Covalent organic framework-based ratiometric electrochemical sensing platform for ultrasensitive determination of amyloid-β 42 oligomer.

Accurate and sensitive detection of amyloid-β 42 oligomer (Aβ42O) is of great significance for early diagnosis of Alzheimer's disease (AD). Herein, a signal on-off ratiometric electrochemical immunosensor was developed for highly selective and quantitative determination of Aβ42O by using novel covalent organic frameworks (COFs) composites as the sensing platform. This immunosensor produced two independent electrochemical signals from the [Fe(CN)6]3-/4- and methylene blue (MB) probes at different potentials based on the electrocatalytic activity of gold nanoparticle-functionalized porphyrinyl COFs nanocomposites toward [Fe(CN)6]3-/4- and the signal probe of MB encapsulated in the aptamer-modified alkynyl COFs. Because the two signals of [Fe(CN)6]3-/4- and MB changed in opposite directions, a signal on-off mode was generated which can correct the results by introducing a reference signal and effectively eliminate background interference. Under optimal experimental conditions, the current ratio (IMB/I[Fe(CN)6]3-/4-) was well linearly related to the logarithmic value of Aβ42O concentrations in the range of 10 pM to 1 μM, and the detection limit was 5.1 pM (S/N = 3). Additionally, the immunosensor exhibited satisfactory performance in case of real cerebrospinal fluid samples. The designed ratiometric electrochemical immunosensor provides a valuable route for early diagnosis of AD and our results also pave the way for designing of sensing platforms using COF-based nanomaterials and extending their functions and applications to bioanalysis.