A Supersmall Single-Cell Nanosensor for Intracellular K ⁺ Detection

Abstract

Intracellular potassium ions (K + ) play pivotal roles in many physiological processes. Several K + sensors have been developed for probing cellular K + fluctuations. Nevertheless, the existing solutions are incompatible and impractical for intracellular K + probing. Herein, we report a supersmall biomimetic K + nanosensor to serve as a transmembrane vector capable of electrochemically detecting intracellular K + in a minimally invasive manner. The sensitive and reversible response of this nanosensor stems from the synergy between a supersmall nanopipette with an orifice of ca. 20 nm and the K + -dependent structural change of the G-quadruplex DNA decorated within the nanopipette. This nanosensor is demonstrated to be an accessible tool for tracking stimulus-induced K + fluctuation under physiological conditions.

Spatiotemporal Visualization of Cell Membrane with Amphiphilic Aggregation-Induced Emission-Active Sensor

“…Distinguishing cell membranes at the complicated multicellular level is conducive to analyze intracellular homeostasis and the intercellular information exchange. 39,40 In light of the good dispersity in both hydrophilic and lipophilic environments benefiting diffusion from surface cells to inner cells, and the "wash-free" property simplifying staining procedure with low background signal, the QMC12 was supposed to stain the multicellular models in spatial dimension. Therefore, the QMC12 was incubated with the 3D biological model, multicellular tumor spheroid, [41][42][43] to evaluate the spatial staining ability.…”

A High Spatiotemporal Iontronic Single-Cell Viscometer

“…Originally found in nature, iontronics has rapidly evolved as an advanced technology based on sophisticated control of ions as signal carriers, underpinning the operating rationale of aqueous circuits made of rationally designed nanostructures and thereon the controllable ionic transport [21][22][23]. Working in aqueous environments, iontronic devices have shown to be promising for sensing, logic circuiting, and brain-machine interfacing.…”

Photocontrolled Nanopipette Biosensor for ATP Gradient Electroanalysis of Single Living Cells

“…Nanoelectrochemistry has been demonstrated as a powerful technology for deeper understanding of cell metabolism and cell heterogeneity. − Glass nanopipette represents a state-of-the-art approach for single-cell analysis. Its unique features in terms of fast fabrication, tunable orifice, and large cavity for customized filling/functionalization, as well as on-demand injection and aspiration, make possible intracellular manipulations and measurements with high temporal and spatial resolutions under different physicochemical principles. − Recently, for example, a double-barrel nanopipette served as minimally invasive nanotweezers for dielectrophoretic single-cell biopsies; the plasmonic gold nanostars functionalized the nanopipette for Raman quantification of O 2 levels in hypoxic single cells; the G-quadruplex (G4) DNA sequence was confined in an ultrasmall nanopipette with K + -dependent conformational transformation for tracking stimulus-induced K + fluctuation under physiological conditions via resistive pulse; and porous Pt was chemically deposited in a nanopipette for bipolar electrochemiluminescent detection of intracellular H 2 O 2 and glucose …”

“…Its unique features in terms of fast fabrication, tunable orifice, and large cavity for customized filling/functionalization, as well as on-demand injection and aspiration, make possible intracellular manipulations and measurements with high temporal and spatial resolutions under different physicochemical principles. 11−25 Recently, for example, a double-barrel nanopipette served as minimally invasive nanotweezers for dielectrophoretic single-cell biopsies; 26 the plasmonic gold nanostars functionalized the nanopipette for Raman quantification of O 2 levels in hypoxic single cells; 27 the G-quadruplex (G4) DNA sequence was confined in an ultrasmall nanopipette with K + -dependent conformational transformation for tracking stimulus-induced K + fluctuation under physiological conditions via resistive pulse; 28 and porous Pt was chemically deposited in a nanopipette for bipolar electrochemiluminescent detection of intracellular H 2 O 2 and glucose. 29 Nature has optimized biochannels capable of exquisite operation in response to external stimuli such as light, voltage, ions, and biomolecules, which has stimulated extensive efforts to develop artificial nanosystems mimicking biological activities.…”