Biologically-driven RAFT polymerization-amplified platform for electrochemical detection of antibody drugs

The individualized administration and pharmacokinetics profiling are integral to the safe use of antibody drugs in immunotherapy. Here, we propose an electrochemical platform for the highly sensitive and selective detection of antibody drugs, taking advantage of the affinity capture by the peptide mimotopes together with the signal amplification by the biologically-driven RAFT polymerization (BDRP). Briefly, the BDRP-based platform involves the capture of antibody drugs by peptide mimotopes, the labeling of multiple reversible addition-fragmentation chain-transfer (RAFT) agents to the glycan chains of antibody drugs, and the BDRP-enabled controlled recruitment of numerous redox labels. The BDRP-based signal amplification relies on the reduction of RAFT agents by NADH coenzymes into the carbon-centered radicals, which can propagate efficiently into long polymer chains by reacting with the ferrocene-derivated monomers, recruiting numerous redox labels to the glycan chains of antibody drugs. The BDRP is conducted at the physiological temperature (i.e., 37 °C) and in the absence of external stimuli or radical sources, holding the advantages of biological compatibility and desirable simplicity over conventional RAFT polymerization approaches. The developed platform is highly selective and the detection limit in the presence of rituximab as the target was determined to be 0.14 ng/mL. Moreover, the applicability of the BDRP-based platform in the sensitive assay of antibody drugs in serum samples has been validated. In view of the biocompatibility, desirable simplicity, and cost-effectiveness, the BDRP-based platform shows great promise in the quantitative assay of antibody drugs.