Fig. 1: Co-calibration of dual-DNA probes in nanoconfined channel (CBA&C4@AAO) for drug monitoring.
From: Sub-femtomolar drug monitoring via co-calibration mechanism with nanoconfined DNA probes
a To address on-site drug detection scenarios, nanoconfined biosensor (NCBS) can be further developed into a wearable sweat sensor by integrating microfluidic technology, enabling non-invasive, privacy-preserving detection in the future. b In biological nanopores, different functional proteins are distributed, including ion-selective proteins (SF) and specific sensing gate proteins (AG). The Cat-specific binding probe (CBA) forms a hairpin structure upon binding to Cat (left diagram). Meanwhile, the pH-responsive C4 DNA undergoes reversible structural changes with varying pH levels (low pH: i-Motif structure, high pH: extended linear structure) (right diagram). c The dual-DNA probes in the CBA&C4@AAO provide ultra-sensitive target recognition by altering the effective pore diameter, surface wettability, and other nanochannel properties through probe conformational changes, affecting the ionic current signal. The CBA&C4@AAO surface is functionalized with two distinct DNA probes, resulting in a rougher texture compared to the single-probe CBA@AAO, which slightly reduces hydrophilicity and amplifies the effective pore size variation before and after Cat binding (left diagram). Additionally, the CBA&C4@AAO surface is enriched with C4 DNA, which binds specifically to protons, reducing signal interference caused by proton transmembrane transport (right diagram). The NCBS also shows more pronounced surface charge changes, and this synergistic effect significantly enhances the NCBS response to Cat detection. This strategy would allow for convenient, rapid, and ultra-sensitive detection of drugs in sweat, as well as applications in health diagnostics.
