Thionine functionalized hollow N-doped carbon nanoboxes: As a high-performance substrate for fabrication of label-free electrochemical aptasensor toward ultrasensitive detection of carcinoembryonic antigen

• A novel electrochemical aptasensor based on Thi@N-C n -box/AuNPs nanocomposites was developed for the determination of CEA. • The Thi@N-C n -box/AuNPs nanocomposites were synthesized to improve the sensitivity of aptasensor. • The aptasensor was successfully used for CEA detection in serum sample. During recent years, the combination of aptamer with new nanomaterials has led to significant improvements in the performance of aptamer-based sensors. The hollow N-doped carbon nanoboxes (N-C n -box) have attracted a lot of attention due to their unique physical and chemical properties and also significant intrinsic cavities which are suitable for loading specific chemicals. In this study, a label free electrochemical aptasensor is described, using thionine (Thi), as a signal molecule, gold nanoparticles (AuNPs) and N-C n -box, as signal amplification platform and high-performance substrate for aptamer strings immobilization for the measurement of carcinoembryonic antigen (CEA), as a model molecule. The presence of the target molecule impedes electron transfer which leads to a decrease in the Thi-associated square wave voltammetry (SWV) peak currents. This approach increases the amount of redox probe at the electrode surface and reduces the distance between the redox probe and the electrode surface. Therefore, this strategy exhibited higher sensitivity and wider linearity in the range of 0.1 fM to 30 nM (17 fg mL −1 –5.4 ng mL −1 ) with a LOD of 0.03 fM (5 fg mL −1 ) and also with good selectivity in the presence of different off-target species. This is the first report on the rational design of N-C n -box shelled with Thi for the electrochemical application.