Electrochemical CYFRA21-1 DNA sensor with PCR-like sensitivity based on AgNPs and cascade polymerization

In this work, a new method of CYFRA21-1 DNA (tDNA) detection based on electrochemically mediated atom transfer radical polymerization (e-ATRP) and surface-initiated reversible addition-fragmentation chain transfer polymerization (SI-RAFT) cascade polymerization and AgNP deposition is proposed. Firstly, the peptide nucleic acid (PNA) probe is captured on a gold electrode by Au-S bonds for specific recognition of tDNA. After hybridization, PNA/DNA strands provide high-density phosphate groups for the subsequent ATRP initiator by the identified carboxylate-Zr⁴⁺-phosphate chemistry. Then, a large number of monomers are successfully grafted from the DNA through the e-ATRP reaction. After that, the chain transfer agent of SI-RAFT and methacrylic acid (MAA) are connected by recognized carboxylate-Zr⁴⁺-carboxylate chemistry. Subsequently, through SI-RAFT, the resulting polymer introduces numerous aldehyde groups, which could deposit many AgNPs on tDNA through silver mirror reaction, causing significant amplification of the electrochemical signal. Under optimal conditions, this designed method exhibits a low detection limit of 0.487 aM. Moreover, the method enables us to detect DNA at the level of PCR-like and shows high selectivity and strong anti-interference ability in the presence of serum. It suggests that this new sensing signal amplification technology exhibits excellent potential of application in the early diagnosis of non-small cell lung cancer (NSCLC). Graphical abstract Electrochemical detection principle for CYFRA21-1 DNA based on e-ATRP and SI-RAFT signal amplification technology.