Gold Nanoparticles-Based Multipedal DNA Walker for Ratiometric Detection of Circulating Tumor Cell

Sensitive and accurate quantification of circulating tumor cell (CTC) can provide new insights for early diagnosis and prognosis of cancers. Herein, we have developed a multipedal DNA walker for ultrasensitive detection of CTC for the first time. Generally, a number of walker strands are simply modified on gold nanoparticle (AuNPs). The integrated aptamer sequence can specially interact with the transmembrane receptor protein of CTC and facilitate the enrichment of AuNPs on the surface of cells. After a low speed centrifugation, the complex of CTC and AuNPs could be precipitated and the supernate represents decreased UV-vis absorbance response of AuNPs. On the other hand, since multiple walker strands are modified on a single AuNP, hybridization with several tracks on the electrode occurs simultaneously for the following nicking endonuclease-catalyzed cleaving. Experimental results verify that the rate of multipedal walking is much faster. In addition, TCEP-mediated electrochemical amplification is employed to further enhance the electrochemical signal. By comparing the variations of electrochemical and UV-vis absorbance responses, ultrahigh sensitivity for CTC assay is achieved. The limit of detection is down to 1 cell/mL. The results of selectivity confirmation and blood sample test are also satisfactory. This AuNPs-based multipedal DNA walker offers a speedy analysis of CTC and shows great potential use for early clinical diagnosis and treatment of cancers.