Anchoring red blood cell with tetrahedral DNA nanostructure: Electrochemical biosensor for the sensitive signage of circulating tumor DNA

Circulating tumor cells (CTCs), as a type of tumor, have attracted wide attention because of their characteristics of shedding from the primary tumor and spreading to other tissues and organs through peripheral blood. The circulating tumor DNA (ctDNA), the DNA released by CTCs and other tumor cells into the peripheral blood, was considered as a promising detection substance for clinical application. By utilizing the biocompatibility of red blood cells to realize the attachment of tetrahedral DNA (TDN), as well as the specific target recognition ability of TDN to enable efficient recognition of targets, a biocompatible electrochemical biosensor for effective and rapid detection of ctDNA was developed using methylene blue (MB) as the signal probe. The current signal and the logarithm of ctDNA concentration were linearly correlated in the range from 1 fM to 100 pM with the detection limit of 0.66 fM. With high specificity, the TDN-based biosensor can detect ctDNA efficiently in the real biological environment such as serum, which provided a potential opportunity for the early clinical diagnosis.

Automated summary

Circulating tumor cells (CTCs) have become a focus of research due to their ability to spread from the primary tumor to other tissues through peripheral blood. Circulating tumor DNA (ctDNA), released by CTCs and other tumor cells, is considered a promising substance for clinical detection. A biocompatible electrochemical biosensor was developed using tetrahedral DNA (TDN) attached to red blood cells and methylene blue (MB) as a signal probe, enabling efficient and rapid detection of ctDNA. The TDN-based biosensor showed linear correlation between current signal and logarithm of ctDNA concentration in the range of 1 fM to 100 pM, with a detection limit of 0.66 fM. This specific and sensitive biosensor can effectively detect ctDNA in real biological environments such as serum, providing potential opportunities for early clinical diagnosis.