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DNA nanotweezers (DTs) are reversible DNA nanodevices that can optionally switch between opened and closed states. Due to their excellent flexibility and high programmability, they have been recognized as a promising platform for constructing a diversity of biosensors and logic gates, as well as a versatile tool for molecular biology studies. In this review, we provide an overview of biosensing applications using DTs. First, the design and working principle of DTs are introduced. Next, the signal producing principles of DTs are summarized. Furthermore, biosensing applications of DTs for varying targets and purposes, both in buffers and complex biological environments, are highlighted. Finally, we provide potential opportunities and challenges for the further development of DTs.

Accurate and sensitive detection of targets in practical biological matrixes such as blood, plasma, serum, or tissue fluid is a frontier issue for most biosensors since the coexistence of both potential reducing agents and protein molecules has the possibility of causing signal interference. Herein, aiming at detection in a complex environment, an advanced and robust peptide-based photocathodic biosensor, which integrated a recognition peptide with an antifouling peptide in one probe electrode, was first proposed. Selecting human chorionic gonadotropin (hCG) as a model target, the recognition peptide with the sequence PPLRINRHILTR was first anchored on the CuBi2O4/Au (CBO/Au) photocathode and then the antifouling peptide with the sequence EKEKEKEPPPPC was further anchored to generate an antifouling biointerface. The peptide-based photocathodic biosensor demonstrated excellent anti-interference to both nonspecific proteins and reducing agents because of the capability of the antifouling peptide. It also exhibited good sensitivity owing to the utilization of the recognition peptide rather than an antibody probe. This peptide-integrated method offers a new perspective for practical applications of photocathodic biosensors.

Currently, one of important research directions of photoelectrochemical (PEC) bioanalysis is to exploit innovative photoactive species and their elegant implementations for selective detection and signal transduction. Different from existing candidates for photoelectrode development, this study, exemplified by the cationic dipeptide nanoparticles (CDNPs), reports the first demonstration of self-assembled peptide nanostructures (SAPNs) for the PEC bioanalysis. Specifically, the CDNPs were prepared as representative materials and then immobilized onto the indium tin oxide (ITO) electrode for the PEC differentiation of several commonly involved biomolecules such as ascorbic acid (AA) and l-cysteine. Significantly, the experimental results disclosed that the CDNPs possessed unique photocathodic responses and good analytical performance toward AA detection in terms of rapid response, high stability, and excellent selectivity. This work demonstrates the great potential of the large SAPN family for the future PEC bioanalysis development and has not been reported to our knowledge.

This work reports the innovative design and application of a three-dimensional (3D) TiO2@Cu2O@nickel foam electrode synergized with enzyme catalysis toward the proof-of-concept study for oxygen-ind...

Energy transfer (ET) in photoelectrochemical (PEC) bioanalysis is usually generated between noble metal nanoparticles (NPs) and traditional inorganic quantum dots (QDs). Using the innovative polymer dot (Pdot)-involved ET, this work reports the first signal-on and cathodic PEC bioanalysis toward telomerase (TE) activity in cell extracts. Specifically, the sequential binding of capture DNA (cDNA), telomerase primer sequence (TS), and Au NP-labeled probe DNA (Au NP-pDNA) on the electrode would place the Au NPs in close proximity of the Pdots, leading to obvious quenching of the cathodic photocurrent. The subsequent extension of the TS by TE in the presence of deoxyribonucleoside triphosphates (dNTPs) would then release the Ag NP-pDNA from the electrode, leading to the recovery of the photocurrent. On the basis of the Au NP-induced photocurrent quenching and the recovery of Pdots, a sensitive biosensor could thus be developed by tracking the photocurrents to probe the TE activity. This strategy allows for signal-on and cathodic PEC bioanalysis of TE, which can be easily extended for numerous other targets of interest. We believe this work could offer a new perspective for the rational implementation of Pdot-involved ET for advanced PEC bioanalysis.

This Letter reports a novel synthetic methodology for the fabrication of three-dimensional (3D) nanostructured CdS@carbon fiber (CF) networks and the validation of its feasibility for applications as a general platform for photoelectrochemical (PEC) bioanalysis. Specifically, 3D architectures are currently attracting increasing attention in various fields due to their intriguing properties, while CdS has been most widely utilized for PEC bioanalysis applications because of its narrow band gap, proper conduction band, and stable photocurrent generation. Using CdS as a representative material, this work realized the innovative synthesis of 3D CdS@CF networks via a simple solvothermal process. Exemplified by the sandwich immunoassay of fatty-acid-binding protein (FABP), the as-fabricated 3D CdS@CF networks exhibited superior properties, and the assay demonstrated good performance in terms of sensitivity and selectivity. This work features a novel fabrication of 3D CdS@CF networks that can serve as a general platform for PEC bioanalysis. The methodology reported here is expected to inspire new interest for the fabrication of other 3D nanostructured Cd-chalcogenide (S, Se, Te)@CF networks for wide applications in biomolecular detection and beyond.

The combination of surface-enhanced Raman scattering (SERS) imaging technology with near-infrared (NIR) light-triggered photothermal therapy is of utmost importance to develop novel theranostic platforms. Herein, an aptamer-conjugated Au nanocage/SiO2 (AuNC/SiO2/Apt) core-shell Raman nanoprobe has been rationally designed as the bifunctional theranostic platform to fulfill this task. In this theranostic system, the Raman-labeled Au nanocage (AuNC) was encapsulated into a bioinert shell of SiO2, followed by conjugating aptamer AS1411 as the target-recognition moiety. AuNC served as the SERS-active and photothermal substrate due to its large free volume, built-in plasmon effect, and NIR photothermal capacity, while the SiO2 coating endowed the nanoprobes with good stability and biocompatibility, as well as abundant anchoring sites for surface functionalization. Considering their prominent SERS and photothermal properties, the application potential of the AuNC/SiO2/Apt nanoprobes was investigated. The proposed nanoprobes could be applied to targeted detection and SERS imaging of nucleolin-overexpressing cancer cells (MCF-7 cells as the model) from normal cells and also exhibited acceptable photothermal efficacy without systematic toxicity. This theranostic nanoplatform provided a possible opportunity for in situ diagnosis and noninvasive treatment of cancer cells by SERS imaging-guided photothermal therapy.

An ultrasensitive photoelectrochemical (PEC) biosensor was developed based on cosensitization of biocompatible CuInS2/ZnS quantum dots (ZCIS QDs) and N-doped carbon dots (N-CDs) coupled with dual c...

Previous work on photoelectrochemical (PEC) biosensors has demonstrated that the photoanode-based type possesses satisfying sensitivity, because photoanode utilize electrons as the majority charge carriers and a distinct photocurrent can be generated when electron donors are furnished. However, as hole-oxidation reaction occurs at the photoanode interface, the photoanode-based PEC sensor has inferior anti-interference capacity to reductive substances coexisting in the biological sample, leading to a challenged selectivity. Herein, a universal design on selectivity-enhanced PEC enzyme sensor was proposed by integrating a photoanode with a biocathode. Specifically, the CuInS2 sensitization layer and ZnS passivation layer were deposited in sequence on the TiO2 film modified indium-tin oxide (ITO) electrode mainly by successive ionic layer adsorption and reaction (SILAR) means, forming the hybrid ZnS/CuInS2/TiO2/ITO photoanode. A carbon fiber paper (CFP) electrode was modified with biocatalysts of enzymes via the assistance of chitosan (CS) to fabricate the biocathode. Utilizing glucose oxidase (GOx) and horserdish peroxidase (HRP) as biocatalysts, a selectivity-enhanced PEC sensor for glucose was developed. The PEC sensing platform integrating photoanode with biocathode not only inherits distinct photocurrent of the photoanode-based sensor but also possesses enhanced selectivity, because just the biocathode was incubated in the biological sample and there is no interaction between the photoanode and coexisting reductive substances.

The ability to rapidly detect apoptotic cells and accurately evaluate therapeutic effects is significant in cancer research. To address this target, a biocompatible, ultrasensitive photoelectrochemical (PEC) cytosensing platform was developed based on electrochemically reduced graphene (EG)/ZnIn2S4 cosensitized TiO2 coupled with specific recognition between apoptotic cells and phosphatidylserine-binding peptide (PSBP). In this strategy, the HL-60 cells were selected as a model and C005, nilotinib, and imatinib were selected as apoptosis inducers to show cytosensing performances. In particular, a TiO2 photoactive substrate was designed as hollow spheres to enhance the PEC performance. Graphene was electrodeposited on the hollow TiO2-modified electrode to accelerate electron transfer and increase conductivity, followed by in situ growth of ZnIn2S4 nanocrystals as photosensitizers via successive ionic layer adsorption and reaction method, forming a TiO2/EG/ZnIn2S4 cosensitized structure that was used as a PE...

Sensitive and accurate analysis of DNA is crucial to better understanding of DNA functions and early diagnosis of fatal disease. Herein, an enhanced photoelectrochemical (PEC) DNA biosensor was proposed based on dual-signal amplification via coupling inorganic-organic nanocomposites sensitization with λ-exonuclease (λ-Exo)-assisted target recycling. The short DNA sequence about chronic myelogenous leukemia (CML, type b3a2) was selected as target DNA (tDNA). ZnO nanoplates were deposited with CdS nanocrystals to form ZnO/CdS hetero-nanostructure, and it was used as PEC substrate for immobilizing hairpin DNA (hDNA). CdTe quantum dots (QDs) covalently linked with meso-tetra(4-carboxyphenyl)porphine (TCPP) to form CdTe/TCPP inorganic-organic nanocomposites, which were utilized as sensitization agents labeling at the terminal of probe DNA (pDNA). When the hDNA-modified sensing electrode was incubated with tDNA and λ-Exo, hDNA hybridized with tDNA, and meanwhile it could be recognized and cleaved by λ-Exo, resulting in the release of tDNA. The rest of nonhybridized hDNA would continuously hybridize with the released tDNA, cleave by λ-Exo, and set free the tDNA again. After λ-Exo-assisted tDNA recycling, more amounts of short DNA (sDNA) fragments coming from digestion of hDNA produced on the electrode and hybridized with CdTe/TCPP-labeled pDNA (pDNA-CdTe/TCPP conjugates). In this case, the sensitization of CdTe/TCPP inorganic-organic nanocomposites occurred, which evidently extend the absorption range and strengthened the absorption intensity of light energy, and accordingly the photocurrent signal significantly promoted. Through introducing the dual-signal amplification tactics, the developed PEC assay allowed a low calculated detection limit of 25.6 aM with a wide detection scope from 0.1 fM to 5 pM for sensitive and selective determination of tDNA.

A new, ultrasensitive photoelectrochemical immunosensing platform was established on the basis of CdSeTe@CdS:Mn core-shell quantum dots-sensitized TiO2 coupled with signal amplification of CuS nanocrystals conjugated signal antibodies. In this proposal, carcinoembryonic antigen (CEA, Ag) was selected as an example of target analyte to show the analytical performances of the platform. Specifically, TiO2-modified electrode was first assembled with CdSeTe alloyed quantum dots (AQDs) via electrostatic adsorption assisted by oppositely charged polyelectrolyte, and then further deposited with CdS:Mn shells on the surface of CdSeTe AQDs via successive ionic layer adsorption and reaction strategy, forming TiO2/CdSeTe@CdS:Mn sensitization structure, which was used as photoelectrochemical matrix to immobilize capture CEA antibodies (Ab1); signal CEA antibodies (Ab2) were labeled with CuS nanocrystals (NCs) to form Ab2-CuS conjugates, which were employed as signal amplification elements when specific immunoreaction occurred. The ultrahigh sensitivity of this immunoassay resulted from the following two aspects. Before detection of target Ag, the TiO2/CdSeTe@CdS:Mn sensitization structure could adequately harvest the exciting light with different bands, evidently expedite the electron transfer, and effectively depress the charge recombination, resulting in noticeably increased photocurrent. When target Ag existed, the Ab2-CuS conjugates could dramatically decrease the photocurrent due to competitive absorption of exciting light and consumption of electron donor for CuS NCs coupled with steric hindrance of Ab2 molecules. The fabricated photoelectrochemical immunosensor showed a low limit of detection of 0.16 pg/mL and a wide linear range from 0.5 pg/mL to 100 ng/mL for CEA detection, and it also exhibited good specificity, reproducibility, and stability.

A novel photoelectrochemical aptasensor for adenosine triphosphate (ATP) detection was developed by introducing inorganic–organic photoactive nanocomposites as sensitization agents to achieve significant signal amplification. Specifically, a TiO2/Au hybrid structure was first fabricated by decorating Au nanoparticles on the surface of TiO2 film, which then was used as the photoelectrochemical matrix for the immobilization of ATP aptamer probes; amino-functionalized CdS:Mn (CdS:Mn-NH2) nanocrystals covalently bound with Ru(bpy)2(dcbpy)2+ (bpy = 2,2′-bipyridine; dcbpy = 2,2′-bipyridine-4,4′-dicarboxylic acid) to form CdS:Mn@Ru(bpy)2(dcbpy) photoactive nanocomposites, which were employed as signal amplification element labeling on the terminal of ATP aptamer probes. The ATP detection was performed via the photocurrent variation produced by the conformation change of ATP aptamer probes after specifically binding with ATP molecules. Before incubation with ATP, the ATP aptamer probe hybridized with its partly c...

An ultrasensitive photoelectrochemical sandwich immunoassay was developed to detect matrix metalloproteinase-2 (MMP-2, antigen, Ag) based on CdS:Mn/CdTe cosensitized TiO2 nanotubes (TiO2-NTs) and signal amplification of SiO2@Ab2 conjugates. Specifically, the TiO2-NTs electrode was first deposited with CdS:Mn by successive ionic layer adsorption and reaction technique and then further coated with CdTe quantum dots (QDs) via the layer-by-layer method, forming TiO2-NTs/CdS:Mn/CdTe cosensitized structure, which was employed as a matrix to immobilize capture MMP-2 antibodies (Ab1); whereas, SiO2 nanoparticles were coated with signal MMP-2 antibodies (Ab2) to form SiO2@Ab2 conjugates, which were used as signal amplification elements via the specific antibody-antigen immunoreaction between Ag and Ab2. The ultrahigh sensitivity of this immunoassay derived from the two major reasons as below. First, the TiO2-NTs/CdS:Mn/CdTe cosensitized structure could adequately absorb the light energy, dramatically promote electron transfer, and effectively inhibit the electron-hole recombination, resulting in significantly enhanced photocurrent intensity of the sensing electrode. However, in the presence of target Ag, the immobilized SiO2@Ab2 conjugates could evidently increase the steric hindrance of the sensing electrode and effectively depress the electron transfer, leading to obviously decreased photocurrent intensity. Accordingly, the well-designed photoelectrochemical immunoassay exhibited a low detection limit of 3.6 fg/mL and a wide linear range from 10 fg/mL to 500 pg/mL for target Ag detection. Meanwhile, it also presented good reproducibility, specificity, and stability and might open a new promising platform for the detection of other important biomarkers.

A TiO2/CdS:Mn hybrid structure cosensitized with two different sizes of CdTe quantum dots (QDs) was designed to develop a novel and ultrasensitive photoelectrochemical DNA assay. In this protocol, TiO2/CdS:Mn hybrid structure was prepared by successive adsorption and reaction of Cd(2+)/Mn(2+) and S(2-) ions on the surface of TiO2 film and then was employed as matrix for immobilization of hairpin DNA probe, whereas large-sized CdTe-COOH QDs and small-sized CdTe-NH2 QDs as signal amplification elements were successively labeled on the terminal of hairpin DNA probe. The target DNA detection was based upon the photocurrent change originated from conformation change of the hairpin DNA probe after hybridization with target DNA. In the absence of target DNA, the immobilized DNA probe was in the hairpin form and the anchored different sizes of CdTe-COOH and CdTe-NH2 QDs were close to the TiO2/CdS:Mn electrode surface, which led to a very strong photocurrent intensity because of the formation of the cosensitized structure. However, in the presence of target DNA, the hairpin DNA probe hybridized with target DNA and changed into a more rigid, rodlike double helix, which forced the multianchored CdTe QDs away from the TiO2/CdS:Mn electrode surface, resulting in significantly decreased photocurrent intensity because of the vanished cosensitization effect. By using this cosensitization signal amplification strategy, the proposed DNA assay could offer an ultrasensitive and specific detection of DNA down to 27 aM, and it opened up a new promising platform to detect various DNA targets at ultralow levels for early diagnoses of different diseases.