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Biosensors have tremendous revolutionary potential for the precise location and rapid detection of biomarkers for human disease. However, the minimization of nonspecific protein adsorption interactions and surface contamination is critical for their application in complex media. We report herein, the antifouling interface was constructed by electrochemical copolymerization of poly (3,4-ethylenedloxythlophene) (PEDOT) and glycyrrhiza polysaccharide (GPS). Hydrophilic PEDOT/GPS can reduce the interference and nonspecific adsorption of biological protein macromolecules, which has been verified by electrochemical and fluorescent characterization. Gold nanoparticles (AuNPs) were subsequently modified onto PEDOT/GPS surface to attach biomacromolecules containing thiol groups. MicroRNA, the promising biomarker of a large numbers of genetic diseases, was used as the testing model. Due to the robust antifouling capability of PEDOT/GPS as well as high biocompatibility of GPS/AuNPs, the fabricated biosensor based on PEDOT/GPS/AuNPs demonstrated excellent sensing performance, such as a wide detection range (0.01 nM–10 nM), a low detection limit (300 fM) and high reproducibility, showing great potential of medical applications.

Ultrasensitive and low-fouling microRNA electrochemical biosensors were successfully constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. For the three kinds of antifouling materials investigated, the newly designed and synthesized peptide exhibited superior antifouling ability to others, and it could effectively reduce the nonspecific adsorption of proteins and even prevent the fouling effect of serum. Compared with microRNA biosensors without antifouling capability, or those modified with polyethylene glycol or mercapto alcohol, the biosensor modified with the designed zwitterionic peptide showed the highest specificity for single-base mismatch, three-base mismatch, and completely complementary microRNAs. Most interestingly, the experimental results indicated that the introduction of antifouling molecules to the sensing interfaces did not significantly change the sensitivity of the biosensor. The strategy of constructing antifouling biosensors based on newly synthesized zwitterionic peptides and conducting polymers can be promisingly extended to the development of other electrochemical sensors and biosensors without encountering biofouling. Graphical abstract Ultrasensitive and low-fouling microRNA electrochemical biosensors were constructed by introducing thiol-terminated antifouling molecules (peptide sequence, polyethylene glycol, or mercapto alcohol) onto the surface of polyaniline-modified electrodes. The biosensor modified with the designed zwitterionic peptide showed the highest specificity amongst four kinds of biosensors.

A rapid, sensitive and low-fouling sensor for application to detect clinical biomarkers directly in biological media is highly desirable. Herein, we report a versatile strategy to prepare polyaniline (PANI) based conducting polymer hydrogel through the assembly of PANI and phytic acid (PA) by dynamic boronate bond. PANI/PA, a conductive hydrogel with high specific area and multiple pore structures have demonstrated excellent antifouling ability and electrochemical property. The electrochemical biosensors for microRNA can be developed by the immobilization of DNA probes onto PANI/PA interface (microRNA24 is used as a model case), and redox currents of PANI were utilized as the sensing signals to assay DNA/RNA hybridization reaction. Owing to the typical characteristics of PANI/PA hydrogel, the biosensor has shown excellent sensing performances with wide linear range (1.0 fM-1.0 pM), low sensing limit (0.34 fM) and efficient ability to detect microRNA mismatches. Given the facile processability, excellent stability and good antifouling property of the PANI/PA hydrogel, the proposed hydrogel-based biosensor may find broad applications in clinical diagnostics and biomedical devices.

C25H17N2O8, triclinic, P1̄ (no. 2), a = 9.6002(5) Å, b = 10.4192(5) Å, c = 11.0226(5) Å, α = 93.412(4)°, β = 98.094(4)°, γ = 98.787(4)°, V = 1075.04(9) Å3, Z = 2, R gt(F) = 0.0547, wR ref(F 2) = 0.1426, T = 293(2) K.

A simple electrochemical patterning strategy has been developed for the construction of ultrasensitive biosensors based on polyethylene glycol (PEG)-polypyrrole (PPy) nanowires substrate in order to supply improved antifouling performances. PPy nanowires array was produced through electrochemical polymerization of pyrrole at constant potential onto glassy carbon electrode (GCE) surface. PPy nanowires surfaces were decorated with 4-armed PEG molecules by electrochemical oxidation of amine groups offered by PEG end chains. The prepared PEG/PPy nanowires have integrated the excellent electrical conductivity of conducting polymer PPy nanowires with the good antifouling property of PEG. MicroRNAs (miRNAs) play very important roles in cancer development and a variety of diseases, which make them become promising biomarkers of the onset, prognosis and risk of diseases. Therefore the establishment of miRNA profiles for diseases and the detection of miRNAs in biological samples are critical milestones in diagnostics. An ultrasensitive electrochemical biosensor for miRNA can be effortlessly developed by the immobilization of DNA probes onto PEG/PPy nanowires. DNA/RNA hybridization was monitored by changes of methylene blue (MB) redox signal using differential pulse voltammetry (DPV) method. A wide linear range (0.10 pM ∼ 1.0 nM) to target miRNA was obtained by the fabricated biosensor, and miRNA mismatches can also be easily identified with satisfactory. Furthermore, the biosensor based on PEG/PPy nanowires can be extended to the development of any type of DNA-based biosensor.

A dual-sensing platform is proposed based on multi-walled carbon nanotubes/Prussian blue-functionalized polypyrrole nanowire array (PPY/MWCNTs/PB). Highly aligned PPY nanowire arrays were electrochemically prepared on the surface of glassy carbon electrodes, which were doped with MWCNTs/PB nanocomposites. The nanomaterial combines the characteristics of the PPY nanowires (high conductivity and large specific surface area) and MWCNTs/PB (excellent catalytic performance and intrinsic redox activity). Owing to the nanowire microstructure and outstanding electrical properties, the PPY/MWCNTs/PB nanowire arrays show excellent electrocatalysis of the reduction of hydrogen peroxide and facilitate the construction of a high-performance biosensing platform for microRNA (miRNA). A linear relationship between analytical signal and concentration of hydrogen peroxide and miRNA was obtained in the range 5 to 503 µM (1.4-5.1 mM) and 0.1 pM to 1 nM, and detection limits of 1.7 μM and 33.4 fM, respectively. This new supersensitive sensing platform has broad application prospects of biomolecule and other analyte determination in drug, biomedical, plant protection, and environmental analysis. Prussian blue/multi-walled carbon nanotubes functionalized polypyrrole nanowire arrays (PPY/MWCNTs/PB) were prepared by a facile one-step electrochemical method. PPY/MWCNTs/PB nanowire arrays show excellent electrocatalysis of the reduction of H

Nine undescribed (1–4, 6–10) sesquiterpene coumarins, together with a new natural one (5) and ten known ones (11–20), were isolated from the low polarity fraction of the 95% ethanol extract of the resin of Ferula sinkiangensis. Their structures were elucidated based on the comprehensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations were determined by comparison of experimental and calculated ECD spectra. All the identified SCs were evaluated for their anti-neuroinflammatory activities in LPS-induced BV-2 cells. Ferusingensine G (8) displayed a significant inhibitory effect on nitric oxide (NO) production with an IC50 value of 1.2 μM. The results suggested that natural SCs might be served as potential neuroinflammatory inhibitors.

The application of polypeptides in bio-interfaces and biosensors is of great interest because polypeptides are biocompatible and easy to design. A novel polymer nanocomposite was prepared by the electropolymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) with a newly designed polypeptide. The nanocomposite polypeptide doped PEDOT (PEDOT/PEP), with a 3D microporous network structure, large surface area and excellent antifouling ability, was utilized for the attachment of BRCA1 complementary oligonucleotides to construct a DNA biosensor. The fabricated DNA biosensor showed favorable selectivity (with a detection limit of 0.0034 pM) and high sensitivity. The biosensor was also capable of detecting the target DNA (BRCA1) in 1% (V/V) human serum samples. The combination of a conducting polymer PEDOT with an antifouling and biocompatible polypeptide demonstrates a new method for preparing electrochemical sensors, that are capable of detecting targets in complex biological samples without strong nonspecific protein adsorption.

A nanocomposite consisting of phytic acid (PA) that was doped with poly(3,4-ethylenedioxy-thiophene) (PEDOT) and modified with copper nanoparticles (CuNPs) was placed on a glassy carbon electrode and then applied in an enzymeless glucose sensor. The undulating PEDOT/PA composite has good conductivity and a large surface area, which was suitable as substrate for the uniform growth of CuNPs. The modified electrode typically operated at a potential near 0.55 V (vs. Ag/AgCl) demonstrated remarkable catalytic activity towards direct oxidation of glucose in NaOH solution (the major limitation of this sensor). Figures of merit include (a) a wide analytical range (5 to 403 μM); (b) high sensitivity (79.27 μA·μM−1·cm−2), (c) a low detection limit (0.28 μM at a signal to noise ratio of 3), and (d) fast response (< 4 s).

Honeycomb-like cobalt nanostructures modified graphene oxide doped polypyrrole (CoNSs/RGO/PPy) nanocomposites were successfully prepared via a simple two-step electrochemical synthesis route. Firstly graphene oxide (GO) doped PPy nanocomposite was electrodeposited onto a pretreated glassy carbon electrode (GCE) to obtain GO/PPy nanocomposite; secondly honeycomb-like cobalt nanostructures were electrochemical reduced onto GO/PPy nanocomposite surface in a cobalt chloride solution at − 1.0 V. During the second reduction process, GO/PPy was reduced to a more conductive RGO/PPy nanocomposite simultaneously. The electrode modified with CoNSs/RGO/PPy nanocomposites exhibited outstanding electrocatalytic performance for enzymeless glucose sensing in alkaline media. Under optimum experimental conditions, the nonenzymatic glucose sensor displayed linear ranges from 0.5 μM to 2.667 mM, a high sensitivity of 297.73 μA mM − 1 cm − 2 , a very low detection limit of 29 nM (at S/N = 3) and a superfast response time of 1 s. The developed glucose sensor displayed favorable selectivity against common interferents, excellent stability and high reproducibility, and it has great potential to successfully detect glucose concentration in real biological samples.

A glassy carbon electrode (GCE) was modified with graphene oxide-doped polypyrrole (PPy), and flower-like cobalt nanostructures were then deposited on GCE by electrochemical reduction. The modified electrode shows improved catalytic behavior towards nitrite oxidation as the result of the nanoporous structure and the synergistic effect between cobalt nanostructures and GO/PPy. It is found that the amperometric oxidation current at 0.80 V (vs SCE) is about 2.5 times larger than that of a GCE modified with carbon nanotubes. Under optimum conditions, the modified electrode displays a linear range that extends over the 1.0 μM to 3.2 mM and 6.8 – 12 mM concentration ranges, a lower detection limit of 15 nM (at an S/N ratio of 3), and a response time of 1 s. The modified electrode is adequately selective, highly stable and highly reproducible. The method was successfully applied to the determination of nitrite in pickled radish.

A reagentless and label-free voltammetric modified electrode was developed for the carcinoembryonic antigen (CEA), an important biomarker for colorectal adenocarcinoma. It is based on the use of a reticular hybrid composite consisting of polyaniline (PANI) nanowires grown on the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) that was doped with an ionic liquid (IL). The composite features excellent electrical conductivity and a porous structure, a high specific surface and inherent redox activity. It was placed on a glassy carbon electrode (GCE) and antibody against CEA was immobilized on its surface. The redox current of PANI, measured typically at 0.16 V (vs. Ag/AgCl) serves as the analytical information. This electrode displays linear range that extends from 0.001 to 10 ng mL−1, with a detection limit as low as 0.7 pg mL−1. It also possesses excellent temporal stability and selectivity.

Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with bovine serum albumin-stabilized Au nanoclusters (AuNCs) was successfully synthesized through electrochemical polymerization in a solution containing EDOT monomer and AuNCs. The obtained PEDOT/AuNCs composite possessed a microstructure with AuNCs evenly distributed within the PEDOT film as dopants. The PEDOT/AuNCs modified electrode exhibited high electrocatalytic activity toward nitrite oxidation, and it was further developed into an amperometric sensor for nitrite. If operated at 0.80 V (vs. SCE), the linear range of the sensor was from 0.05 to 2600 μM, with a very low limit of detection of 17 nM (S/N = 3).

Vertically aligned conducting polymer nanowire arrays had great potential applications in supercapacitor electrode material and exhibited enhanced electrocatalytic behavior towards the reduction of nitrite. In this paper, a facial template-free approach to synthesize large arrays of vertically aligned polyaniline (PANI) nanowires on electrochemically pretreated glassy carbon electrodes was reported by using a galvanostatic current method. The as-prepared large arrays of PANI nanowires had very narrow diameters and were oriented perpendicular to the substrate, which was a benefit to the ion diffusion when being used as the supercapacitor electrode. The highest specific capacitance of PANI nanowire arrays was measured and kept high at a large charge-discharge current density. Furthermore, it also can detect nitrite with ultrahigh sensitivity of 62.99 µA mM−1 cm−2 and a remarkable fast response time of less 1 s. The results indicated that the vertically aligned PANI nanowires could dramatically enhance the electrochemical performance.

Conducting polymer polyaniline (PANI) nanowire arrays were electrochemically in situ synthesized on the surface of glassy carbon electrodes, which were modified with self-assembled multi-walled carbon nanotubes (CNTs) networks. The ordered PANI nanowire arrays and CNTs networks were integrated to create 3D nanostructured PANI/CNTs composites. Owing to their unique microstructure and conductivity, the PANI/CNTs nanocomposite exhibited excellent electrical properties such as remarkable supercapacitor performance and catalytic activity toward nitrite electrochemical reduction. It was found that the PANI/CNTs nanocomposite was capable of delivering high specific capacitance and showed excellent cycling stability. Moreover, it could be utilized as an electrochemical sensor for the detection of nitrite, with an outstanding sensitivity, low detection limit (6.1 μM, a signal to noise ratio of 3) and a fast response time of less than 5 s.

Kellerin, a sesquiterpene coumarin derivative, has been identified as a major constituent of Ferula sinkiangensis K. M. Shen. It has been proved to be a potential natural therapeutic agent for Alzheimer's disease because of its inhibition of inflammatory cytokines nitric oxide (NO), tumor necrosis factor-α (IL-6) (TNF-α), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in over-activated BV2 mouse microglial cells. Because of the multi chiral centers and the chemical instability of the sesquiterpene, coumarin, it is rather difficult to obtain this bioactive natural product by synthesis. Thus, biotransformation of kellerin was carried out to afford more novel derivatives using the callus of Angelica sinensis (Oliv.) Diels, which has an abundance of biosynthetic enzymes of phenylpropanoids. As a result, 14 products were obtained and identified, including four new sesquiterpene coumarin derivatives: 14′-hydroxy-(3′S,4′R,5′S,8′R,9′S,10′R)-kellerin (1), 5′,6′-ene-14′-hydroxy-(3′S,4′R,8′R,9′S,10′R)-kellerin (2), 5′,6′-ene-(3′R,8′R,9′S,10′R)-ferukrin (3), and 14′-hydroxy-(3′S,4′R,5′S,8′R,9′S,10′R)-deacetylkellerin (4), together with 10 other known compounds. Their structures were elucidated using comprehensive spectroscopic techniques and their possible biosynthetic pathways were proposed on the basis of the structural analyses. Furthermore, their anti-neuroinflammatory activities were assessed in BV2 cells by monitoring lipopolysaccharide-induced NO production, and the structure–activity relationships were discussed.

Biocompatible materials, such as zwitterionic poly(carboxybetaine methacrylate) (polyCBMA), are of extraordinary importance in growth of bioelectronics and biosensors, because they not only greatly suppress nonspecific protein adsorption, but also have rich functional groups to facilitate the fixation of biological molecules. A novel nanocomposite was synthesized herein through modification polyCBMA onto conducting polymer polyaniline (PANI) nanowire surface. The prepared polyCBMA/PANI composite, integrating the good conductivity of PANI nanowires with the excellent antifouling capability of polyCBMA, provided a wonderful matrix for the growth of ultrasensitive and low fouling biosensor. Carcinoembryonic antigen (CEA), an important biomarker for a variety of cancers, was utilized as a model test. Furthermore its antibody was fixed onto polyCBMA/PANI for the preparation of CEA biosensor. DPV was applied as a sensing principle with information at which peak potential and current the signals were recorded. The peak currents were in inverse proportion to the logarithm of CEA concentration in the range from 1.0 × 10−14 g mL−1 to 1.0 × 10−10 g mL−1, with a detect limit of 3.05 fg mL−1. Furthermore, this low fouling, label-free biosensor has been utilized for assaying in undiluted human serum samples with resisting serious nonspecific protein adsorption, demonstrating its feasible potential application in clinical analysis of CEA.

A non-fouling electrochemical immunosensor is described for determination of the tumor biomarker carcinoembryonic antigen (CEA). It is based on the use of composite wires made by chemical grafting of hyaluronic acid onto polyaniline nanowires. The modified nanowires possess excellent antifouling property both in single protein solutions and in dilute serum samples. The current of immunoelectrode exhibits a linear response in the 0.01 pg mL−1 to 10,000 pg mL−1 CEA concentration range and 0.0075 pg mL−1 detection limit. This work demonstrates that coating an electrode with hyaluronic acid can largely reduce unspecific adsorption of proteins on the electrode surface.

Biofouling arising from nonspecific adsorption is a substantial outstanding challenge in diagnostics and disease monitoring, and antifouling sensing interfaces capable of reducing the nonspecific adsorption of proteins from biological complex samples are highly desirable. We present herein the preparation of novel composite nanofibers through the grafting of polyethylene glycol (PEG) polymer onto polyaniline (PANI) nanofibers and their application in the development of antifouling electrochemical biosensors. The PEGylated PANI (PANI/PEG) nanofibers possessed large surface area and remained conductive and at the same time demonstrated excellent antifouling performances in single protein solutions as well as complex human serum samples. Sensitive and low fouling electrochemical biosensors for the breast cancer susceptibility gene (BRCA1) can be easily fabricated through the attachment of DNA probes to the PANI/PEG nanofibers. The biosensor showed a very high sensitivity to target BRCA1 with a linear range from 0.01 pM to 1 nM and was also efficient enough to detect DNA mismatches with satisfactory selectivity. Moreover, the DNA biosensor based on the PEGylated PANI nanofibers supported the quantification of BRCA1 in complex human serum, indicating great potential of this novel biomaterial for application in biosensors and bioelectronics.

An ultrasensitive biosensor for alpha-fetoprotein was developed based on electrochemically synthesized polyaniline (PANI) nanowires, which were functionalized with gold nanoparticles (AuNPs) and polyethylene glycols (PEG). The prepared PEG/AuNPs/PANI composite, combining the electrical conductivity of the AuNPs/PANI with the robust antifouling ability of PEG, offered an ideal substrate for the development of low fouling electrochemical biosensors. Alpha-fetoprotein (AFP), a well-known hepatocellular carcinoma biomarker, was used as a model analyte, and its antibody was immobilized on the PEG/AuNPs/PANI for the construction of the AFP immunosensor. Using the redox current of PANI as the sensing signal, in addition to the good biocompatibility of PEG/AuNPs and the anti-biofouling property of PEG, the developed immunosensor showed improved biosensing performances, such as wide linear range and ultralow detection limit (0.007 pg mL−1). More importantly, it is label-free, reagentless and low fouling, making it capable of assaying AFP in real serum samples without suffering from significant interference or biofouling.