A novel fluorescent sensor with an overtone peak reference for highly sensitive detection of mercury (II) ions and hydrogen sulfide: Mechanisms and applications in environmental monitoring and bioanalysis.

The present study introduces a novel fluorescent sensor with an overtone peak reference designed for the detection of mercury (Ⅱ) ions (Hg2+) and hydrogen sulfide (H2S). The study proposes two novel response mechanisms that hinges on the synergistic effect of cation exchange dissociation (CED) and photo-induced electron transfer (PET). This sensor exhibits a remarkable detection limit of 2.9 nM for Hg2+. Additionally, the sensor reacts with H2S to generate nickel sulfide (NiS) semiconductor nanoparticles, which amplify the fluorescence signal and enable a detection limit of 3.1 nM for H2S. The detection limit for H2S is further improved to 29.1 pM through the surface functionalization of the nanomaterial with pyridine groups (increasing reactivity) and chelation of gold nanoparticles (AuNPs), which enhances the sensor's specificity. This improvement is primarily due to the surface plasmon resonance (SPR) of AuNPs and their affinity for H2S. The single-emission strategy can yield skewed results due to environmental changes, whereas the overtone peak reference strategy enhances result accuracy and reliability by detecting environmental interference through reference emission peaks. In another observation, the low-toxicity dihydropyrene-bipyridine nanorods (TPP-BPY) has been successfully utilized for both endogenous and exogenous H2S detection in vivo using a mouse model. The successful development of TPP-BPY is expected to provide an effective tool for studying the role of H2S in biomedical systems.

Dual-mode fluorescence and electrochemiluminescence sensors based on Ru-MOF nanosheets for sensitive detection of apoE genes.

A fluorescence-electrochemiluminescence (FL-ECL) dual-mode sensor for apoE gene detection has been developed, leveraging the unique properties of ruthenium metal organic framework nanosheets (RuMOFNSs). The system utilizes the quenching effect of the Ru(bpy)32+ ECL signal by ferrocene, leading to the synthesis of a multi-electron electrical signal marker, bisferrocene. By immobilizing the P-DNA on RuMOFNSs, bisferrocene quenches both FL and ECL signals. The addition of T-DNA and the consequent formation of double-stranded DNA enable the ExoIII enzyme to excise the bisferrocene fragment, restoring the signals. The sensor demonstrates wide detection linear ranges (1 fM to 1 nM for FL and 0.01 fM to 10 pM for ECL) and remarkable sensitivity (0.048 fM for FL and 0.016 fM for ECL). The dual-mode design offers enhanced reliability through a self-correction feature, reducing false positives. Compared to single-mode sensors, the dual-mode sensor shows significant advantages. Real-world testing confirms the sensor's capacity for robust detection in actual samples, underscoring its promising application in early disease diagnosis. This innovative approach opens up avenues for multi-signal response sensors, offering significant potential for diagnostic technologies.

A fluorescence-electrochemiluminescence dual-mode sensor based on a "switch" system for highly selective and sensitive K-ras gene detection.

Herein, an fluorescence (FL)-electrochemiluminescence (ECL) dual-mode biosensor is constructed based on the dual-signal "turn-on" strategy of functionalized metal-organic frameworks nanosheets (RuMOFNSs)-tetraferrocene for K-ras gene detection, and the mechanism of bursting through front-line orbital theory is explained for the first time. Amino-functionalized tetraferrocene-labeled probe DNA molecules are linked to RuMOFNSs by covalent amide bonds, acting as FL and ECL intensity switches. The target DNA, complementary to the probe DNA, triggers cyclic amplification of the target by nucleic acid exonuclease III (Exo III), repelling tetraferrocene reporter groups away from RuMOFNSs and inhibiting the electron transfer process and photoinduced electron transfer (PET) effect. These phenomena induce a double turn-on of FL and ECL signals with a high signal-to-noise ratio. The developed FL-ECL dual-mode sensing platform provides sensitive detection of the K-ras gene with detection limits of 0.01 fM (the detection range is 1 fM to 1 nM) and 0.003 fM (the detection range is 0.01 fM to 10 pM), respectively. In addition, the proposed dual-mode sensor can be easily extended to detect other disease-related biomarkers by changing the specific target and probe base sequences, depicting potential applications in bioanalysis and early disease diagnosis.

An autonomous driven DNA walker-based electrochemical aptasensor for on-site detection of Ochratoxin A.

Herein, an autonomous driven DNA walker-based aptasensor is proposed for the detection of Ochratoxin A (OTA). A nanoscale metal-organic framework (MOF) is synthesized and used to load Mn2+, a cofactor for DNAzyme. The DNA walker and Mn2+@MOF are assembled on the Au surface, integrating the DNA walker and metal auxiliary ions. The proposed sensor avoids the addition of metal auxiliary ions of DNAzyme from the external environment, which achieves the fully autonomous driving of DNA walker and facilitates the on-site detection of OTA. In addition, the substrate strands are modified with a newly synthesized tetraferrocene signal marker, further achieving signal amplification. The sensor demonstrates a sensitivity of 0.289 pg/mL and is successfully applied to real food sample analysis.

A self-powered and reagent-less electrochemical aptasensor based on a DNA walker and tetraferrocene for the detection of aflatoxin B1.

We constructed a self-powered and reagent-less electrochemical aptamer sensor for sensitive detection of aflatoxin B1 (AFB1). Here, the metal ion Mn2+ required for the DNAzyme to drive a DNA walker is wrapped in UIO-66(Zr)-(COOH)2 and AFB1 triggers the DNAzyme walking strands to automatically and continuously cut the tetraferrocene-labeled substrate strands, which results in a significant decrease in the electrochemical signal. Under the optimal conditions, the concentration dependence of AFB1 is linear in the concentration range of 0.1 pg mL-1 to 0.195 µg mL-1, and the limit of detection is as low as 4.8 fg mL-1. The sensor displayed good performance even for samples with a complex matrix, such as a peanut sample. The recoveries of AFB1 obtained ranged from 95.5 to 106.8%. The developed sensing platform is reagent-less, self-powered, and highly sensitive. It holds great potential for detection of AFB1 in environmental and food samples.

An electrochemical DNA sensor based on an integrated and automated DNA walker.

As an artificial nanomachine, a DNA walker demonstrates the potential for biosensing. In this study, a highly integrated, biostable, and autonomous electrochemical DNA walker sensor was rationally designed by a simple assembly of a Mn2+-dependent DNAzyme-powered DNA walker with nanoscale Mn2+ @MOFs containing free carboxylic acid groups UiO-66(Zr)-(COOH)2. In this study, the release of Mn2+ from Mn2+@MOFs was exploited to drive the autonomous and progressive operation of the DNA walker, and the DNAzyme-driven DNA walker was constructed by the co-modification of walking strands and track strands onto the gold electrode (GE) surface. The walking strand was a single-stranded DNA containing a DNAzyme sequence, which was pre-silenced by the locking strand. The track strand was a specially designed DNA sequence that the target can hybridize with the locking strand; hence, the walking strand is unlocked, and the liberated DNAzyme catalyzes the cleavage of track strands to drive the DNA walker operation, shifting tetraferrocene away from the electrode and producing a significant signal change. A detection limit of 38 fM was obtained with our new system, exhibiting a wide linear range from 1.5625 × 10-9 M to 1 × 10-13 M. The proposed approach provided a novel means for constructing an highly integrated, automated, and DNAzyme-driven DNA walker for bioanalysis.

Three-dimensional self-powered DNA walking machine based on catalyzed hairpin assembly energy transfer strategy.

Herein, catalyzed hairpin assembly is implemented as an automated strategy, which can respond in living cells to detect specific target DNA. Using the principle of catalyzed hairpin assembly (CHA), the auxiliary chain connects the fuel and starting chain to form a triple-stranded DNA to complete such a single system. Hundreds of single systems are modified on gold nanoparticles as DNA orbitals. Through the specific recognition of base complementation, the target DNA can realize the automatic walking of the three-dimensional fluorescence machine. This is a novel walking nanomachine that has a simple structure and can independently exist in cells to achieve automatic operation.

Immobilization-free electrochemical DNA sensor based on signal cascade amplification strategy.

The development of convenient and efficient strategies without using complex nanomaterials or enzymes for signal amplification is very important for bioanalytical applications. Herein, a novel electrochemical DNA sensor was developed by harnessing the signal amplification efficiency of catalytic hairpin assembly (CHA) and a brand-new signal marker tetraferrocene. The prepared sensor had both ends of the probe H2 labeled with tetraferrocene; both ends have a large number of unhybridized T bases, which cause tetraferrocene to move closer to the electrode surface, generating a high-efficiency amplification signal. In the presence of target DNA, it induced strand exchange reactions promoting the formation of double-stranded DNA and recycling of target DNA. Under optimal conditions, the sensor showed a good linear correlation between the peak currents and logarithm of target DNA concentrations (ranging from 0.1 fM to 0.3125 pM) with a detection limit of 0.06 fM, which is obtained by a triple signal-to-noise ratio. Additionally, the prepared sensor possesses excellent selectivity, reproducibility, and stability, demonstrating efficient and stable DNA detection methodology.

A homogeneous electrochemical DNA sensor on the basis of a self-assembled thiol layer on a gold support and by using tetraferrocene for signal amplification.

An unmodified electrochemical biosensor has been constructed, which can directly detect DNA in homogeneous solution. The synthesized new compound tetraferrocene was used for signal amplification. The dual-hairpin probe DNA was tagged with a tetraferrocene at the 3' terminal and a thiol at the 5' terminal. Without being hybridized with target DNA, the loop of probe prevented the thiol from contacting the exposed gold electrode surface with an applied potential. After hybridization with the target DNA, the loop-stem structure of the probe was opened, which led to the formation of the hairpin DNA structure. Afterwards, the thiol easily contacted the electrode and accomplished potential-assisted Au-S self-assembly. Its current signal depends on the concentration of target DNA in the 1.8 × 10-13 to 1.8 × 10-9 M concentration range, and the detection limit is 0.14 pM. The technique is a meaningful study because of its high selectivity and sensitivity. Graphical abstract Schematic diagram of the electrochemical DNA sensor operation. Target DNA and probe DNA hybridization, resulting in the disappearance of the steric hindrance of the probe stem ring. A higher signal was generated when tetraferrocene reached the electrode. The electrochemical signals were determined by differential voltammetric pulses (DPV).

A sensitive homogenous aptasensor based on tetraferrocene labeling for thrombin detection.

In this work, a novel homogeneous electrochemical aptasensor based on electrically assisted bond and tetraferrocene signal amplification was constructed for thrombin detection. Importantly, modification of the electrode is not necessary for this sensor, requiring only the construction of a simple and efficient probe. In addition, a brand new signal marker-tetraferrocene, containing four ferrocene molecules, was employed as a label to the terminal position of the probe. Compared with a single ferrocene moiety, tetraferrocene possesses a larger amplification signal for rapid detection of thrombin. In the detection of thrombin, the selected aptamer probe with a stem-loop structure was labeled with tetraferrocene at the 3' terminal and thiol at the 5' terminal, respectively. Confinement of the thiol to the stem-loop structure of the probe, the ability of thiol to reach the surface of electrode lossed even with the aid of the applied potential. However, upon treatment with the target protein of thrombin the stem-loop structure opened, promoting rapid attachment of the thiol group to the electrode interface generating Au-S self-assembly with the action of potential-assistance. The electrochemical signal of tetraferrocene could be measured by differential pulse voltammetry (DPV), which was subsequently used for target quantitative detection. This strategy displayed a detection limit as low as 0.126 pM, and an inherently high specificity for the detection of a single mismatch. Moreover, it exhibited advanced specificity against common interfering proteins.

Highly sensitive host-guest mode homogenous electrochemical thrombin signal amplification aptasensor based on tetraferrocene label.

The development of sensitive and convenient detection methods to monitor thrombin without the use of enzymes or complex nanomaterials is highly desirable for the diagnosis of cardiovascular diseases. In this article, tetraferrocene was first synthesized and then a sensitive and homogeneous electrochemical aptasensor was developed for thrombin detection based on host-guest recognition between tetraferrocene and ß-cyclodextrin (ß-CD). In the absence of thrombin, the double stem-loop of thrombin aptamer (TBA) prevented tetraferrocenes labeled at both ends from entering the cavity of ß-CD deposited on gold electrode surface. After binding with thrombin, the stem-loop structure of TBA opened and transformed into special G-quarter structure, forcing tetraferrocene into the cavity of ß-CD. As a result, thrombin allowed eight ferrocene molecules to reach the gold electrode surface, greatly amplifying the response signal. The obtained aptasensors showed dynamic detection range from 4 pM to 12.5 nM with detection limit around 1.2 pM. Overall, the results indicate that the proposed aptasensors are promising for future rapid clinical detection of thrombin and development of signal amplification strategies for detection of various proteins.

Multi-signal amplification electrochemical DNA biosensor based on exonuclease III and tetraferrocene.

Homogeneous electrochemical DNA biosensors' unique qualities have been of great interest to researchers, mainly due to their high recognition efficiency in solutions. However, the processes of introducing additional markers and extra operations to obtain a signal are tedious and time consuming, which limits their overall potential applications. Herein, a novel tetraferrocene was synthesized and used as a homogeneous electrochemical DNA biosensor probe label. It contains four ferrocene units, which provide greater signaling potential compared to monoferrocene. Furthermore, the target DNA triggers the digestion of the double hairpin DNA probe with the aid of exonuclease III, promoting short single stranded DNA probe formation. With the combination of the incorporated tetraferrocene labeled short DNA probe strands and graphene's ability to adsorb single stranded DNA, the hybridization process can produce an electrode signal provided by tetraferrocene. A low detection limit of 8.2 fM toward target DNA with excellent selectivity was achieved. The proposed sensing system avoids tedious and time-consuming steps of DNA modification, making the experimental processes simpler and convenient. The advantages of high sensitivity, selectivity and simple operation make this strategy applicable to DNA detection.

"Off-On"switching electrochemiluminescence biosensor for mercury(II) detection based on molecular recognition technology.

A novel "off-On" electrogenerated chemiluminescence (ECL) biosensor has been developed for the detection of mercury(II) based on molecular recognition technology. The ECL mercury(II) biosensor comprises two main parts: an ECL substrate and an ECL intensity switch. The ECL substrate was made by modifying the complex of Ruthenium(II) tris-(bipyridine)(Ru(bpy)32+)/Cyclodextrins-Au nanoparticles(CD-AuNps)/Nafion on the surface of glass carbon electrode (GCE), and the ECL intensity switch is the single hairpin DNA probe designed according to the "molecular recognition" strategy which was functionalized with ferrocene tag at one end and attached to Cyclodextrins (CD) on modified GCE through supramolecular noncovalent interaction. We demonstrated that, in the absence of Hg(II) ion, the probe keeps single hairpin structure and resulted in a quenching of ECL of Ru(bpy)32+. Whereas, in the presence of Hg(II) ion, the probe prefers to form the T-Hg(II)-T complex and lead to an obvious recovery of ECL of Ru(bpy)32+, which provided a sensing platform for the detection of Hg(II) ion. Using this sensing platform, a simple, rapid and selective "off-On" ECL biosensor for the detection of mercury(II) with a detection limit of 0.1 nM has been developed.

An electrochemical DNA sensor without electrode pre-modification.

We present a non-modification electrochemical DNA sensing strategy, which used Potential-Assisted Au-S Deposition and a clamp-like DNA probe. The dual-hairpin probe DNA was tagged with a methylene blue (MB) at the 3' terminal and a thiol at the 5' terminal., Without being hybridized with target DNA, the loop of probe prevented the thiol from reaching the bare gold electrode surface with an applied potential., After hybridization with the target DNA, the probe' s loop-stem structure opened through two distinct and sequential events, which led to the formation of a triplex DNA structure. Then the thiol easily contacted with electrode and resulted in potential-assisted Au-S self-assembly. Electrochemical signals of MB were measured by differential pulse voltammetry (DPV) and used for target quantitative detection. This strategy offered a detection limit down to 2.3pM. and an inherently high specificity for detecting even single mismatch.

An electrochemical molecular recognition-based aptasensor for multiple protein detection.

This article reports a simple electrochemical approach for the detection of multiple proteins (thrombin and lysozyme) using Dabcyl-labeled aptamer modified metal nanoparticles (DLAPs). DLAPs were immobilized on ß-cyclodextrins (ß-CDs) modified electrode by means of host-guest self-assembly. During the time of detection, the aptamers' structure will change due to the specific binding with corresponding proteins that forced DLAPs far away from the electrode that had been modified by ß-CDs. Thus, the capture of target proteins onto DLAPs was translated via the electrochemical current signal offered by metal nanoparticles. Linearity of the aptasensor for quantitative measurements was demonstrated. Determinations of proteins in human real serum samples were also performed to demonstrate detection in real clinical samples.

An electrochemical DNA sensor for sequence-specific DNA recognization in a homogeneous solution.

In this work, a sensitive electrochemical DNA sensor based on an avidin modified electrode and a DNA-functionalized Au nanoparticle (DFNP) was developed. The DNA-functionalized Au nanoparticle contained two kinds of DNA, one is hairpin probe DNA with a biotin at the 3' terminal and a thiol at the 5' terminal, the other is methylene blue (MB)-labeled linear signal DNA. Without hybridizing with the target DNA, the loop of the hairpin impeded biotin linked with avidin on electrode. However, after target hybridization, the hairpin was opened and biotin was recognized by avidin which resulted in a DNA-functionalized Au nanoparticle brought on the electrode surface. Electrochemical signals of MB bound to signal DNA were measured by differential pulse voltammetry (DPV). Taking advantage of amplification effects of the AuNP and binding specificity of the hairpin probe, this DNA biosensor greatly simplified the electrochemical DNA detection method and displayed high specificity in DNA detection. By using this new method, we demonstrate that this prototype sensor has been able to detect as low as picomolar DNA targets with excellent differentiation ability even for a single mismatch.

A powerful synergistic effect for highly efficient diastereo- and enantioselective phase-transfer catalyzed conjugate additions.

An efficient, catalytic, diastereo- and enantioselective conjugate addition of N-(diphenylmethylene)glycine tert-butyl ester to ß-aryl substituted enones was realized in the presence of 1 mol% of newly desired dinuclear N-spiro-ammonium salts, affording functionalized α-amino acid derivatives in 57-98% yields with high diastereoselectivity (up to 99:1 dr) and enantioselectivity (up to 96.5:3.5 er).

Catalytic stereoselective synthesis of highly substituted indanones via tandem Nazarov cyclization and electrophilic fluorination trapping.

A new catalytic stereoselective tandem transformation via Nazarov cyclization/electrophilic fluorination has been accomplished. This sequence is efficiently catalyzed by a Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity (trans/cis up to 49/1). Three examples of catalytic enantioselective tandem transformation are presented.

Stereoselective construction of fluorinated indanone derivatives via a triple cascade Lewis acid-catalyzed reaction.

A one-pot three-component cascade reaction proceeds by way of a Lewis acid-catalyzed Knoevenagel condensation/Nazarov cyclization/electrophilic fluorination sequence to afford fluorinated 1-indanone derivatives in moderate to good yields with high diastereoselectivities.