SERS-Based Immunoassay Enhanced with Silver Probe for Selective Separation and Detection of Alzheimer’s Disease Biomarkers

Abstract

Dan Yu,1,2,* Qilong Yin,1,3,* Jiwei Wang,1,* Jian Yang,1 Zimeng Chen,1 Zihan Gao,1 Qingli Huang,1,4 Shibao Li1,3 1Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 4Public Experimental Research of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingli HuangPublic Experimental Research of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] LiDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Developing a sensitive SERS-based method to quantitatively detect serum biomarkers (Aβ 1-42 and P-Tau-181) for the early diagnosis of Alzheimer’s disease (AD).Methods: In this study, a novel SERS-based sandwich immunoassay, which consists of tannin-capped silver nanoparticles and magnetic graphene oxide (Fe3O4@GOs), was developed. We firstly applied this method for the detection of protein standards in buffer solution, obtaining the regression equation. Then, its potential value on real serum samples of AD was further explored.Results: The detection linear range of Aβ 1-42 and P-Tau-181 protein standards were observed to range from 100 pg mL− 1 to 10 fg mL− 1, 100 pg mL− 1 to 1 fg mL− 1 respectively. We finally explored clinical application of the proposed method in 63 serum samples. As a result, P-tau-181 differentiated AD from non-AD dementia patients (AUC = 0.770), with a more favored ROC than Aβ 1-42 (AUC =  0.383).Conclusion: The developed SERS-based immunoassay is successfully applied to the determination of Aβ 1-42 and P-Tau-181 in human serum specimens, which provides a promising tool for the early diagnosis of AD.Keywords: surface-enhanced Raman scattering, silver probe, Alzheimer’s disease, biomarker, diagnosis

Keywords

• surface-enhanced raman scattering
• silver probe
• alzheimer’ s disease
• biomarker
• diagnosis