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(Na/K)) at cellular level, herein we describe an engineered θ‐nanopipette for measuring single‐cell R(Na/K). 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(Na/K). The applicability of this nanotool is validated by practical probing intracellular R(Na/K) during the drug‐induced primary stage of apoptotic volume decrease. Especially, the R(Na/K) 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(Na/K) in various physiological and pathological processes.