posted on 2022-01-28, 18:33authored byBiao Chen, Wenjie Ma, Xu Long, Hong Cheng, Huanhuan Sun, Jin Huang, Ruichen Jia, Xiaoxiao He, Kemin Wang
DNA
logic gates, as a class of smart molecular devices with excellent
biocompatibility and convenient information processing mode, have
been widely used for identification of cancer cells based on logic
analysis of cancer biomarkers. However, most of the developed DNA
logic gates for identification of cancer cells are mainly driven by
homogeneous biomarkers such as membrane proteins or RNAs, which may
suffer from insufficient accuracy. Herein, we reported a membrane
protein and extracellular acid heterogeneity-driven amplified DNA
logic gate (HDLG) for accurate and sensitive identification of cancer
cells by combining the superior signal amplification characteristics
of the hybridization chain reaction (HCR) and the precise computation
ability of the logic operation. In this strategy, a DNA aptamer was
employed for membrane protein recognition, and a split i-motif was
used for the response of the extracellular acid. Only when the two
heterogeneous biomarkers existed simultaneously, the DNA logic gate
could be driven to perform the “AND” logic operation
and induce the formation of an intact trigger to initiate a HCR process
on the cell surface, generating an amplified “ON” fluorescence
signal. Benefiting from the design of heterogeneity-driven and signal
amplification, this DNA logic gate could not only autonomously perform
high-resolution fluorescence imaging on the surface of target cancer
cells, but also perform sensitive analysis of target cancer cells
with a cell number of 70 detected in 200 μL of buffer and desirable
accuracy in differentiating target cancer cells from complicated cell
mixtures. We anticipate that this novel HDLG is expected to be applied
in precise disease diagnosis.