Carbon-Based Electrochemical (Bio)sensors for the Detection of Carbendazim: A Review.

Carbendazim, a fungicide widely used in agriculture, has been classified as a hazardous chemical by the World Health Organization due to its environmental persistence. It is prohibited in several countries; therefore, detecting it in food and environmental samples is highly necessary. A reliable, rapid, and low-cost method uses electrochemical sensors and biosensors, especially those modified with carbon-based materials with good analytical performance. In this review, we summarize the use of carbon-based electrochemical (bio)sensors for detecting carbendazim in environmental and food matrixes, with a particular interest in the role of carbon materials. Focus on publications between 2018 and 2023 that have been describing the use of carbon nanotubes, carbon nitride, graphene, and its derivatives, and carbon-based materials as modifiers, emphasizing the analytical performance obtained, such as linear range, detection limit, selectivity, and the matrix where the detection was applied.

Biosensing strategies for the detection of SARS-CoV-2 nucleic acids.

The COVID-19 pandemic had devastating effects throughout the world, producing a severe crisis in the health systems and in the economy of a long list of countries, even developed ones. Therefore, highly sensitive and selective analytical bioplatforms that allow the descentralized and fast detection of the severe acute respiratory síndrome coronavirus 2 (SARS-CoV-2), are extremely necessary. Since 2020, several reviews have been published, most of them focused on the different strategies to detect the SARS-CoV-2, either from RNA, viral proteins or host antibodies produced due to the presence of the virus. In this review, the most relevant biosensors for the detection of SARS-CoV-2 RNA are particularly addressed, with special emphasis on the discussion of the biorecognition layers and the different schemes for transducing the hybridization event.

In situ or Ex situ Synthesis for Electrochemical Detection of Hydrogen Peroxide-An Evaluation of Co2SnO4/RGO Nanohybrids.

Nowadays, there is no doubt about the high electrocatalytic efficiency that is obtained when using hybrid materials between carbonaceous nanomaterials and transition metal oxides. However, the method to prepare them may involve differences in the observed analytical responses, making it necessary to evaluate them for each new material. The goal of this work was to obtain for the first time Co2SnO4 (CSO)/RGO nanohybrids via in situ and ex situ methods and to evaluate their performance in the amperometric detection of hydrogen peroxide. The electroanalytical response was evaluated in NaOH pH 12 solution using detection potentials of -0.400 V or 0.300 V for the reduction or oxidation of H2O2. The results show that for CSO there were no differences between the nanohybrids either by oxidation or by reduction, unlike what we previously observed with cobalt titanate hybrids, in which the in situ nanohybrid clearly had the best performance. On the other hand, no influence in the study of interferents and more stable signals were obtained when the reduction mode was used. In conclusion, for detecting hydrogen peroxide, any of the nanohybrids studied, i.e., in situ or ex situ, are suitable to be used, and more efficiency is obtained using the reduction mode.

Two birds with one stone: integrating exfoliation and immunoaffinity properties in multi-walled carbon nanotubes by non-covalent functionalization with human immunoglobulin G.

An innovative strategy is proposed to simultaneously exfoliate multi-walled carbon nanotubes (MWCNTs) and generate MWCNTs with immunoaffinity properties. This strategy was based on the non-covalent functionalization of MWCNTs with human immunoglobulin G (IgG) by sonicating 2.5 mg mL-1 MWCNTs in 2.0 mg mL-1 IgG for 15 min with sonicator bath. Impedimetric experiments performed at glassy carbon electrodes (GCE) modified with the resulting MWCNT-IgG nanohybrid in the presence of anti-human immunoglobulin G antibody (Anti-IgG) demonstrated that the immunoglobulin retains their biorecognition properties even after the treatment during the MWCNT functionalization. We proposed, as proof-of-concept, two model electrochemical sensors, a voltammetric one for uric acid quantification by taking advantages of the exfoliated MWCNTs electroactivity (linear range, 5.0 × 10-7 M - 5.0 × 10-6 M; detection limit, 165 nM) and an impedimetric immunosensor for the detection of Anti-IgG through the use of the bioaffinity properties of the IgG present in the nanohybrid (linear range, 5-50 µg mL-1; detection limit, 2 µg mL-1).

Genosensing Applications of Glassy Carbon Electrodes Modified with Multi-Walled Carbon Nanotubes Non-Covalently Functionalized with Polyarginine.

We report the advantages of glassy carbon electrodes (GCE) modified with multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with polyarginine (PolyArg) for the adsorption and electrooxidation of different DNAs and the analytical applications of the resulting platform. The presence of the carbon nanostructures, and mainly the charge of the PolyArg that supports them, facilitates the adsorption of calf-thymus and salmon sperm double-stranded DNAs and produces an important decrease in the overvoltages for the oxidation of guanine and adenine residues and a significant enhancement in the associated currents. As a proof-of-concept of possible GCE/MWCNTs-PolyArg biosensing applications, we develop an impedimetric genosensor for the quantification of microRNA-21 at femtomolar levels, using GCE/MWCNTs-PolyArg as a platform for immobilizing the DNA probe, with a detection limit of 3fM, a sensitivity of 1.544 × 103 Ω M-1, and a successful application in enriched biological fluids.

Synergistic Effect of Composite Nickel Phosphide Nanoparticles and Carbon Fiber on the Enhancement of Salivary Enzyme-Free Glucose Sensing.

An electrospinning method was used for the preparation of an in situ composite based on Ni2P nanoparticles and carbon fiber (FC). The material was tested for the first time against direct glucose oxidation reaction. The Ni2P nanoparticles were distributed homogeneously throughout the carbon fibers with a composition determined by thermogravimetric analysis (TGA) of 40 wt% Ni2P and 60 wt% carbon fiber without impurities in the sample. The electrochemical measurement results indicate that the GCE/FC/Ni2P in situ sensor exhibits excellent catalytic activity compared to the GCE/Ni2P and GCE/FC/Ni2P ex situ electrodes. The GCE/FC/Ni2P in situ sensor presents a sensitivity of 1050 µAmM-1cm-2 in the range of 5-208 µM and a detection limit of 0.25 µM. The sensor was applied for glucose detection in artificial saliva, with a low interference observed from normally coexisting electroactive species. In conclusion, our sensor represents a novel and analytical competitive alternative for the development of non-enzymatic glucose sensors in the future.

Functionalization of Gold Nanostars with Cationic ß-Cyclodextrin-Based Polymer for Drug Co-Loading and SERS Monitoring.

Gold nanostars (AuNSs) exhibit modulated plasmon resonance and have a high SERS enhancement factor. However, their low colloidal stability limits their biomedical application as a nanomaterial. Cationic ß-cyclodextrin-based polymer (CCD/P) has low cytotoxicity, can load and transport drugs more efficiently than the corresponding monomeric form, and has an appropriate cationic group to stabilize gold nanoparticles. In this work, we functionalized AuNSs with CCD/P to load phenylethylamine (PhEA) and piperine (PIP) and evaluated SERS-based applications of the products. PhEA and PIP were included in the polymer and used to functionalize AuNSs, forming a new AuNS-CCD/P-PhEA-PIP nanosystem. The system was characterized by UV-VIS, IR, and NMR spectroscopy, TGA, SPR, DLS, zeta potential analysis, FE-SEM, and TEM. Additionally, Raman optical activity, SERS analysis and complementary theoretical studies were used for characterization. Minor adjustments increased the colloidal stability of AuNSs. The loading capacity of the CCD/P with PhEA-PIP was 95 ± 7%. The physicochemical parameters of the AuNS-CCD/P-PhEA-PIP system, such as size and Z potential, are suitable for potential biomedical applications Raman and SERS studies were used to monitor PhEA and PIP loading and their preferential orientation upon interaction with the surface of AuNSs. This unique nanomaterial could be used for simultaneous drug loading and SERS-based detection.

Label-Free Oligonucleotide-Based SPR Biosensor for the Detection of the Gene Mutation Causing Prothrombin-Related Thrombophilia.

Prothrombin-related thrombophilia is a genetic disorder produced by a substitution of a single DNA base pair, replacing guanine with adenine, and is detected mainly by polymerase chain reaction (PCR). A suitable alternative that could detect the single point mutation without requiring sample amplification is the surface plasmon resonance (SPR) technique. SPR biosensors are of great interest: they offer a platform to monitor biomolecular interactions, are highly selective, and enable rapid analysis in real time. Oligonucleotide-based SPR biosensors can be used to differentiate complementary sequences from partially complementary or noncomplementary strands. In this work, a glass chip covered with an ultrathin (50 nm) gold film was modified with oligonucleotide strands complementary to the mutated or normal (nonmutated) DNA responsible for prothrombin-related thrombophilia, forming two detection platforms called mutated thrombophilia (MT) biosensor and normal thrombophilia (NT) biosensor. The results show that the hybridization response is obtained in 30 min, label free and with high reproducibility. The sensitivity obtained in both systems was approximately 4 ΔµRIU/nM. The dissociation constant and limits of detection calculated were 12.2 nM and 20 pM (3 fmol), respectively, for the MT biosensor, and 8.5 nM and 30 pM (4.5 fmol) for the NT biosensor. The two biosensors selectively recognize their complementary strand (mutated or normal) in buffer solution. In addition, each platform can be reused up to 24 times when the surface is regenerated with HCl. This work contributes to the design of the first SPR biosensor for the detection of prothrombin-related thrombophilia based on oligonucleotides with single point mutations, label-free and without the need to apply an amplification method.

New trends in the development of electrochemical biosensors for the quantification of microRNAs.

MicroRNAs (miRNAs) are non-coding regulatory RNAs that play an important role in RNA silencing and post-transcriptional gene expression regulation. Since their dysregulation has been associated with Alzheimer disease, cardiovascular diseases and different types of cancer, among others, miRNAs can be used as biomarkers for early diagnosis and prognosis of these diseases. The methods commonly used to quantify miRNAs are, in general, complex, costly, with limited application for point-of-care devices or resource-limited facilities. Electrochemical biosensors, mainly those based on nanomaterials, have emerged as a promising alternative to the conventional miRNA detection methods and have paved the way to the development of sensitive, fast, and low-cost detection systems. This review is focused on the most relevant contributions performed in the field of electrochemical miRNAs biosensors between 2017 and the beginning of 2020. The main contribution of this article is the critical discussion of the different amplification strategies and the comparative analysis between amplified and non-amplified miRNA electrochemical biosensing and between the different amplification schemes. Particular emphasis was given to the importance of the nanostructures, enzymes, labelling molecules, and special sequences of nucleic acids or analogues on the organization of the different bioanalytical platforms, the transduction of the hybridization event and the generation the analytical signal.

Co2TiO4/Reduced Graphene Oxide Nanohybrids for Electrochemical Sensing Applications.

For the first time, the synthesis, characterization, and analytical application for hydrogen peroxide quantification of the hybrid materials of Co2TiO4 (CTO) and reduced graphene oxide (RGO) is reported, using in situ (CTO/RGO) and ex situ (CTO+RGO) preparations. This synthesis for obtaining nanostructured CTO is based on a one-step hydrothermal synthesis, with new precursors and low temperatures. The morphology, structure, and composition of the synthesized materials were examined using scanning electron microscopy, X-ray diffraction (XRD), neutron powder diffraction (NPD), and X-ray photoelectron spectroscopy (XPS). Rietveld refinements using neutron diffraction data were conducted to determine the cation distributions in CTO. Hybrid materials were also characterized by Brunauer-Emmett-Teller adsorption isotherms, Scanning Electron microscopy, and scanning electrochemical microscopy. From an analytical point of view, we evaluated the electrochemical reduction of hydrogen peroxide on glassy carbon electrodes modified with hybrid materials. The analytical detection of hydrogen peroxide using CTO/RGO showed 11 and 5 times greater sensitivity in the detection of hydrogen peroxide compared with that of pristine CTO and RGO, respectively, and a two-fold increase compared with that of the RGO+CTO modified electrode. These results demonstrate that there is a synergistic effect between CTO and RGO that is more significant when the hybrid is synthetized through in situ methodology.

Phytoestrogen coumestrol: Antioxidant capacity and its loading in albumin nanoparticles.

Coumestrol is a polyphenol with promising therapeutic applications as phytoestrogen, antioxidant and potential cancer chemoprevention agent. The presence of two hydroxyl groups on its chemical structure, with orientation analogous to estradiol, is responsible of both, its antioxidant capacity and its estrogenic activity. However, several studies show that the interaction of polyphenols with food and plasma proteins reduces their antioxidant efficacy. We studied the interaction of coumestrol with bovine serum albumin protein (BSA) by fluorescence spectroscopy and circular dichroism techniques, and the effect of this interaction on its antioxidant activity as a hydroxyl radical scavenger. In addition, coumestrol antioxidant capacity profile using different assays (DPPH, ORAC-FL and ORAC-EPR) was studied. To explain its reactivity we used several methodologies, including DFT calculations, to define its antioxidant mechanism. Coumestrol antioxidant activity unveiled interesting antioxidant properties. BSA interaction with coumestrol reduces significantly photolytic degradation in several media thus preserving its antioxidant properties. Results suggest no significant changes in BSA structure and activity when interacting with coumestrol. Furthermore, this interaction is stronger than for other phytoestrogens such as daidzein and genistein. Considering our promising results, we reported for the first time the fabrication and characterization of coumestrol-loaded albumin nanoparticles. The resulting spherical and homogeneous nanoparticles showed a diameter close to 96 nm. The coumestrol incorporation efficiency in BSA NPs was 22.4%, which is equivalent to 3 molecules of coumestrol for every 10 molecules of BSA.

Label-Free Graphene Oxide-Based Surface Plasmon Resonance Immunosensor for the Quantification of Galectin-3, a Novel Cardiac Biomarker.

We report the first optical biosensor for the novel and important cardiac biomarker, galectin-3 (Gal3), using the anti-Gal3 antibody as a biorecognition element and surface plasmon resonance (SPR) for transducing the bioaffinity event. The immunosensing platform was built at a thiolated Au surface modified by self-assembling four bilayers of poly(diallyldimethylammonium chloride) and graphene oxide (GO), followed by the covalent attachment of 3-aminephenylboronic acid (3ABA). The importance of GO, both as the anchoring point of the antibody and as a field enhancer for improving the biosensor sensitivity, was critically discussed. The advantages of using 3ABA to orientate the anti-Gal3 antibody through the selective link to the Fc region were also demonstrated. The new platform represents an interesting alternative for the label-free biosensing of Gal3 in the whole range of clinically relevant concentrations (linear range between 10.0 and 50.0 ng mL-1, detection limit of 2.0 ng mL-1) with successful application for Gal3 biosensing in enriched human serum samples.

Reduced Graphene Oxides: Influence of the Reduction Method on the Electrocatalytic Effect towards Nucleic Acid Oxidation.

For the first time a critical analysis of the influence that four different graphene oxide reduction methods have on the electrochemical properties of the resulting reduced graphene oxides (RGOs) is reported. Starting from the same graphene oxide, chemical (CRGO), hydrothermal (hTRGO), electrochemical (ERGO), and thermal (TRGO) reduced graphene oxide were produced. The materials were fully characterized and the topography and electroactivity of the resulting glassy carbon modified electrodes were also evaluated. An oligonucleotide molecule was used as a model of DNA electrochemical biosensing. The results allow for the conclusion that TRGO produced the RGOs with the best electrochemical performance for oligonucleotide electroanalysis. A clear shift in the guanine oxidation peak potential to lower values (~0.100 V) and an almost two-fold increase in the current intensity were observed compared with the other RGOs. The electrocatalytic effect has a multifactorial explanation because the TRGO was the material that presented a higher polydispersity and lower sheet size, thus exposing a larger quantity of defects to the electrode surface, which produces larger physical and electrochemical areas.

Organic and Inorganic Nanoparticles for Prevention and Diagnosis of Gastric Cancer.

Organic and inorganic nanoparticles show great potential for cancer diagnosis and treatment. Because gastric cancer (GC) represents the second most deadly type of neoplasia worldwide, continued research efforts by scientists and clinicians are essential to improve diagnosis and treatment. This paper reviews significant findings in the area of nanoparticles (organic and inorganic origin) that may aid in prevention and diagnosis of GC. This review focuses in the first section on H. pylori and the connection to GC, highlighting nanoformulations designed to control bacterial growth. The second section evaluates the potential of different imaging techniques (especially using inorganic nanoparticles) in the detection of GC, and the third section summarizes how nanotechnology may be employed in the analytical detection of GC biomarkers (metallic plasmons, electrochemical biosensors and colorimetric sensors). We foresee that the prevention and diagnosis of GC will require the development of complex collaborative studies. Additionally, scientists also need to be tightly connected to industry in order to facilitate upscaling and rapid transfer of promising products to the clinic.

Dispersion of bamboo type multi-wall carbon nanotubes in calf-thymus double stranded DNA.

We report for the first time the use of double stranded calf-thymus DNA (dsDNA) to successfully disperse bamboo-like multi-walled carbon nanotubes (bCNT). The dispersion and the modified electrodes were studied by different spectroscopic, microscopic and electrochemical techniques. The drastic treatment for dispersing the bCNT (45min sonication in a 50% (v/v) ethanol:water solution), produces a partial denaturation and a decrease in the length of dsDNA that facilitates the dispersion of CNT and makes possible an efficient electron transfer of guanine residues to the electrode. A critical analysis of the influence of different experimental conditions on the efficiency of the dispersion and on the performance of glassy carbon electrodes (GCE) modified with bCNT-dsDNA dispersion is also reported. The electron transfer of redox probes and guanine residues was more efficient at GCE modified with bCNT dispersed in dsDNA than at GCE modified with hollow CNT (hCNT) dispersed in dsDNA, demonstrating the importance of the presence of bCNT.

The effect of 5-substitution on the electrochemical behavior and antitubercular activity of PA-824.

Nitroimidazole PA-824 is part of an exciting new class of compounds currently undergoing clinical evaluation as novel TB therapeutics. The recently elucidated mechanism of action of PA-824 involves reduction of the nitroimidazole ring and subsequent nitric oxide release. The importance of this compound and its unique activity prompted us to explore how substitution of the nitroimidazole ring would affect electrochemical reduction and antitubercular activity. We prepared analogs of PA-824 with bromo, chloro, cyano, and amino substituents in the 5-position of the aromatic ring. We found that substitution of the imidazole ring greatly influences reduction and the stability of the corresponding nitro radical anion. Further, the antitubercular activities of the bromo and chloro analogs may indicate that an alternate nitroreductase pathway within Mycobacterium tuberculosis exists.

Stability and drug metabolism assessed by electrochemical methods.

This review is focused on the use of the electrochemical techniques, voltammetry and polarography, as well as biosensors, for the study of drug stability. In addition, this review also details the study of drug metabolism by electrochemistry and mass spectrometry. This is used as a tool to mimic drug metabolism and because it is a purely instrumental method, may have advantages over, or be complementary to, the existing biological assays.

Electrochemistry of interaction of 2-(2-nitrophenyl)-benzimidazole derivatives with DNA.

In this study the interaction between new benzimidazole molecules, 2-(2-nitrophenyl)-1H-benzimidazole (NB) and N-benzoyl-2-(2-nitrophenyl)-benzimidazole (BNB), with dsDNA and ssDNA was assessed at pH 7.4. Using differential pulse voltammetry at glassy carbon electrode, both molecules were electrochemically reduced due to the presence of a nitro group in their structures. When DNA was added to the solution, the electrochemical signal of NB and BNB decreased and shifted to more negative potentials. The interaction mode was electrostatic when ionic strength was low. Under this condition DNA-nitro complexes were characterized and binding constant values of 8.22 x 10(4)M(-1) and 3.08 x 10(6)M(-1) for NB and BNB with dsDNA were determined. On the other hand, only NB was able to interact when a high concentration of NaCl was used. Finally, a glassy carbon electrode modified with carbon nanotubes and DNA was tested in order to determine the nitrocompound in solution. The electrochemical reduction of the nitrocompound adsorbed on GCE/CHIT-CNT/DNA was used as an analytical signal. Using 10 min as accumulation time, a linear dependence was observed between 20 and 80 microM nitrocompound concentrations and the electrode response. Detection and quantification limits in the range of microM were determined.

Voltammetric behavior of zaleplon and its differential pulse polarographic determination in capsules.

In this work both the electrochemical behavior and the analysis of the hypnotic pyrazolopyrimidine derivative zaleplon were studied. Zaleplon in ethanol-0.1M Britton Robinson buffer solution (30-70) showed 2 irreversible, well-defined cathodic responses in the pH range of 2-12 using differential pulse polarography (DPP), tast polarography, and cyclic voltammetry. From chronocoulometric studies, it was possible to conclude that one electron was transferred in each reduction peak or wave. For analytical purposes, the DPP technique working at pH 4.5 for peak I was selected, which exhibited adequate repeatability, reproducibility, and selectivity. The recovery was 99.97 +/- 1.52%, and the detection and quantitation limits were 5.13 x 10(-7)M and 1.11 x 10(-6)M, respectively. The DPP method was applied successfully to the individual assay of capsules in order to verify the content uniformity of zaleplon. Treatment of the sample is not required because the excipients do not interfere, the method is not time consuming, and it is less expensive than column liquid chromatography.

Trypanosoma cruzi: effect and mode of action of nitroimidazole and nitrofuran derivatives.

With the aim of determining the actual target(s) of nitro-group bearing compounds considered as possible leads for the development of drugs against Chagas' disease, we studied in parallel nitrofurans and nitroimidazoles. We investigated nine representative compounds for the following properties: efficacy on different Trypanosoma cruzi strains, redox cyclers, inhibition of respiration, production of corresponding nitroso derivatives and intracellular thiol scavengers. Our results indicate that nifurtimox and related compounds act as redox cyclers, whereas the most active in the series, the 5-nitroimidazole megazol essentially acts as thiol scavenger particularly for trypanothione, the cofactor for trypanothione reductase, an essential enzyme in the detoxification process.