Detection of Unfolded Cellular Proteins Using Nanochannel Array with Probe‐Functionalized Outer‐Surfaces

Abstract Nanochannel technology has emerged as a powerful tool for label‐free and highly sensitive detection of protein folding/unfolding status. However, utilizing the inner walls nanochannel array may cause multiple events even proteins with same conformation, posing challenges accurate identification. Herein, we present platform to detect unfolded through electrical optical signals using arrays outer‐surface probes. The principle relies on specific binding between maleimide groups in probes cysteine thiols that induce changes ionic current fluorescence intensity responses array. By taking advantage this mechanism, ability differentiate folded state based exposure single thiol group. integration these two enhances reliability sensitivity identification states enables distinction normal cells Huntington's disease mutant cells. This study provides an effective approach precise analysis distinct conformations holds promise facilitating diagnoses conformation‐related diseases.