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 devices to halt the disease remains a critical challenge. In this study, an electrochemical biosensor for amyloid-β (42) oligomers (AβOs) detection based on immobilized DNA aptamer onto vertical aligned tin disulfide nanosheets (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 Aβ (42)-specific capture aptamer covalently immobilized onto self-assembled-3-mercaptopropyl-trimethoxysilane (MPTMS)-SnS₂ binds specifically toward AβOs. The biosensor can detect the AβOs at wide linear concentration 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 AβOs 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.