Functional nucleic acid engineered double‐barreled nanopores for measuring sodium to potassium ratio at single‐cell level

The use of double-barreled nanopipette (θ-nanopipette) to electrically sample, manipulate, or detect biomaterials has recently seen strong growth in single-cell studies, driven by the potential of the nanodevices and applications that they may enable. Considering the pivotal roles of Na/K ratio (R) at cellular level, herein we describe an engineered θ-nanopipette for measuring single-cell R. The two independently addressable nanopores, located within one nanotip, allow respective customization of functional nucleic acids but simultaneous deciphering of Na and K levels inside a single cell of a non-Faradic manner. Two ionic current rectification signals, corresponding to the Na- and K-specific smart DNA responses, could be easily used to derive the R. The applicability of this nanotool is validated by practical probing intracellular R during the drug-induced primary stage of apoptotic volume decrease. Especially, the R has been shown by our nanotool to be different in cell lines with different metastatic potential. This work is expected to contribute to futuristic study of single-cell R in various physiological and pathological processes.