Dual-aptamer modification generates a unique interface for highly sensitive and specific electrochemical detection of tumor cells.

Because circulating tumor cells (CTCs) have been proven to be an important clue of the tumor metastasis, their detection thus plays a pivotal role in the diagnosis and prognosis of cancer. Herein, we fabricate an electrochemical sensor by directly conjugating two cell-specific aptamers, TLS1c and TLS11a, which specifically recognize MEAR cancer cells, to the surface of a glassy carbon electrode (GCE) via the formation of amide bonds. The two aptamers are simultaneously conjugated to the GCE surface via precisely controlled linkers: TLS1c through a flexible linker (a single-stranded DNA T15; ss-TLS1c) and TLS11a through a rigid linker (a double-stranded DNA T15/A15; ds-TLS11a). It is found that such ss-TLS1c/ds-TLS11a dual-modified GCEs show greatly improved sensitivity in comparison with those modified with a single type of aptamer alone or ds-TLS1c/ds-TLS11a with both rigid linkers, suggesting that our optimized, rationally designed electrode-aptamer biosensing interface may enable better recognition and thus more sensitive detection of tumor cells. Through the utilization of this dual-aptamer-modified GCE, as few as a single MEAR cell in 10(9) whole blood cells can be successfully detected with a linear range of 1-14 MEAR cells. Our work demonstrates a rather simple yet well-designed and ultrasensitive tumor cell detection method based on the cell-specific aptamer-modified GCE, showing a promising potential for further CTC-related clinical applications.