Recent Advances in Electrochemical Sensors for Formaldehyde.

Formaldehyde, a ubiquitous indoor air pollutant, plays a significant role in various biological processes, posing both environmental and health challenges. This comprehensive review delves into the latest advancements in electrochemical methods for detecting formaldehyde, a compound of growing concern due to its widespread use and potential health hazards. This review underscores the inherent advantages of electrochemical techniques, such as high sensitivity, selectivity, and capability for real-time analysis, making them highly effective for formaldehyde monitoring. We explore the fundamental principles, mechanisms, and diverse methodologies employed in electrochemical formaldehyde detection, highlighting the role of innovative sensing materials and electrodes. Special attention is given to recent developments in nanotechnology and sensor design, which significantly enhance the sensitivity and selectivity of these detection systems. Moreover, this review identifies current challenges and discusses future research directions. Our aim is to encourage ongoing research and innovation in this field, ultimately leading to the development of advanced, practical solutions for formaldehyde detection in various environmental and biological contexts.

A ternary nucleotide-lanthanide coordination nanoprobe for ratiometric fluorescence detection of ciprofloxacin.

Ciprofloxacin (CIP) is a widely used broad-spectrum antibiotic and has been associated with various side effects, making its accurate detection crucial for patient safety, drug quality compliance, and environmental and food safety. This study presents the development of a ternary nucleotide-lanthanide coordination nanoprobe, GMP-Tb-BDC (GMP: guanosine 5'-monophosphate, BDC: 2-amino-1,4-benzenedicarboxylic acid), for the sensitive and ratiometric detection of CIP. The GMP-Tb-BDC nanoprobe was constructed by incorporating the blue-emissive ligand BDC into the Tb/GMP coordination polymers. Upon the addition of CIP, the fluorescence of terbium ion (Tb3+ ) was significantly enhanced due to the coordination and fluorescence sensitization properties of CIP, while the emission of the BDC ligand remained unchanged. The nanoprobe demonstrated good linearity in the concentration range of 0-10 µM CIP. By leveraging mobile phone software to analyze the color signals, rapid on-site analysis of CIP was achieved. Furthermore, the nanoprobe exhibited accurate analysis of CIP in actual drug and milk samples. This study showcases the potential of the GMP-Tb-BDC nanoprobe for practical applications in CIP detection.

Advancements in Biosensors Based on the Assembles of Small Organic Molecules and Peptides.

Over the past few decades, molecular self-assembly has witnessed tremendous progress in a variety of biosensing and biomedical applications. In particular, self-assembled nanostructures of small organic molecules and peptides with intriguing characteristics (e.g., structure tailoring, facile processability, and excellent biocompatibility) have shown outstanding potential in the development of various biosensors. In this review, we introduced the unique properties of self-assembled nanostructures with small organic molecules and peptides for biosensing applications. We first discussed the applications of such nanostructures in electrochemical biosensors as electrode supports for enzymes and cells and as signal labels with a large number of electroactive units for signal amplification. Secondly, the utilization of fluorescent nanomaterials by self-assembled dyes or peptides was introduced. Thereinto, typical examples based on target-responsive aggregation-induced emission and decomposition-induced fluorescent enhancement were discussed. Finally, the applications of self-assembled nanomaterials in the colorimetric assays were summarized. We also briefly addressed the challenges and future prospects of biosensors based on self-assembled nanostructures.

Biosensors with Metal Ion-Phosphate Chelation Interaction for Molecular Recognition.

Biosensors show promising prospects in the assays of various targets due to their advantages of high sensitivity, good selectivity and rapid response. Molecular recognition is a key event of biosensors, which usually involves the interaction of antigen-antibody, aptamer-target, lectin-sugar, boronic acid-diol, metal chelation and DNA hybridization. Metal ions or complexes can specifically recognize phosphate groups in peptides or proteins, obviating the use of biorecognition elements. In this review, we summarized the design and applications of biosensors with metal ion-phosphate chelation interaction for molecular recognition. The sensing techniques include electrochemistry, fluorescence, colorimetry and so on.

Switch-on Fluorescence Analysis of Protease Activity with the Assistance of a Nickel Ion-Nitrilotriacetic Acid-Conjugated Magnetic Nanoparticle.

Heterogeneous protease biosensors show high sensitivity and selectivity but usually require the immobilization of peptide substrates on a solid interface. Such methods exhibit the disadvantages of complex immobilization steps and low enzymatic efficiency induced by steric hindrance. In this work, we proposed an immobilization-free strategy for protease detection with high simplicity, sensitivity and selectivity. Specifically, a single-labeled peptide with oligohistidine-tag (His-tag) was designed as the protease substrate, which can be captured by a nickel ion-nitrilotriacetic acid (Ni-NTA)-conjugated magnetic nanoparticle (MNP) through the coordination interaction between His-tag and Ni-NTA. When the peptide was digested by protease in a homogeneous solution, the signal-labeled segment was released from the substrate. The unreacted peptide substrates could be removed by Ni-NTA-MNP, and the released segments remained in solution to emit strong fluorescence. The method was used to determine protease of caspase-3 with a low detection limit (4 pg/mL). By changing the peptide sequence and signal reporters, the proposal could be used to develop novel homogeneous biosensors for the detection of other proteases.

A near-infrared ratiometric fluorescent probe for hydrazine and its application for gaseous sensing and cell imaging.

Hydrazine (N2H4) is a widely used raw material in the chemical industry, but at the same time hydrazine has extremely high toxicity. Therefore, the development of efficient detection methods is crucial for monitoring hydrazine in the environment and evaluating the biological toxicity of hydrazine. This study reports a near-infrared ratiometric fluorescent probe (DCPBCl2-Hz) for the detection of hydrazine by coupling a chlorine-substituted D-π-A fluorophore (DCPBCl2) to the recognition group acetyl. Due to the halogen effect of chlorine substitution, the fluorophore has an elevated fluorescence efficiency and a lowered pKa value and is suitable for physiological pH conditions. Hydrazine can specifically react with the acetyl group of the fluorescent probe to release the fluorophore DCPBCl2, so the fluorescence emission of the probe system significantly shifted from 490 nm to 660 nm. The fluorescent probe has many advantages, such as good selectivity, high sensitivity, large Stokes shift, and wide applicable pH range. The probe-loaded silica plates can realize convenient sensing gaseous hydrazine with content down to 1 ppm (mg/m3). Subsequently, DCPBCl2-Hz was successfully applied to detect hydrazine in soils. In addition, the probe can also penetrate living cells and allow the visualization of intracellular hydrazine. It can be anticipated that probe DCPBCl2-Hz will be a useful tool for sensing hydrazine in biological and environmental applications.

All-in-One Luminescent Lanthanide Coordination Polymer Nanoprobe for Facile Detection of Protein Kinase Activity.

This study developed a novel luminescent assay for kinase activity using metal-organic coordination polymer nanoparticles (Tb/ATP-Zn) as the probe. Tb/ATP-Zn, self-assembled by adenosine triphosphate (ATP), Zn2+, and Tb3+, is non-luminescent. Protein kinase A (PKA) can catalyze the transformation of ATP within Tb/ATP-Zn nanoparticles to adenosine diphosphate (ADP), which in turn effectively sensitizes the luminescence of Tb3+. Based on this mechanism, Tb/ATP-Zn can realize the facile luminescent "turn-on" sensing of protein kinase activity without the use of external ATP and substrate peptide. Under optimized conditions, the fluorescence intensities of Tb/ATP-Zn at 550 nm are linear with the PKA activity within a range of 0.3-1.5 U·µL-1. The LOD (S/N = 3) of this method is down to 0.001 U·µL-1. The presented assay also features high selectivity, long-term stability, fast response, and convenient operation. Furthermore, Tb/ATP-Zn was successfully employed for monitoring PKA activity in cell lysis solutions. Probe Tb/ATP-Zn is thus expectable to be a powerful tool for the practical study of PKA in relevant biological events.

Design and Synthesis of Dipeptidomimetic Isocyanonaphthalene as Enhanced-Fluorescent Chemodosimeter for Sensing Mercury Ion and Living Cells.

A novel valine-based isocyanonaphthalene (NpI) was designed and synthesized by using an easy method and enabled the selective fluorescence detection of Hg2+. The chemodosimeter can display an immediate turn-on fluorescence response (500-fold) towards target metal ions upon the Hg2+-mediated conversion of isocyano to amino within NpI. Based on this specific reaction, the fluorescence-enhancement probe revealed a high sensitivity toward Hg2+ over other common metal ions and exhibited excellent aqueous solubility, good antijamming capability, high sensitivity (detection limit: 14.2 nM), and real-time detection. The response mechanism of NpI was supported by NMR spectroscopy, MS analysis and DFT theoretical calculation using various techniques. Moreover, a dipeptidomimetic NpI probe was successfully applied to visualize intracellular Hg2+ in living cells and monitor Hg2+ in real water samples with good recoveries and small relative standard deviations.

Target-Induced In Situ Formation of Organic Photosensitizer: A New Strategy for Photoelectrochemical Sensing.

Small-molecule photosensitizers have great application prospects in photoelectrochemical (PEC) sensing due to their defined composition, diversified structure, and adjustable photophysical properties. Herein, we propose a new strategy for PEC analysis based on the target-induced in situ formation of the organic photosensitizer. Taking thiophenol (PhSH) as a model analyte, we designed and synthesized a 2,4-dinitrophenyl (DNP)-caged coumarin precursor (Dye-PhSH), which was then covalently coupled onto the TiO2 nanoarray substrate to obtain the working photoanode. Due to the intramolecular photoinduced electron transfer process, Dye-PhSH has only a very weak photoelectric response. Upon reacting with the target, Dye-PhSH undergoes a tandem reaction of the detachment of the DNP moiety and the intramolecular cyclization process, which leads to a coumarin dye with a pronounced photoelectric effect, thus achieving a highly selective turn-on PEC response to PhSH. For the first time, this study was to construct a PEC sensor by exploiting specific organic reactions for the in situ generation of small molecule-based photoactive material. It can be anticipated that the proposed strategy will expand the paradigm of PEC sensing and holds great potential for detecting various other analytes.

Two phenanthroimidazole turn-on probes for the rapid detection of selenocysteine and its application in living cells imaging.

Detection of selenocysteine (Sec) content in cells by fluorescence probe is of great significance for the identification of human related diseases. To achieve fast and sensitive detection of Sec, two isomers A4 and B4 as turn-on fluorescent probes to detect Sec were designed and synthesized. Both A4 and B4 display fast turn-on response, high selectivity and sensitivity toward Sec, which can be applied for fluorescence imaging of Sec in living cells. Compared with B4, A4 has a larger Stokes shift (125 nm), wider pH range (5-10) and lower detection limit (65.4 nM) due to its ESIPT (excited state intramolecular proton transfer) effect. In view of the detection performance of these two probes, they can be used as effective tools for detecting Sec in biological systems.

Progress in Nanomaterials-Based Optical and Electrochemical Methods for the Assays of Exosomes.

Exosomes with diameters of 30-150 nm are small membrane-bound vesicles secreted by a variety of cells. They play an important role in many biological processes, such as tumor-related immune response and intercellular signal transduction. Exosomes have been considered as emerging and noninvasive biomarkers for cancer diagnosis. Recently, a large number of optical and electrochemical biosensors have been proposed for sensitive detection of exosomes. To meet the increasing demands for ultrasensitive detection, nanomaterials have been integrated with various techniques as powerful components. Because of their intrinsic merits of biological compatibility, excellent physicochemical features and unique catalytic ability, nanomaterials have significantly improved the analytical performances of exosome biosensors. In this review, we summarized the recent progress in nanomaterials-based biosensors for the detection of cancer-derived exosomes, including fluorescence, colorimetry, surface plasmon resonance spectroscopy, surface enhanced Raman scattering spectroscopy, electrochemistry, electrochemiluminescence and so on.

Electrochemical detection of kinase by converting homogeneous analysis into heterogeneous assay through avidin-biotin interaction.

In the classical heterogeneous electrochemical assay, phosphorylation of peptide substrate is usually performed on the solid-liquid surface. However, immobilization of probe on the solid surface may limit the interaction between the reaction site of probe and the active center of kinase due to the steric hindrance effect. In this work, we proposed a heterogeneous electrochemical method for kinase detection, in which the probe is immobilization-free during the phosphorylation reaction. A biotinylated peptide was used as the kinase substrate. After phosphorylation, the biotinylated phosphopeptide was captured by the neutravidin (NA)-modified electrode through the avidin-biotin interaction. The phosphate groups on the electrode surface were then recognized by the conjugates preformed between biotinylated Phos-tag™ (Bio-tag-Phos) and ferrocene (Fc)-capped NA-modified gold nanoparticle (Fc-AuNP-NA). The method integrates the advantages of homogeneous reaction and heterogeneous detection with high simplicity, sensitivity and specificity. The strategy can be applied to design other heterogeneous biosensors without the immobilization of probe during the enzyme catalyzed reaction.

Electrochemical Immunosensors with PQQ-Decorated Carbon Nanotubes as Signal Labels for Electrocatalytic Oxidation of Tris(2-carboxyethyl)phosphine.

Nanocatalysts are a promising alternative to natural enzymes as the signal labels of electrochemical biosensors. However, the surface modification of nanocatalysts and sensor electrodes with recognition elements and blockers may form a barrier to direct electron transfer, thus limiting the application of nanocatalysts in electrochemical immunoassays. Electron mediators can accelerate the electron transfer between nanocatalysts and electrodes. Nevertheless, it is hard to simultaneously achieve fast electron exchange between nanocatalysts and redox mediators as well as substrates. This work presents a scheme for the design of electrochemical immunosensors with nanocatalysts as signal labels, in which pyrroloquinoline quinone (PQQ) is the redox-active center of the nanocatalyst. PQQ was decorated on the surface of carbon nanotubes to catalyze the electrochemical oxidation of tris(2-carboxyethyl)phosphine (TCEP) with ferrocenylmethanol (FcM) as the electron mediator. With prostate-specific antigen (PSA) as the model analyte, the detection limit of the sandwich-type immunosensor was found to be 5 pg/mL. The keys to success for this scheme are the slow chemical reaction between TCEP and ferricinum ions, and the high turnover frequency between ferricinum ions, PQQ. and TCEP. This work should be valuable for designing of novel nanolabels and nanocatalytic schemes for electrochemical biosensors.

Photodynamic Therapy of Cancers With Internal Light Sources: Chemiluminescence, Bioluminescence, and Cerenkov Radiation.

Photodynamic therapy (PDT) is a promising and minimally invasive modality for the treatment of cancers. The use of a self-illuminating system as a light source provides an intriguing solution to the light penetration issues of conventional PDT, which have gained considerable research interest in the past few years. This mini review aimed to present an overview of self-illuminating PDT systems by using internal light sources (chemiluminescence, bioluminescence, and Cerenkov radiation) and to give a brief discussion on the current challenges and future perspectives.

Dual-Response Ratiometric Electrochemical Microsensor for Effective Simultaneous Monitoring of Hypochlorous Acid and Ascorbic Acid in Human Body Fluids.

Redox homeostasis between hypochlorous acid (HClO/ClO-) and ascorbic acid (AA) significantly impacts many physiological and pathological processes. Herein, we report a new electrochemical sensor for the simultaneous determination of HClO and AA in body fluids. We first coated a carbon fiber microelectrode (CFME) with a three-dimensional nanocomposite consisting of graphene oxide (GO) and carbon nanotubes (CNTs) to fabricate the CFME/GO-CNT electrode. After the electrochemical reduction of GO (ERGO), we integrated a latent 1-(3,7-bis(dimethylamino)-10H-phenothiazin-10-yl)-2-methylpropan-1-one (MBS) electrochemical molecular recognition probe to monitor HClO and employed anthraquinone (AQ) as an internal reference. The compact CFME/ERGO-CNT/AQ + MBS sensor enabled the accurate and simultaneous measurement of HClO and AA with excellent selectivity and sensitivity. Measurements were highly reproducible, and the sensor was stable and exceptionally biocompatible. We successfully detected changes in the redox cycles of HClO and AA in human body fluids. This sensor is a significant advance for the investigation of reactions involved in cellular redox regulation. More importantly, we have devised a strategy for the design and construction of ratiometric electrochemical biosensors for the simultaneous determination of various bioactive species.

"Turn-on" ratiometric electrochemical detection of H2O2 in one drop of whole blood sample via a novel microelectrode sensor.

Oxidative stress plays an important role in the pathogenesis of many diseases, while the exact mechanism that hydrogen peroxide (H2O2) as one of the most abundant reactive oxygen species (ROS) exerts its influence on oxidative stress remains unclear. We developed a novel turn-on ratiometric electrochemical sensor for the detection of H2O2 in blood samples. The electrochemical probe 5-(1,2-dithiolan-3-yl)-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pent-anamide (BA) was designed and synthesized for the selective detection of H2O2 via a one-step amide reaction. Meanwhile, Nile Blue A (NB) was optimized as an internal reference molecule, thus enabling accurate quantification of H2O2 in a complex environment. BA and NB were then co-assembled onto a carbon fiber microelectrode (CFME) coated with Au cones. The oxidation peak current ratio between BA and NB demonstrated good linearity with the logarithm of the H2O2 concentration values ranging from 0.5 µM to 400 µM with a low detection limit of 0.02 µM. The developed sensor showed remarkable selectivity against potential interferences in whole blood samples, especially for ascorbic acid, uric acid, and dopamine. In combination with the unique characteristics of CFME, such as a small size and good biocompatibility, the microsensor was used for rapid analysis of one drop of whole blood sample. This sensor not only creates a new platform for the detection of H2O2 in whole blood samples, but also provides a new design strategy of other ROS analysis for early diagnosis of ROS-related diseases, drug discovery processes, and pathological mechanisms.

A dicyanoisophorone-based highly sensitive and selective near-infrared fluorescent probe for sensing thiophenol in water samples and living cells.

Thiophenol (PhSH) is an important sulfhydryl compound in organic synthesis, but it is also a volatile environmental pollutant with high toxicity to organisms. Herein, we reported a novel near-infrared (NIR) probe (1) for turn-on fluorescence detection of PhSH. The probe was prepared by coupling 2,4-dinitrophenyl (DNP) to a dicyanoisophorone-based fluorophore (2). PhSH can specifically perform a nucleophilic aromatic substitution on probe 1 and result in the release of fluorophore 2, thus achieving a turn-on fluorescence response (λem = 693 nm). A dramatic color change from red (λabs = 525 nm) to blue (λabs = 668 nm) was also observed. This fluorescent assay displayed a large Stokes shift (∼133 nm) and a high sensitivity for PhSH, as well as a low detection limit (34 nM). Moreover, probe 1 was successfully applied to monitor PhSH in real water samples and image PhSH in living cells.

A benzothiazole-based ratiometric fluorescent probe for detection of formaldehyde and its applications for bioimaging.

We presented a new benzothiazole-based fluorescent probe for ratiometric sensing of formaldehyde. Upon treatment with formaldehyde, the alkylamine-functionalized probe can be converted to its aldehyde analogue via the target-mediated 2-aza-Cope rearrangement, which led to significant shifts in both absorption (from 392 to 452 nm) and emission (from 492 to 552 nm) bands. The sensing mechanism was confirmed by HPLC, UV/Vis and fluorescence spectroscopy. The probe is capable of sensing formaldehyde under physiological conditions with high selectivity over potentially competing biological analytes. The probe also displayed sensitive ratiometric fluorescence response (up to 35.7 fold) for formaldehyde with a low limit detection of 0.58 µM. Furthermore, the probe was successfully employed for ratiometric imaging of formaldehyde in living cells as well as in zebrafish.

Phenothiazine-based fluorescence probe for ratiometric imaging of hydrazine in living cells with remarkable Stokes shift.

By modifying the 10-butyl-2-methoxy-10H-phenothiazine-3-carbaldehyde with malonontrile group, a new fluorescent sensor PBM for selective detection of hydrazine in ratiometric mode has been developed. Probe PBM owned the advantages of quick response (10 min), remarkable Stokes shift (168 nm for PBM, 161 nm for PBM-NH2), excellent selectivity, high sensitivity (detection limit of 63.2 nM was obtained from in vitro experiment), profound ratiometric change (82-fold) and low cytotoxicity in response to hydrazine. Additionally, it could be utilized to monitor hydrazine in gas state with various concentrations through vivid color changes and imaged hydrazine in living MCF-7 cells with excellent performance.

Recent Progress in the Development of Fluorescent Probes for Thiophenol.

Thiophenol (PhSH) belongs to a class of highly reactive and toxic aromatic thiols with widespread applications in the chemical industry for preparing pesticides, polymers, and pharmaceuticals. In this review, we comprehensively summarize recent progress in the development of fluorescent probes for detecting and imaging PhSH. These probes are classified according to recognition moieties and are detailed on the basis of their structures and sensing performances. In addition, prospects for future research are also discussed.