Abstract
The accurate, rapid, and sensitive identification of cancer cells in complex physiological environments is significant in biological studies, personalized medicine, and biomedical engineering. Inspired by the natural confined enzyme on fluidic cell membrane, afluidically confined CRISPR-based DNA reporter (FINDER) was developed on living cell membranes, which was successfully applied for rapid and sensitive cancer cell identification in clinical blood samples. Benefiting from the spatial confinement effect for improved local concentration, and membrane fluidity for higher collision efficiency, the activity of CRISPR-Cas12a was, for the first time, found to be significantly enhanced on living cell membranes. This new phenomenon was then combined with multiple aptamers-based DNA logic gate for cell recognition, thus a FINDER system with accurate, rapid and sensitive cancer cell identification was constructed. The FINDER can rapidly identified target cells in only 20 min, and achieved over 80% recognition efficiency with only 0.1% of target cells presented in clinical blood samples, indicating its potential application in biological studies, personalized medicine, and biomedical engineering.
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