Microbiosensor for Alzheimer's disease diagnostics: detection of amyloid beta biomarkers.

Microbiosensor for Alzheimer's disease diagnostics: detection of amyloid beta biomarkers.
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DOI:
10.1111/j.1471-4159.2012.07709.x
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发表时间:
2012-07
影响因子:
4.7
通讯作者:
Li CZ
Li CZ
中科院分区:
医学2区
文献类型:
--
作者:
Prabhulkar S;Piatyszek R;Cirrito JR;Wu ZZ;Li CZ

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阿尔茨海默病(AD)影响着全球约3560万人,如果目前的趋势继续下去,而没有医学进步,到2050年,每85人中就有1人会受到影响。因此,迫切需要开发一种具有成本效益,易于使用的传感器平台来诊断和研究AD。在脑脊液(CSF)中发现的β-淀粉样肽(Aβ)的测量已被评估为诊断和研究该疾病的一种途径。通过人体临床试验,Aβ1-40/42比值(或Aβ比值)的定量已被确定为诊断AD的可靠检测方法。因此,我们开发了一种多路复用,植入式免疫传感器检测淀粉样蛋白β(Aβ)异构体使用三桶碳纤维微电极作为传感器平台。抗体作为传感器的生物识别元件,选择性地捕获Aβ1-40和Aβ1-42并将其结合到电极表面。电化学用于测量Aβ在0.65 V(vs Ag/AgCl)下的固有氧化信号,该信号源自其氨基酸序列中第10位发现的单个酪氨酸(Tyr)残基。该免疫传感器可在20 nM ~ 50 nM和20 nM ~ 140 nM范围内特异性检测到小鼠脑脊液中的Aβ1-40和Aβ1-42。该免疫传感器能够实时、高灵敏度地检测Aβ,并为诊断性离体应用和基于研究的体内研究开辟了可能性。
Alzheimer’s disease (AD) affects about 35.6 million people worldwide, and if current trends continue with no medical advancement, 1 in 85 people will be affected by 2050. Thus, there is an urgent need to develop a cost effective, easy to use, sensor platform to diagnose and study AD. The measurement of peptide amyloid beta (Aβ) found in cerebrospinal fluid (CSF) has been assessed as an avenue to diagnose and study the disease. The quantification of the ratio of Aβ1-40/42 (or Aβ ratio) has been established as a reliable test to diagnose AD through human clinical trials. Therefore we have developed a multiplexed, implantable immunosensor to detect amyloid beta (Aβ) isoforms using triple barrel carbon fiber microelectrodes as the sensor platform. Antibodies act as the biorecognition element of the sensor and selectively capture and bind Aβ1-40 and Aβ1-42 to the electrode surface. Electrochemistry was used to measure the intrinsic oxidation signal of Aβ at 0.65 V (vs Ag/AgCl), originating from a single tyrosine (Tyr) residue found at position 10 in its amino acid sequence. Using the proposed immunosensor Aβ1-40 and Aβ1-42 could be specifically detected in CSF from mice within a detection range of 20 nM to 50 nM and 20 nM to 140 nM respectively. The immunosensor enables real-time, highly sensitive detection of Aβ and opens up the possibilities for diagnostic ex-vivo applications and research-based in-vivo studies.
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