As a steroid hormone, cortisol has a close relationship with the stress response, and therefore, can be used as a biomarker for early detection of stress. An electrochemical immunosensor is one of the most widely used methods to detect cortisol, with antibodies as its bioreceptor. Apart from conventional laboratory-based methods, the trend for cortisol detection has seemed to be exploiting antibodies and aptamers. Both can provide satisfactory performance with high selectivity and sensitivity, but they still face issues with their short shelf life. Molecularly imprinted polymers (MIPs) have been widely used to detect macro- and micro-molecules by forming artificial antibodies as bioreceptors. MIPs are an alternative to natural antibodies, which despite demonstrating high selectivity and a low degree of cross-reactivity, often also show a high sensitivity to the environment, leading to their denaturation. MIPs can be prepared with convenient and relatively affordable fabrication processes. They also have high durability in ambient conditions, a long shelf life, and the ability to detect cortisol molecules at a concentration as low as 2 ag/mL. By collecting data from the past five years, this review summarizes the antibody and aptamer-based amperometric sensors as well as the latest developments exploiting MIPs rather than antibodies. Lastly, factors that can improve MIPs performance and are expected to be developed in the future are also explained.
Keywords: antibody; aptamer; bulk imprinting; cortisol; electrode functionalization; molecularly imprinted polymer; stress; surface imprinting.