed. Hemin was detected using both photomultiplier tube (PMT) and smartphone as detector. The detection limit for hemin using smartphone as detector is 20 nM, enabling the visual detection of hemin in blood sample with a dilution factor of blood up to 120,000. While PMT detector is used, the system is able to detect hemin down to 0.22 nM. In addition to high sensitivity, this sensing system exhibit high selectivity. It can successfully distinguish bloodstain from other stains while applying the system for point of care testing using smart phone as detector. Moreover, the system can detect artesunate with a linear range from 0.1 nM to 1.0 µM with a limit of detection of 0.078 nM.

Electrogenerated Chemiluminescence for Chronopotentiometric Sensors.

We introduce here a general strategy to read out chronopotentiometric sensors by electrogenerated chemiluminescence (ECL). The potentials generated in chronopotentiometry in a sample compartment are used to control the ECL in a separate detection compartment. A three-electrode cell is used to monitor the concentration changes of the analyte, while the luminol-H2O2 system is responsible for ECL. The principle was shown to be feasible by theoretical simulations, indicating that the sampled times at a chosen potential, rather than traditional transition times, similarly give linear behavior between concentration and the square root of sampled time. With the help of a voltage adapter, the experimental combination between chronopotentiometry and ECL was successfully implemented. As an initial proof of concept, the ferro/ferricyanide redox couple was investigated. The square root of time giving maximum light output changed linearly with ferrocyanide concentration in the range from 0.70 to 4.81 mM. The method was successfully applied to the visual detection of carbonate alkalinity from 0.06 to 0.62 mM using chronopotentiometry at an ionophore-based hydrogen ion-selective membrane electrode. The measurements of carbonate in real samples including river water and commercial mineral water were successfully demonstrated.

Stainless steel electrode for simultaneous stripping analysis of Cd(II), Pb(II), Cu(II) and Hg(II).

Traditional electrodes for stripping analysis generally have narrow electrochemical window, require the modification of electrode or the addition of additional ions. To solve these problems, stainless steel has been used as the electrode for electrochemical stripping analysis for the first time. Square wave anodic stripping voltammetry (SWASV) has been used for the detection of Cd2+, Pb2+, Cu2+, and Hg2+. Type 304 stainless steel electrode gives well-defined, sharp, and separated stripping peaks for these metal ions. The electrode, best operated at + 0.3 V (Hg2+), - 0.05 V (Cu2+), - 0.41 V (Pb2+), and - 0.7 V (Cd2+) and after a 300 s deposition at - 1.0 V, has linear responses in the concentration ranges of 0.075-5 µM for Pb2+ and Cu2+, 0.5-5 µM for Cd2+, and 0.1-5 µM for Hg2+. The limits of detection (at S/N = 3) are 0.033 µM for Pb2+, 0.0073 µM for Cu2+, 0.23 µM for Cd2+, and 0.028 µM for Hg2+. The reproducibility, expressed as relative standard deviation, is 3.2% for Pb2+, 2.6% for Cu2+, 5.1% for Cd2+, and 2.5% for Hg2+ (each 1 µM levels; for n = 6). The electrode was successfully applied to the determination of the ions in spiked groundwater samples. This study shows that stainless steel is a better alternative to mercury electrode for stripping analysis because of its well-defined and sharp stripping peaks, high sensitivity, low background, low toxicity, good reproducibility, and much wider electrochemical window.

Pyridoxal 5'-phosphate assay based on lucigenin chemiluminescence.

The authors describe the first chemiluminescence (CL) based method for determination of pyridoxal 5'-phosphate (PLP). PLP is found to generate intense CL with lucigenin higher than that of the conventional lucigenin-H2O2 system by a factor of about 9.0. This new finding is used to be in a detection method for PLP via flow injection analysis (FIA). Response is linear in the 50 nM to 200 µM PLP concentration range with a correlation coefficient of 0.998, and the detection limit (at an S/N of 3) is 6.9 nM. The assay is highly selective over various amino acids, vitamins, sugars, coenzymes and metal ions cofactors. It exhibits advantages over the commonly employed HPLC methods in that it is rapid, more economic, eco-friendly and high throughput FIA detection of PLP without the need for toxic derivatization reagents, organic solvents, and HPLC instrumentation. The method was successfully applied to the determination of PLP in (spiked) human blood samples with recoveries in the range from 96.2-101.6% with % RSD < 4.0. The new system is also employed to determine lucigenin in the linear range of 0.3 to 100.0 µM with a correlation coefficient of 0.994 and the limit of detection is 0.04 µM. Graphical abstract Schematic of the chemiluminescent assay for pyridoxal 5'-phosphate (PLP). Lucigenin-PLP demonstrates 9-fold stronger chemiluminescence intensity than the lucigenin-H2O2 system. The detection limit of PLP is 6.9 nM. The method can detect PLP in human serum with good recoveries.

A single-electrode electrochemical system for multiplex electrochemiluminescence analysis based on a resistance induced potential difference.

Developing low-cost and simple electrochemical systems is becoming increasingly important but still challenged for multiplex experiments. Here we report a single-electrode electrochemical system (SEES) using only one electrode not only for a single experiment but also for multiplex experiments based on a resistance induced potential difference. SEESs for a single experiment and multiplex experiments are fabricated by attaching a self-adhesive label with a hole and multiple holes onto an ITO electrode, respectively. This enables multiplex electrochemiluminescence analysis with high sensitivity at a very low safe voltage using a smartphone as a detector. For the multiplex analysis, the SEES using a single electrode is much simpler, cheaper and more user-friendly than conventional electrochemical systems and bipolar electrochemical systems using electrode arrays. Moreover, SEESs are free from the electrochemiluminescent background problem from driving electrodes in bipolar electrochemical systems. Since numerous electrodes and cover materials can be used to fabricate SEESs readily and electrochemistry is being extensively used, SEESs are very promising for broad applications, such as drug screening and high throughput analysis.

Detection of 1,3-dihydroxyacetone by tris(2,2'-bipyridine)ruthenium(II) electrochemiluminescence.

1,3-Dihydroxyacetone, a common cosmetic material and food additive, has been successfully explored as an efficient electrochemiluminescence coreactant of Ru(bpy)32+ for the first time. It is about 25 times more effective than the well-known coreactant sodium oxalate. The high electrochemiluminescence efficiency allows sensitive detection of 1,3-dihydroxyacetone without any derivatization. The electrochemiluminescence method shows two linear electrochemiluminescence responses over the range of 5.0-500 µM and 500 µM-6.0 mM with a detection limit of 1.79 µM. The proposed method is at least two orders of magnitude more sensitive than other reported methods. Graphical abstract ECL intensity-potential profile of 1,3-dihydroxyacetone (DHA) and oxalate.

Stainless Steel Electrode for Sensitive Luminol Electrochemiluminescent Detection of H2O2, Glucose, and Glucose Oxidase Activity.

Electrogenerated chemiluminescence (ECL) application of stainless steel, a robust and cost-effective material, has been developed for the first time. Type 304 stainless steel electrode shows appealing ECL performance in the luminol-H2O2 system. It enables the detection of H2O2 with a linear range from 1 to 1000 nM and a limit of detection of 0.456 nM [signal-to-noise ratio (S/N) = 3]. The ECL method based on type 304 stainless steel electrode is more sensitive, more cost-effective, and much simpler than other ECL methods reported before. Because the stainless steel electrode has excellent performance for H2O2 detection and H2O2 participates in many important enzymatic reactions, applications of stainless steel electrode-based ECL for detection of enzyme activities and enzyme substrates were further investigated by use of glucose oxidase (GODx) and glucose as representative enzyme and substrate. The concentrations of glucose and the activity of GODx were directly proportional to ECL intensities over a range of 0.1-1000 µM and 0.001-0.7 units/mL with limits of detection of 0.076 µM and 0.00087 unit/mL (S/N = 3), respectively. This method was successfully used for determining glucose in honey. Because of their remarkable performance and user-friendly features, stainless steel electrodes hold great promise in various electroanalytical applications, such as biosensing, disposable sensors, and wearable sensors.

Artemisinin-Luminol Chemiluminescence for Forensic Bloodstain Detection Using a Smart Phone as a Detector.

Forensic luminol chemiluminescence test is one of the most sensitive and popular methods for the determination of latent bloodstains. It mainly uses hydrogen peroxide or sodium perborate as coreactants. The easy decomposition of hydrogen peroxide and sodium perborate in the presence of many ions significantly affects the selectivity. Artemisinin is a natural peroxide that is quite stable in the presence of common ions. In the present study, artemisinin has been exploited for the forensic bloodstain chemiluminescence detection for the first time. Using smart phone as cost-effective portable detector, the visual detection of bloodstains has been achieved with a dilution factor of blood up to 100 000. Moreover, this system shows excellent selectivity against many common species. It can well differentiate bloodstains from other stains, such as coffee, brown sugar, and black tea. Both favorable sensitivity and selectivity makes the present method promising in forensic detection.