Machine Learning-Assisted Nanoenzyme/Bioenzyme Dual-Coupled Array for Rapid Detection of Amyloids
Yu Xu, Qian Cheng, Yang Yu, Shijie Yang, Fangfang Shi, Lian Xu, Xu Gao, Yuhang Liu, Hui Huang, Callum Stewart, Fei Li, Jinsong Han
Abstract
Array-based sensing methods offer significant advantages in the simultaneous detection of multiple amyloid biomarkers and thus have great potential for diagnosing early-stage Alzheimer's disease. Yet, detecting low concentrations of amyloids remains exceptionally challenging. Here, we have developed a fluorescent sensor array based on the dual coupling of a nanoenzyme (AuNPs) and bioenzyme (horseradish peroxidase) to detect amyloids. Various ss-DNAs were bound to the nanoenzyme for regulating enzymatic activity and recognizing amyloids. A simplified sensor array was generated from a screening model via machine learning algorithms and achieved signal amplification through a two-step enzymatic reaction. As a result, our sensing system could discriminate the aggregation species and aggregation kinetics at 200 nM with 100% accuracy. Moreover, AD model mice and healthy mice were distinguished with 100% accuracy through the sensor array, providing a powerful sensing platform for diagnosing AD.