A novel non-invasive detection method for the FGFR3 gene mutation in maternal plasma for a fetal achondroplasia diagnosis based on signal amplification by hemin-MOFs/PtNPs.

The small amount of cell-free fetal DNA (cffDNA) can be a useful biomarker for early non-invasive prenatal diagnosis (NIPD) of achondroplasia. In this study, a novel non-invasive electrochemical DNA sensor for ultrasensitive detecting FGFR3 mutation gene, a pathogenic gene of achondroplasia, based on biocatalytic signal materials and the biotin-streptavidin system are presented. Notably encapsulation of hemin in metal-organic frameworks-based materials (hemin-MOFs) and platinum nanoparticles (PtNPs) were used to prepare hemin-MOFs/PtNPs composites via a one-beaker-one-step reduction. We utilized hemin-MOFs/PtNPs for signal amplification because the promising hemin-MOFs/PtNPs nanomaterial has remarkable ability of catalyze H2O2 as well as excellent conductivity. To further amplify the electrochemical signal, reduced graphene oxide-tetraethylene pentamine (rGO-TEPA), gold nanoparticles and streptavidin were selected for modification of the electrode to enhance the conductivity and immobilize more biotin-modified capture probe (Bio-CP) through the high specificity and superior affinity between streptavidin and biotin. The electrochemical signal was primarily derived from the synergistic catalysis of H2O2 by hemin and PtNPs and recorded by Chronoamperometry. Under the optimal conditions, this newly designed biosensor exhibited sensitive detection of FGFR3 from 0.1fM to 1nM with a low detection limit of 0.033fM (S/N=3). We proposed that this ultrasensitive biosensor is useful for the early non-invasive prenatal diagnosis of achondroplasia.