Dual-Mode Ratiometric Electrochemical and Turn-On Fluorescent Detection of Butyrylcholinesterase Utilizing a Single Probe for the Diagnosis of Alzheimer's Disease

Biomarkers detection in blood withhigh accuracy is crucial forthe diagnosis and treatment of many diseases. In this study, the proof-of-conceptfabrication of a dual-mode sensor based on a single probe (Re-BChE)using a dual-signaling electrochemical ratiometric strategy and aturn-on fluorescent method is presented. The probeRe-BChE was synthesized in a single step and demonstrated dual moderesponse toward butyrylcholinesterase (BChE), a promising biomarkerof Alzheimer's disease (AD). Due to the specific hydrolysisreaction, the probe Re-BChE demonstrated a turn-on current responsefor BChE at -0.28 V, followed by a turn-off current responseat -0.18 V, while the fluorescence spectrum demonstrated aturn-on response with an emission wavelength of 600 nm. The developedratiometric electrochemical sensor and fluorescence detection demonstratedhigh sensitivity with BChE concentrations with a low detection limitof 0.08 mu g mL(-1) and 0.05 mu g mL(-1), respectively. Importantly, the dual-mode sensor presents the followingadvantages: (1) dual-mode readout can correct the impact of systematicor background error, thereby achieving more accurate results; (2)the responses of dual-mode readout originate from two distinct mechanismsand relatively independent signal transduction, in which there isno interference between two signaling routes. Additionally, comparedwith the reported single-signal electrochemical assays for BChE, bothredox potential signals were detected in the absence of biologicalinterference within a negative potential window. Furthermore, it wasdiscovered that the outcomes of direct dual-mode electrochemical andfluorescence quantifications of the level of BChE in serum were inagreement with those obtained from the use of commercially availableassay kits for BChE sensing. This method has the potential to serveas a useful point-of-care tool for the early detection of AD.

Automated summary

In this study, a dual-mode sensor based on a single probe (Re-BChE) was developed for accurate detection of biomarkers in blood. The sensor demonstrated high sensitivity and low detection limit for BChE using both electrochemical and fluorescence methods. The dual-mode readout of the sensor can correct errors and achieve more accurate results.