The ability to accurately identify
and isolate cells is the cornerstone
of precise disease diagnosis and therapies. A single-step cell identification
method based on logic analysis of multiple surface markers will have
unique advantages because of its accuracy and efficacy. Herein, using
multiple DNA aptamers for cancer biomarker recognition and associative
toehold activation for signal integration and amplification as two
molecular keys, we have successfully operated a cell-surface device
that can perform AND Boolean logic analysis of multiple biomarkers
and precisely label the target cell subtype in large populations of
similar cells via the presence or absence of different biomarkers.
Our approach can achieve single-step cancer cell identification and
isolation with excellent sensitivity and accuracy and thus will have
broad applications in biological science, biomedical engineering,
and personalized medicine.
Cells interact with the extracellular environment through molecules expressed on the membrane. Disruption of these membrane-bound interactions (or encounters) can result in disease progression. Advances in super-resolution microscopy have allowed membrane encounters to be examined, however, these methods cannot image entire membranes and cannot provide information on the dynamic interactions between membrane-bound molecules. Here, we show a novel DNA probe that can transduce transient membrane encounter events into readable cumulative fluorescence signals. The probe, which translocates from one anchor site to another, such as motor proteins, is realized through a toehold-mediated DNA strand displacement reaction. Using this probe, we successfully monitored rapid encounter events of membrane lipid domains using flow cytometry and fluorescence microscopy. Our results show a preference for encounters within different lipid domains.
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