Detection of FGFR2 : FAM76A Fusion Gene in Circulating Tumor RNA Based on Catalytic Signal Amplification of Graphene Oxide‐loaded Magnetic Nanoparticles

Abstract

Circulating tumor nucleic acids (ctNAs) are promising biomarkers for minimally invasive cancer assessment. The FGFR2 : FAM76A fusion gene is one of the highly promising ovarian cancer biomarkers detectable in ctNAs. Herein, we introduce a new amplification‐free electrochemical assay for the detection of FGFR2 : FAM76A fusion gene in ctNAs extracted from ovarian cancer patients. The assay relies on the electrocatalytic activity of a new class of superparamagnetic graphene‐loaded iron oxide nanoparticles (GO‐NPFe2O3). After isolation and purification, the target RNA was directly adsorbed onto the GO‐NPFe2O3 surface through graphene‐RNA affinity interaction. The electrocatalytic signal was achieved by the reduction of surface‐attached ruthenium hexaammine(III) chloride which was further amplified by using the ferricyanide redox system. Our assay depicted an excellent detection sensitivity down to 1.0 fM, high specificity and excellent reproducibility (% RSD=<5 %, for n=3). The analytical performance of our method was validated with standard qRT‐PCR analysis. We believe that this newly developed assay would be practically applicable in clinical research.

Enhanced Peroxidase Mimetic Activity of Porous Iron Oxide Nanoflakes

“…The catalytic reaction typically generates a blue‐colored charge transfer complex (diamine), which in turn becomes yellow upon the addition of acid. This reaction has been widely used to design sensitive biosensors for detecting hydrogen peroxide, glucose, cells, and disease‐specific biomolecules ,,,. Recently, we have reported the synthesis and peroxidase mimetic activity of gold‐loaded nanoporous iron oxide materials for colorimetric and electrochemical detection of cancer biomarker, p53 autoantibody .…”

“…Among various nanostructures, iron oxides (particularly maghemite, γ‐Fe 2 O 3 and hematite, α‐Fe 2 O 3 ) have been widely used for environmental and biomedical applications, such as magnetic isolation, bio‐separation, and purification, due to their excellent magnetic properties, good biocompatibility, low‐cost preparation, easy biofunctionalization and high‐stability . In our recent reports, we have demonstrated the excellent electrocatalytic properties of mesoporous iron oxide materials for detecting circulating tumor RNA and desease‐specific microRNA (miRNA) . These materials were employed to modify the conventional electrode surface, capture target sequence onto transduction surface and catalyze the electrochemical signals to achieve ultrasensitive enzyme‐free miRNA sensor.…”

High‐Performance Nucleic Acid Sensors for Liquid Biopsy Applications

“…[32] This assay relies on the electrocatalytic activity of as uperparamagnetic grapheneloaded iron oxide nanoparticle (GO-NPFe 2 O 3 ). [32] This assay relies on the electrocatalytic activity of as uperparamagnetic grapheneloaded iron oxide nanoparticle (GO-NPFe 2 O 3 ).…”

Advances on the Use of Graphene as a Label for Electrochemical Biosensors

“…In electrochemical sensing and biosensing graphene materials have been widely used as platforms for the immobilization of various receptors (see illustration from Figure A) . One of the greatest challenges that are faced when developing a biosensor include the formation of a stable and specific layer of the biorecognition element.…”