Dual labeled mesoporous silica nanospheres based electrochemical immunosensor for ultrasensitive detection of carcinoembryonic antigen

Abstract

Carcinoembryonic antigen (CEA) is a well-known cancer biomarker for the detection of several malignancies. The development of ultrasensitive CEA diagnostic tools is crucial for early detection and progression observation of tumors. Herein, a dual signal amplified sandwich-type electrochemical immunoassay was developed based on dual-labeled mesoporous silica nanospheres as a signal amplifier, combined with NiO@Au decorated graphene as a conductive layer for ultrasensitive and rapid determination of CEA. The dual-labeled mesoporous silica (DLMS) nanosphere, which was synthesized by entrapping Au nanorod (Au NR) and horseradish peroxidase (HRP) in the channels of amine-functionalized SBA-15 followed by subordinate antibody (Ab₂) conjugation which was denoted as Au NR@SBA-15/Ab₂-HRP. The dual signal amplification from Au NR@SBA-15 and HRP enhanced the sensitivity of the proposed immunoassay. Consequently, the developed DLMS based immunosensor displayed ultra-low limits of detection of 5.25 fg/mL and a wide range of linearity (0.1-5 pg/mL), which was extended for CEA determination in real-time samples with improved recoveries of >98%. Therefore, this dual amplification prototype would cater to the clinical requirements for the ultrasensitive detection of CEA biomarkers.

Keywords: Carcinoembryonic antigen; Dual signal amplification; Dual-labeled; Electrochemical sensor; Immunoassay; Mesoporous silica; NiO@Au; Sandwich-type; Tumor biomarker.