A double-tetrahedral DNA framework based electrochemical biosensor for ultrasensitive detection and release of circulating tumor cells.

Detecting circulating tumor cells (CTCs) in patients' blood is essential for early diagnosis, precise treatment and prognosis of cancer. Yet due to CTCs being extremely rare in the peripheral blood of patients, it is still a challenge to detect CTCs with high sensitivity and high selectivity. Here, we developed a double-tetrahedral DNA framework (DTDF) based electrochemical biosensor system (E-CTC sensor system) for ultrasensitive detection and release of CTCs. In this work, an upright tetrahedral DNA framework (UTDF) was used as a rigid scaffold to modify a screen-printed gold electrode (SPGE), and an inverted tetrahedral DNA framework (ITDF) provided three vertex chains to multivalently bind with aptamers. Meanwhile, a streptavidin tagged horseradish peroxidase homopolymer (SA-polyHRP) was linked to biotin-modified aptamers to significantly amplify the signal. Moreover, the captured CTCs could be effectively released via benzonase nuclease with little cell damage. Our E-CTC sensor system achieved a linear range from 1 to 105 MCF-7 cells with an ultralow detection limit of 1 cell. The release efficiency reached 88.1%-97.6% and the viability of the released cells reached up to 98%. We also detected the MCF-7 cells in mimic whole blood samples, suggesting that the E-CTC sensor system shows promise for use in clinical research.