Rationally remodeled biomimetic aptasensor enhances the detection performance of heterogeneous circulating tumor cells

Cell membrane biomimetic aptasensors stand out as a highly promising approach for detecting heterogeneous circulating tumor cells (CTCs) thanks to the integration of the benefits of cell membranes and aptasensors. Although previous studies have been devoted to exploring high-performance biomimetic aptasensors, inadequate attention has been paid to their design keys, making it difficult to tailor them to the complex application environment. Herein, we reasonably remodeled the biomimetic aptasensor to achieve sensitive detection of heterogeneous CTCs based on the two fundamental designs of the stability of cell membrane and the performance of aptasensors. In this system, the stability of cell membrane coating ensures efficient aptamer coupling and stable anti-fouling performance, while the aptasensor can enrich heterogeneous CTCs via ordered multiple aptamers and trigger two independent signal transductions, thus improving the detection accuracy. As compared to conventional aptasensors, this novel biomimetic aptasensor can effectively enrich heterogeneous CTCs, minimize the interference of leukocytes, and provide cross-validated results through dual-mode detection to improve analysis sensitivity and reliability. The progress provides a practical way to rationally remodel biomimetic aptasensors with tunable structures and enhanced properties for CTCs detection, facilitating the development of early cancer diagnosis and prognosis evaluation.