Impedimetric biosensors for the quantification of serum biomarkers for early detection of lung cancer

Abstract

Lung cancer is the most common type of cancer diagnosed worldwide and is also among the most fatal. Early detection, before symptoms become evident, is fundamental for patients’ survival. Therefore, several lung cancer biomarkers have been proposed to enable a prompt diagnosis, including neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA). NSE and CEA are two serum proteins whose elevated levels have been associated with lung cancer. Hence, in this study, impedimetric biosensors (immunosensors) able to quantify NSE and CEA were developed as proof-of-concept devices for lung cancer diagnosis. The sensing platform exploited for the immunosensors comprises a novel combination of a magnetic platform, screen-printed gold electrode (SPGE), and magnetic nanobeads (MB). The MB were functionalized with antibodies to capture the analyte from the sample and to move it over the sensing area. The immunosensors were then developed by immobilizing another set of antibodies for either CEA or NSE on the SPGE through formation of self-assembled monolayer (SAM). The second set of antibodies enabled a sandwich assay to be formed on the surface of the sensor, while MB manipulation was applied during the sensor performance to depict a microfluidic system and increase antigen–antibody complex formation prior to CEA or NSE detection and quantification. The optimized immunosensors were successfully tested to measure various concentrations of CEA and NSE (0–100 ng/mL) in both phosphate buffer and 100% human serum samples. Clinically relevant detection limits of 0.26 ng/mL and 0.18 ng/mL in buffer and 0.76 ng/mL and 0.52 ng/mL in 100% serum for CEA and NSE, respectively, were achieved via electrochemical impedance spectroscopy with the use of potassium ferri/ferrocyanide as a redox probe. Hence, the two immunosensors demonstrated great potential as tools to be implemented for the early detection of lung cancer.