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 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.

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.

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.

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.