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The misregulation of protein phosphatases is a key factor in the development of many human diseases, notably cancers. Here, based on a 100 MHz quartz crystal microbalance (QCM) biosensing platform, the dephosphorylation process of phosphopeptide (P-peptide) caused by protein tyrosine phosphatase 1B (PTP1B) was monitored in real time for the first time and PTP1B activity was assayed rapidly and sensitively. The QCM chip, coated with a gold (Au) film, was used to immobilized thiol-labeled single-stranded 5'-phosphate-DNAs (P-DNA) through Au-S bond. The P-peptide, specific to PTP1B, was then connected to the P-DNA via chelation between Zr 4+ and phosphate groups. When PTP1B was injected into the QCM flow cell where the P-peptide/Zr 4+ /MCH/P-DNA/Au chip was placed, the P-peptide was dephosphorylated and released from the Au chip surface, resulting in an increase in the frequency of the QCM Au chip. This allowed the real-time monitoring of the P-peptide dephosphorylation process and sensitive detection of PTP1B activity within 6 min with a linear detection range of 0.01-100 pM and a detection limit of 0.008 pM. In addition, the maximum inhibitory ratios of inhibitors were evaluated using this proposed 100 MHz QCM biosensor. The developed 100 MHz QCM biosensing platform shows immense potential for early diagnosis of diseases related to protein phosphatases and the development of drugs targeting protein phosphatases., 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.)

Herein, high-frequency quartz crystal microbalance biosensing platforms were constructed using an aptamer and antibody as bioreceptors for fast and label-free detection of the SARS-CoV-2 RBD.

Mercury ion (Hg 2+ ) is one of the most harmful heavy metal ions with the greatest impact on public health. Herein, based on the excellent catalytic activity toward 3,3',5,5'-tetramethylbenzidine (TMB) and the strong photocurrent-polarity-switching ability to SnS 2 photoanode of the split G-quadruplex-hemin complex, the magnetic NiCo 2 O 4 @SiO 2 -NH 2 sphere-assisted colorimetric and photoelectrochemical (PEC) dual-mode sensing platform was developed for the Hg 2+ assay. First, the amino-labelled single-stranded DNA1 (S1) was immobilized on NiCo 2 O 4 @SiO 2 -NH 2 and then partly hybridized with another single-stranded DNA2 (S2). When Hg 2+ was present, the thymine-Hg 2+ -thymine base pairs between S1 and S2 were formed, causing the formation of the split G-quadruplex in the presence of K + . After addition of hemin, the split G-quadruplex-hemin complex was obtained and effectually catalyzed the H 2 O 2 -mediated oxidation of TMB. Thus, the color and absorbance intensity of the TMB solution were changed, resulting in the visual and colorimetric detection of Hg 2+ . The linear response range is 10 pM to 10 nM, and the detection limit is 3.8 pM. Meanwhile, the above G-quadruplex-hemin complex effectively switched the photocurrent polarity of SnS 2 -modified indium tin oxide electrode, leading to the sensitive and selective PEC assay of Hg 2+ with a linear response range of 5 pM to 500 nM and a detection limit of 2.3 pM. Moreover, the developed dual-mode sensing platform provided mutual authentication of detection results in different modes, effectively improving the assay accuracy and confidence, and may have a good potential application in highly sensitive, selective, and accurate determination of Hg 2+ in environmental fields.

Dysregulation of protein phosphatases is associated with the progression of various human diseases and cancers. Herein, a photoelectrochemical (PEC)-quartz crystal microbalance (QCM) dual-mode sensing platform was developed for protein tyrosine phosphatase 1B (PTP1B) activity assay based on bifunctional magnetic Fe 3 O 4 @Cu 2 O@TiO 2 nanosphere-mediated PEC photocurrent polarity switching and QCM signal amplification strategies. The PTP1B-specific phosphopeptide (P-peptide) with a cysteine end was designed and immobilized onto the QCM Au chip via the Au-S bond. Subsequently, the Fe 3 O 4 @Cu 2 O@TiO 2 nanosphere was connected to the P-peptide via the specific interaction between the phosphate group on the P-peptide and TiO 2 . After incubation with PTP1B, the dephosphorylation of the P-peptide occurred, causing some Fe 3 O 4 @Cu 2 O@TiO 2 nanospheres to be released from the chip surface. The released magnetic Fe 3 O 4 @Cu 2 O@TiO 2 nanospheres (labeled as R-Fe 3 O 4 @Cu 2 O@TiO 2 ) were quickly separated via magnetic separation technology and attached to the Bi 2 S 3 -decorated magnetic indium-tin oxide (Bi 2 S 3 /MITO) electrode by magnetic force, inducing the switch of the photocurrent polarity of the electrode from anodic current (the Bi 2 S 3 /MITO electrode) to cathodic current (the R-Fe 3 O 4 @Cu 2 O@TiO 2 /Bi 2 S 3 /MITO electrode). Also, the nondephosphorylated P-peptide linked Fe 3 O 4 @Cu 2 O@TiO 2 nanospheres as nanozymes with horseradish peroxidase activity to catalyze the formation of precipitation on the surface of the Au chip, leading to a frequency change of the QCM. Thus, the proposed PEC-QCM dual-mode sensing platform achieved accurate and reliable assay of PTP1B activity because of the different mechanisms and independent signal transductions. In addition, this dual-mode sensing platform can be easily extended for other protein phosphatase activity analysis and shows great potential in the early diagnosis of the protein phosphatase-related diseases and the protein phosphatase-targeted drug discovery.

The self-powered sensors have attracted widespread attention in the analysis field due to a huge demand of point-of-care testing (POCT) in the early diagnosis of diseases. However, the output voltage of the reported self-powered sensors is always small, resulting in a narrow linear detection range and low assay sensitivity. Herein, a self-powered photoelectrochemical (PEC) sensor with zinc-air batteries as a power source was developed for activity assay of protein tyrosine phosphatase 1B (PTP1B) based on perovskite quantum dots encapsulated in the vinyl-functionalized covalent organic framework (COF-V). CsPbBr 3 nanocrystals were stabilized by the confinement effect of the COF-V cage without aggregation, and the resulting CsPbBr 3 @COF-V composite was used as the cathodic photoelectric material to construct the zinc-air battery with a large open-circuit voltage (OCV, 1.556 V). Before PTP1B activity assay, an auxiliary peptide-polyamidoamine-phosphopeptide (P2-PAMAM-P1) hybrid was introduced into the photocathode via thiol-ene click reaction between the thiol group on the P1 and the vinyl group on the COF-V. The steric hindrance effect of the P1-PAMAM-P2 hybrid inhibited the PEC performance of the photocathode, resulting in a small OCV of the zinc-air battery. When the PTP1B existed, PTP1B-catalyzed dephosphorylation of tyrosine on P1 facilitated the cleavage process of P1 by chymotrypsin, leading to the removal of the P2-PAMAM-P1 hybrid from the photocathode and consequently the enhancement of the OCV. Therefore, the activity of PTP1B was sensitively detected. The developed self-powered PEC sensor showed superior performance for PTP1B activity assay (broad linear response range, 0.1 pM to 10 nM and low detection limit, 0.032 pM) due to the large output voltage of the constructed zinc-air battery and has great potential in POCT of protein phosphatase-related diseases and the discovery of protein phosphatase-targeted drugs.

Herein, a label-free and ultra-low-background-noise PEC biosensor was developed for lead ion (Pb 2+ ) assay based on the Cu 2 O-CuO-TiO 2 heterojunction. By calcination of cupric ion (Cu 2+ ) doped-titanium based metal organic framework (MOF) material (NH 2 -MIL-125), the Cu 2 O-CuO-TiO 2 heterojunction was synthesized. With Pb 2+ , lots of DNA single strands (S1) could be released based on the Pb 2+ assisted cyclic amplification strategy and hybridized with hairpin DNA (HP1) on the modified electrode. The exposed phosphate groups on S1 can adsorb Cu 2 O-CuO-TiO 2 heterojunction, which results in a large cathode photocurrent. Due to the good photoelectric property of Cu 2 O-CuO-TiO 2 and Pb 2+ -triggering cyclic amplification strategy, the constructed PEC biosensor achieves a wide linear detection range (10 fM - 1 μM) and a low detection limit (6.8 fM), which provides potential applications in ultrasensitive determination of Pb 2+ in environmental water samples and organisms., 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 © 2022 Elsevier B.V. All rights reserved.)

Water pollution presents a significant environmental concern on earth. Herein, due to the serious environmental harmfulness of arsenate [As(V)], an iron phthalocyanine (FePc)-induced switchable photocurrent-polarity platform was developed for highly selective assay of As(V). First, magnetic Co 3 O 4 -Fe 3 O 4 cubes were obtained by calcination of the CoFe Prussian blue analogue and then functionalized with oligonucleotide (S1). In the presence of As(V), S1 could be released based on the stronger affinity between As(V) and Co 3 O 4 -Fe 3 O 4 cubes. After magnetic separation by Co 3 O 4 -Fe 3 O 4 cubes, the released S1 was used to trigger the catalytic hairpin assembly (CHA) and hybridization chain reaction, resulting in the formation of lots of G-quadruplex structures on the AgInS 2 /ITO electrode. Then, the capture of FePc by the G-quadruplex led to the switch of the photocurrent polarity of the AgInS 2 /ITO electrode from the anode to the cathode. Thus, As(V) was sensitively assayed with a low detection limit of 1.0 nM and a wide linear response range from 10 nM to 200 μM. This meets the detection requirement of the World Health Organization for the arsenic concentration in drinking water [less than 10 μg L -1 (130 nM)]. In addition, whether it was cationic or anionic interferents except phosphate (PO 4 3- ), only As(V) could generate the cathodic photocurrent, effectively avoiding the false-positive or false-negative results during As(V) assay. Interestingly, As(V) was also simultaneously separated from the detection system by Co 3 O 4 -Fe 3 O 4 magnetic cubes. The proposed photoelectrochemical platform may have a great potential application for the selective detection of As(V) in environmental fields.

Herein, a photocurrent polarity switching platform for highly selective assay of mucin 1 (MUC1) was developed based on target-induced hemin transfer from ZrO 2 hollow spheres (ZrO 2 HSs) to G-quadruplex nanowires (G wires). In this system, SiO 2 spheres were used as templates to synthesize the uniform and mesoporous ZrO 2 HSs. As nanocontainers, ZrO 2 HSs could load hemin in its cavity via pores. Then, the aptamers of MUC1, as bio-gates, blocked the pores of ZrO 2 HSs based on the specific binding of Zr 4+ and the phosphate groups of aptamer. In the presence of MUC1, the aptamer could specifically recognize and bind with MUC1, and then leave away from the surface of ZrO 2 HSs, which resulted in the opening of the bio-gates and releasing of hemin. Assisted with the G wires formed on the Au NPs/In 2 S 3 /ITO, the released hemin was captured on the electrode through the formation of hemin/G-quadruplex structure, leading to the switch of the photocurrent polarity of the electrode from anodic photocurrent to cathodic photocurrent. The proposed photoelectrochemical biosensor showed outstanding performance for MUC1 assay with high selectivity, wide linear response range (1 fg mL -1 -10 ng mL -1 ) and lower detection limit (0.48 fg mL -1 ). And the strategy could be easily extended to a triple-mode detection of MUC1 because the hemin/G-quadruplex structure was widely used in electrochemical and colorimetric methods as a hydrogen peroxide mimetic enzyme, which might provide wide applications in biological or clinical studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Highly sensitive and selective microRNA (miRNA) assay is of great significance for disease diagnosis and therapy. Herein, a magnetic-assisted electrochemistry (EC)-photoelectrochemistry (PEC) dual-mode biosensing platform was developed for miRNA-210 detection based on dual-signaling EC and photocurrent-polarity-switching PEC strategies. Porous magnetic Fe 3 O 4 octahedra with a large surface area were synthesized by calcining Fe-based metal-organic frameworks. Subsequently, the magnetic photoelectric materials (Fe 3 O 4 @CdS) were developed by the successive ionic layer adsorption and reaction method in Cd 2+ and S 2- solutions. Then, the self-assembled DNA nanoprisms contained three thiols/hanging arms that could capture miRNA-210 efficiently and were anchored to the Fe 3 O 4 @CdS octahedra via the Cd-S bond. When miRNA-210 was present, the double-stranded DNA concatemers [the self-assembled duplex helixes based on a pair of methylene blue (MB)-labeled single-stranded DNAs (AP1 and AP2) through the hybridization chain reaction and then intercalated with adriamycin (Dox) into their grooves] were connected with the Fe 3 O 4 @CdS-DNA nanoprisms. MB and Dox not only acted as the electrochemical probes but also synergistically switched the photocurrent polarity of the Fe 3 O 4 @CdS octahedra. Thus, miRNA-210 was assayed sensitively and selectively via the proposed EC-PEC dual-mode biosensing platform. Additionally, the abovementioned recognition steps occurred in a homogeneous system, and the effects of the impurities and interferences on the miRNA-210 assay could be easily avoided by magnetic separation due to the good magnetic properties of Fe 3 O 4 octahedra. The proposed EC-PEC dual-mode biosensing platform showed a wide range of potential applications in bioanalysis and early diagnosis of disease.

Herein, an electrochemical (EC)-photoelectrochemical (PEC) dual-mode biosensor was constructed for cytokeratin 19 fragment 21-1 (CYFRA21-1) assay based on the dual-signaling electrochemical ratiometric strategy and "on-off-on" PEC method. The indium tin oxide (ITO) electrode was modified by 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA)@C 60 and gold nanoparticles (Au NPs), and the double-stranded DNA composed of thiol/methylene blue (MB)-labeled single-stranded DNA (ssDNA) (S0-MB) and antibody/ferrocene (Fc)-labeled ssDNA (Ab1-S1-Fc) was immobilized on the Au NPs/PTCDA@C 60 /ITO electrode via the Au-S bond between Au NPs and thiol of S0-MB. With the help of another antibody-labeled ssDNA (Ab2-S2), the presence of CYFRA21-1 triggered a typical antigen-antibody sandwich immune reaction (Ab1, CYFRA21-1, and Ab2) and proximity hybridization between Ab1-S1-Fc and Ab2-S2. This caused the release of Ab1-S1-Fc from the modified electrode and the change of S0-MB to a hairpin structure, resulting in a decrease (an increase) of the oxidation peak current of Fc (MB) and an increase of the photocurrent due to the enhancing (inhibiting) effect of MB (Fc) on the photoelectric performance of the Au NPs/PTCDA@C 60 /ITO electrode. Thus, CYFRA21-1 was detected by the developed EC-PEC dual-mode sensing platform sensitively, and the linear response ranges of 0.001-40 ng/mL with a detection limit of 0.3 pg/mL for the EC technique and 0.0001-4 ng/mL with a detection limit of 0.03 pg/mL for the PEC method were obtained. Furthermore, by changing the specific antibodies of disease-related biomarkers, the developed dual-mode biosensing platform could be readily extended to detect other antigens, implying its great potential applications in biological analysis and early disease diagnosis.

As the most important serum biomarker for prostate cancer, sensitive and accurate detection of prostate-specific antigen (PSA) is of great reference value for the clinical diagnosis and treatment of prostate cancer. Herein, a peptide cleavage-mediated and environmentally friendly photocurrent polarity switching system was developed for ultrasensitive and highly selective detection of PSA based on the efficiently switching of photocurrent polarity of silver indium sulfide nanoparticles (AgInS 2 NPs)-coated indium tin oxide (ITO) electrode by amino-functionalized CuO cubes (NH 2 -CuO). The porous CuO cubes were synthesized by calcination of HKUST-1 and functionalized with aminosilane. In the presence of PSA, the biotin and rhodamine B-labeled peptide (Bio-Pep-RhB) was cleaved and part of the peptide (P-Pep-RhB) was obtained by magnetic separation. Through host-guest recognition between β-CD and RhB, the P-Pep-RhB was immobilized on the β-CD/AgInS 2 NPs/ITO electrode. Then, the amino-rich sequence on P-Pep-RhB combined with NH 2 -CuO via glutaraldehyde results in the switch of anodic photocurrent to cathodic photocurrent. On account of the high-efficient peptide cleaving strategy and the new photocurrent polarity switching system of porous CuO cubes//AgInS 2 NPs, the prepared sensing platform displayed outstanding analytical performance for PSA with a wide linear response range (0.1 pg mL -1 -100 ng mL -1 ) and a lower detection limit of 0.06 pg mL -1 . The proposed analytical method could be easily extended to analyze other proteins via changing the peptide sequence, which has a potential application in the fields of biological analysis and medical diagnosis.

Herein, a novel label-free photoelectrochemical (PEC) sensing platform with near-zero background noise was developed for M.SssI CpG methyltransferase (M.SssI MTase) activity assay based on a new Schottky junction of Bi 2 S 3 /Ti 3 C 2 nanosheets. The proposed PEC sensor exhibited a low detection limit and a high signal-to-noise ratio for M.SssI MTase assay.

By direct calcination of Cu 2+ -doped ZIF-8 in oxygen atmosphere, a new photoelectric material, CuO-ZnO heterojunction, was prepared. The morphology and structure were investigated in detail by several methods, such as scanning electron microscopy, transmission electron microscopy, nitrogen adsorption-desorption method and X-ray diffraction. Under visible light irradiation, CuO-ZnO heterojunction exhibits excellent PEC behavior in aqueous media with the presence of ascorbic acid (AA) and dissolved oxygen at -0.3 V. Taking the CA125-antibody functionalized CuO-ZnO heterojunction (CuO-ZnO-Ab 2 ) as a signal source, a novel photoelectrochemical (PEC) immunosensing platform was developed for ultrasensitive assay of CA125. Because of the target-induced introduction of photoelectric material to the sensing platform, the proposed PEC immunosensor has excellent performance for CA125 assay: near-zero background noise, wide linear response range (1 × 10 -5 U/mL to 100 U/mL) and low detection limit (3.16 × 10 -6 U/mL). The developed CuO-ZnO heterojunction and the related PEC sensing platform may have promising applications in ultrasensitive and highly accurate monitoring of various proteins in bioanalysis and disease 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 © 2019 Elsevier B.V. All rights reserved.)

DNA methylation catalyzed by M.SssI methyltransferases (MTase) has important roles in gene expression and other cellular activities, and relates to some diseases, especially cancers. Therefore, it is important to develop a sensitive sensing platform for M.SssI MTase activity assay. Here, taking zeolitic imidazolate framework-8 (ZIF-8) polyhedra as the carriers of graphene quantum dots (GQDs), GQDs-embedded ZIF-8 polyhedra (denoted as GQDs@ZIF-8 polyhedra) were successfully prepared and used as the multi-functional signal quencher to construct a novel signal-off photoelectrochemical (PEC) biosensor for M.SssI MTase activity assay. Firstly, the indium tin oxide (ITO) slice was modified with TiO 2 , poly(diallyldimethylammonium chloride) and CdTe quantum dots (QDs). The obtained electrode was used as the photoelectrode and labeled as ITO/TiO 2 /CdTe QDs. Then, single-stranded DNA (S1) was anchored on the photoelectrode surface via S-Cd bond. After hybridization between S1 and biotinylated single-stranded DNA (S2), the streptavidin (SA)-labeled GQDs@ZIF-8 polyhedra were introduced to the modified electrode via the specific reaction between biotin and SA. As the signal quencher, GQDs@ZIF-8 polyhedra could not only inhibit the photocurrent signal of the ITO/TiO 2 /CdTe QDs electrode due to the steric hindrance effect, but also act as peroxidase mimetics to catalyze precipitation reaction of 4-chloro-1-naphthol, resulting in the evident depression of the photocurrent signal. For the specially designed S1/S2 double-strand DNA, the decreased photocurrent was quantitatively correlated with the M.SssI MTase activity (linear response range, 0.005-150 U mL -1 ; detection limit, 0.004 U mL -1 ). The developed GQDs@ZIF-8 polyhedra and related PEC biosensor may have potential applications in clinical research and disease diagnosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Herein, a highly selective and sensitive photoelectrochemical (PEC) sensing platform was developed for vascular endothelial growth factor 165 (VEGF165) assay based on the porous Cu 2 O-CuO flower-induced photocurrent-polarity switching of the CdS quantum dots (QDs) modified indium-tin oxide (ITO) electrode. The porous Cu 2 O-CuO flower with uniform size and large surface area was successfully synthesized by taking Cu-MOF (HKUST-1) as the precursor. Through VEGF165-triggered catalytic hairpin assembly process, the porous Cu 2 O-CuO flower was introduced to the surface of the CdS QDs/ITO electrode, resulting in the switching of the photocurrent polarity from anodic current to cathodic current. Based on the uniform particle size, high specific surface area, good photoelectric conversion efficiency, and photocurrent polarity switching ability of porous Cu 2 O-CuO flower, the proposed sensing platform showed excellent assay performance for VEGF165 with a linear response range from 1 to 3000 fM, a detection limit of 0.3 fM, and high selectivity. By changing the specific aptamer, the proposed sensing platform could be easily extended to detect other proteins, and may have a promising application in bioanalysis and early disease diagnosis.

As a significant biomarker of prion diseases, ultrasensitive assay of infectious isoform of prion (PrP Sc ) is highly desirable for early diagnostics of prion diseases. Herein, taking normal cellular form of prion (PrP C ) as a model owing to a high risk of pathogenicity of PrP Sc , a new photoelectrochemical immunosensor has been developed based on hemin-induced switching of photocurrent direction. In the presence of PrP C , nitrogen-doped porous carbon-hemin polyhedra labeled with secondary antibody were introduced onto the CdS-chitosan (CS) nanoparticles-modified indium-tin oxide (ITO) electrode via the antigen-antibody specific recognition. Because of the matched energy level between CdS and hemin, the high-efficiency switch of photocurrent direction of the ITO/CdS-CS photoelectrode from anodic to cathodic photocurrent was observed even at very low concentration (0.4 aM) of PrP C . Through changing the specific antibody, this method can be easily expanded to PrP Sc assay. Such low detectable limit is very useful in the early diagnosis and screening of prion diseases. The developed method has also promising applications in bioanalysis, disease diagnostics, and clinical biomedicine., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The sensitive and specific determination of nucleic acids is very important in clinical diagnosis and biological studies. In this work, an ultrasensitive photoelectrochemical (PEC) biosensor has been developed for DNA detection based on a "signal-on" sensing strategy and a three-stage cascade signal amplification method (catalytic hairpin assembly (CHA), hybridization chain reaction (HCR) and alkaline phosphatase (ALP)-triggered in situ generation of ascorbic acid (AA)). Here, CHA hairpin 1 (CHA-HP1) is opened by the target DNA (T-DNA) owing to the hybridization between T-DNA and CHA-HP1, and then the opened CHA-HP1 hybridizes with CHA hairpin 2 (CHA-HP2) to displace the T-DNA, generating a CHA-HP1/CHA-HP2 complex. The displaced T-DNA triggers the next cycle of CHA, resulting in the generation of numerous CHA-HP1/CHA-HP2 complexes. Subsequently, one end of the CHA-HP1/CHA-HP2 complex hybridizes with the capture DNA immobilized on the indium tin oxide/TiO2/CdS : Mn electrode. After the introduction of dual-biotin labeled HCR hairpin 1 (HCR-HP1-Bio) and dual-biotin labeled HCR hairpin 2 (HCR-HP2-Bio), the other end of the CHA-HP1/CHA-HP2 complex opens HCR-HP1-Bio. The opened HCR-HP1-Bio triggers the HCR reaction between HCR-HP1-Bio and HCR-HP2-Bio, leading to the formation of long nicked duplex DNA structures. The dual-biotin modified HCR-hairpins can anchor more streptavidin-ALP to catalyze 2-phospho-l-ascorbic acid trisodium salt to yield more AA, leading to a larger PEC response. The proposed PEC biosensor shows superior analytical performance for T-DNA detection with a linear response ranging from 0.1 fM to 100 pM and a detection limit of 0.052 fM, and may provide a powerful biosensing platform for bioanalysis and early disease diagnosis.

In this work, a new electrochemical immunosensor was developed for prion protein assay based on hybridization chain reaction (HCR) with hemin/G-quadruplex DNAzyme for signal amplification. In this amplification system, the hemin/G-quadruplex DNAzyme simultaneously mimicked the biocatalytic functions for H 2 O 2 reduction and L-cysteine oxidation. In the presence of L-cysteine, the hemin/G-quadruplex catalyzed the oxidation of L-cysteine to L-cystine. At the same time, H 2 O 2 was produced under the oxygen condition. Then, the hemin/G-quadruplex could quickly catalyze the reduction of H 2 O 2 , mimicking the catalytic performance of horseradish peroxidase (HRP). Under the optimal conditions, the immunosensor showed a wide linear response range from 0.5 pg/mL to 100 ng/mL with the low detection limit of 0.38 pg/mL (3σ). By changing the specific antibody, this strategy could be easily extended to detect the infectious isoform of prion (PrP Sc ) and other proteins. Based on its good analytical performance, the developed method shows great potential applications in diagnosis of prion diseases at presymptomatic stage and bioanalysis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this work, high-performance non-enzymatic catalysts based on 3D hierarchical hollow porous Co 3 O 4 nanododecahedras in situ decorated on carbon nanotubes (3D Co 3 O 4 -HPND/CNTs) were successfully prepared via direct carbonizing metal-organic framework-67 in situ grown on carbon nanotubes. The morphology, microstructure, and composite of 3D Co 3 O 4 -HPND/CNTs were characterized by scanning electron microscopy, transmission electron microscopy, micropore and chemisorption analyzer, and X-ray diffraction. The electrochemical characterizations indicated that 3D Co 3 O 4 -HPND/CNTs present considerably catalytic activity toward glucose oxidation and could be promising for constructing high-performance electrochemical non-enzymatic glucose sensors and glucose/O 2 biofuel cell. When used for non-enzymatic glucose detection, the 3D Co 3 O 4 -HPND/CNTs modified glassy carbon electrode (3D Co 3 O 4 -HPND/CNTs/GCE) exhibited excellent analytical performance with high sensitivity (22.21 mA mM -1  cm -2 ), low detection limit of 0.35 μM (S/N = 3), fast response (less than 5 s) and good stability. On the other hand, when the 3D Co 3 O 4 -HPND/CNTs/GCE worked as an anode of a biofuel cell, a maximum power density of 210 μW cm -2 at 0.15 V could be obtained, and the open circuit potential was 0.68 V. The attractive 3D hierarchical porous structural features, the large surface area, and the excellent conductivity based on the continuous and effective electron transport network in 3D Co 3 O 4 -HPND/CNTs endow 3D Co 3 O 4 -HPND/CNTs with the enhanced electrochemical performance and promising applications in electrochemical sensing, biofuel cell, and other energy storage and conversion devices such as supercapacitor. Graphical abstract High-performance non-enzymatic catalysts for enzymeless glucose sensing and biofuel cell based on 3D hierarchical hollow porous Co 3 O 4 nanododecahedras anchored on carbon nanotubes were successfully prepared via direct carbonizing metal-organic framework-67 in situ grown on carbon nanotubes.

Based on Co-Co Prussian blue analogue (Co-Co PBA), a novel immunosensor has been developed for sensitive detection of prion protein (PrP C ). Gold nanoparticles (AuNPs)-modified Co-Co PBA nanocubes (PBA-AuNPs) worked as a support of the antibody (Ab2) of PrP C to obtain Ab2-PBA-AuNPs composite and also as the signal source for PrP C assay. When PrP C existed, Ab2-PBA-AuNPs could be introduced to the surface of another antibody of PrP C (Ab1) modified AuNPs/GC electrode (the gold nanoparticles-modified glassy carbon electrode) through specific antigen-antibody interaction between PrP C and its antibodies to form the Ab1-PrP C -Ab2 sandwich structure. With the help of KOH aqueous solution, PBA generated a large DPV response. The response peak currents were linear with the logarithmic values of the concentration of PrP C in the range from 0.075pgmL -1 to 100pgmL -1 with the detection limit of 0.014pgmL -1 . Also, the immunosensor showed good selectivity and reproducibility. Based on the simple sensing structure and good analytical performance, the developed immunosensor may have promising applications in practical assay of infectious isoform of prion (PrP Sc ) and other proteins by simply changing the related antibody., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Biomolecular receptors such as nucleic acids that switch between two or more conformations upon binding to a specific target can be used to build specific and sensitive biosensors. In this work, based on the electrochemical dual-signaling ratiometric strategy and triple-helix molecular switch, we developed a selective, reusable, and simple electrochemical DNA (E-DNA) biosensor for target DNA (T-DNA) detection. A hairpin DNA capture probe labeled with methylene blue (MB-DNA) self-assembles on the surface of a gold electrode (GE) through Au-S bond, and then a single-strand DNA modified with two ferrocenes (Fc-DNA) on each end to enhance the oxidation signal hybridizes with the MB-DNA to form a triple-helix conformation. When T-DNA exists, the Fc-DNA hybridizes with T-DNA disassembling the triple-helix stem and allowing the MB-DNA to revert to its hairpin structure. Hence, the Fc tags diffuse away from the GE surface while the MB tags remain affixed close to it, resulting in a decrease in the peak current of Fc (I Fc ) and an increase in that of MB (I MB ). The linear relationship between the value of I MB /I Fc and the T-DNA concentration is observed from 0.5 to 80 pM, and the limit of detection is as low as 0.12 pM. The developed E-DNA biosensor may have great potential in the electrochemical detection of a wide range of analytes and be a biosensing platform for early clinical diagnosis and biomedical research.

In this work, a simple, signal-on and label-free electrochemical biosensor for ultrasensitive DNA detection is reported on the basis of an autocatalytic and exonuclease III (Exo III)-assisted cascade signal amplification strategy. In the presence of target DNA (T-DNA), the hybridization between the 3'-protruding DNA fragment of hairpin DNA probe (HP1) and T-DNA triggered the Exo III cleavage process, accompanied by the releasing of T-DNA and autonomous generation of new DNA fragment which was used for the successive hybridization with the another hairpin DNA (HP2) on the electrode. After the Exo III cleavage process, numerous quadruplex-forming oligomers which caged in HP2 were liberated on the electrode surface and folded into G-quadruplex-hemin complexes with the help of K + and hemin to give a remarkable electrochemical response. As a result, a low detection limit of 4.83fM with an excellent selectivity toward T-DNA was achieved. The developed electrochemical biosensor should be further extended for the detection of a wide spectrum of analytes and has great potential for the development of ultrasensitive biosensing platform for early diagnosis in gene-related diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Prion proteins, as an important biomarker of prion disease, are responsible for the transmissible spongiform encephalopathies (a group of fatal neurodegenerative diseases). Hence, the sensitive detection of prion protein is very essential for biological studies and medical diagnostics. In this paper, a novel label-free and cascaded dual-signaling amplified electrochemical strategy was developed for sensitive and selective analysis of cellular prion protein (PrP(C)). The recognition elements included double-stranded DNA consisted of PrP(C)-binding aptamer (DNA1) and its partially complementary DNA (DNA2), and ordered mesoporous carbon probe (OMCP) fabricated by sealing the electroactive ferrocenecarboxylic acid (Fc) into its inner pores and then using single-stranded DNA (DNA3) as the gatekeeper. In the presence of PrP(C), DNA1 could bind the target protein and free DNA2. More importantly, DNA2 could hybridize with DNA3 to form a rigid duplex DNA and thus triggered the exonuclease III (Exo III) cleavage process to realize the DNA2 recycling, accompanied by opening more biogates and releasing more Fc. The released Fc could be further used as a competitive guest of β-cyclodextrin (β-CD) to displace the Rhodamine B (RhB) on the electrode. As a result, an amplified oxidation peak current of Fc (RhB) increased (decreased) with the increase of PrP(C) concentration. When "ΔI=ΔIFc+|ΔIRhB|" (ΔIFc and ΔIRhB were the change values of the oxidation peak currents of Fc and RhB, respectively.) was used as the response signal for quantitative determination of PrP(C), the detection limit was 7.6fM (3σ), which was much lower than that of the most reported methods for PrP(C) assay. This strategy provided a simple and sensitive approach for the detection of PrP(C) and has a great potential for bioanalysis, disease diagnostics, and clinical biomedicine applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Based on a triple-signaling strategy, a novel electrochemical aptasensor has been developed for sensitive and selective detection of bisphenol A (BPA). The thiolated ferrocene (Fc)-modified BPA-binding aptamer probe (Fc-P) was immobilized on the gold electrode and then hybridized with the methylene blue (MB)-modified complementary DNA probe (MB-P) to form a rigid double-stranded DNA (ds-DNA). The specific interaction between BPA and Fc-P led to the release of MB-P from the sensing interface and the conformational change of Fc-P. As a result, the oxidation peak currents of Fc and BPA increased with the increase of the concentration of target (BPA) according to the "signal-on" mode while that of MB decreased with the increase of the BPA concentration according to the "signal-off" mode. By superimposing the triple signal changes, BPA was detected sensitively with a linear range from 1 pM to 100 pM. The detection limit is 0.19 pM, and much lower than that obtained by most of the reported electrochemical methods. The aptasensor also exhibited satisfactory specificity, selectivity, reproducibility and stability. By changing the specific aptamers, this strategy could be easily extended to detect other redox targets, showing promising applications in environmental analysis, food safety monitoring, and bioanalysis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A novel competitive host-guest strategy regulated by protein biogate was developed for sensitive and selective analysis of prion protein. The methylene blue (MB)-tagged prion aptamer (MB-Apt) was introduced to the multiwalled carbon nanotubes-β-cyclodextrins (MWCNTs-β-CD) composites-modified glassy carbon (GC) electrode through the host-guest interaction between β-CD and MB. In the absence of prion, MB-Apt could be displaced by ferrocenecarboxylic acid (FCA) due to its stronger binding affinity to β-CD, resulting in a large oxidation peak of FCA. However, in the presence of prion, the specific prion-aptamer interaction drove the formation of protein biogate to seal the cavity of β-CD, which hindered the guest displacement of MB by FCA and resulted in the oxidation peak current of MB (IMB) increased and that of FCA (IFCA) decreased. The developed aptasensor showed good response towards the target (prion protein) with a low detection limit of 160 fM. By changing the specific aptamers, this strategy could be easily extended to detect other proteins, showing promising potential for extensive applications in bioanalysis.

Because of the intrinsic importance of nucleic acids as biotargets, the simple and sensitive detection of nucleic acids is very essential for biological studies and medical diagnostics. In this work, a novel, simple, and selective electrochemical DNA biosensor for the sensitive detection of target DNA (T-DNA) has been developed based on the dual-signaling electrochemical ratiometric method and exonuclease III (Exo III)-assisted target recycling amplification strategy. The assay strategy includes both "signal-on" and "signal-off" elements. The stem-loop (hairpin) DNA capture probe (HP), which was labeled by thiolated methylene blue (MB) at the 3'-protruding termini and ferrocene (Fc) in the middle of the loop, first self-assembled on the gold electrode surface via a Au-S bond. In the presence of T-DNA, the T-DNA hybridized with HP, which triggered the Exo III cleavage process and accompanied the release of T-DNA. As a result, the MB tags were away from and the Fc tags close to the gold electrode surface, leading to the decrease of the oxidation peak current of MB (I(MB)) and the increase of that of Fc (I(Fc)). The value of ΔI(Fc)/|ΔI(MB)| (ΔI(Fc) and ΔI(MB) are the change values of the oxidation peak currents of Fc and MB, respectively) is linear with the concentration of T-DNA from 0.01 pM to 0.8 pM. The detection limit (4.16 fM) of the developed method is much lower than that of the most reported electrochemical DNA biosensors. This strategy provides a simple and sensitive approach for the detection of T-DNA and has promising applications in bioanalysis, disease diagnostics, and clinical biomedicine.

Based on the superior electrocatalytic property of graphene (GN) toward ascorbic acid (AA) oxidation, a new electrochemical aptasensor has been developed. Here, adenosine triphosphate (ATP) is used as the model to demonstrate the performance of the developed aptasensor. Briefly, GN is attached to the thiolated ATP binding aptamer (ABA) modified gold electrode through π-π stacking interaction, resulting in a significant oxidation signal of AA. In the presence of ATP, the formation of ATP-ABA complex leads to the release of GN from sensing interface, resulting in a sharp decrease of the oxidation peak current of AA and an obviously positive shift of the related peak potential. Taking both the change values of the peak current and peak potential of AA oxidation as the response signals, ATP can be detected sensitively. This is the first time to demonstrate the application of GN as the nanocatalyst in an amplified aptasensor. It can be expected that GN, as nanocatalyst, should become the very promising amplifying-elements in DNA-based electrochemical biosensors., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this paper, a simple, selective and reusable electrochemical biosensor for the sensitive detection of mercury ions (Hg(2+)) has been developed based on thymine (T)-rich stem-loop (hairpin) DNA probe and a dual-signaling electrochemical ratiometric strategy. The assay strategy includes both "signal-on" and "signal-off" elements. The thiolated methylene blue (MB)-modified T-rich hairpin DNA capture probe (MB-P) firstly self-assembled on the gold electrode surface via Au-S bond. In the presence of Hg(2+), the ferrocene (Fc)-labeled T-rich DNA probe (Fc-P) hybridized with MB-P via the Hg(2+)-mediated coordination of T-Hg(2+)-T base pairs. As a result, the hairpin MB-P was opened, the MB tags were away from the gold electrode surface and the Fc tags closed to the gold electrode surface. These conformation changes led to the decrease of the oxidation peak current of MB (IMB), accompanied with the increase of that of Fc (IFc). The logarithmic value of IFc/IMB is linear with the logarithm of Hg(2+) concentration in the range from 0.5 nM to 5000 nM, and the detection limit of 0.08 nM is much lower than 10nM (the US Environmental Protection Agency (EPA) limit of Hg(2+) in drinking water). What is more, the developed DNA-based electrochemical biosensor could be regenerated by adding cysteine and Mg(2+). This strategy provides a simple and rapid approach for the detection of Hg(2+), and has promising application in the detection of Hg(2+) in real environmental samples., (Copyright © 2014 Elsevier B.V. All rights reserved.)

It has been well established that essentially all microbial mutagens are rodent carcinogens, yet current mutagen detection systems are limited by their detection sensitivity. Here we report the construction of a pair of hypersensitive biosensors by optimizing both reporters and the host strain. The resulting RNR3-yEGFP and HUG1-yEGFP reporters and the septuple yeast mutant in combination with the automated protocol not only remarkably enhance the detection sensitivity, but also allow a high throughput screen of environmental genotoxins. This system is deemed much more sensitive than similar yeast and bacterium-based tests for all selected chemicals examined in this study., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Based on electro-immobilization of guanine on graphene nanoribbon (GNR) modified glassy carbon (GC) electrode, a new electrochemical DNA biosensor was developed for the evaluation of total antioxidant capacities (TAC) in fruit juices. The biosensor relies on the guanine damage that is induced by hydroxyl radical (·OH) generated by Fenton-type reaction. Ascorbic acid (AA), which has the ability to scavenge the ·OH and to protect the guanine immobilized on the electrode surface, was used as the standard antioxidant to evaluate the TAC in fruit juice. Under optimized conditions, the proposed biosensor has excellent analytical performance for antioxidant capacity assessment: wide linear range (0.1 to 4 mg L(-1)), high sensitivity (4.16 μA/mg L(-1)) and low detection limit (0.05 mg L(-1)). Compared with the other electrochemical sensors developed previously, the proposed electrode demonstrates the improved detection limit of about 5 times to one order of magnitude for antioxidant capacity assessment. Additionally, the biosensor was successfully applied to the determination of the TAC in fruit juices., (Copyright © 2012 Elsevier B.V. All rights reserved.)

By using biobarcode nanoparticles, we have successfully constructed a DNA-based biosensor for amplified electrochemical detection of hydroxyl radical (·OH). Thiolated DNA1 (SH-DNA1) was firstly immobilized on the planar gold (Au) electrode. ·OH generated from Fenton reaction could induce serious oxidative damage of the DNA layer adsorbed on the electrode surface, which was monitored by an intercalating probe, methylene blue (MB). In order to enhance the sensitivity of the biosensor, DNA2-functionalized Au nanoparticles (DNA2-AuNPs) were used to amplify the response signal. The developed DNA-based biosensor could detect ·OH quantitatively with wide linear range up to 10mM and low detection limit of 3 μM, and exhibited satisfactory selectivity. On the other hand, this electrochemical biosensor could have potential application in the evaluation of antioxidant capacity., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Hollow nitrogen-doped carbon microspheres (HNCMS) as a novel carbon material have been prepared and the catalytic activities of HNCMS-modified glassy carbon (GC) electrode towards the electro-oxidation of uric acid (UA), ascorbic acid (AA) and dopamine (DA) have also been investigated. Comparing with the bare GC and carbon nanotubes (CNTs) modified GC (CNTs/GC) electrodes, the HNCMS modified GC (HNCMS/GC) electrode has higher catalytic activities towards the oxidation of UA, AA and DA. Moreover, the peak separations between AA and DA, and DA and UA at the HNCMS/GC electrode are up to 212 and 136 mV, respectively, which are superior to those at the CNTs/GC electrode (168 and 114 mV). Thus the simultaneous determination of UA, AA and DA was carried out successfully. In the co-existence system of UA, AA and DA, the linear response range for UA, AA and DA are 5-30 μM, 100-1000 μM and 3-75 μM, respectively and the detection limits (S/N = 3) are 0.04 μM, 0.91 μM and 0.02 μM, respectively. Meanwhile, the HNCMS/GC electrode can be applied to measure uric acid in human urine, and may be useful for measuring abnormally high concentration of AA or DA. The attractive features of HNCMS provide potential applications in the simultaneous determination of UA, AA and DA., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Polymerized ionic liquid-wrapped carbon nanotubes (PIL-CNTs) were firstly designed for direct electrochemistry and biosensing of redox proteins. The CNTs were coated successfully with polymerized ionic liquid (PIL) layer, as verified by transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and Fourier transform infrared (FT-IR) spectroscopy. The PIL-CNTs were dispersed better in water and showed superior electrocatalysis toward O(2) and H(2)O(2) comparing to pristine CNTs and the mixture of IL monomer and CNTs. With glucose oxidase (GOD) as a protein model, the direct electrochemistry of the redox protein was investigated on the PIL-CNTs modified glassy carbon (GC) electrode and excellent direct electrochemical performance of GOD molecules was observed. The proposed biosensor (GOD/PIL-CNTs/GC electrode) displayed good analytical performance for glucose with linear response up to 6mM, response sensitivity of 0.853 microA mM(-1), good stability and selectivity., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)