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Background: Gold nanoclusters (AuNCs) obtained by electroreduction have excellent electrochemiluminescence (ECL) properties, and its ECL intensity is regulated by the valence state. In addition, their ECL signals can be rapidly quenched by reactive oxygen species (ROS). Based on this observation, a sensitive ROS biosensor was designed based on valence regulation of AuNCs. Excessive ROS in seminal plasma can lead to male infertility, and the short half-life and instability of ROS pose a challenge for their detection. Since valence regulation can be done quickly and is very sensitive, this ECL biosensor holds promise to address this issue., Results: The ECL mechanism of AuNCs and the quenching mechanism of AuNCs by ROS were explored, mainly because ROS change the valence state of AuNCs. The ECL signals of the biosensor have a linear relationship with logarithm of the target concentration in the range of 1.0 × 10 -8 to 1.0 × 10 -3  M and 1.0 × 10 -3 to 1.0 × 10 -1  M, with a detection limit of 0.75 × 10 -10  M (S/N = 3). The biosensor enables rapid one-step detection of ROS and has the advantage of being stable and reusable. More notably, the results of 57 real samples showed that the biosensor can be used to accurately assess the concentration of seminal plasma ROS, guiding the monitoring of sperm quality and the diagnosis of male infertility., Significance: Compared with the traditional strategy of applying AuNCs only as a luminescent body, this strategy of regulating the valence state of AuNCs to achieve sensitive and rapid detection broadens the application of AuNCs in the field of analysis. Compared with other ROS detection strategies, the one-step immediate detection method effectively avoids the inaccuracy caused by the short half-life and natural dissipation of ROS, and is expected to improve the accuracy and efficiency of clinical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Diabetic retinopathy (DR), a chronic and progressive microvascular complication of diabetes mellitus, substantially threatens vision and is a leading cause of blindness among working-age individuals worldwide. Traditional diagnostic methods, such as ophthalmoscopy and fluorescein angiography are nonquantitative, invasive, and time consuming. Analysis of protein biomarkers in tear fluid offers noninvasive insights into ocular and systemic health, aiding in early DR detection. This study introduces a surface acoustic wave (SAW) microchip that rapidly enhances fluorescence in bead-based immunoassays for the sensitive and noninvasive DR detection from human tear samples., Results: The device facilitated particle mixing for immunoassay formation and particle concentration in the droplet, resulting in an enhanced immunofluorescence signal. This detachable SAW microchip allows the disposal of the cover glass after every use, thereby improving the reusability of the interdigital transducer and minimizing potential cross-contamination. A preliminary clinical test was conducted on a cohort of 10 volunteers, including DR patients and healthy individuals. The results demonstrated strong agreement with ELISA studies, validating the high accuracy rate of the SAW microchip., Significance: This comprehensive study offers significant insights into the potential application of a novel SAW microchip for the early detection of DR in individuals with diabetes. By utilizing protein biomarkers found in tear fluid, the device facilitates noninvasive, rapid, and sensitive detection, potentially revolutionizing DR diagnostics and improving patient outcomes through timely intervention and management of this vision-threatening condition., Competing Interests: Declaration of competing interest Authors hereby declare that this article is original, unpublished, and is not being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We have also duly acknowledged all the funding agencies. Thus, the authors declare no conflict of interest. The corresponding author will be the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions, and final approval of proofs., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Diabetes is a significant health threat, with its prevalence and burden increasing worldwide indicating its challenge for global healthcare management. To decrease the disease severity, the diabetic patients are recommended to regularly check their blood glucose levels. The conventional finger-pricking test possesses some drawbacks, including painfulness and infection risk. Nowadays, smartphone has become a part of our lives offering an important benefit in self-health monitoring. Thus, non-invasive wearable sweat glucose sensor connected with a smartphone readout is of interest for real-time glucose detection., Results: Wearable sweat glucose sensing device is fabricated for self-monitoring of diabetes. This device is designed as a body strap consisting of a sensing strip and a portable potentiostat connected with a smartphone readout via Bluetooth. The sensing strip is modified by carbon nanotubes (CNTs)-cellulose nanofibers (CNFs), followed by electrodeposition of Prussian blue. To preserve the activity of glucose oxidase (GOx) immobilized on the modified sensing strip, chitosan is coated on the top layer of the electrode strip. Herein, machine learning is implemented to correlate between the electrochemical results and the nanomaterial content along with deposition cycle of prussian blue, which provide the highest current response signal. The optimized regression models provide an insight, establishing a robust framework for design of high-performance glucose sensor., Significance: This wearable glucose sensing device connected with a smartphone readout offers a user-friendly platform for real-time sweat glucose monitoring. This device provides a linear range of 0.1-1.5 mM with a detection limit of 0.1 mM that is sufficient enough for distinguishing between normal and diabetes patient with a cut-off level of 0.3 mM. This platform might be an alternative tool for improving health management for diabetes patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Understanding the binding affinities and kinetics of protein-ligand interactions using a label-free method is crucial for identifying therapeutic candidates in clinical diagnostics and drug development. In this work, the IGZO-TFT (thin-film transistor) biosensor integrated with a tailored microfluidic chip was developed to explore binding kinetics of protein-ligand biochemical interactions in the real-time manner. The IGZO-TFT sensor extracts the binding characteristics through sensing biomolecules by their electrical charges. Using lysozyme and tri-N-acetyl-D-glucosamine (NAG 3 ) as an example, we established a procedure to obtain the parameters, such as the dissociation constant, K d , and association rate constant, k a , that are critical to biochemical reactions. The correlation between the lysozyme concentration and TFT drain current signal was first constructed. Next, solutions of lysozyme and NAG 3 of different mixing ratios were prepared. They were pre-mixed for various periods of reaction time before applying to the TFT sensor to extract signals of lysozyme molecules and the concentration remaining. With the knowledge of drain current changes at different reaction times, k a and K d can be obtained. The values from our experiment are comparable to other methods, which suggests the proposed approach can be employed to explore protein-ligand interaction kinetics in the massively parallel manner if the TFT array is considered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Developing a real-time, portable, and inexpensive sensor for pathogenic bacteria is crucial since the conventional detection approaches such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) assays are high cost, time-consuming, and require an expert operator. Here we present a portable, inexpensive, and convenient impedance-based biosensor using Interdigitated Electrode (IDE) arrays to detect Escherichia coli (E. coli) as a model to demonstrate the feasibility of an impedance-based biosensor. We manipulated the affinity of the IDE array towards E. coli (E. coli BL21 series) by functionalizing the IDEs' surface with an E. coli outer membrane protein (OMP) Ag1 Aptamer. To determine the dominant factors affecting the sensitivity and the performance of the biosensor in detecting E. coli, we investigated the roles of the substrate material used in the fabrication of the IDE, the concentration of the aptamer, and the composition of the carboxy aliphatic thiol mixture used in the pre-treatment of the IDE surface. In the sensing experiments we used an E. coli concentration range of 25-1000 cfu mL -1 and confirmed the binding of the OMP Ag1 Aptamer to the outer membrane protein of the E. coli by Field Emission Scanning Electron Microscopy (FESEM), Optical Microscopy, and Atomic Force Microscopy (AFM). By tuning the surface chemistry, the IDEs' substrate material, and the concentration of the OMP Ag1 Aptamer, our sensor could detect E. coli with the analytical sensitivity of approximately 1.8 Ohm/cfu and limit of detection of 9 cfu mL -1 . We found that the molecular composition of the self-assembled monolayer (SAM) formed on the top of the IDEs before the attachment of the OMP Ag1 Aptamer significantly impacted the sensitivity of the sensor. Notably, with straightforward changes to the molecular recognition elements, this platform device can be used to detect a wide range of other microorganisms and chemicals relevant for environmental monitoring and public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A novel fluorescence sensing strategy for ultrasensitive and highly specific detection of adenosine triphosphate (ATP) has been developed by the combination of the proximity ligation assay with bidirectional enzymatic repairing amplification (BERA). The strategy relies on proximity binding-triggered the release of palindromic tail that initiates bidirectional cyclic enzymatic repairing amplification reaction with the aid of polymerase and two DNA repairing enzymes, uracil-DNA glycosylase (UDG) and endonuclease IV (Endo IV). A fluorescence-quenched hairpin probe with a palindromic tail at the 3' end is skillfully designed that functions as not only the recognition element, primer, and polymerization template for BERA but also the indicator for fluorescence signal output. On the basis of the amplification strategy, this biosensor displays excellent sensitivity and selectivity for ATP detection with an outstanding detection limit of 0.81 pM. Through simultaneously enhancing the target response signal value and reducing nonspecific background, this work deducted the background effect, and showed high sensitivity and reproducibility. Moreover, our biosensor also shows promising potential in real sample analysis. Therefore, the proximity-enabled BERA strategy indeed creates a simple and valuable fluorescence sensing platform for ATP identification and related disease diagnosis and biomedical research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hydrazone chemistry has been firstly explored as capturing mode for interface supported toehold strand displacement cascade (TSDC). The method has been further established for analysis of 5-hydroxymethylfurfural (HMF) based on hydrazone chemistry-mediated TSDC. HMF containing aldehyde group can be covalently captured by hydrazine group around magnetic bead through the formation of hydrazone bond, so as to inhibit the immobilization of hybrid duplex and the occurrence of TSDC. Thereby, HMF will cause the change of the fluorescence of modified magnetic bead. With simplicity, specificity, and sensitivity, the method has been successfully applied to analyze HMF in food samples. This paper gives a new insight to explore capturing mode for interface supported TSDC and the established method can be extended for analysis of saccharic derivatives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Paper-based microfluidic device was designed with wax-printing to combine potentiometric, fluorimetric and colorimetric detection zones. This newly developed trimodal paper chip has been used for on-site determination of ketamine hydrochloride (KET) as a date rape drug in beverages. The device employed polyaniline nano-dispersion as conducting polymer in ion sensing paper electrodes designed to fit USB plug connector. Carbon dots-gold nanoparticles and cobalt thiocyanate were used in fluorescence and color detection zones, respectively. Cellular phone's camera facilitated the on-site fluorimetric and color detection. The implemented trimodal detection system exhibited specificity for KET detection in the presence of several other beverage interferences i.e., biogenic amines. This innovative sensor brings together analytical figures of merit for effective KET detection in single aliquot of spiked beverages. The proposed paper-based chip also fulfils WHO criteria for point-of-care devices posing the proposed trimodal paper device as an active part for rapid, on-site drug diagnostics and to be applied further for other similar drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Inspired by the rapid progress and existing limitations in surface plasmon resonance (SPR) biosensing technology, we have summarized the recent trends in the fields of both chip-SPR and fiber optic (FO)-SPR biosensors during the past five years, primarily regarding smart layers design, multiplexing, continuous monitoring and in vivo sensing. Versatile surface chemistries, biomaterials and nanomaterials have been utilized thus far to generate smart layers on SPR platforms and as such achieve oriented immobilization of bioreceptors, improved fouling resistance and sensitivity enhancement, collectively aiming to improve the biosensing performance. Furthermore, often driven by the desires for time- and cost-effective quantification of multiple targets in a single measurement, efforts have been made to implement multiplex bioassays on SPR platforms. While this aspect largely remains difficult to attain, numerous alternative strategies arose for obtaining parallel analysis of multiple analytes in one single device. Additionally, one of the upcoming challenges in this field will be to succeed in using SPR platforms for continuous measurements and in vivo sensing, and as such match up other biosensing platforms where these goals have been already conquered. Overall, this review will give insight into multiple possibilities that have become available over the years for boosting the performance of SPR biosensors. However, because combining them all into one optimal sensor is practically not feasible, the final application needs to be considered while designing an SPR biosensor, as this will determine the requirements of the bioassay and will thus help in selecting the essential elements from the recent progress made in SPR sensing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Jeroen Lammertyn is a board member of FOx Biosystems, a spin-off company of KU Leuven commercializing FO-SPR platforms, next to the principal investigator of the Biosensors group., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We report on the synthesis of manganese oxide doped CDs (MnO x -CDs) by a hydrothermal strategy using manganese (III) acetylacetonate (Mn(III) (C 5 H 7 O 2 ) 3 ) as the only raw materials. The MnO x -CDs exhibit water solubility, favorable biocompatibility, low cytotoxicity, and show blue fluorescence with excitation/emission maxima at 326/442 nm with a quantum yield of 11.3%, allowing efficient cellular imaging. The MnO x -CDs have a reversible temperature-sensitive fluorescent property in vitro within 10-60 °C, which can also be used as a sensitive thermometer in living cells. By a scratch assay, the MnO x -CDs can restrain the migration of HepG2 cancer cells, which make the MnO x -CDs be attractive candidates for liver cancer adjuvant treatment. Besides, the fluorescence of the MnO x -CDs is quenched in the presence of Fe 3+ due to the formation of a nonfluorescent MnO x -CDs-Fe 3+ complex between oxygen-containing groups on the surface of MnO x -CDs and Fe 3+ , and the quenched fluorescence of MnO x -CDs can be turn-on by dissociation of MnO x -CDs-Fe 3+ complexes by biothiols including L-cysteine, homocysteine and glutathione. Therefore, the Fe 3+ and biothiols can be sequentially detected with high reliability and accuracy via exploiting the on-off-on nanosensor at room temperature, respectively. Further application to detection biothiols in human serum indicated that the probe was practicality and feasibility in medical field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Abnormal concentration of adenosine triphosphate (ATP) is directly asscociate with several diseases. Thus, sensitive detection of ATP is essential to early diagnosis of disease. Herein, we described an ultrasensitive strategy for ATP detection by using positively charged gold nanorods ((+)AuNRs) as an efficient fluorescence quenching platform, coupled with exonuclease Ⅲ (Exo Ⅲ) assisted target recycling amplification. To construct the sensor, DNA template that contained ATP aptamer was used for the formation of Ag nanoclusters signal probe (DNA/AgNCs), the structure of it could change to duplex after the interaction of it with ATP. Such DNA template or duplex DNA product could electrostatically adsorb onto (+)AuNRs surface, resulting in the quenching of the fluorescence signal due to the vicinity of AgNCs to (+)AuNRs. With the addition of Exo Ⅲ, DNA duplex could be hydrolyzed and released from (+)AuNRs surface, leading to the recovery of a strong fluorescent signal, while ATP could be regenerated for next target recycling. Combing the good fluorescence quenching ability of (+)AuNRs and the Exo Ⅲ assisted signal amplification, a low detection limit of 26 pM was achieved for ATP detection. Notably, the proposed method can be successfully applied for detecting ATP in serum samples, indicating a potential application value in early cancer diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This work presents a novel development that exploits the concept of in-situ gas-separation together with a specific enzymatic colorimetric detection to produce a portable biosensor called "Blood Alcohol Micro-pad" for direct quantitation of ethanol in whole blood. The thin square device (25 mm × 25 mm × 1.8 mm) comprises two layers of patterned filter paper held together with a double-sided mounting tape with an 8-mm circular hole (the headspace). In operation, the reagent is deposited on one layer and covered with sticky tape. Then 8 μL of a blood sample is dispensed onto the opposite layer and covered with sticky tape. Diffusion of ethanol across the 1.6 mm narrow headspace permits selective detection of ethanol by the enzymatic reagents deposited on the opposite layer. This reagent zone contains alcohol oxidase, horseradish peroxidase and 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, as the chromogenic reagent. The color intensity, measured from the recorded digital image, resulting from the enzymatic assay of ethanol, correlates with the concentration of blood alcohol. The results obtained with spiked mice and sheep blood samples, using an external calibration in the range of 1-120 mg dL -1 ethanol, gave recoveries of 93.2-104.4% (n = 12). The "Blood Alcohol Micro-pad" gave good precision with %RSD <1 (50 mg dL -1 ethanol, n = 10) and limit of quantification (10SD of intercept/slope) of 11.56 mg dL -1 . The method was successfully validated against a headspace gas chromatography-mass spectrometric method. It has good potential for development as a simple and convenient blood alcohol sensor for on-site testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This work details the usage of EFIRM® (Electric Field Induced Release and Measurement) for PCR-free rapid electrochemical detection of mitochondrial DNA. EFIRM® was able to perform highly sensitive detection of animal species for meat contamination testing without multistep sample lysis, DNA extraction, or PCR amplification steps, demonstrating the capability to detect the presence of foreign meat species that only constituted 0.1% of the total mass of a food sample (achieving sensitivity equivalent to that of PCR). The EFIRM® strategy utilizes surface immobilized nucleic acid probes that complement to mitochondrial sequence of Ovis Aries, Sus Scrofa, and Bos Taurus and are immobilized in a polypyrrole matrix on a 96-electrode array. Quantification was performed through amperometric measurement of oxidation-reduction reactions on a streptavidin-peroxidase enzyme chain that completes the nucleic acid complex. All electrochemical procedures were performed using a high-throughput potentiostat system that allows parallelized electrochemical measurement and interfacing to the 96-electrode array., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Many authors (MT, MW, XS, MD, RH, YC, XL, WL) of this work were employed by EZLife Bio during the scope of this research project. Wei Liao is founder/CEO of EZLife Bio Inc and owns equity in EZLife Bio Inc. Michael Tu owns equity in EZLife Bio Inc. Work performed in this study was funded by EZLife Bio Inc., (Copyright © 2019. Published by Elsevier B.V.)

A near-infrared (NIR) photothermal immunoassay was designed for the sensitive monitoring of CA 19-9 on the capture antibody-coated microplate, coupling a 3D-printed device with a digital thermometer in this work. Prussian blue nanoparticles (PBNPs)-encapsulated CaCO 3 microspheres were not only utilized for labeling of detection antibody, but used as the photo-heat conversion materials for the signal amplification. With the sandwiched immunocomplex, the as-released PBNPs under acidic conditions adsorbed and converted NIR-light wavelength to heat under 808-nm laser irradiation, thereby resulting in the temperature change of the detection solution. Under optimum conditions, a linear range from 1.0 U mL -1 to 100 U mL -1 and a detection limit of 0.83 U mL -1 were acquired for the CA 19-9 detection on the portable photothermal immunosensing platform with PBNP-CaCO 3 -labeling system. Relative standard deviations for reproducibility were ≤9.7% for intra-assay and ≤11.9% for inter-assay. High specificity, long-time storage stability (>10 months) and good accuracy (relative to gold standard with commercial human ELISA kit) with the photothermal immunoassay were encountered for the evaluation of target CA 19-9 in complex system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this paper, horseradish peroxidase (HRP) was successfully immobilized on heated Au disk electrode (HAuDE) by biotin-streptavidin specific interaction through HS-ssDNA-biotin self-assembled on HAuDE for investigation the electrocatalytic activity of HRP. With elevated electrode temperature, the significant temperature effect of the electrocatalytic activity of HRP for H 2 O 2 reduction was demonstrated by using this bio-sensing platform. With an electrode temperature of 40 °C, a detection limit of 1.5 × 10 -6  mol L -1 for H 2 O 2 reduction could be obtained, which was more than one magnitude lower than that with an electrode temperature of 0 °C. Because HRP can be widely used as an enzyme label for amplification detection, this sensing platform can be broadly applied to analytical chemistry such as nucleic acid detection, and aptamer-based biosensors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We report a microfluidic immunosensor for the electrochemical determination of IgG antibodies anti-Toxocara canis (IgG anti-T. canis). In order to improve the selectivity and sensitivity of the sensor, core-shell gold-ferric oxide nanoparticles (AuNPs@Fe 3 O 4 ), and ordered mesoporous carbon (CMK-8) in chitosan (CH) were used. IgG anti-T. canis antibodies detection was carried out using a non-competitive immunoassay, in which excretory secretory antigens from T. canis second-stage larvae (TES) were covalently immobilized on AuNPs@Fe 3 O 4 . CMK-8-CH and AuNPs@Fe 3 O 4 were characterized by transmission electron microscopy, scanning electron microscopy, energy dispersive spectrometry, cyclic voltammetry, electrochemical impedance spectroscopy, and N 2 adsorption-desorption isotherms. Antibodies present in serum samples immunologically reacted with TES, and then were quantified by using a second antibody labeled with horseradish peroxidase (HRP-anti-IgG). HRP catalyzes the reduction from H 2 O 2 to H 2 O with the subsequent oxidation of catechol (H2Q) to p-benzoquinone (Q). The enzymatic product was detected electrochemically at &#95; 100 mV on a modified sputtered gold electrode. The detection limit was 0.10 ng mL -1 , and the coefficients of intra- and inter-assay variation were less than 6%, with a total assay time of 20 min. As can be seen, the electrochemical immunosensor is a useful tool for in situ IgG antibodies anti-T. canis determination., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A novel 3D paper-based microfluidic screen-printed electrode (SPE) composed of two layers was constructed by photolithography and screen-printing technology. Aldehyde functionalized hydrophilic zone of the counter and reference electrodes layer was prepared for glucose oxidase immobilization. Highly conductive prussian blue deposited reduced graphene oxide-tetraethylene pentamine (rGO-TEPA/PB) modified paper working electrode layer can be used as an electrochemical sensitive membrane for quantitative detection of hydrogen peroxide (H 2 O 2 ), which was the enzyme-catalyzed reaction product. Therefore, this 3D paper-based microfluidic electrochemical biosensor can be used for quantitative detection of glucose. Under optimum conditions, the proposed biosensor can be used for quantitative determination of glucose over a wide linear range of 0.1 mM-25 mM with detection limit of 25 μM. Finally, the 3D paper-based microfluidic electrochemical biosensor was applied to determine glucose in human sweat and blood, and the obtained results were in good consistency with values measured by Roche's blood glucose meter. In addition, the proposed 3D paper-based electrochemical device showed good repeatability, stability, and anti-interference, which would be of great potential to monitor glucose in complex biological fluids., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hemoglobin A1c (HbA1c) is a standard biomarker to measure long-term average glucose concentration for diagnosis and monitoring of diabetes. Various methods have been reported for measuring HbA1c, however, portable and precise determination is still challenging. Herein, a new highly sensitive electrochemical nanobiosensor is developed for the specific determination of HbA1c. A nanocomposite of reduced graphene oxide (rGO) and gold with hierarchical architecture structure was electrochemically deposited on a cheap and flexible graphite sheet (GS) electrode. The nanocomposite increased the surface area, improved the electron transfer on the electrode surface and augmented the signal. It also provided a suitable substrate for linkage of thiolated DNA aptamer as a bioreceptor on the electrode surface by strong covalent bonding. The quantitative label free detection was carried out by differential pulse voltammetry (DPV) in a phosphate-buffered saline (PBS) solution containing redox probe Fe(CN) 6 3-/4- . The detection is based on insulating the surface in presence of HbA1c and decreasing the current, which is directly related to the HbA1c concentration. The nanobiosensor demonstrated high sensitivity of 269.2 μA. cm -2 , wide linear range of 1 nM-13.83 μM with a low detection limit of 1 nM. The biosensor was successfully used for measuring HbA1c in blood real sample. Furthermore, it is promising to use it as a part of a point of care device for low-invasive screening and management of diabetes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We synthesized three kinds of nitrogen-doped nanoporous carbon nanomaterials (represented by N-mC) through a cost-effective method, that is, pyrolysis of plant biomasses (grass, flower, and peanut shells). We further explored their potential as sensitive bioplatforms for electrochemical label-free aptasensors to facilitate the early detection of alpha-fetoprotein (AFP). Chemical structure characterizations revealed that rich functional groups coexisted in as-synthesized N-mC nanomaterials, such as C-C, C-O, C=O, C-N, and COOH. Among the three kinds of N-mC nanomaterials, the one derived from grass (N-mC g ) exhibited the lowest carbon defect degree, the highest I D /I G ratio in the Raman spectra, and the largest specific surface area (186.2 m 2  g -1 ). Consequently, N-mC g displayed excellent electrochemical activity and strong affinity toward aptamer strands, further endowing the corresponding aptasensor with sensitive detection ability for AFP. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were used to investigate the whole detection procedure for AFP. The EIS and DPV results showed that the fabricated N-mC g -based aptasensor possessed an extremely low limit of detection of 60.8 and 61.8 fg·mL -1 (s/n = 3), respectively, for detecting AFP within a wide linear range from 0.1 pg mL -1 to 100 ng mL -1 . Moreover, the aptasensor displayed acceptable selectivity and applicability, high reproducibility, and excellent stability in serum samples of cancer patients. Therefore, the proposed cost-effective and label-free strategy based on the nitrogen-doped nanoporous carbon derived from plant biomass is a promising approach for the early detection of various tumor markers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Sarcosine is a recently identified biomarker for prostate cancer. However, the rapid detection methods for sarcosine are relatively lack because of the low concentration and the presence of complicated interfering substances in serum or urine. In this manuscript, hollow nanospheres of Fe 3 O 4 was synthesized and used as carrier to disperse Pt (Pt) nanoparticles. In order to achieve excellent electron transfer ability, we use polyaniline to coat Pt-Fe 3 O 4 nanoparticles, and pyrolyze the polyaniline to carbon (C). Thus, hollow magnetic Pt-Fe 3 O 4 @C nanocomposites with good electron transfer ability are formed. The Pt-Fe 3 O 4 @C nanocomposites have high catalytic activity and stability. The nanocomposites were immobilized on glassy carbon electrode (GCE) to construct a nonenzyme hydrogen peroxide (H 2 O 2 ) sensor (Pt-Fe 3 O 4 @C/GCE). We further construct a sensitive sarcosine biosensor by immobilizing sarcosine oxidase (SOx) on the Pt-Fe 3 O 4 @C/GCE. The high catalytic activity and good biocompatibility of Pt-Fe 3 O 4 @C nanocomposites greatly retained the bioactivity of immobilized SOx, and the prepared sarcosine biosensor has good electrocatalytic performance towards sarcosine. It has a linear detection range between 0.5 and 60 μM with a limit of detection (LOD) of 0.43 μM (the signal to noise ratio is 3), and the sensitivity is 3.45 nA μM -1 (48.8 nA μM -1  cm -2 ), which has the potential to be used for rapid screening of prostate cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Sepsis is a condition characterized by a severe stage of blood-infection often leading to tissue damage, organ failure and finally death. Fast diagnosis and identification of the sepsis stage (sepsis, severe sepsis or septic shock) is critical for the patient's evolution and could help in defining the most adequate treatment in order to reduce its mortality. The combined detection of several biomarkers in a timely, specific and simultaneous way could ensure a more accurate diagnosis. We have designed a new optical point-of-care (POC) device based on a phase-sensitive interferometric biosensor with a label-free microarray configuration for potential high-throughput evaluation of specific sepsis biomarkers. The sensor chip, which relies on the use of metallic nanostructures, provides versatility in terms of biofunctionalization, allowing the efficient immobilization of different kind of receptors such as antibodies or oligonucleotides. We have focused on two structurally different types of biomarkers: proteins, including C-reactive protein (CRP) and Interleukin 6 (IL6), and miRNAs, using miRNA-16 as an example. Limits of Detection (LoD) of 18 μg mL -1 , 88 μg mL -1 and 1 μM (6 μg mL -1 ) have been respectively obtained for CRP, IL6 and miRNA-16 in individual assays, with high accuracy and reproducibility. The multiplexing capabilities have also been assessed with the simultaneous analysis of both protein biomarkers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this work, an implantable and minimally invasive micro-aptasensor for adenosine monitoring in vivo, based on flexible integrated electrodes, was developed. Firstly the sensor was made by the modification of a needle-type electrode with reduced graphene oxide and gold nanoclusters (rGO-AuNCs) using two-step electrodeposition. Secondly Sulfhydryl-terminated capture probe (ssDNA1) was immobilized on rGO-AuNCs modified electrode surface by self-assembly, and then it was hybridized with adenosine aptamer (ssDNA2). Lastly methylene blue (MB) as an electrochemical indicator was adsorbed on the aptamer through specific interaction of MB with guanine base. The peak current of MB decreased linearly with increasing adenosine concentration due to the formation of aptamer-adenosine complex and displacement of the aptamer from the modified electrode surface. The sensor showed a low detection limit of 0.1 nM with signal-to-noise ratio equal to 3 as well as a wide linear response range (0.1 nM-1 mM) in vitro. Also, a high selectivity was demonstrated for adenosine in relation to uridine, guanosine, and cytidine. Experiments in vivo demonstrated fast responses for a range of adenosine concentrations. This work demonstrates a promising path for implantable devices for the determination of biomolecules in vivo, thus allowing for health tests, detection of infectious diseases, and other medical conditions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Antioxidants are important to protect and maintain biological barriers, such as the skin. Antioxidant effects are often assessed using clinical trials, however these tests are costly and time consuming. In this work we introduce a skin membrane-covered oxygen electrode (SCOE) as an in vitro tool for monitoring H 2 O 2 and antioxidant reactions in skin. The SCOE gives amperometric response to H 2 O 2 concentrations down to 0.05 mM. More importantly, the electrode allows measurements of polyphenol penetration and reaction with H 2 O 2 in skin. Measurements with SCOE show that lipophilic polyphenols such as quercetin, piceatannol, resveratrol, and plant extract from Plantago major impose their antioxidant effect in skin within 2-20 min. Rutin is however too hydrophilic to penetrate into stratum corneum and therefore cannot deliver its antioxidant effect during similar time interval. The measurements are interpreted considering polyphenol partition-penetration through stratum corneum and the reaction with the H 2 O 2 -catalase system in the skin. The contribution of other enzymes will be addressed in the future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Quantitatively paper-based senor is performed with simple distance-readout on mixed cellulose ester (MCE) filter paper based on acetylcholinesterase (AChE)-mediated alginate hydrogel. The method is accomplished with the aid of the inhibition effect of target samples on the AChE enzyme-catalyzed hydrolysis of acetylcholine, which changes the pH value of the solution to release Ca 2+ and trigger alginate hydrogelation. The viscosity of the solution is thus regulated with the presence of target samples in the reaction mixture, leading to a significant change in the diffusion diameter of the solution spotted on the filter paper. The concentration in the sample is quantitatively determined by ruler-measureable diffusion diameter of the spot on the paper. With successfully application for quantitatively sensing of organophosphorus pesticides (OPs), we show that the method exhibits excellent reproducibility with RSD (n = 5) as low as 0.09% and good selectivity for detection of OPs. The dynamic range of the method is up to 66.7 ng/mL with the limit-of-detection (LOD) of 3.3 ng/mL. The present study provides a new approach for developing paper-based sensors with quantitative distance-readout, by utilizing enzymatic inhibition to modulate liquid viscosity, which would be of value for target detection in complex samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, a simple paper-based aptasensor has been developed for the ultrasensitive detection of lead (Pb 2+ ) ion within about 10 min. The aptasensor has been successfully designed by taking advantages of the Förster Resonance Energy Transfer (FRET) process and the super fluorescence quenching property of graphene oxide (GO) sheet. The sensing mechanism of the aptasensor is based on the conformational switch of the Pb 2+ -specific aptamer from a random coil to a G-quadruplex structure. An injection of Pb 2+ on the paper-based platform induces the release of the specific aptamer from the GO surface that recovers the fluorescence emission. Under the optimal experimental conditions, there is a good linear relationship between the fluorescence recovery and the Pb 2+ concentration in the ranges of 5-70 pM and 0.07-20 nM. Moreover, the aptasensing array exhibits a high sensitivity to Pb 2+ with an ultra-low detection limit of 0.5 pM. The developed aptasensor has been successfully applied to determine Pb 2+ in tap water, lake water, milk, and human blood serum. The paper-based aptasensor can be efficiently utilized to detect other metal ions and biological molecules by substituting target specific aptamer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Paper based biosensor devices have the benefit of easy-use, low-cost and environmental friendly for point-of-care diagnostic application. In this research, we report a novel form of paper based biosensor with hierarchical assembled nanomaterials and MOF enhanced bio-probes for the simultaneous detection of microRNA-141 (miR-141) and microRNA-21 (miR-21) which have the potential for early cancer detection. The combination of multi-dimensional nanomaterial allows low impedance and high sensing area on typical poorly defined paper substrate. MOF conjugated bio-probe, methylene blue (MB) and ferrocene (Fc) with distinguishable electrochemical signal, further contributed to the high selectivity and sensitivity. Simultaneously detection of miR-141 and miR-21 with a detection limit of 0.1 fM was demonstrated under optimal conditions. All these features enable accurately target detection in serum samples. Therefore, this strategy is of promising as an inexpensive, easy access diagnosis platform for cancers by means of simultaneously detection of a variety of miRNA biomarkers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We report results of the studies relating to the fabrication of a label-free, flexible, light weight and disposable conducting paper based immunosensing platform comprising of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) and nanostructured iron oxide (nFe 2 O 3 @PEDOT:PSS) nanocomposite for detection of carcinoembryonic antigen (CEA), a cancer biomarker. The effect of various solvents such as sorbitol, ethanol, propanol, n-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO) on the electrical conductivity of Whatman filter paper (WP) modified with nFe 2 O 3 @PEDOT:PSS/WP was investigated. The electrical conductivity of the PEDOT:PSS/WP electrode was found to be enhanced by two orders of magnitude (from 6.8× 10 -4 to 1.92 × 10 -2 Scm -1 ) after its treatment with DMSO. Further, nFe 2 O 3 doped PEDOT:PSS/WP electrode exhibited the electrical conductivity as 2.4 × 10 -2 Scm -1 . Besides this, the incorporation of iron oxide nanoparticles (nFe 2 O 3 ) into PEDOT:PSS/WP resulted in improved electrochemical performance and signal stability. This nFe 2 O 3 @PEDOT:PSS/WP based platform was used for immobilization of the anti-carcinoembronic antigen (anti-CEA) protein for quantitative estimation of cancer biomarker (CEA). The results of electrochemical response studies revealed that this conducting paper based immunoelectrode had a sensitivity of 10.2 μAng -1 mLcm -2 in the physiological range (4-25 ngmL -1 ) and shelf life of 34 days. Further, the proposed immunoelectrode was validated with conventional ELISA for the detection of CEA in serum samples of cancer patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A microfluidic system that incorporates both dendrimers and aptamers to detect E. coli O157:H7 is developed. To achieve this, generation 7-polyamidoamine dendrimers were immobilized onto the detection surfaces of PDMS microfluidic channels; subsequently aptamers against E. coli O157:H7 were conjugated onto the microchannel surfaces via the immobilized dendrimers as templates. Surface modifications were characterized by FTIR, XPS, water contact angles, fluorescence microscopy and AFM to confirm the success of each surface modification steps. The efficacy of this simple microchannel in detection was investigated using E. coli O157:H7 spiked samples. Our results showed that this interesting approach significantly increased the amount of aptamers available on the microfluidic channel surfaces to capture E. coli O157:H7 cells to allow sensitive detection, which in turn resulted in detections of E. coli O157:H7 cells at a low limit of detection of 10 2  cells mL -1 . The results also demonstrated that in comparison with the generation 4-polyamidoamine dendrimers (G4) modified microchannels, those modified with G7 showed enhanced detection signals, improved target capturing efficiencies, and at higher throughput. This simple whole cell detection design has not been reported in the literature and it is an interesting and effective approach to developing a sensitive and rapid detection platform for foodborne pathogenic bacteria., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Accurate and facile differentiation of cell types is essential for accurate diagnosis and therapy of diseases. However, it remains challenging due to low specificity, requirement of sophisticated instruments, and tedious operation steps. Herein, a simple, washing- and label-free chemical tongue was constructed for differentiation of cell types. In the array-based sensing platform, DNA-ligand ensembles adsorbed on the surface of MnO 2 nanosheets were used as sensing probes. Instead of aptamers from cell-SELEX, the randomly designed DNA strands were used, offering versatile interactions with cells. The property that MnO 2 nanosheets can be degraded by intracellular glutathione makes the platform avoid the washing step. Eight types of cell lines were distinguished from each other after the data were treated with principal component analysis (PCA). In addition, a 95% of identification accuracy for the randomly selected unknown samples was achieved. The strategy shows an excellent performance not only in distinguishing cell lines but also in the identification of unknown cell samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ratiometric sensing suffers from less interference and can obtain more accurate results than single-signal assay. Here, a new ratiometric optical sensing strategy for H 2 O 2 detection is developed by etching silver nanoparticles (AgNPs) to deactivate fluorescence resonance energy transfer (FRET) and reduce Rayleigh scattering based on a hyphenated technique of fluorescence and second-order Rayleigh scattering (SRS). The ratiometric detection of H 2 O 2 is achieved through exploiting a hybrid system fabricated by fluorescent carbon dots and silver nanoparticles (CDs/AgNPs). In the CDs/AgNPs system, the fluorescence of CDs is quenched because of FRET, and the scattering is strong due to the intrinsic high light-scattering power of AgNPs. With the introduction of H 2 O 2 , the AgNPs are etched and the CDs are released from the AgNP surface, resulting in the fluorescence enhancement and scattering decline. As a result, ratiometric sensing of H 2 O 2 can be achieved based on the CDs/AgNPs system by simultaneous collection of fluorescence and SRS signals. The sensing system is further used for H 2 O 2 -generation bioanalysis, and as a proof-of-concept, ratiometric assay of glucose and evaluation of glucose oxidase activity are performed successfully. This work provides a new perspective for sensing applications of plasmonic nanoparticles., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Herein, a novel electrochemical biosensor for sensitive analysis of prostate specific antigen (PSA) is demonstrated. A specific peptide is employed on the gold electrode as a molecular recognition element for target induced cleavage. In the absence of PSA, graphene oxide (GO) is directly immobilized on the peptide modified electrode, which triggers the aggregation of silver ions and subsequent reduction reaction to form silver nanoparticles (AgNPs). Well defined sharp silver stripping peak can thus be achieved, which stands for a highly characteristic solid-state Ag/AgCl reaction. However, in the presence of PSA, the peptide is specifically recognized and cleaved. The resulted product on the electrode surface cannot aid the immobilization of GO and subsequent formation of AgNPs. Therefore, electrochemical response is decreased remarkably, which can be used to indicate the concentration of PSA. This work demonstrates that the combination of the transduction of peptide cleavage event with GO/AgNPs nanocomposites is a promising attempt for PSA analysis with high sensitivity and selectivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study introduces a new strategy for periodic stacking of positively charged NiAl layered double hydroxides (LDHs) nanosheets with negatively charged monolayers of graphene (G) by systematically optimizing several parameters in a controlled co-feeding fashion and resultant heterostacked NiAl LDH/G LBL nanocomposites have been practically applied in sensitive detection of dopamine released from live cells as early Parkinson's disease (PD) diagnostic tool. PD is the second most chronic neurodegenerative disorder with gradual progressive loss of movement and muscle control causing substantial disability and threatening the life seriously. Unfortunately majority of dopaminergic neurons present in substantia nigra of PD patients are destroyed before it is being clinically diagnosed, so early stages PD diagnosis is essential. Because of direct neighboring of extremely conductive graphene to semiconductive LDHs layers, enhanced intercalation capability of LDHs, and huge surface area with numerous active sites, good synergy effect is harvested in heteroassembled NiAl LDH/G LBL material, which in turn shows admirable electrocatalytic ability in DA detection. The interference induced by UA and AA is effectively eliminated especially after the modifying the electrode with Nafion. The outstanding electrochemical sensing performance of NiAl LDH/G LBL modified electrode has been achieved in terms of broad linear range and lowest real detection limit of 2 nM (S/N = 3) towards DA oxidation. Benefitting from superior efficiency, biosensor has been successfully used for real-time in-vitro tracking of DA efflux from live human nerve cell after being stimulated. We believe that our biosensing platform of structurally integrated well-ordered LBL heteroassembly by inserting graphene directly to the interlayer galleries of LDHs material will open up new avenue in diseases determination window., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, we constructed a new and sensitive ITO based electrochemical immunosensor for detection of interleukin 1β (IL-1β), a cancer biomarker found in serum and saliva. 6-phosphonohexanoic acid (PHA) was used as a biomolecule immobilization matrix for the first time. Anti-IL-1β antibody was utilized as a biorecognition molecule that immobilized onto carboxyl groups of 6-phosphohexanoic acid (PHA) via amide bond. Selective interaction between anti- IL-1β antibodies and IL-1β antigens was investigated by Electrochemical Impedance Spectroscopy (EIS), Cyclic Voltammetry (CV) and Single Frequency Impedance (SFI) methods. The surface characterization of the immunosensor was performed by fourier transform infrared spectroscopy (FTIR), raman spectroscopy, scanning electron microscopy (SEM), SEM-energy dispersive X-ray spectroscopy (EDX) and atomic force microscopy (AFM) in order to illustrate individual steps of biosensor construction. Under the optimized experimental conditions, the change in impedance was proportional to IL-1β concentrations in the range of 0.025-3 pg/mL (R 2  = 0.99) with detection limit of 7.5 fg/mL. The reproducibility, repeatability, stability, and specificity of the developed immunosensor were analyzed. In addition, the developed immunosensor was successfully utilized for the determination of IL-1β in serum and saliva samples by using the standard addition method with recoveries of 96.7-105.4%. This immunosensor was applicable for the requirements of routine analysis with respect to performance, functionality and cost., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Herein, a simple and efficient fluorescent assay for Ag + ions and l-cysteine (L-Cys) in complex biological fluids and living cells was first developed based on the fluorescent "on-off-on" mode of red emission nitrogen, boron, sulfur co-doped carbon dots (NBS-CDs). Red emission NBS-CDs were prepared via one-step hydrothermal synthesis by using 3-aminobenzeneboronic acid and 2,5-diaminobenzenesulfonic acid as precursors. Such NBS-CDs exhibited excellent optical properties and relatively high absolute fluorescent quantum yield compared with some reported NBS-CDs. Due to the strong quenching ability of Ag + ions on the fluorescence of NBS-CDs, red emission NBS-CDs were used for the determination of Ag + ions with high sensitivity and excellent selectivity. The fluorescence of NBS-CDs was recovered after the interaction between Ag + ions and L-Cys, which realized the specific determination of L-Cys in human urine samples and human plasma samples. The established NBS-CDs-based fluorescent "on-off-on" sensor offered a relatively low detection limits of 0.35 μM for Ag + ions and 0.045 μM for L-Cys based on three times signal-to-noise criteria. Notably, this strategy was applied for the visual detections of Ag + ions and L-Cys in living human cancer cells (HeLa cells and MCF-7 cells). This method is simple, high sensitive, and excellent selectivity, which provided a new insight on the potential applications of NBS-CDs to develop the biosensor in clinical diagnosis and other biologically related areas., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Here, a simple electrochemical biosensor was proposed based on the specific recognition between trypsin and peptide. Initially, NiCo 2 O 4 -PAMAM nanocomposite was casted on the bare electrode to achieve the electrochemical signal amplification in 0.1 mM [Ru(NH 3 ) 6 ] 3+ solution owing to the great electronic conductivity and high electrochemical activity induced by the special structure of NiCo 2 O 4 nanosheets (Ni 3+ cations in octachedral sites of the Co 3 O 4 ). Subsequently, a declined electrochemical signal was obtained when g-C 3 N 4 labeled peptide composites were anchored on the electrode. However, after trypsin was added into solution and incubated with the biosensor, the electrochemical signal was re-promoted. Therefore, the as-synthesized biosensor could realize the sensitive detection of trypsin by virtue of the specific recognition between trypsin and peptide. As a result, the developed peptide-based exhibited a linear range from 10 -10 to 10 -4  mg mL -1 with an ultralow detection limit of 10 -10  mg mL -1 , providing sensitive analytical performance and acceptable application potential in clinical test and disease diagnosis due to its high stability, excellent selectivity, acceptable reproducibility and accurate signal output., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We report herein a new dual-color fluorescent aptasensor for detection of tumor marker mucin 1 (MUC1) and targeted imaging of MCF-7 cancer cells based on the specific interaction between MUC1 and its aptamer S2.2. The aptasensor was prepared by covalent attachment of the cyanine (Cy5)-tagged aptamer S2.2 to fluorescent silicon nanodot (SiND). The fluorescence of S2.2-Cy5 could be quenched by the SiND carrier in the absence of MUC1, and its fluorescence was restored in the presence of MUC1 due to structure switching of S2.2. This aptasensor exhibits specificity for MUC1-possitive MCF-7 cells rather than MUC1-negative MCF-10A cells and Vero cells. The SiND plays multiple roles in this fluorescence assay, making the method easier compared with other approaches. The limit of detection and precision of this method for MUC1 was 1.52 nM and 3.6% (10 nM, n = 7), respectively. The linear range was 3.33-250 nM, and the recoveries in spiked human serum were in the range of 87-108%. This is a simple, selective, sensitive and reliable method, which can well achieve not only quantitative analysis of tumor marker but also dual-color visualization of single cancer cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sensitive and specific detection of protein is of great significance for early diagnosis and prognosis of many diseases. However, great challenges remain unsolved including relative low sensitivity, high cost, long testing time, complicated instrument and laborious operation. To improve the performance of protein detection methods, development of fine reaction interface for recognition and signal amplification is of great importance. In this work, we construct a novel mode of DNA assembly at electrode interface based on a tripodal surface anchor and an electrochemical aptasensor for protein assay is developed. The orientation of the immobilized DNA is optimized, which promises the efficiency of protein recognition. In addition, hybridization chain reaction is employed for further signal amplification. Therefore, this detection method shows high sensitivity with excellent specificity. The strategy can be universally applicable by simply modifying the sequences of used DNA probes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this work, glassy carbon electrode (GCE) surface was modified by drop-coating graphene oxide (GO) and nile blue (NB) to form GO/NB/GCE. By using a one-step coreduction treatment under cyclic voltammetry (CV) scanning, gold nanoparticles (AuNPs) were electrodeposited onto GO/NB/GCE surface, simultaneously generating reduced GO (rGO). AuNPs from the prepared rGO/NB/AuNPs/GCE was combined with 5'-SH-terminated aptamer of dopamine (DA) via Au-S coupling to fabricate aptamer-rGO/NB/AuNPs/GCE system. DA specifically combined with its aptamer modified on rGO/NB/AuNPs/GCE surface. CV, electrochemical impedance spectroscopy, square wave voltammetry responses of this system as the working electrode were measured. With the addition of DA, the peak current intensities located at -0.45 V (I NB ) and 0.15 V (I DA ) showed gradually decreased and increased changes, respectively. There was a good linear (R 2  = 0.9922) relationship between lg(I DA /I NB ) and the logarithm of DA concentration (lgC DA ) in the C DA range from 10 nM to 0.2 mM, showing a low detection limit of 1 nM. This system as a novel, sensitive and label-free aptasensor was used for ratiometric electrochemical sensing of DA. Experimental results verified that this aptasensor possessed high stability, selectivity and sensitivity towards DA detection, over potential interferents. This aptasensor efficiently determined DA in real biological samples, together with high detection recoveries of 97.0-104.0%., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Herein, we established a novel ultrasensitive photoelectrochemical biosensor for detecting urokinase-type plasminogen activator (u-PA), based on a g-C 3 N 4 /CdS nanocomposite. The prepared nanocomposite was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, ultraviolet-visible absorption spectroscopy, and Fourier transform infrared spectroscopy, thus indicating that the nanocomposite was prepared successfully. In the typical process, the prepared nanocomposite was deposited on the surface of a bare FTO electrode. After being air-dried, the g-C 3 N 4 /CdS nanocomposite modified electrode was successively incubated with antibody against urokinase-type plasminogen activator and the blocking agent BSA to produce a photoelectrochemical biosensor for u-PA. In the presence of target u-PA antigen, the photocurrent response of the prepared biosensor electrode decreased significantly. The proposed novel photoelectrochemical biosensor exhibited good sensitivity, specificity, and reproducibility for u-PA detection, and a low detection limit of 33 fg mL -1 , ranging from 1 μg mL -1 -0.1 pg mL -1 . The proposed strategy should provide a promising method for detection of other biomarkers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This paper presents a dual functional extracellular recording biosensor based on a light-addressable potentiometric sensor (LAPS). The design and fabrication of this biosensor make it possible to record both extracellular membrane potential changes and ATP release from a single taste bud cell for the first time. For detecting ATP release, LAPS chip was functionalized with ATP-sensitive DNA aptamer by covalent immobilization. Taste bud cells isolated from rat were cultured on LAPS surface. When the desired single taste bud cell was illuminated by modulated light, ATP release from single taste bud cells can be measured by recording the shifts of bias voltage-photocurrent curves (I-V curves) when the LAPS chip is working in discrete mode. On the other hand, extracellular membrane potential changes can be monitored by recording the fluctuation of LAPS photocurrent when the LAPS chip is working in continuous mode. The results show this biosensor can effectively record the enhancive effect of the bitter substance and inhibitory effect of the carbenoxolone (CBX) on the extracellular membrane potential changes and ATP release of single taste bud cells. In addition, the inhibitory effect of CBX also confirms LAPS extracellular recordings are originated from bitter signal transduction. It is proved this biosensor is suitable for extracellular recording of ATP release and membrane potential changes of single taste bud cells. It is suggested this biosensor could be applied to investigating taste signal transduction at the single-cell level as well as applied to other types of cells which have similar functions to taste bud cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aiming to overcome the obstacles of power supply requirement and chip usefulness in practice, a low-cost and convenient portable electrochemical sensing device is introduced for the first time, featuring bipolar electrode system, LED read-out, laminated paper-based devices, and low-voltage button cells. The electric circuits of this practical device are constructed on laminating films with copper and conductive carbon tapes, and the reservoirs facilitating chemical reactions are made with chromatography paper. The device is sensitive to electrochemical responses, validated by the demonstrative hydrogen peroxide and enzyme-assisted glucose detection. The business-card-size chip achieves sensitive analyte detection by naked eyes as well as further image processing in both laboratory samples and human serum samples testing, featuring detection limit as low as 1.79 μM and a dynamic range from 10 μM to 10 mM. This new practical design of point-of-care sensing chip entails the properties of facile fabrication, simple usage, high robustness, low power consumption, and accurate sensing showing the attainability of fabricating a useful and portable analytical device., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) have been recognized as messengers delivering various active molecules between cells. This feature of EVs drew the attention of clinicians as well as researchers from different fields. However, exciting ideas to employ EVs as means of drug delivery or to test them as biomarkers of cellular status require very thoughtful and attentive approaches to the selection of analytical techniques for EV characterization. Optical and surface plasmonic analytical methods offer a researcher an invaluable opportunity to use already sized and/or quantified EVs in further functional cell-based assays and in focused biochemical tests (nucleic acid and protein arrays, etc.). Moreover, a high sensitivity and relative flexibility of surface plasmonic sensors open a possibility to develop instruments performing quantitative, metrical and EV surface/content analysis in a single device. This review aims to consider the applicability of established and modern optical techniques as well as novel surface plasmonic approaches for different aspects of EV analysis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

DNA methyltransferase (MTase) plays an important role in many biological processes and has been recognized as a predictive cancer biomarker far before other signs of malignancy and a therapeutic target in cancer treatment. Thus simple and sensitive determination of DNA MTase activity is urgently required. The commercially available glucometer is considered as the most successful point-of-care (POC) sensor up to date, and researchers extend its application in monitoring different types of targets rather than only glucose. Here, we developed a simple strategy for the sensitive detection of the DNA MTase (using M.SssI as an example) activity by using a glucometer as the signal transducer. A S1/S2 hybrid probe was designed including a specific recognition sequence for both DNA MTase and restriction endonuclease, and a complementary sequence for biotin-S3. Firstly, the S1/S2 hybrid probe was self-assembled on the gold electrode and methylated by M.SssI MTase to form the methylated dsDNA. Then, HpaII endonuclease specifically cleaved the residue of the unmethylated dsDNA. Subsequently, biotin-S3 hybridized with the overhang sequence of the methylated dsDNA. Finally, the biotin tag was successively combined with streptavidin (STV) and biotin-invertase. The invertase efficiently catalyzed the hydrolysis of sucrose to generate abundant glucose, which led to an amplified response of glucometer. This strategy could detect DNA MTase activity as low as 0.3 U mL -1 with good selectivity against other two cytosine MTases (HaeIII MTase and AluI MTase), and be successfully applied for screening the DNA MTase inhibitors (5-azacytidine and 5-aza-2'-deoxycytidine), implying our proposed method holds great promising application in early cancer diagnosis and therapeutics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

For use in the voltammetric sensing of galactose-dependent proteins, we modified magnetic beads with a peptide that had both electroactive- and molecular recognition properties. The peptide consisted of a YXY sequence and behaved as an electron-transfer carbohydrate-mimetic peptide that would combine with proteins. With this tool, the protein could be detected via a label-free system. We synthesized several penta- and hexa-peptides with a cysteine residue on the C-terminals to examine the properties of peptides. These peptides contained amino acid residues (X) of alanine, serine, or tyrosine. The peptides were immobilized on magnetic beads via N-(8-maleimidocapryloxy) succinimide. Soybean agglutinin(SBA), the in vivo function of which has been well established in animals, was selected as a model protein. The protein was detected via the changes in electrode response due to the oxidation of tyrosine residues from the phenol group to quinone. As a result, SBA was selectively accumulated on the beads modified with YYYYC. The calibration curve of SBA was linear and ranged from 2.5 × 10 -12 to 1.0 × 10 -10  M. With this system, SBA was recovered in human serum at values that ranged from 98 to 103%. Furthermore, the beads with peptides were regenerated five times using a protein denaturant. Accordingly, this electrochemical system was simple and could be rapidly applied to the detection of galactose-recognition proteins., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The development of a novel flexible and ultrasensitive aptasensor based on carboxylated multiwalled carbon nanotubes (MWCNTs)/ reduced graphene oxide-based field effect transistor (FET) has been reported for label-free detection of the ovarian cancer antigen (CA125). The fabricated sensor has a straightforward design based on the noncovalent attachment of MWCNTs/aptamer conjugated onto few layers reduced graphene oxide nanosheets and its integration with poly-methyl methacrylate (PMMA) as a suitable platform for designing flexible field-effect transistors. The surface properties of the aptasensor were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). Under optimal conditions, the proposed aptasensor exhibited a wide linear dynamic range for CA125 (1.0 × 10 -9 -1.0 U/mL) with a low detection limit of 5.0 × 10 -10 U/mL. The proposed aptasensor was also successfully applied to detect CA125 in real human serum samples. Furthermore, sensor flexibility is also a challenging area in chemical and biological sensors, especially for portable, wearable, or even implantable sensors, so, the reduced graphene oxide-based FET-type aptasensor showed bendable flexibility on the PMMA substrate. In addition, the aptasensor exhibited high sensitivity, selectivity, stability and reproducibility which offers great promise as a high performance and flexible FET-type aptasensor to detect CA125 and other cancer biomarkers in clinical samples and biological fluids., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A biosensor for mouse Immunoglobulin G (IgG) was generated from responsive polymer-based interference filters (etalons). To accomplish this, an excess amount of alkaline phosphatase-modified goat anti-mouse IgG (AP-GAM, F(ab') 2 fragment specific to mouse IgG) was added to mouse IgG, and allowed to react for some time. After a given reaction time, the bound AP-GAM could be isolated from the unbound, excess AP-GAM by addition of goat anti-mouse IgG (Fc fragment specific)-modified magnetic microspheres (GAM-M) that bind the mouse IgG bound to AP-GAM. After application of a magnetic field, the free, unbound AP-GAM was isolated from the mixture and exposed to an etalon that has its upper Au surface modified with phosphate-containing polymer that can be degraded by AP-GAM. By the phosphate-containing polymer being degraded by the excess AP-GAM, the cleaved phosphate groups can diffuse into the interference filter's active polymer layer that yields a change in the optical properties that can be related to the amount of IgG in the sample. This concept is extremely straightforward to implement, and can be modified to detect a variety of other analytes of interest., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Theophylline is a common bronchodilator for the treatment of diseases like asthma, bronchitis and emphysema. However, it should be strictly used and monitored due to its toxicity when the concentration is above certain levels. In this work, an electrochemical biosensor for theophylline detection is proposed by recognition of RNA aptamer and gold nanoparticle (AuNP)-based amplification technique. First, RNA aptamer is splitted into two single-stranded RNA probes. One is hybridized with DNA tetrahedron and the resulted nanostructure is then immobilized onto a gold electrode; the other is modified on the surface of AuNPs which is also labeled with methylene blue (MB) as electrochemical species. The recognition process between the two RNA probes and theophylline causes the localization of AuNPs and the enrichment of MB on the electrode interface. A significant electrochemical response is thus generated which is related to the concentration of initial theophylline. This proposed aptasensor shows excellent sensitivity and selectivity which could also be applied in quantitatively detection of theophylline in serums samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Herein, we report the first example of a paper-based screen-printed biosensor for the detection of ethanol in beer samples. Common office paper was adopted to fabricate the analytical device. The properties of this paper-based screen-printed electrode (SPE) were investigated by cyclic voltammetry, electrochemical impedance spectroscopy, and scanning electron microscopy, and they were compared with the well-established polyester-based SPEs as well. Paper demonstrated similar properties when compared with polyester, highlighting suitability towards its utilization in sensor development, with the advantages of low cost and simple disposal by incineration. A nanocomposite formed by Carbon Black (CB) and Prussian Blue nanoparticles (PBNPs), namely CB/PBNPs, was utilized as an electrocatalyst to detect the hydrogen peroxide generated by the enzymatic reaction between alcohol oxidase (AOx) and ethanol. After optimizing the analytical parameters, such as pH, enzyme, concentration, and working potential, the developed biosensor allowed a facile quantification of ethanol up to 10 mM (0.058 % vol ), with a sensitivity of 9.13 μA/mM cm 2 (1574 μA/% vol cm 2 ) and a detection limit equal to 0.52 mM (0.003% vol ). These satisfactory performances rendered the realized paper-based biosensor reliable over the analysis of ethanol contained in four different types of beers, including Pilsner, Weiss, Lager, and alcohol-free. The proposed manufacturing approach offers an affordable and sustainable tool for food quality control and for the realization of different electrochemical sensors and biosensors as well., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A bioelectronic tongue based on nanostructured biosensors specific for the simultaneous detection of sugars and phenols has been developed. The array combined oxidases and dehydrogenases immobilized on a lipidic layer prepared using the Langmuir-Blodgett technique where Glucose oxidase, d-Fructose dehydrogenase, Tyrosinase or Laccase were imbibed. A phthalocyanine was co-immobilized in the sensing layer and used as electron mediator. The array thus formed has been used to analyze grapes and provides global information about the samples while providing specific information about their phenolic and their sugar content. Using Principal Component Analysis (PCA) the array of voltammetric biosensors has been successfully used to discriminate musts prepared from different varieties of grapes (Tempranillo, Garnacha, Cabernet-Sauvignon, Prieto Picudo and Mencía). Differences could be also detected between grapes of the same variety and cultivar harvested in two successive vintages (2012 and 2013). Moreover, the ripening of grapes could be monitored from veraison to maturity due to the changes in their phenolic and sugar content. Using Partial Least Squares (PLS-1) analysis, excellent correlations have been found between the responses provided by the array of biosensors and classical parameters directly related to phenols (total polyphenol index, TPI) and sugar concentration (degree Brix) measured by chemical methods with correlation coefficients close to 1 and errors close to 0. It is also worthy to notice the good correlations found with parameters associated with the pH and acidity that can be explained by taking into account the influence of the pH in the oxidation potentials of the phenols and in the enzymatic activity. This bioelectronic tongue can assess simultaneously the sugar and the phenolic content of grapes and could be used to monitor the maturity of the fruit and could be adapted easily to field analysis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ochratoxin A (OTA) is a carcinogenic mycotoxin that contaminates food such as cereals, wine and beer; therefore it represents a risk for human health. Consequently, the allowed concentration of OTA in food is regulated by governmental organizations and its detection is of major agronomical interest. In the current study we report the development of an electrochemical aptasensor able to directly detect trace OTA without any amplification procedure. This aptasensor was constructed by coating the surface of a gold electrode with a film layer of modified polypyrrole (PPy), which was thereafter covalently bound to polyamidoamine dendrimers of the fourth generation (PAMAM G4). Finally, DNA aptamers that specifically binds OTA were covalently bound to the PAMAM G4 providing the aptasensor, which was characterized by using both Atomic Force Microscopy (AFM) and Surface Plasmon Resonance (SPR) techniques. The study of OTA detection by the constructed electrochemical aptasensor was performed using Electrochemical Impedance Spectroscopy (EIS) and revealed that the presence of OTA led to the modification of the electrical properties of the PPy layer. These modifications could be assigned to conformational changes in the folding of the aptamers upon specific binding of OTA. The aptasensor had a dynamic range of up to 5 μg L(-1) of OTA and a detection limit of 2 ng L(-1) of OTA, which is below the OTA concentration allowed in food by the European regulations. The efficient detection of OTA by this electrochemical aptasensor provides an unforeseen platform that could be used for the detection of various small molecules through specific aptamer association., (Copyright © 2016 Elsevier B.V. All rights reserved.)