Electrochemical immunosensors based on the solubility difference of electroactive probe and the dual signal amplification of nanocarrier plus redox cycling

This work reported a redox cycling system for the design of electrochemical immunosensors by using pyrroloquinoline quinone (PQQ) to promote the oxidation of tris(2-carboxyethyl)phosphine (TCEP). The consumption of TCEP was monitored with ferrocenium (Fc+) as the electroactive probe, which was based on the difference in the solubility of Fc+ with its reduced format (ferrocene, Fc). Metal-organic framework (MOF) was used as the nanocarrier to load biotinylated recognition antibody and PQQ with recombinant streptavidin as the linker. In the absence of target, TCEP could reduce Fc+ into insoluble Fc aggregates, thus leading to the decrease in the electrochemical signal. Capture of target allowed for the attachment of antibody-modified MOF-PQQ on the sensing electrode, thus promoting the oxidation of TCEP by O2 through the redox cycling. In this case, the reduction of Fc+ into insoluble Fc aggregates was limited, and Fc+ remained in the solution exhibited a high electrochemical signal. The peak current was linearly proportional to the target concentration in the range of 0.001-1 ng/mL with prostate specific antigen as an example. The work should be useful for the design of novel biosensors through the signal amplification of redox cycling.