Ferritin-Enhanced Direct MicroRNA Detection via Controlled Radical Polymerization

Accurate quantitative detection of tracing nucleic acids remains a great challenge in cancer genetic testing. It is crucial to propose a low-cost and highly sensitive direct gene detection method for cancer prevention and treatment. Herein, this work reports an ultrasensitive biosensor via a ferritin-enhanced atom-transfer radical polymerization (Ft-ATRP) process. Intriguingly, microRNA-21, an early marker of lung cancer, can be detected without being transcribed in advance by an innovative signal amplification strategy using ferritin-mediated aggregation of hydrophilic nitroxide radical monomers as an electrochemical biosensor. The sensor uses peptide nucleic acid probes modified on a gold electrode to accurately bind the target lung cancer marker in the sample, and then ferritin, which is naturally present in human blood, induces Ft-ATRP on the electrode surface under mild conditions. Many of 4-methacryloyloxy-2,2,6,6-tetramethylpiperidine 1-oxyl free radical (MATMP) monomers with electrochemical signals are combined into polymeric chains to be modified on target assays. The limit of detection (LOD) of microRNA-21 is as low as 6.03 fM, and the detection concentration ranges from 0.01 to 100 pM (R2 = 0.994). The RNA biosensor can realize great performance analysis of complicated samples in simple operation, in addition, the detection process used by the catalyst, polymers containing electrochemical signals, and the electrolyte solution all have good water solubility. The superior performance of the RNA biosensor demonstrates its potential to screen and identify lung cancer in target patients.