MXene Nanoconfinement of SAM-Modified Molecularly Imprinted Electrochemical Biosensor for Point-of-Care Monitoring of Carcinoembryonic Antigen

The high rate of cancer worldwide and the heavy costs imposed on governments and humanity have always motivated researchers to develop point-of-care (POC) biosensors for easy diagnosis and monitoring of cancer treatment. Herein, we report on a label-free impedimetric biosensor based on Ti₃C₂T_<i>x</i> MXene and imprinted ortho-phenylenediamine (o-PD) for the detection of carcinoembryonic antigen (CEA), a biomarker for various cancers surveillance, especially colorectal cancer (CRC). Accordingly, MXene was drop-casted on the surface of a disposable silver electrode to increase the sensitivity and create high-energy nanoareas on the surface, which are usable for protein immobilization and detection. A self-assembled monolayer (SAM) was exploited for oriented CEA immobilization on the MXene-modified electrode. The monomer-protein interaction and successful protein removal were confirmed by molecular docking and atomic force microscopy (AFM) investigations to evaluate the quality of the fabricated molecularly imprinted polymer (MIP). Also, the role of MXene in increasing the electrical field inside the nanoareas was simulated using COMSOL Multiphysics software. A suitable limit of detection (9.41 ng/mL), an appropriate linear range of detection (10 to 100 ng/mL) in human serum, and a short detection time (10 min) resulted from the use of SAM/MIP next to MXene. This biosensor presented outstanding repeatability (97.60%) and reproducibility (98.61%). Moreover, acceptable accuracy (between 93.04 and 116.04%) in clinical serum samples was obtained compared with immunoassay results, indicating the high potential of our biosensor for real sample analysis. This biomimetic and disposable sensor provides a cost-effective method for facile and POC monitoring of cancer patients during treatment.