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Flexible and Label-Free 2D Nanomaterials-Based Biosensors for Alzheimer’s Disease
Other Title
Flexible and Label-Free 2D Nanomaterials-Based Biosensors for Alzheimer’s Disease
Type
thesis
Date Issued
2022-12-29
Author(s)
BAYU TRI MURTI
Advisor
彭志維
Subjects
系所名稱：生醫材料暨組織工程研究所博士班
Description
學位別：博士
語文別：英文
口試委員：楊 伯康 PO-KANG YANG;賴建宏 CHIEN-HUNG LAI;李權倍 CHUAN-PEI LEE;蔡孟霖 MENG-LIN TSAI;彭志維 CHIH-WEI PENG
授權範圍：網際網路,開放日期為2028-01-01
語文別：英文
口試委員：楊 伯康 PO-KANG YANG;賴建宏 CHIEN-HUNG LAI;李權倍 CHUAN-PEI LEE;蔡孟霖 MENG-LIN TSAI;彭志維 CHIH-WEI PENG
授權範圍：網際網路,開放日期為2028-01-01
Abstract
Abstract
Alzheimer’s disease (AD) is a detrimental, irreversible, and progressive neurologic disorder which steadily declines the memory, thinking, and behavioral skills. The recent attempt to characterize AD is by quantifying pathological markers, including amyloid-β (Aβ) plaques in biofluids. However, a label-free, highly sensitive, and flexible bioelectrode-based impedimetric aptasensor for amyloid detection has not been addressed yet. This study aimed to develop an electrochemical biosensor for Aβ (42) oligomers (AβOs) detection based on unconventional vertically arranged tin disulfide nanosheets (SnS2 NSs). The sensor platform, including thiol-modified DNA aptamer immobilized onto self-assembled-3-mercaptopropyl-trimethoxysilane-SnS2 binds specifically to AβO analytes via strong disulfide bond interactions. The stepwise procedure of biosensor construction was characterized by cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The charge-transfer resistance at the sensor surface were proportionally recorded using EIS in response to the chemical modification as well as the aptamer-analyte binding event. The fabricated biosensor could detect the oligomeric Aβ (42) at the wide range of linear concentration of 10-4 - 103 ng/mL (seven order of magnitudes) with an extremely low detection limit of 238.9 fg/mL and 56.9 fg/mL in phosphate buffered saline and human serum, respectively. The LOD values are much lower than that of Alzheimer’s patient’s level of Aβ (42) in blood (25 - 85 pg/mL), in cerebrospinal fluid (~500 pg/mL), or other previously reported studies. Importantly, the biosensor was applied to detect AβOs in the mice blood serum suggesting its clinical applicability in AD biomarker detection. Furthermore, the SnS2-aptasensor exhibits excellent selectivity, interference-resistance, and stability. The edge-plane active site of SnS2 and its energetic advantage over the planar structure of SnS2 were revealed by density functional theory calculations demonstrating the benefits of nanomaterials oriented vertically into electrocatalytic reactions. We believe that the proposed sensor design could shed light in future Alzheimer’s diagnosis particularly in flexible and wearable sensor design.
Alzheimer’s disease (AD) is a detrimental, irreversible, and progressive neurologic disorder which steadily declines the memory, thinking, and behavioral skills. The recent attempt to characterize AD is by quantifying pathological markers, including amyloid-β (Aβ) plaques in biofluids. However, a label-free, highly sensitive, and flexible bioelectrode-based impedimetric aptasensor for amyloid detection has not been addressed yet. This study aimed to develop an electrochemical biosensor for Aβ (42) oligomers (AβOs) detection based on unconventional vertically arranged tin disulfide nanosheets (SnS2 NSs). The sensor platform, including thiol-modified DNA aptamer immobilized onto self-assembled-3-mercaptopropyl-trimethoxysilane-SnS2 binds specifically to AβO analytes via strong disulfide bond interactions. The stepwise procedure of biosensor construction was characterized by cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The charge-transfer resistance at the sensor surface were proportionally recorded using EIS in response to the chemical modification as well as the aptamer-analyte binding event. The fabricated biosensor could detect the oligomeric Aβ (42) at the wide range of linear concentration of 10-4 - 103 ng/mL (seven order of magnitudes) with an extremely low detection limit of 238.9 fg/mL and 56.9 fg/mL in phosphate buffered saline and human serum, respectively. The LOD values are much lower than that of Alzheimer’s patient’s level of Aβ (42) in blood (25 - 85 pg/mL), in cerebrospinal fluid (~500 pg/mL), or other previously reported studies. Importantly, the biosensor was applied to detect AβOs in the mice blood serum suggesting its clinical applicability in AD biomarker detection. Furthermore, the SnS2-aptasensor exhibits excellent selectivity, interference-resistance, and stability. The edge-plane active site of SnS2 and its energetic advantage over the planar structure of SnS2 were revealed by density functional theory calculations demonstrating the benefits of nanomaterials oriented vertically into electrocatalytic reactions. We believe that the proposed sensor design could shed light in future Alzheimer’s diagnosis particularly in flexible and wearable sensor design.