Fluorescence-Enhanced Dual-Driven “OR-AND” DNA Logic Platform for Accurate Cell Subtype Identification

Developing an endogenous stimuli-responsive and ultrasensitive DNA sensing platform that contains a logic gate biocomputation for precise cell subtype identification holds great potential for disease diagnosis and prognostic estimation. Herein, a fluorescence-enhanced "OR-AND" DNA logic platform dual-driven by intracellular apurinic/apyrimidinic endonuclease 1 (APE 1) or a DNA strand anchored on membrane protein Mucin 1 (MUC 1) for sensitive and accurate cell subtype identification was rationally designed. The recognition toehold of the traditional activated probe (TP) was restrained by introducing a blocking sequence containing an APE 1 cleavable site (AP-site) that can be either cleaved by APE 1 or replaced by Mk-apt, ensuring the "OR-AND" gated molecular imaging for cell subtype identification. It is worth noting that this "OR-AND" gated design can effectively avoid the missing logical computation caused by membrane protein heterogeneous spatial distribution as a single input. In addition, a benefit from the excellent plasmon-enhanced fluorescence (PEF) ability of Au NSTs is that the detection limit can be decreased by nearly 165 times. Based on this, not only different kinds of MCF-7, HepG2, and L02 cells, but also different breast cancer cell subtypes, including malignant MCF-7, metastatic MDA-MB-231, and nontumorigenic MCF-10A cells, can be accurately identified by the proposed "OR-AND" gated DNA logic platform, indicating the prospect of this simple and universal design in accurate cancer screening.