A dual-mode nano-microelectrode for PTH detection at the single-cell level

Parathyroid hormone (PTH) is essential for calcium-phosphate homeostasis and bone metabolism. Abnormal PTH levels are closely associated with chronic kidney disease and several types of cancer. Current mainstream immunological PTH detection methods cannot achieve single-cell analysis, and dual-signal detection strategies are scarce. Herein, we designed a dual-signal nano-microelectrode for single-cell PTH detection by modifying gold-deposited nanopipettes with ferrocene (Fc)-labeled DNA-complementary DNA double strands and 6-mercaptohexanol (6-MCH). Under optimized conditions, square-wave voltammetry (SWV) showed a linear response to PTH in the range of 1-500 pg mL^-1 (R² = 0.99), and EIS exhibited linearity in the range of 1-1000 pg mL^-1 (R² = 0.98). The sensor demonstrated high selectivity against common intracellular interferents and good electrode-to-electrode consistency. Using three-dimensional micro-manipulation technology, minimally invasive detection of individual cells was achieved, and significant changes in electrochemical signals before and after cell penetration were revealed. Furthermore, the intracellular PTH concentration gradually decreased with prolonged extracellular Ca²⁺ incubation, consistent with the regulatory mechanism of calcium-sensing receptors. This dual-mode nano-micro electrode is a new type of tool that enables rapid, low-cost, label-free and highly specific single-cell PTH analysis.