G-Quadruplex-Filtered Selective Ion-to-Ion Current Amplification for Non-Invasive Ion Monitoring in Real Time

Living cells efflux intracellular ions for maintaining cellular life, so intravital measurements of specific ion signals are of significant importance for studying cellular functions and pharmacokinetics. In this work, de novo synthesis of artificial K⁺ -selective membrane and its integration with polyelectrolyte hydrogel-based open-junction ionic diode (OJID) is demonstrated, achieving a real-time K⁺ -selective ion-to-ion current amplification in complex bioenvironments. By mimicking biological K⁺ channels and nerve impulse transmitters, in-line K⁺ -binding G-quartets are introduced across freestanding lipid bilayers by G-specific hexylation of monolithic G-quadruplex, and the pre-filtered K⁺ flow is directly converted to amplified ionic currents by the OJID with a fast response time at 100 ms intervals. By the synergistic combination of charge repulsion, sieving, and ion recognition, the synthetic membrane allows K⁺ transport exclusively without water leakage; it is 250× and 17× more permeable toward K⁺ than monovalent anion, Cl^- , and polyatomic cation, N-methyl-d-glucamine⁺ , respectively. The molecular recognition-mediated ion channeling provides a 500% larger signal for K⁺ as compared to Li⁺ (0.6× smaller than K⁺ ) despite the same valence. Using the miniaturized device, non-invasive, direct, and real-time K⁺ efflux monitoring from living cell spheroids is achieved with minimal crosstalk, specifically in identifying osmotic shock-induced necrosis and drug-antidote dynamics.