Cyclic Enzymatic Signal Amplification-Driven DNA Logic Nanodevices on Framework Nucleic Acid for Highly Sensitive Electrochemiluminescence Detection of Dual Myocardial miRNAs.

MicroRNAs (miRNAs) have emerged as promising biomarkers for acute myocardial infarction (AMI). There is an urgent imperative to develop analytical methodologies capable of intelligently discerning multiple circulating miRNAs. Here, we present a dual miRNA detection platform for AMI using DNA logic gates coupled with an electrochemiluminescence (ECL) response.

The Compact Integration of Multiple Exonuclease III-Assisted Cyclic Amplification Units for High-Efficiency Ratiometric Electrochemiluminescence Detection of MRSA.

Methicillin-resistant (MRSA) exhibits multiresistance to a plethora of antibiotics, therefore, accurate detection methods must be employed for timely identification to facilitate effective infection control measures. Herein, we construct a high-efficiency ratiometric electrochemiluminescent (ECL) biosensor that integrates multiple exonuclease (Exo) III-assisted cyclic amplification units for rapid detection of trace amounts of MRSA. The target bacteria selectively bind to the aptamer, triggering the release of two single-stranded DNAs.

Three-Dimensional Surface-Enhanced Raman Scattering Platform with Hotspots Built by a Nano-mower for Rapid Detection of MRSA.

Methicillin-resistant (MRSA) has become one of the greatest threats to human health due to its strong drug resistance, wide distribution range, and high infection rate. Rapid identification of MRSA strains is very important for accurate diagnosis and early treatment of MRSA infections. Here, we introduced an Exo III-assisted nanomotor mower to build 3D hotspots for rapid detection of MRSA by surface-enhanced Raman scattering (SERS).

Spectrally tunable humic acid-based carbon dots: a simple platform for metronidazole and ornidazole sensing in multiple real samples.

Humic acid-based carbon dots (HACDs) have excellent properties and are widely used in environmental detection, bioimaging, and optoelectronic materials. Herein, we investigated the structure-activity relationship between the morphology and optical properties of HACDs, and reported on a novel strategy for metronidazole (MNZ) and ornidazole (ONZ) sensing in multiple real samples. It was found that the average particle size decreased from 3.

Multistage nucleic acid amplification induced nano-aggregation for 3D hotspots-improved SERS detection of circulating miRNAs.

Circulating miRNAs in the blood can regulate disease development and thus indicate disease states via their various expression levels. For these reasons, circulating miRNAs constitute useful biomarkers, and an approach to the accurate detection of circulating miRNAs is attractive in the diagnosis and treatment of diseases. However, methods for clinical detecting of circulating miRNA that take both sensitivity and practicality into account are still needed.

Reversible Ratiometric Electrochemiluminescence Biosensor Based on DNAzyme Regulated Resonance Energy Transfer for Myocardial miRNA Detection.

Myocardial miRNAs in peripheral blood are closely related to the pathogenic process of myocardial infarction. Rapid identification and accurate quantification of myocardial miRNAs are of great significance to clinical interventions for treating cardiovascular lesions. Therefore, a ratiometric electrochemiluminescence (ECL) biosensor integrating DNAzyme with a resonance energy transfer (RET) system was designed to detect myocardial miRNA.

Band-pass filter-assisted ratiometric fluorescent nanoprobe composed of N-(2-aminoethyl-1,8-naphthalimide)-functionalized gold nanoclusters for the determination of alkaline phosphatase using digital image analysis.

A smartphone-based dual-wavelength digital imaging platform containing red (539-695 nm) and blue (389-511 nm) band-pass filters was developed for point-of-care (POC) testing of alkaline phosphatase (ALP) activity. The platform was based on dual-emitting fluorescent nanohybrids (AuNC@NAN), the ratiometric probe, which had a fluorescence "on-off-on-off" response. The probe comprised red-emitting gold nanoclusters (AuNCs) acting as the signal report units and blue-emitting N-(2-aminoethyl-1,8-naphthalimide) (NAN) acting as an internal reference.

A Multitargeted Electrochemiluminescent Biosensor Coupling DNAzyme with Cascading Amplification for Analyzing Myocardial miRNAs.

Several circulating miRNAs are associated with the pathogenic process of acute myocardial infarction (AMI). Thus, analyzing myocardial miRNAs in the circulatory system is important for the diagnosis and treatment of AMI, especially for early-stage diagnosis. Based on the characteristics of myocardial miRNAs, an ultrasensitive and multitargeted electrochemiluminescence (ECL) sensing platform was developed with a versatile probe that can couple DNAzyme with hybridization chain reaction amplification.

Hemin-Bridged MOF Interface with Double Amplification of G-Quadruplex Payload and DNAzyme Catalysis: Ultrasensitive Lasting Chemiluminescence MicroRNA Imaging.

Here, we report a double-amplified sensing platform for ultrasensitive chemiluminescence (CL) miRNA detection in real patients' blood in which a hemin-bridged metal-organic framework (MOF) is employed as a functional interface to boost the payload and catalysis of G-quadruplex (G4) DNAzymes. Hemin is here used as the organic ligand for the MOF synthesis, which endows the MOF with an intrinsic peroxidase-like catalytic activity. Most importantly, the MOF surface provides a large amount of binding sites for polymeric G4 DNAzymes that are produced by miRNA-triggered rolling circle amplification reactions, and meanwhile, the interfaced G4 DNAzymes on MOFs (G4/MOFzymes) display an about 100-fold higher catalytic activity than those in solution.

Target-Catalyzed Self-Growing Spherical Nucleic Acid Enzyme (SNAzyme) as a Double Amplifier for Ultrasensitive Chemiluminescence MicroRNA Detection.

Portable chemiluminescence (CL) imaging with a smartphone has shown a great promise for point-of-care testing of diseases, especially for acute myocardial infarction (AMI), which may occur abruptly. A challenge remains how to improve the imaging sensitivity that usually is several orders of magnitude lower than those of counterpart methodologies using the sophisticated equipment. Toward this goal, here, we report the target-triggered in situ growth of AuNP@hairpin-DNA nanoprobes into spherical nucleic acid enzymes (SNAzymes), which serve as both nanolabels and amplifiers for portable CL imaging of microRNAs (miRNAs) with an ultrahigh sensitivity comparable to that of the instrumental measurement under same conditions.

Target-Induced Payload Amplification for Spherical Nucleic Acid Enzyme (SNAzyme)-Catalyzed Electrochemiluminescence Detection of Circulating microRNAs.

A high level of circulating myocardial microRNAs (miRNAs) is commonly considered as one indicator of acute myocardial infarction (AMI) for early stage diagnosis, and hence, it is of particular significance to develop ultrasensitive methodologies for detecting these miRNAs in circulating blood. Here we build an electrochemiluminescence (ECL) sensing platform for circulating miRNAs utilizing AuNPs@G-quadruplex (G4) spherical nucleic acid enzyme (SNAzyme) as the nanocatalyst, which shows good stability, strong nuclease resistance, and improved catalytic performance toward a luminol-HO ECL system than the commonly used G4 DNAzyme. Target miRNA is employed to open the probe hairpin DNA to trigger the cascade amplification and then produce a long dsDNA chain with many sticky linkers that capture the SNAzyme nanocatalyst onto the electrode.

Spherical Nucleic Acid Enzyme (SNAzyme) Boosted Chemiluminescence miRNA Imaging Using a Smartphone.

As acute myocardial infarction (AMI) has now become a severe death threat to humans and may abruptly occur at home or outdoors where sophisticated equipment is not available, it is of great importance to develop facile methodologies for the point-of-care (POC) diagnosis of AMI. Toward this goal, here we build a sensing platform for chemiluminescence (CL) microRNA (miRNA) imaging with a smartphone as the portable detector, and for the first time we achieve visualization of AMI-related miRNAs in real patients' serum. We first construct a spherical nucleic acid enzyme (termed SNAzyme) derived from a dense layer of G-quadruplex (G4) DNAzyme formed on the gold nanoparticle core, which displays ∼100-fold and higher catalytic activity and improved resistance to nuclease degradation in a real blood sample as compared to those of the G4 DNAzyme itself.

Composition-Tunable Hollow Au/Ag SERS Nanoprobes Coupled with Target-Catalyzed Hairpin Assembly for Triple-Amplification Detection of miRNA.

Detecting disease-related biomarkers is of great significance for disease diagnosis and therapy. In this work, we develop an ultrasensitive surface-enhanced Raman scattering (SERS) biosensor for the detection of an acute myocardial infarction-related miRNA (miR-133a) using composition-adjustable hollow Ag/Au nanosphere-based SERS probes coupled with the target-catalyzed hairpin assembly (CHA) strategy. Bimetallic probes displaying high stability and a strong surface plasmon resonance effect were synthesized with a controllable ratio of silver and gold by a galvanic replacement method and then captured by a duplex linker produced in the CHA process to accomplish signal amplification.

Cellular environment-responsive intelligent DNA logic circuits for controllable molecular sensing.

Here we report smart molecular logic circuits built on a well-designed H-shaped DNA nanostructure that can recognize cell-simulated bioenvironments and modulate the operations of a DNA nanosensor. By assembling a wild-type ATP aptamer and a parallel G-quadruplex into the H-shaped DNA scaffold, two intrinsic cellular components, ATP and K, are utilized to activate the logic circuits, enabling fluorescent detection of the target DNA via toehold-mediated strand displacement. In this way, two logic circuits consisting of cascaded "AND-AND" and "OR-AND" gates are achieved, which are responsive to the ATP and/or K concentration change outside and inside cells, and therefore control whether or not the downstream DNA sensor works.

Ultrasensitive Simultaneous Detection of Multiplex Disease-Related Nucleic Acids Using Double-Enhanced Surface-Enhanced Raman Scattering Nanosensors.

Developing ultrasensitive probes holds great significance for simultaneous detection of multiplexed cancer-associated nucleic acids. Bimetallic nanoparticles containing silver may be exploited as nanoprobes for disease detection, which can produce stable and strong surface-enhanced Raman scattering (SERS) signals. However, it remains extremely challenging that such SERS nanoprobes are directly synthesized.

Probing the propeller-like loops of DNA G-quadruplexes with looped-out 2-aminopurine for label-free switchable molecular sensing.

We report a new signal readout mechanism for DNA molecular sensing devices using ligand-free fluorogenic G-quadruplexes in which the propeller-like loops are distinguished from the diagonal and lateral loops with incorporated 2-aminopurine (2-AP, a fluorescent analogue of adenine). We study the fluorescence behavior of looped-out 2-AP in duplexes and G-quadruplexes and demonstrate that it shows better fluorescence properties in shorter loops. In particular, 2-AP in the propeller-like loops of parallel or hybrid G-quadruplexes displays a perfect fluorescence emission whereas that in the diagonal and lateral loops does not.

Exonuclease III-boosted cascade reactions for ultrasensitive SERS detection of nucleic acids.

A variety of nucleic acid amplification techniques have been integrated into different detection methods to promote the development of sensitive and convenient analysis of nucleic acids. However, it is still in urgent need to develop amplified nucleic acid biosensors for the analysis of susceptible gene and even distinguishing single-base mismatched DNA in complex biological samples. Benefiting from the achieved detection strategies, here we boost isothermal nucleic acid amplification by resorting to enzyme amplification, and combine this two-stage amplification method with surface-enhanced Raman spectroscopy (SERS) to develop a signal-on nucleic acid detection platform.

Three-dimensional hotspots in evaporating nanoparticle sols for ultrahigh Raman scattering: solid-liquid interface effects.

Three-dimensional (3D) hotspots for ultrahigh surface-enhanced Raman scattering (SERS) has been experimentally demonstrated by evaporating a droplet of citrate-Ag sols on both hydrophobic and hydrophilic flat surfaces. Interestingly, the hydrophobic surface increased the Raman enhancement by two orders of magnitude and exhibits a better signal stability than the hydrophilic one. This study highlights the differences between hydrophilic and hydrophobic surfaces in enhanced Raman scattering by the use of extremely diluted rhodamine 6G (R6G) as the SERS reporter.

Unravelling the relationship between Raman enhancement and photocatalytic activity on single anisotropic Au microplates.

Anisotropic noble-metal structures are attracting increasing attention because of interesting size- and shape-dependent properties and have emerging applications in the fields of optics and catalysis. However, it remains a significant challenge to overcome chemical contributions and acquire molecular insight into the relationship between Raman enhancement and photocatalytic activity. This study gives visualized experimental evidence of the anisotropic spatial distribution of Raman signals and photocatalytic activity at the level of single nanometer-thin Au microtriangles and microhexagons.

Three-dimensional and time-ordered surface-enhanced Raman scattering hotspot matrix.

The "fixed" or "flexible" design of plasmonic hotspots is a frontier area of research in the field of surface-enhanced Raman scattering (SERS). Most reported SERS hotspots have been shown to exist in zero-dimensional point-like, one-dimensional linear, or two-dimensional planar geometries. Here, we demonstrate a novel three-dimensional (3D) hotspot matrix that can hold hotspots between every two adjacent particles in 3D space, simply achieved by evaporating a droplet of citrate-Ag sols on a fluorosilylated silicon wafer.

Cetylpyridinium chloride activated trinitrotoluene explosive lights up robust and ultrahigh surface-enhanced resonance Raman scattering in a silver sol.

Surface-enhanced resonance Raman scattering (SERRS) is not realized for most molecules of interest. Here, we developed a new SERRS platform for the fast and sensitive detection of 2,4,6-trinitrotoluene (TNT), a molecule with low Raman cross section. A cationic surfactant, cetylpyridinium chloride (CPC) was modified on the surface of silver sols (CP-capped Ag).