Engineering- nanochannels with pH-responsive gates for direct detection of glucose in human blood serum

An abnormal blood glucose (Glu) level is a key signal of diabetes. The gluconic acid produced by Glu catalytic oxidation can cause changes in pH value.

Inspired by nature, in which organisms use pH as a chemical gate to regulate ion transport through cell membranes, we report a pH-gated electrochemical luminescence (ECL) sensing system for Glu detection based on the relationship between Glu metabolism and pH. The pH gate was designed on a TiO₂ nanochannel membrane (NM) by modifying the channel entrance with polystyrene-b-poly(4-vinylpyridine) (P4VP) chains that convert from a hydrophobic into a hydrophilic state via a pH-responsive conformational switching at pKa 5.2. Due to the nanoconfinement effect of zeolite imidazolate (ZIF-8) frameworks and TiO₂ nanochannels, the glucose oxidase (GOD) embedded in ZIF-8 exhibits enhanced catalytic efficiency for Glu oxidation, enabling the acidic product to regulate the hydrophilicity of the P4VP-based pH-responsive gate. The ECL luminophore Ru(dcbpy)₃²⁺ subsequently passes through the hydrophilic gate to reach the detection cell. This pH-gated Glu-responsive NM can effectively separate biological matrices from the detection cell, allowing direct sensing of Glu in complex biomatrices.

The ECL technology, combined with the pH-triggered gate design enables straightforward Glu determination in undiluted serum, demonstrating an alternative ECL device for pretreatment-free clinical analysis.