Lighting Up Dual-Aptamer-Based DNA Logic-Gated Series Lamp Probes with Specific Membrane Proteins for Sensitive and Accurate Cancer Cell Identification

Accurate identification of cancer cells under complex physiological environments holds great promise for noninvasive diagnosis and personalized medicine. Herein, we developed dual-aptamer-based DNA logic-gated series lamp probes (^DApt-SLP) by coupling a DNA cell-classifier (DCC) with a self-powered signal-amplifier (SSA), enabling rapid and sensitive identification of cancer cells in a blood sample. DCC is endowed with two extended-aptamer based modules for recognizing the two cascade cell membrane receptors and serves as a DNA logic gate to pinpoint a particular and narrow subpopulation of cells from a larger population of similar cells. DCC leverages a dual-receptor co-recognition strategy for enhanced specificity of cell identification by performing the matching operation between aptamer and receptor twice on cell membranes. SSA is a signal converter attached at the end of DCC that changes the cell identification process into detectable signals, as well as a signal amplifier to output amplified signals by using a simple and efficient hybridization chain reaction. Unique from those who are multicomponent systems, ^DApt-SLP is an all-in-one compact DNA nanodevice, exhibiting an enhanced nuclease-degradation resistance and targeting ability. In vitro feasibility, cell imaging, and flow cytometry analysis showed that the ^DApt-SLP system successfully operated under buffered solution and physiological environment and precisely differentiated the target cell from large populations of similar cells. Benefiting from its integrated design and single-step cancer cell identification with high sensitivity and accuracy, the ^DApt-SLP system is a practical tool in personalized medicine and biomedical engineering.