Free-Standing Vertically Aligned Tin Disulfide Nanosheets for Ultrasensitive Aptasensor Design toward Alzheimer’s Diagnosis Applications

Despite a single drug, Aducanumab, recently approved by the U.S. Food and Drug Administration for Alzheimer's disease (AD)-modifying treatments, the development of non-invasive, highly sensitive, and early screening de-vices to halt the disease remains a critical challenge. In this study, an electrochemical biosensor for amyloid-beta (42) oligomers (A beta Os) detection based on immobilized DNA aptamer onto vertical aligned tin disulfide nano -sheets (SnS2 NSs) is developed for the first time. Highly crystalline, uniform, and vertical aligned SnS2 NSs were synthesized via a facile chemical vapor deposition (CVD) process. The sensing platform, comprising of A beta (42) -specific capture aptamer covalently immobilized onto self-assembled-3-mercaptopropyl-trimethoxysilane (MPTMS)-SnS2 binds specifically toward A beta Os. The biosensor can detect the A beta Os at wide linear concentra-tion range from 10-4 to 103 ng/mL with a low limit of detection (LOD) of 238.9 fg/mL and 56.9 fg/mL in physiological buffer and human serum (HS), respectively. The developed biosensor was successfully used to detect A beta Os in the mice blood serum samples indicating its potential for clinical application in Alzheimer's biomarker detection. Moreover, the SnS2-aptasensor shows good stability, selectivity, and interference -resistance. The predominant edge-plane active site and energetically preference for vertical SnS2 over its planar structure were unveiled by density-functional theory calculations which emphasize the advantages of applying nanomaterial with vertical orientated configuration into electrocatalytic reaction. The as-designed SnS2-aptasensor could shed light not only on multifunctional electrochemical biosensor design, but also for advancements on future Alzheimer's diagnosis.