Electrochemiluminescent/colorimetric biosensors for ultrasensitive detection of Aβ based on CdS quantum dot-modulated HOFs-Cu2+-g-C₃N₄

In this work, we presented an electrochemiluminescent (ECL)/colorimetric biosensors for ultrasensitive detection of β-amyloid peptide (Aβ) based on hydrogen-bonded organic framework (HOFs)-Cu²⁺-graphitic carbon nitride (g-C₃N₄) nanocomposites. HOFs-Cu²⁺-g-C₃N₄ could be used both as an ECL luminescent substrate and as a nanozyme to catalyze the chromogenic reaction of 3,3′,5,5′-tetramethylbenzidine (TMB). Specifically, in the ECL mode, HOFs-Cu²⁺-g-C₃N₄ were firstly loaded on the surface of the electrode. The target analyte Aβ could simultaneously bind both Cu²⁺ and the peptide fragment KLVFF, thereby capturing the CdS quantum dots (QDs)-KLVFF on the electrode. The CdS QDs could perform ECL resonance energy transfer with HOFs-Cu²⁺-g-C₃N₄, resulting the increase in the ECL intensity. Meanwhile, in the colorimetric mode, the aptamer loaded on the magnetic beads could specifically capture the target Aβ. HOFs-Cu²⁺-g-C₃N₄ used as the nanozyme in the TMB-H₂O₂ chromogenic system could be sequentially bound with the target Aβ. The convenient colorimetric detection of Aβ was achieved after magnetically separating using the functionalized magnetic beads. The concentration range of Aβ detected by ECL mode was 0.1 pM ∼ 0.1 μM with a detection limit of 0.07 pM, while the concentration range of Aβ detected by colorimetric assay was 0.1 pM ∼ 0.1 μM with a detection limit of 0.032 pM. These two different assay modes enhanced the sensitivity and reliability of the detection of Aβ and demonstrated potential applicability in the early diagnosis of Alzheimer's disease.