Electron Transfer Mediated Electrochemical Biosensor for MicroRNAs Detection Based on Metal Ion Functionalized Titanium Phosphate Nanospheres at Attomole Level

MicroRNAs (miRNAs) have emerged as new candidates as diagnostic and prognostic biomarkers for the detection of a wide variety of cancers; thus, sensitive and selective detection of microRNAs is significant for early-phase cancer diagnosis and disease prevention. A novel and simple electrochemical miRNA biosensor was developed using Cd2+-modified titanium phosphate nanoparticles as signal unit, two DNA as capture probes, and Ru(NH3)(63)(+) as electron transfer mediator. Large quantities of cadmium ions were mounted in titanium phosphate spheres to output the electrochemical signal. Because of the presence of Ru(NH3)(63)(+) molecules that interacted with DNA base-pairs as electron wire, the electrochemical signal significantly increased more than 5 times. This approach achieved a wide dynamic linear range from 1.0 aM to 10.0 pM with an ultralow limit detection of 0.76 aM, exerting a substantial enhancement in sensitivity. Moreover, the proposed biosensor was sufficiently selective to discriminate the target miRNAs from homologous miRNAs and could be used for rapid and direct analysis of miRNAs in human serum. Therefore, this strategy provides a new and ultrasensitive platform for miRNA expression profiling in biomedical research and clinical diagnosis.