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The ability to design nanostructures with arbitrary shapes and controllable motions has made DNA nanomaterials used widely to construct diverse nanomachines with various structures and functions. The DNA nanostructures exhibit excellent properties, including programmability, stability, biocompatibility, and can be modified with different functional groups. Among these nanoscale architectures, DNA walker is one of the most popular nanodevices with ingenious design and flexible function. In the past several years, DNA walkers have made amazing progress ranging from structural design to biological applications including constructing biosensors for the detection of cancer‐associated biomarkers. In this review, the key driving forces of DNA walkers are first summarized. Then, the DNA walkers with different numbers of legs are introduced. Furthermore, the biosensing applications of DNA walkers including the detection‐ of nucleic acids, proteins, ions, and bacteria are summarized. Finally, the new frontiers and opportunities for developing DNA walker‐based biosensors are discussed. [ABSTRACT FROM AUTHOR]

Development of new nanostructured materials has shown high impact for improving the performance of chemical and biological sensors. In this work, we show that by controlling the dimensions of the gold flower microelectrode (GFME), it is possible to regulate detection sensitivity of a sensor for rapid analysis of chemical species. A ~13-fold increase in sensitivity was achieved by enlarging the dimension of GFMEs from 70 to 330 μm, whereas the response dynamics are dimension-independent, with the signal attaining saturation ~20 s. Due to the intrinsic nanostructure on the microelectrode surface, our GFME exhibits excellent anti-interference property when applied to detect dopamine (DA) in the presence of 10-fold excess of ascorbic acid (AA). The regulable sensitivity, fast response dynamics, and excellent anti-interference property will make GFME an ideal sensing platform for biomedical applications. [ABSTRACT FROM AUTHOR]

Biosensors are a type of important biodevice that integrate biological recognition elements, such as enzyme, antibody and DNA, and physical or chemical transducers, which have revolutionized clinical diagnosis especially under the context of point-of-care tests. Since the performance of a biosensor depends largely on the bio–solid interface, design and engineering of the interface play a pivotal role in developing quality biosensors. Along this line, a number of strategies have been developed to improve the homogeneity of the interface or the precision in regulating the interactions between biomolecules and the interface. Especially, intense efforts have been devoted to controlling the surface chemistry, orientation of immobilization, molecular conformation and packing density of surface-confined biomolecular probes (proteins and nucleic acids). By finely tuning these surface properties, through either gene manipulation or self-assembly, one may reduce the heterogeneity of self-assembled monolayers, increase the accessibility of target molecules and decrease the binding energy barrier to realize high sensitivity and specificity. In this review, we summarize recent progress in interfacial engineering of biosensors with particular focus on the use of protein and DNA nanostructures. These biomacromolecular nanostructures with atomistic precision lead to highly regulated interfacial assemblies at the nanoscale. We further describe the potential use of the high-performance biosensors for precision diagnostics. [ABSTRACT FROM AUTHOR]

Abstract: Weak ligand–receptor recognition events are often amplified by recruiting multiple regulatory biomolecules to the action site in biological systems. However, signal amplification in in vitro biomimetic systems generally lack the spatiotemporal regulation in vivo. Herein we report a framework nucleic acid (FNA)‐programmed strategy to develop valence‐controlled signal amplifiers with high modularity for ultrasensitive biosensing. We demonstrated that the FNA‐programmed signal amplifiers could recruit nucleic acids, proteins, and inorganic nanoparticles in a stoichiometric manner. The valence‐controlled signal amplifier enhanced the quantification ability of electrochemical biosensors, and enabled ultrasensitive detection of tumor‐relevant circulating free DNA (cfDNA) with sensitivity enhancement of 3–5 orders of magnitude and improved dynamic range. [ABSTRACT FROM AUTHOR]

Fast, portable and sensitive analysis of E. coli is becoming an important challenge in many critical fields (e.g., food safety, environmental monitoring and clinical diagnosis). Thus, electrochemical biosensing of PCR amplicons from the bacterial genome has attracted reasonable research attention. In this work, we utilized a 3D DNA tetrahedral probe to establish a “sandwich-type” electrochemical DNA biosensor for sensitive and specific analysis of a 250 bp unpurified PCR amplicon from the uidA gene of the E. coli genome. Asymmetric PCR was used to produce single-stranded PCR products. Streptavidin–polyHRP80 was employed to improve the signal gain during electrochemical detection. We optimized important experimental conditions for DNA sensing, including the streptavidin–polyHRP, the signal probe and the ion strength. Finally, we achieved a remarkable sensitivity of 10 fM synthetic DNA target, and successfully performed the analysis of PCR amplicons from as low as 0.2 pg μL−1 of E. coli genome. Compared with traditional single stranded DNA (ssDNA) probe based detection, our present work demonstrated 3 orders of magnitude improvement in sensitivity. In addition, our electrochemical DNA biosensor was 4 orders of magnitude more sensitive than normal electrophoretic analysis of PCR products. Our work made important progress in DNA nanostructured probe-based biosensors toward application in real applications. [ABSTRACT FROM AUTHOR]

Self-assembled DNA nanostructures with precise sizes allow a programmable 'soft lithography' approach to engineer the interface of electrochemical DNA sensors. By using millimeter-sized gold electrodes modified with several types of tetrahedral DNA nanostructures (TDNs) of different sizes, both the kinetics and thermodynamics of DNA hybridization were profoundly affected. Because each DNA probe is anchored on an individual TDN, its lateral spacing and interactions are finely tuned by the TDN size. By simply varying the size of the TDNs, the hybridization time was decreased and the hybridization efficiency was increased. More significantly, the detection limit for DNA detection was tuned over four orders of magnitude with differentially nanostructured electrodes, and achieved attomolar sensitivity with polymeric enzyme amplification. [ABSTRACT FROM AUTHOR]

Electrochemical DNA biosensor has unique advantages for on-site pathogenic microorganism detection, yet the detection of long DNA towards genome DNA (gDNA) analysis remains challenge. In this work, we report a novel electrochemical biosensor for the ultrasensitive analysis of mecA DNA on methicillin-resistant Staphylococcus aureus (MRSA) genome, using a multi-signal probes (MSP) system. The MSP consists of 7 biotin-labelled signal probes that will combine to the target DNA in a prehybridization step, and then the complex will be captured by a DNA tetrahedron structure probe (TSP) on the electrode surface. Then, after the introduction of the streptavidin-labelled HRP enzyme, a catalysis current signal is detected that is found to be corresponding to the concentration of the target DNA. MSP in this work plays a critical role not only for the signal amplification through bringing 7 biotins, but also dramatically improves the accessibility of the target sequence embedded in the double-strand DNA molecules and complex second structures. The 3-D DNA TSP here provides steady support and optimized surface density for the very "large" complex of MSP system and gDNA, as a base of the capture probe. Finally, as low as 10 fM synthetic target DNA was successfully detected, which is at least 3 magnitudes lower than that using single signal probe. Most importantly, we demonstrated the practicability of our analysis method by analyzing a 57 fM MRSA gDNA sample showing excellent selectivity, and the reliability of the analysis was also demonstrated by digital PCR. [ABSTRACT FROM AUTHOR]

During the past few years, graphene and graphene oxide (GO) have attracted numerous attentions for the potential applications in various fields from energy technology, biosensing to biomedical diagnosis and therapy due to their various functionalization, high volume surface ratio, unique physical and electrical properties. Among which, graphene and graphene oxide based fluorescent biosensors enabled by their fluorescence-quenching properties have attracted great interests. The fluorescence of fluorophore or dye labeled on probes (such as molecular beacon, aptamer, DNAzymes and so on) was quenched after adsorbed on to the surface of graphene. While in the present of the targets, due to the strong interactions between probes and targets, the probes were detached from the surface of graphene, generating dramatic fluorescence, which could be used as signals for detection of the targets. This strategy was simple and economy, together with great programmable abilities of probes; we could realize detection of different kinds of species. In this review, we first briefly introduced the history of graphene and graphene oxide, and then summarized the fluorescent biosensors enabled by graphene and GO, with a detailed account of the design mechanism and comparison with other nanomaterials (e.g. carbon nanotubes and gold nanoparticles). Following that, different sensing platforms for detection of DNAs, ions, biomolecules and pathogens or cells as well as the cytotoxicity issue of graphene and GO based in vivo biosensing were further discussed. We hope that this review would do some help to researchers who are interested in graphene related biosening research work. [ABSTRACT FROM AUTHOR]

Microarrays of biomolecules hold great promise in the fields of genomics, proteomics, and clinical assays on account of their remarkably parallel and high-throughput assay capability. However, the fluorescence detection used in most conventional DNA microarrays is still limited by sensitivity. In this study, we have demonstrated a novel universal and highly sensitive platform for fluorescent detection of sequence specific DNA at the femtomolar level by combining dextran-coated microarrays with hybridization chain reaction (HCR) signal amplification. Three-dimensional dextran matrix was covalently coated on glass surface as the scaffold to immobilize DNA recognition probes to increase the surface binding capacity and accessibility. DNA nanowire tentacles were formed on the matrix surface for efficient signal amplification by capturing multiple fluorescent molecules in a highly ordered way. By quantifying microscopic fluorescent signals, the synergetic effects of dextran and HCR greatly improved sensitivity of DNA microarrays, with a detection limit of 10 fM (1×10 5 molecules). This detection assay could recognize one-base mismatch with fluorescence signals dropped down to ~20%. This cost-effective microarray platform also worked well with samples in serum and thus shows great potential for clinical diagnosis. [ABSTRACT FROM AUTHOR]

Mercury (II) ion (Hg 2+ ) contamination can be accumulated along the food chain and cause serious threat to the public health. Plenty of research effort thus has been devoted to the development of fast, sensitive and selective biosensors for monitoring Hg 2+ . Thymine was demonstrated to specifically combine with Hg 2+ and form a thymine–Hg 2+ –thymine (T–Hg 2+ –T) structure, with binding constant even higher than T-A Watson-Crick pair in DNA duplex. Recently, various novel Hg 2+ biosensors have been developed based on T-rich Mercury-Specific Oligonucleotide (MSO) probes, and exhibited advanced selectivity and excellent sensitivity for Hg 2+ detection. In this review, we explained recent development of MSO-based Hg 2+ biosensors mainly in 3 groups: fluorescent biosensors, colorimetric biosensors and electrochemical biosensors. [ABSTRACT FROM AUTHOR]