Ultrasensitive electrochemical miR-155 nanocomposite biosensor based on functionalized/conjugated graphene materials and gold nanostars

Abstract

Electrochemical nanobiosensors have revolutionized the field of medical diagnosis owing to the unique properties of the utilized nanomaterial that can boost the sensitivity of these devices. The higher sensitivity is especially critical when a small sample containing little quantity of the biomarker, miRNAs for instance, should be quantified for medical diagnosis. Here, a novel sensitive electrochemical nanobiosensor for miR-155, an early breast cancer detection biomarker, is introduced. A combination of reduced graphene oxide modified with nickel-iron (Fe-Ni@rGO), silver-conjugated graphene quantum dots (GQD-Ag), and gold nanostars (GNS) were used. This novel and advanced nanocomposite expanded the surface area and conductivity of the electrode surface to remarkably enhance the sensitivity of the nanobiosensor. A series of systematic characterization, both electrochemical and microscopic, were employed to assess the nanocomposite features using SEM, EDS, TEM, AFM, CV, and EIS. Thiolated single-stranded capture probes were immobilized on the GNS to selectively capture the target miR-155, and hematoxylin was the electrochemical label. The results showed high sensitivity with a low detection limit of 20.2 aM and a wide dynamic range of 0.05 fM-50.0 pM, which is superior to most of the previously reported miRNA nanobiosensors. The specificity was suitable towards the miR-155 compared to its one- and three-base mismatched oligos, a non-complementary and a mixture of the target with all the other non-complementary. Finally, the results of the real sample study in the serum environment revealed a very low interference in measurements which, along with the high sensitivity and selectivity, raises the possibility of using these nanobiosensors as promising candidates for breast cancer detection/screening applications in the future.