Urease-mediated homogeneous dual-mode biosensor for on-site qualitative and accurate sensitive quantitative detection of toxic soluble Aβ oligomers in undiluted samples

In different contexts of Alzheimer's disease (AD), specific criteria for detecting toxic soluble amyloid β (Aβ) oligomers are crucial: Early detection requires highly-sensitive and accurate technology, while assessing treatment efficacy requires qualitative analysis using predefined thresholds. However, traditional methods, particularly single signal output, struggle to fulfill these criteria. Here, we present a urease-mediated homogeneous dual-mode biosensor that combines colorimetry and field-effect transistor (FET) through dual-aptamer recognition for the analysis of Aβ oligomers. This approach overcomes the challenges associated with surface modification of FET biosensors, allowing for both qualitative on-site detection (at pM levels) and highly-sensitive quantitative analysis (at fM levels) of Aβ oligomers in undiluted samples. The dual-mode biosensor displayed excellent performance in fetal bovine serum (FBS), artificial cerebrospinal fluid (aCSF) and rabbit whole blood samples, achieving a high recovery rate ranging from 96.1 % to 101 % and a low relative standard deviation between 1.7 % and 5.1 % when detecting Aβ oligomers in undiluted samples. Furthermore, clinical tests of serum and plasma samples from AD patients and healthy individuals also verified the sensitivity and specificity of the proposed dual-mode biosensor, demonstrating its potential application in early screening and monitoring of AD treatment processes.