Ultrasensitive and Highly Selective Detection of Calcium Ions Using KD₅-Modified Asymmetric Nanochannels

Artificial solid-state nanochannels have attracted significant interest as promising nanofluidic tools for ion/molecule detection, DNA sequencing, and biomimetic applications. In this work, we designed an aspartic acid-rich peptide, KD₅ (Lys-Asp₅, KDDDDD), via a green tag-assisted approach. Leveraging its strong Ca²⁺ recognition and coordination capability, KD₅ was covalently grafted onto the inner surface of asymmetric nanochannels, inspired by the intelligent gating of biological ion channels. The resulting system enabled highly specific recognition and ultratrace detection of Ca²⁺ ions, achieving a detection limit as low as 10^-17 M. This remarkable sensitivity arises from Ca²⁺ binding to KD₅, which remodels interfacial charge distribution and modulates the current-voltage (I-V) characteristics of the nanochannels. The KD₅-modified multinanochannel platform demonstrated excellent applicability and reliability in real environmental sample testing. Furthermore, the KD₅-Ca²⁺ complexes could be effectively dissociated by ethylenediaminetetraacetic acid (EDTA), allowing regeneration and reuse of this ultrasensitive, label-free sensor. By integrating the molecular recognition capability of selective peptides with the electrochemical advantages of nanochannels, this work not only offers a breakthrough strategy for ultratrace Ca²⁺ detection but also provides a novel paradigm for the design of intelligent nanofluidic sensors.