Improved thromboresistance and analytical performance of intravascular amperometric glucose sensors using optimized nitric oxide release coatings

In this work, nitric oxide (NO) release coatings designed for intravenous amperometric glucose sensors are optimized through the use of a polylactic acid (PLA) layer doped with a lipophilic diazeniumdiolated species that releases NO through a proton-driven mechanism. An Elast-Eon E2As polyurethane coating is used to both moderate NO release from the sensor surface and increase the sensor''s linear detection range toward glucose. These sensors were evaluated for thromboresistance and in vivo glucose performance through implantation in rabbit veins. By maintaining NO flux on a similar scale to endogenous endothelial cells, implanted glucose sensors exhibited reduced surface clot formation which enables more accurate quantitative glucose measurements continuously. An in vivo time trace of implanted venous sensors demonstrated glucose values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. The raw measured currents from the implanted glucose sensors over 7 h time periods were converted to glucose concentration through use of both a one-point in vivo calibration and a calibration curve obtained in vitro within a bovine serum solution. Control sensors, assembled without NO release functionality, exhibit distinctive surface clotting over the 7 h in vivo implantation period.     

一氧化氮荧光分子探针

一氧化氮（NO）在生物体中扮演重要的角色,对其选择性识别引起了人们极大的兴趣。本文综述了两类NO荧光分子探针的研究进展,即含金属离子的NO荧光分子探针：如Co(Ⅱ)、Fe(Ⅱ)、 Ru(Ⅱ)、Rh(Ⅱ)和Cu(Ⅱ)配合物作为荧光打开的NO分子探针;邻苯二胺类荧光分子探针：如2,3-二氨基萘（DAN）、二氨基荧光素衍生物（DAFs）、二氨基罗丹明衍生物（DARs）、硼二吡咯甲基衍生物（BODIPY）和三碳菁衍生物（DAC）等。     

Nitric oxide measurements in biological samples

The crucial role of nitric oxide (NO) in controlling many physiological functions in mammals is now established. To aid understanding this crucial role, sensitive and selective methods for its in vivo and in vitro detection are vital. The unique chemical and physical properties of NO set the tone for its detection strategies. This review summarizes different techniques and methodologies used in measuring NO in biological samples. Those include gas and liquid phase chemiluminescence, electron spin resonance spectroscopy, UV-visible spectroscopy, fluorescence, electrochemical sensors, and reporter cell assay. The principles, applications, merits, and limitations of each technique are discussed.     

Visual pH Sensors: From a Chemical Perspective to New Bioengineered Materials

Many human activities and cellular functions depend upon precise pH values, and pH monitoring is considered a fundamental task. Colorimetric and fluorescence sensors for pH measurements are chemical and biochemical tools able to sense protons and produce a visible signal. These pH sensors are gaining widespread attention as non-destructive tools, visible to the human eye, that are capable of a real-time and in-situ response. Optical “visual” sensors are expanding researchers’ interests in many chemical contexts and are routinely used for biological, environmental, and medical applications. In this review we provide an overview of trending colorimetric, fluorescent, or dual-mode responsive visual pH sensors. These sensors include molecular synthetic organic sensors, metal organic frameworks (MOF), engineered sensing nanomaterials, and bioengineered sensors. We review different typological chemical entities of visual pH sensors, three-dimensional structures, and signaling mechanisms for pH sensing and applications; developed in the past five years. The progression of this review from simple organic molecules to biological macromolecules seeks to benefit beginners and scientists embarking on a project of pH sensing development, who needs background information and a quick update on advances in the field. Lessons learned from these tools will aid pH determination projects and provide new ways of thinking for cell bioimaging or other cutting-edge in vivo applications.     

Recent Developments in Nitric Oxide Donors and Delivery for Antimicrobial and Anti-Biofilm Applications

The use of nitric oxide (NO) is emerging as a promising, novel approach for the treatment of antibiotic resistant bacteria and biofilm infections. Depending on the concentration, NO can induce biofilm dispersal, increase bacteria susceptibility to antibiotic treatment, and induce cell damage or cell death via the formation of reactive oxygen or reactive nitrogen species. The use of NO is, however, limited by its reactivity, which can affect NO delivery to its target site and result in off-target effects. To overcome these issues, and enable spatial or temporal control over NO release, various strategies for the design of NO-releasing materials, including the incorporation of photo-activable, charge-switchable, or bacteria-targeting groups, have been developed. Other strategies have focused on increased NO storage and delivery by encapsulation or conjugation of NO donors within a single polymeric framework. This review compiles recent developments in NO drugs and NO-releasing materials designed for applications in antimicrobial or anti-biofilm treatment and discusses limitations and variability in biological responses in response to the use of NO for bacterial eradiation.     

Molecularly imprinted polymer based enantioselective sensing devices: A review

Chiral recognition is the fundamental property of many biological molecules and is a quite important field in pharmaceutical analysis because of the pharmacologically different activities of enantiomers in living systems. Enantio-differentiating signal of the sensor requires specific interaction between the chiral compounds (one or a mixture of enantiomers) in question and the selector. This type of interaction is controlled normally by at least three binding centers, whose mutual arrangement and interacting characteristics with one of the enantiomers effectively control the selectivity of recognition. Molecular imprinting technology provides a unique opportunity for the creation of three-dimensional cavities with tailored recognition properties. Over the past decade, this field has expanded considerably across the variety of disciplines, leading to novel transduction approaches and many potential applications. The state-of-art of molecularly imprinted polymer-based chiral recognition might set an exotic trend toward the development of chiral sensors. The objective of this review is to provide comprehensive knowledge and information to all researchers who are interested in exploiting molecular imprinting technology toward the rational design of chiral sensors operating on different transduction principles, ranging from electrochemical to piezoelectric, being used for the detection of chiral compounds as they pose significant impact on the understanding of the origin of life and all processes that occur in living organisms.     

A New Electrochemical Sensor Based on Carbon Black Modified With Palladium Nanoparticles for Direct Determination of 17α-Ethinylestradiol in Real Samples

Electrochemical sensors to quantify concentrations of emerging pollutants have attracted great attention from the industry and scientific community. Nanomaterials such as carbon black have been applied in sensors to identify substances that are toxic to the environment and human health due to their excellent electroanalytical properties. The aim of the study was to develop a novel electrochemical sensor for the endocrine disruptor hormone determination. To our knowledge, for the first time the synthesis of material based on carbon black containing immobilized palladium nanoparticles, with the application for the hormone ethinylestradiol, is reported in the literature. The material was synthesized, characterized, and applied to the determination in tap water and human urine of the synthetic hormone 17α-ethinylestradiol (EE2), which is currently considered an emerging pollutant. The morphology, structure and electrochemical performance of the sensors were characterized by scanning electron microscopy (SEM) and cyclic voltammetry (CV). Differential pulse voltammetry (DPV) in sodium phosphate buffer solution at pH 5.0 allowed the generation of a method to quantify the concentration of 17α-ethinylestradiol in a linear range of 0.5–119.0 μmol L⁻¹, obtaining 81.0 nmol L⁻¹ of calculated limit of detection (LOD). The system was efficient in detecting 17α-ethinylestradiol in real urine samples and showed no interferences for ascorbic acid, uric acid, progesterone, and dopamine. It is noteworthy that the results obtained showed good recovery values, considering that the urine samples were not previously treated or pre-concentrated, which suggests the development of an electrochemical sensor that works in situ and in real time to monitor relevant substances in the control clinical and environmental, with the possibility of point-of-care analyses.     

Fluorescent sensors for the detection of chemical warfare agents

Along with biological and nuclear threats, chemical warfare agents are some of the most feared weapons of mass destruction. Compared to nuclear weapons they are relatively easy to access and deploy, which makes them in some aspects a greater threat to national and global security. A particularly hazardous class of chemical warfare agents are the nerve agents. Their rapid and severe effects on human health originate in their ability to block the function of acetylcholinesterase, an enzyme that is vital to the central nervous system. This article outlines recent activities regarding the development of molecular sensors that can visualize the presence of nerve agents (and related pesticides) through changes of their fluorescence properties. Three different sensing principles are discussed: enzyme-based sensors, chemically reactive sensors, and supramolecular sensors. Typical examples are presented for each class and different fluorescent sensors for the detection of chemical warfare agents are summarized and compared.     

Compartmentalized nanocomposite for dynamic nitric oxide release

Nitric oxide (NO) is an important cell-signaling molecule whose role in a variety of cellular processes such as differentiation and apoptosis depends strongly on its concentration and flux levels. This work describes and characterizes a novel nitric oxide releasing nanocomposite, capable of photostimulated NO flux that can by dynamically modulated in within a range of biological levels. This material mimics the common compartmentalization strategies used by living cells to achieve its novel features. The material is constructed by encapsulating a photosensitive nitric oxide donor within lipid vesicles with an average diameter of 150 nm. The vesicles are then doped into the interstitial liquid phase of a solid porous silica matrix, which has previously demonstrated biological compatibility and capabilities as a growth surface for mammalian cells. Stimulation by a light source produces a step increase in NO concentration within seconds. The NO flux at the surface of the material is measured to be 14 pmol-cm(-2) sec(-1) using a NO selective self-referencing amperometric microsensor. The NO concentration profile decreases with distance perpendicular to the surface as expected for diffusion from a surface through an aqueous environment. A pattern of one minute light pulses produced uniform pulses of increased NO concentration of one minute duration. A linear relationship exists between NO surface concentration and photon flux, and this relationship can be used to tune the material response.     

Electrochemical sensors for oxidative stress monitoring

Electrochemical sensors are ideally suited for the detection of reactive oxygen and nitrogen species (ROS and RNS) generated during biological processes. This review discusses the latest work in the development of electrochemical microsensors for ROS/RNS and their applications for monitoring oxidative stress in biological systems. The performance of recent designs of microelectrodes and electrode materials is discussed along with their functionality in preclinical models of drug efficacy, mitochondrial distress, and endothelial dysfunction. Challenges and opportunities in translating this methodology to study the pathophysiology associated with various diseases are discussed.     

Nitric Oxide Release for Enhanced Biocompatibility and Analytical Performance of Implantable Electrochemical Sensors

The real-time, continuous monitoring of glucose/lactate, blood gases and electrolytes by implantable electrochemical sensors holds significant value for critically ill and diabetic patients. However, the wide-spread use of such devices has been seriously hampered by implant-initiated host responses (e. g., thrombus formation, inflammatory responses and bacterial infection) when sensors are implanted in blood or tissue. As a result, the accuracy and usable lifetime of in vivo sensors are often compromised. Nitric oxide (NO) is an endogenous gas molecule able to inhibit platelet adhesion/activation, inflammatory responses and bacterial growth. As such, the release of NO from the surfaces of in vivo sensors is a promising strategy for enhancement of their biocompatibility and analytical performance. In this review, the physiological functions of NO to improve the biocompatibility of implantable electrochemical sensors are introduced, followed by a brief analysis of chemical approaches to realize NO release from such devices. A detailed summary of the various types of NO releasing electrochemical sensors reported to date and their performance in benchtop and/or in vivo testing are also provided. Finally, the prospects of future developments to further advance NO releasing sensor technology for clinical use are discussed.     

非酶葡萄糖传感器电极材料构建策略

电化学传感器因具有灵敏度高、检测限低等优点而得到广泛应用,将非酶电化学传感器应用于葡萄糖浓度的检测具备重要的研究价值。以金属有机骨架、碳材料和导电聚合物为基底与金属及其衍生物复合,构建的纳米复合材料修饰电极对于葡萄糖的检测具有极高的灵敏度、较低的检测限和快速响应的能力,可应用于实际样品的检测。本文综述了近年来非酶葡萄糖电化学传感器的研究进展,通过对纳米复合材料的性能比较,为非酶葡萄糖传感器的构建提供思路。     

Calix[4]arene‐Based Bis(Nitric Oxide) Complexes: Synthesis,Physical Properties,and Structural Characterization

Calix[4]arene‐based molecules hold great promise as candidate sensors and storage materials for nitric oxide (NO), owing to their unprecedented binding affinity for NO. However, the structure of calix[4]arene is complicated by the availability of four possible conformers: 1,3‐alternate, 1,2‐alternate, cone, and partial cone (paco). Whilst complexes of NO with several of these conformers have previously been established, the 1,2‐alternate conformer complex, that is, [1,2‐alter ? NO]⁺, has not been previously reported. Herein, we determine the crystal structure of the NO complex with the 1,2‐alternate conformer for the first time. In addition, we have also found that the 1,2‐alternate and 1,3‐alternate conformers can combine with two NO molecules to form stable bis(nitric oxide) complexes. These new complexes, which exhibit remarkable binding capacity for the construction of NO‐storage molecules, were characterized by using X‐ray crystallography and NMR, IR, and UV/Vis spectroscopy. These findings will extend our understanding of the interactions between nitric oxide and cofacially and non‐cofacially arrayed aromatic rings, and we expect them to aid in the design and development of new supramolecular sensors and storage materials for NO with high capacity and efficacy.     

Nitric oxide release during evoked neuronal activity in cerebellum slices: detection with platinized carbon-fiber microelectrodes.

Nitric oxide is an important biological messenger that particularly induces the relaxation of smooth muscle cells surrounding vessels, and, hence, controls the flow of blood. This mechanism is essential for brain function, and its fine control, termed functional hyperemia, is supposed to be realized by certain neurons that may release bursts of NO*. The aim of the present study is to examine the advantages of platinized carbon-fiber microelectrodes (5-7 microm tip diameter) for the direct and in situ electrochemical detection of NO* released by neurons into ex vivo cerebellum slices. After establishing the different analytical properties of the platinized carbon-fiber microelectrodes in vitro on NO* solutions at 50 nM to 1 mM concentration, they were characterized using DEA-NONOate solutions that chemically decompose into NO*, and therefore mimic the measurement of transient variations of NO* concentration in biological samples. This validated the present approach, so that direct, in situ ex vivo measurements of nitric oxide released by neurons in a rat cerebellar slice are presented and discussed.     

Recent Advances in Electrochemical Sensors for Mycotoxin Detection in Food

Mycotoxins pose a grave global threat to human life and health by contaminating food and feed and cause enormous losses in healthcare and trading. Trace mycotoxin concentrations and diverse matrices in food make identification and measurement challenges, necessitating highly specific and sensitive detection methods. Electrochemical (EC) sensors are characterized by simple operation, outstanding sensitivity, low cost, and facile miniaturization and have become a promising strategy for addressing specificity and sensitivity in detection. Recent studies on EC sensors for mycotoxin detection for food safety are reviewed here. First, we summarize the fabrication of EC sensors and techniques with enhanced specificity and sensitivity. Then, we review state-of-the-art EC sensors for detecting major mycotoxins. Challenges and opportunities for this technology are further discussed. Finally, in-depth information is provided on using EC sensors to detect mycotoxins for food safety, as well as the development of EC sensors for academic study and practical application.     

Design and Synthesis of New Acridone-Based Nitric Oxide Fluorescent Probe

Nitric oxide (NO) is an important signaling molecule involved in a wide range of physiological and pathological processes. Fluorescent imaging is a useful tool for monitoring NO concentration, which could be essential in various biological and biochemical studies. Here, we report the design of a novel small-molecule fluorescent probe based on 9(10H)acridone moiety for nitric oxide sensing. 7,8-Diamino-4-carboxy-10-methyl-9(10H)acridone reacts with NO in aqueous media in the presence of O₂, yielding a corresponding triazole derivative with fivefold increased fluorescence intensity. The probe was shown to be capable of nitric oxide sensing in living Jurkat cells.     

Molecularly Imprinted Polymers Combined with Electrochemical Sensors for Food Contaminants Analysis

Detection of relevant contaminants using screening approaches is a key issue to ensure food safety and respect for the regulatory limits established. Electrochemical sensors present several advantages such as rapidity; ease of use; possibility of on-site analysis and low cost. The lack of selectivity for electrochemical sensors working in complex samples as food may be overcome by coupling them with molecularly imprinted polymers (MIPs). MIPs are synthetic materials that mimic biological receptors and are produced by the polymerization of functional monomers in presence of a target analyte. This paper critically reviews and discusses the recent progress in MIP-based electrochemical sensors for food safety. A brief introduction on MIPs and electrochemical sensors is given; followed by a discussion of the recent achievements for various MIPs-based electrochemical sensors for food contaminants analysis. Both electropolymerization and chemical synthesis of MIP-based electrochemical sensing are discussed as well as the relevant applications of MIPs used in sample preparation and then coupled to electrochemical analysis. Future perspectives and challenges have been eventually given.     

Nanomolar Nitric Oxide Concentrations in Living Cells Measured by Means of Fluorescence Correlation Spectroscopy

Measurement of the nitric oxide (NO) concentration in living cells in the physiological nanomolar range is crucial in understanding NO biochemical functions, as well as in characterizing the efficiency and kinetics of NO delivery by NO-releasing drugs. Here, we show that fluorescence correlation spectroscopy (FCS) is perfectly suited for these purposes, due to its sensitivity, selectivity, and spatial resolution. Using the fluorescent indicators, diaminofluoresceins (DAFs), and FCS, we measured the NO concentrations in NO-producing living human primary endothelial cells, as well as NO delivery kinetics, by an external NO donor to the immortal human epithelial living cells. Due to the high spatial resolution of FCS, the NO concentration in different parts of the cells were also measured. The detection of nitric oxide by means of diaminofluoresceins is much more efficient and faster in living cells than in PBS solutions, even though the conversion to the fluorescent form is a multi-step reaction.     

What Flow Injection has to Offer in the Environmental Analytical Field

NO plays an important role in the regulation of physiological and pathophysiological mechanisms, and quite a lot of investigations have been focused on this kind of special molecule. It is difficult to achieve reliable ex vivo NO measurements with the existing analytical methods, and developing a reliable in vivo monitoring method for NO is still an urgent task. In this review, the techniques utilized for the determination of endogenous NO formed by enzymatic action and its reactions with other biological substances found in living organisms are discussed with respect to applications both in vivo or in vitro. In addition, various NO (micro)sensors and trap probes based on different principles are presented with their respective advantages and limitations. Finally, an NO monitoring system based on the combination of microdialysis sampling and chemiluminescence is introduced which is considered to be a prospective method for in vivo monitoring.     

Molecularly imprinted polymer-carbon paste electrode (MIP-CPE)-based sensors for the sensitive detection of organic and inorganic environmental pollutants: A review

The rapidly growing existence of a number of contaminants (i.e. heavy metals, dye compounds, explosives and pesticides etc.) in environment is an alarming concern not only due to their harmful impacts for the environment bur also due to their potential high risk for human health. Thus, the careful and sensitive detection of these environmental contaminants is ver crucial. Electrochemical sensors combined with molecularly imprinted polymers (MIPs) become an attractive area for environmental monitoring. Benefiting from their great features such as high chemical and physical stability, cheap preparation process, excellent selectivity, sensitivity and fast response towards the target compound/s.This review paper aims to present and highlight the latest progresses in the design and development of novel electrochemical sensor systems composed of MIPs and carbon paste electrodes (CPEs) for the sensitive detection of pollutants in environmental samples.