Recent advances in electrochemical proximity ligation assay

Proximity ligation assay (PLA) is a vigorously developed homogeneous immunoassay assisted by DNA combining dual recognition of target protein by pairs of proximity probes, in which the detection of protein is tactfully converted to the detection of DNA. The booming developments in PLA have enabled a variety of ultrasensitive assays for the detection of protein and this concept of PLA is also extended to the detection of nucleic acids and some small molecule. The association between PLA and electrochemical method, defined as electrochemical proximity ligation assay (ECPLA), has gained much interests in disease diagnosis, food safety and environmental assays with the advantages, such as broad range of targets, simplicity, low cost and rapid response. In this review, we took a different perspective to present the history of PLA, the classical ECPLA biosensing methodology as well as the developments of ECPLA based on several key parameters, such as sensitivity, selectivity, reusability and generalization. In addition, the developments of PLA with electrochemiluminescence as readout are also presented. Finally, perspective and some unresolved challenges in ECPLA that can potentially be addressed have also been discussed.