DNA-Walker-Induced Allosteric Switch for Tandem Signal Amplification with Palladium Nanoparticles/Metal–Organic Framework Tags in Electrochemical Biosensing

Abstract

A DNA walker as a new molecular machine can walk on defined tracks to directly generate signal indicators in biosensing and biomedical applications. In this work, a tandem signal amplification strategy was developed on the basis of the DNA-walker-induced conformation switch for bridging palladium nanoparticles/metal−organic framework tags in ultrasensitive electrochemical DNA biosensing. The signal tags were synthesized by in situ reduction of Pd nanocrystals on porphyrinic metal− organic frameworks (PCN-224), followed by conjugation with streptavidin (SA). The as-prepared Pd/PCN-224-SA tag could electrocatalyze the oxidation of NaBH 4 with high efficiency for signal readout. The presence of target DNA released swing arms that were each silenced by a blocker, and then the activated swing arms could hybridize with hairpin DNA. The movement of swing arms was powered by enzymatic cleavage of conjugated oligonucleotides, inducing the allosteric switch from hairpin to SA aptamer. Therefore, Pd/PCN-224-SA tags were brought onto the electrode surface via SA-aptamer biorecognition to generate the enhanced electrochemical signal. The DNA walker-based electrochemical biosensor demonstrated good performance such as 6 orders of magnitude linear range, femtomolar detection limit, and single mismatch differentiation ability. Moreover, the feasibility of the biosensor was identified in serum matrixes. The tandem signal amplification of metal−organic frameworks and DNA walkers provided a new avenue in trace electrochemical biosensing.

Ultrasensitive Electrochemical DNA Biosensor Fabrication by Coupling an Integral Multifunctional Zirconia-Reduced Graphene Oxide-Thionine Nanocomposite and Exonuclease I-Assisted Cleavage

“…Upon hybridization with the target DNA, the bioprobe-labeled nanomaterial or enzyme was then recognized for signal amplification. Until now, various nanomaterials such as noble metal nanoparticles, carbon nanotube, graphene, and semiconductor nanoparticles have been fully explored for biosensor fabrication (Swain et al, 2008 ; Wu et al, 2009 ; Nie et al, 2012 ; Benvidi et al, 2015 ; Jahanbani and Benvidi, 2016 ; Baluta et al, 2018 ; Yan et al, 2018 ; Yu et al, 2019 ). However, the careful and tedious modification, control, or labeling of biomolecules or reporters onto nanomaterials increases the assay complexity.…”

Recent advances in aptamer applications for analytical biochemistry

“…were immobilized on a gold electrode surface as bio-recognition elements to capture MCF-7 cancer cells and improve the density and orientation of surface nanoprobes. The MOF, termed PCN-224, which is a zirconium-based porphyrine-containg structure that can be metalated [ 79 ], was homogeneously decorated by platinum nanoparticles and further modified by a known G-quadruplex-hemin horseradish peroxidase-mimicking DNAzyme [ 80 ]. The fabricated nanoprobes catalyze the oxidation of hydroquinone with hydrogen peroxide for amplifying the electrochemical signal.…”

Nanomaterials for molecular signal amplification in electrochemical nucleic acid biosensing: recent advances and future prospects for point-of-care diagnostics

“…66 Catalytically active nanoparticles benefit from a support material that maximizes the number of catalytic sites, whilst minimizing the amount of material used. 67 A number of systems have been recently reported in the literature for miRNA and DNA detection using supported catalysts for signal amplification, such as Pt nanoparticles supported by TiO 2 nanospheres, 68 Pt or Pd nanoparticles supported by metal-organic frameworks (MOFs), 69,70 Pt nanoparticles supported by graphene, 71 fullerene-CeO 2 composites with Pt nanoparticles 72 and Fe 3 O 4 /CeO 2 composites decorated with Au nanoparticles. 73 These approaches demonstrate superior performance when compared to associated bare catalyst nanoparticle systems, owing to the increase of active surface area and synergetic interactions with the support materials.…”