Metal-Organic Framework UiO-66-Mediated Dual-Signal Ratiometric Electrochemical Sensor for microRNA Detection with DNA Walker Amplification.

Electrochemical nanotags with strong signal input are necessary for a ratiometric electrochemical sensor to overcome the drawbacks of inaccurate detection results. In this paper, the metal-organic framework (MOF) UiO-66 was utilized as an electrochemical signal tag. A stable and strong current response at +0.9 V can be detected in neutral conditions. MicroRNA (miRNA) was employed as the model analyte. Herein, an enzyme-free DNA-walker-based ultrasensitive ratiometric electrochemical biosensor in combination with Zr MOF (UiO-66) signal tags to detect miRNA was demonstrated. In the presence of miRNA, the autonomous walker movement can be initiated by miRNA, leading to the release of biotin-modified fragments. Thus, streptavidin-labeled UiO-66 nanomaterials were not bound to the electrode, generating a low signal response of UiO-66 at +0.9 V. However, the current signal of electrolyte solution as reference at +0.2 V was increased due to the enhancement of electrode conductivity. This ratiometic sensor demonstrated high sensitivity, selectivity, and reproducibility. It can eliminate the disturbance of environmental factors and basic electrode characteristics, providing more accurate signals. A limit of detection (LOD) of 0.17 fM was achieved. Moreover, the method was also used to detect miRNA-21 spiked in real serum samples.

A DNA tetrahedral nanomaterial-based dual-signal ratiometric electrochemical aptasensor for the detection of ochratoxin A in corn kernel samples.

Ochratoxin A (OTA) is a highly toxic food contaminant and is harmful to human beings. Herein, a ratiometric electrochemical aptasensor based on a DNA tetrahedral nanomaterial (NTH) was developed in combination with the signal tag of a zirconium metal-organic framework (UiO-66) for the detection of OTA. In the sensor, UiO-66 and a [Fe(CN)6]3-/4- electrolyte solution were used as the signal probe and the internal reference probe, respectively. In the presence of OTA, the OTA aptamer was released from the electrode due to the specific binding of OTA. Thus, signal probe P1 labeled-UiO-66 was captured on the electrode surface by hybridization with DNA NTH. Since signal probe P1 labeled-UiO-66 was close to the electrode, it leads to an increased signal current of UiO-66 at +0.9 V. As the conductivity of the modified electrode decreased, the current signal of [Fe(CN)6]3-/4- at +0.2 V also decreased. The proposed ratiometric electrochemical aptasensor could effectively eliminate external environmental influences and could avoid electrochemical background signals. The aptasensor demonstrated high specificity for OTA, and achieved a good linear range of 1 pg mL-1-100 ng mL-1 with a detection limit of 330 fg mL-1. The developed electrochemical aptamer biosensor effectively detected OTA in corn kernel samples, verifying its practical application for the determination of OTA in actual samples.

Ultrasensitive dual-signal electrochemical ratiometric aptasensor based on Co-MOFs with intrinsic self-calibration property for Mucin 1.

The concentration of tumor biomarker Mucin 1 (MUC 1) is highly related with many diseases, which can be employed for the early diagnosis of cancer. In this paper, an electrochemical ratiometric aptasensor with intrinsic self-calibration property for the detection of MUC 1 is presented. In this paper, Co-MOFs themselves were employed as signal substances. This strategy was fabricated by using gold nanoparticles@black phosphorus (BP) as the substrate on the electrode, followed by modification of DNA nanotetrahedrons (DTN) via Au-S bond. The terminal of DTN contains MUC 1 aptamer. In the presence of MUC 1, the signal of DNA-labeled Co-MOFs can be detected. The current signal of Co-MOFs increased and that of thionine (as reference) was unchanged upon the addition of MUC 1. Thus, an intrinsic self-calibration aptasensor was achieved. In order to simplify the modification procedure, the electrolyte solution thionine was employed as an inner reference probe. Moreover, coupling of the hybridization chain reaction (HCR) with these MOFs signal tags presents an enzyme-free method for signal amplification, endowing the proposed ratiometric biosensor detection with high reproducibility and high sensitivity. The current ratio (IIR/ISP) remained stable over 30 individual measurements performed on ten different working electrodes. Even ten repeated scans performed on a single electrode exhibited a constant current ratio. The electrochemical ratiometric aptasensor is highly sensitivity for MUC 1 with the detection limit of 1.34 fM. Our proposed ratiometric sensor has great potential for the detection of cancer-related biomarkers.

Iodide-enhanced Co/Fe-MOFs nanozyme for sensitively colorimetric detection of H2S.

In this paper, a simple, rapid, and low-cost colorimetric method was designed based on Co/Fe-MOFs-iodide composite for the quantitative detection of H2S. It is know that iodide can improve the catalytic activity of bimetallic porous material Co/Fe-MOFs via adsorption into the framework of MOFs. Herein, we demonstrate a novel strategy to enhance the peroxidase-like activity of MOFs. Compared to horseradish peroxidase (HRP), the kinetic measurement results show that Co/Fe-MOFs-iodide exhibits excellent affinity to substrates, promoting electron transfer. Due to the synergetic effect of Co/Fe-MOFs and iodide, and rapid electron transfer process, Co/Fe-MOFs-iodide demonstrates improved peroxidase-like activity. As a proof-of-concept application, a novel, highly sensitive H2S colorimetric method is established with a detection limit (LOD) of 0.33 nM. In the absence of iodide, LOD is approx. 200-fold higher than that of the amplified colorimetric assay. The proposed method can also accurately detect traces of H2S in serum samples.

Fe-MOFs as signal probes coupling with DNA tetrahedral nanostructures for construction of ratiometric electrochemical aptasensor.

A ratiometric electrochemical aptasensor is proposed for the detection of thrombin. In the sensor, the iron metal-organic frameworks (Fe MOFs)-labeled aptamer as signal tags was used as signal probe (SP), and the electrolyte solution [Fe(CN)6]3-/4- was utilized as an inner reference probe (IR). In the presence of thrombin, the signal of Fe-MOFs can be detected. Meanwhile, the signal of [Fe(CN)6]3-/4-IR almost remains stable. Accordingly, thrombin concentration can be monitored with the ratio response of IFe-MOFs-SP/I[Fe(CN)6]3-/4--IR. The proposed ratiometric biosensor owns a strong ability to eliminate the disturbance that arises from different DNA loading densities, environmental impact and instrumental efficiency. DNA nanotetrahedron (NTH) with three-dimensional (3D) scaffold can effectively eliminate nonspecific adsorption of DNA and protein. The accessibility of target molecules and loading amounts of signal substances could be increased because of the enhanced mechanical rigidity of well-designed 3D NTH. Thus, detection reproducibility and sensitivity can be further improved. Moreover, the biosensor only requires conjugation with one electroactive substance. The modification procedure can be greatly simplified. The biosensor owns high sensitivity with the detection limit of 59.6 fM. We expect that it will emerge as a generalized ratiometric sensor that may be useful for detecting target analytes.