A single nucleotide polymorphism electrochemical sensor based on DNA-functionalized Cd-MOFs-74 as cascade signal amplification probes

Abstract

An ultrasensitive electrochemical sensor has been constructed for the detection of single nucleotide polymorphisms (SNPs) based on DNA-functionalized Cd-MOFs-74 as cascade signal amplification probe under enzyme-free conditions. Interestingly, the introduction of an auxiliary probe did not disturb the detection of SNP targets, but could bind more Cd-MOFs-74 signal elements to enhance the different pulse voltammetry electrochemical signal 2~3 times as compared to sensing system without auxiliary probe, which obviously improves the sensitivity of the proposed sensor. Experimental results taking p53 tumor suppressor gene as SNP model demonstrated that the proposed method can be employed to sensitively and selectively detect target p53 gene fragment with a linear response ranging from 0.01 to 30 pmol/L (detection limit of 6.3 fmol/L) under enzyme-free conditions. Utilizing this strategy, the ultrasensitive SNP electrochemical sensor is a promising tool for the determination of SNPs in biomedicine.

Length-Dependent Gold Nanoparticle-Labeled Nucleic Acid Probe Based Dual Test Strip for Visualized Discrimination of Single Nucleotide Polymorphism

“…Despite relatively higher LOD compared with the other SNP sensors (e.g., fluorescent, electrochemical sensors , ), this sensor shows the advantage of visualization with portable test strips, which avoids the employment of sophisticated instruments and specific signal capture devices. Thus, the dual strip biosensor is promising for on-site detection in the biomedical field.…”

Electrochemical biosensors for analysis of DNA point mutations in cancer research

“…In addition to a commonly used recovery test in a spiked medium, authors also detected endogenous TP53 gene extracted from breast cancer cell line MCF-7 after asymmetric PCR amplification, but no distinction between wt and mutated sequence was done in this case. In another work, Liu et al developed an assay to search for a mutation in TP53 gene by utilizing DNA-functionalized cadmium-doped metal organic framework (Cd-MOF-74) to initiate cascade amplification and target gene detection [101]. The detection limit of this assay was in a femtomolar range under enzyme-free conditions, but again, only recovery test in spiked human serum was conducted.…”

Generic Platform for the Multiplexed Targeted Electrochemical Detection of Osteoporosis-Associated Single Nucleotide Polymorphisms Using Recombinase Polymerase Solid-Phase Primer Elongation and Ferrocene-Modified Nucleoside Triphosphates

“…A wide range of diverse SNP detection methods have been developed, including single base extension using fluorescently labeled chain-terminating dideoxynucleotides (ddNTPs). − Fluorescently labeled ddNTPs were also used in approaches using surface-tethered primers , and in array-based primer extension (APEX) , as well as alternate array-based technologies exploiting primer elongation and solid-phase polymerase chain reactions . As an alternative to fluorescence detection, SNP detection technologies based on electrochemical detection have been detailed, including an approach based on DNA-functionalized Cd-MOFs-74 as a cascade signal amplification probe under enzyme-free conditions for the detection of an SNP in the p53 tumor suppressor gene as well as the SNP detection based on silicon semiconductors and the use of electroactive rather than fluorescent labels for ddNTPs …”

“…46−49 Fluorescently labeled ddNTPs were also used in approaches using surface-tethered primers 50,51 and in array-based primer extension (APEX) 52,53 as well as alternate array-based technologies exploiting primer elongation 54 and solid-phase polymerase chain reactions. 55 As an alternative to fluorescence detection, SNP detection technologies based on electrochemical detection have been detailed, including an approach based on DNA-functionalized Cd-MOFs-74 as a cascade signal amplification probe under enzyme-free conditions for the detection of an SNP in the p53 tumor suppressor gene 56 as well as the SNP detection based on silicon semiconductors 57 and the use of electroactive rather than fluorescent labels for ddNTPs. 58 Electrochemical devices are cost-effective, portable, and rapid, and we recently exploited these advantages to develop an approach for the electrochemical detection of an SNP directly from a fingerprick blood sample, without the need for DNA extraction or purification, which was completed in less than 20 min.…”