An aptazyme-based logic gate biosensor for tumor detection in postoperative analysis

Postoperative tissue analysis is essential for the evaluation of surgical outcome in the tumor therapy. The identification of tumor biomarkers represents a supplementary approach to histochemical observation, facilitating the diagnosis of cancers at molecular level. Herein, a biosensor was developed by integrating an ATP-responsive aptazyme and its substrate on the surface of streptavidin magnetic beads to achieve the simultaneous detection of ATP and apurinic/apyrimidinic endonuclease 1 (APE1) within cancer cells. This strategy enabled the biosensor to respond to excessive ATP in cancer cells, thereby generating the primer. Meanwhile, the biosensor contained a double-stranded DNA with apurinic/apyrimidinic site, which allowed it to respond to APE1 and produce a padlock. The released primer and padlock triggered the rolling cycle amplification to yield an amplified fluorescent or colorimetric signal. The biosensor functioned as the “AND”-logic gate, effectively distinguishing cancer and non-cancerous cells. Moreover, the biosensor exhibited high specificity and sensitivity in discriminating the tumor and non-tumor tissues isolated from the patients bearing non-small cell lung cancer. Taken together, the biosensor showed the potential in clinical molecular diagnosis, serving as a promising supplementary approach for the postoperative tissue analysis.