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Driving force to detect Alzheimer's disease biomarkers: application of a thioflavine T@Er-MOF ratiometric fluorescent sensor for smart detection of presenilin 1, amyloid β-protein and acetylcholine.
Analyst ( IF 3.6 ) Pub Date : 2020-05-05 , DOI: 10.1039/d0an00440e
Xing Ze Wang 1 , Jing Du , Nan Nan Xiao , Yan Zhang , Ling Fei , Jed D LaCoste , Zhuo Huang , Qian Wang , Xin Rui Wang , Bin Ding
Analyst ( IF 3.6 ) Pub Date : 2020-05-05 , DOI: 10.1039/d0an00440e
Xing Ze Wang 1 , Jing Du , Nan Nan Xiao , Yan Zhang , Ling Fei , Jed D LaCoste , Zhuo Huang , Qian Wang , Xin Rui Wang , Bin Ding
Affiliation
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Currently, the highly sensitive detection of Alzheimer's Disease (AD) biomarkers, namely presenilin 1, amyloid β-protein (Aβ), and acetylcholine (ACh), is vital to helping us prevent and diagnose AD. In this work, a novel metal–organic framework [Er(L)(DMF)1.27]n (Er-MOF) (H3L = terphenyl-3,4′′,5-tricarboxylic acid) has been synthesized by solvothermal and ultrasonic methods. Further, through the post-synthesis assembly strategy, the fluorescent dye thioflavine T (ThT) has been introduced into Er-MOF to construct a dual-emission ThT@Er-MOF ratiometric fluorescent sensor. This is the first time that ThT@Er-MOF has been successfully applied in the highly sensitive detection of three main Alzheimer's disease biomarkers in the cerebrospinal fluid through three different low cost and facile detection strategies. Firstly, with the spilted DNA strategy, this is the first time that ThT@Er-MOF can be applied in the label-free detection of SSODN (part of the presenilin 1 gene). Secondly, for the detection of Aβ, because ThT can be specifically combined with Aβ and has an excellent characteristic fluorescence band, the dual-emission ThT@Er-MOF sensor can be selectively applied to detect Aβ over the analog protein, which shows far more sensitivity than other Aβ sensors. Thirdly, through the acetylcholine esterase (AchE) enzymatic cleavage and release strategy, ThT@Er-MOF enhances the detection of acetylcholine (ACh) with a low limit of detection (LOD) value (0.03226 nM). It should be noticed that the three different detection methods are low cost and facile. This study also provides the first example of utilizing laser scanning confocal microscopy (LSCM) to investigate the fluorescence resonance energy transfer (FRET) detection mechanism by ThT@Er-MOF in more detail. The location of FRET occurrence and FRET efficiency can also be investigated by LSCM, which can be helpful to understand the FRET detection process by these unique MOF-based hybrid materials.
中文翻译:
检测阿尔茨海默氏病生物标志物的驱动力:硫黄素T @ Er-MOF比例荧光传感器在智能检测早老素1,淀粉样β蛋白和乙酰胆碱中的应用。
当前,高灵敏度检测阿尔茨海默氏病(AD)生物标记物,即早老素1,淀粉样β蛋白(Aβ)和乙酰胆碱(ACh),对于帮助我们预防和诊断AD至关重要。在这项工作中,通过溶剂热合成了一种新颖的金属有机骨架[Er(L)(DMF)1.27 ] n(Er-MOF)(H 3 L =联苯-3,4'',5-三羧酸)。超声波方法。此外,通过后合成组装策略,将荧光染料硫黄素T(ThT)引入Er-MOF,以构建双发射ThT @ Er-MOF比率荧光传感器。这是ThT @ Er-MOF的第一次通过三种低成本且简便的检测策略,已成功应用于脑脊液中三种主要的阿尔茨海默氏病生物标志物的高灵敏度检测。首先,采用分散DNA策略,这是ThT @ Er-MOF首次可用于SSODN(早老素1基因的一部分)的无标记检测。其次,对于Aβ的检测,由于ThT可以与Aβ特异结合并具有出色的特征荧光带,因此可以选择性地应用双发射ThT @ Er-MOF传感器检测类似蛋白上的Aβ,这显示了更多灵敏度高于其他Aβ传感器。第三,通过乙酰胆碱酯酶(AchE)的酶促裂解和释放策略,ThT @ Er-MOF以较低的检测下限(LOD)值(0.03226 nM)增强了乙酰胆碱(ACh)的检测。应当注意,三种不同的检测方法是低成本且容易实现的。这项研究还提供了第一个利用激光扫描共聚焦显微镜(LSCM)来研究ThT @ Er-MOF进行的荧光共振能量转移(FRET)检测机制的第一个例子。LSCM还可以调查FRET发生的位置和FRET效率,这有助于了解这些基于MOF的独特混合材料的FRET检测过程。
更新日期:2020-06-29
中文翻译:
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检测阿尔茨海默氏病生物标志物的驱动力:硫黄素T @ Er-MOF比例荧光传感器在智能检测早老素1,淀粉样β蛋白和乙酰胆碱中的应用。
当前,高灵敏度检测阿尔茨海默氏病(AD)生物标记物,即早老素1,淀粉样β蛋白(Aβ)和乙酰胆碱(ACh),对于帮助我们预防和诊断AD至关重要。在这项工作中,通过溶剂热合成了一种新颖的金属有机骨架[Er(L)(DMF)1.27 ] n(Er-MOF)(H 3 L =联苯-3,4'',5-三羧酸)。超声波方法。此外,通过后合成组装策略,将荧光染料硫黄素T(ThT)引入Er-MOF,以构建双发射ThT @ Er-MOF比率荧光传感器。这是ThT @ Er-MOF的第一次通过三种低成本且简便的检测策略,已成功应用于脑脊液中三种主要的阿尔茨海默氏病生物标志物的高灵敏度检测。首先,采用分散DNA策略,这是ThT @ Er-MOF首次可用于SSODN(早老素1基因的一部分)的无标记检测。其次,对于Aβ的检测,由于ThT可以与Aβ特异结合并具有出色的特征荧光带,因此可以选择性地应用双发射ThT @ Er-MOF传感器检测类似蛋白上的Aβ,这显示了更多灵敏度高于其他Aβ传感器。第三,通过乙酰胆碱酯酶(AchE)的酶促裂解和释放策略,ThT @ Er-MOF以较低的检测下限(LOD)值(0.03226 nM)增强了乙酰胆碱(ACh)的检测。应当注意,三种不同的检测方法是低成本且容易实现的。这项研究还提供了第一个利用激光扫描共聚焦显微镜(LSCM)来研究ThT @ Er-MOF进行的荧光共振能量转移(FRET)检测机制的第一个例子。LSCM还可以调查FRET发生的位置和FRET效率,这有助于了解这些基于MOF的独特混合材料的FRET检测过程。