Faraday-Cage-Type Electrochemiluminescence Immunoassay: A Rise of Advanced Biosensing Strategy.

Electrochemiluminescence immunoassays are usually carried out through "on-electrode" strategy, i.e., sandwich-type immunoassay format, the sensitivity of which is restricted by two key bottlenecks: (1) the number of signal labels is limited and (2) only a part of signal labels could participate in the electrode reaction. In this Perspective, we discuss the development of an "in-electrode" Faraday-cage-type concept-based immunocomplex immobilization strategy. The biggest difference from the traditional sandwich-type one is that the designed "in-electrode" Faraday-cage-type immunoassay uses a conductive two-dimensional (2-D) nanomaterial simultaneously coated with signal labels and a recognition component as the detection unit, which could directly overlap on the electrode surface. In such a case, electrons could flow freely from the electrode to the detection unit, the outer Helmholtz plane (OHP) of the electrode is extended, and thousands of signal labels coated on the 2-D nanomaterial are all electrochemically "effective." Thus, then, the above-mentioned bottlenecks obstructing the improvement of the sensitivity in sandwich-type immunoassay are eliminated, and as a result a much higher sensitivity of the Faraday-cage-type immunoassay can be obtained. And, the applications of the proposed versatile "in-electrode" Faraday-cage-type immunoassay have been explored in the detection of target polypeptide, protein, pathogen, and microRNA, with the detection sensitivity improved tens to hundreds of times. Finally, the outlook and challenges in the field are summarized. The rise of Faraday-cage-type electrochemiluminescence immunoassay (FCT-ECLIA)-based biosensing strategies opens new horizons for a wide range of early clinical identification and diagnostic applications.