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用于即时检测神经疾病低丰度生物标志物的电化学生物传感器。

Electrochemical Biosensor for Point-of-Care Testing of Low-Abundance Biomarkers of Neurological Diseases.

机构信息

Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Anal Chem. 2024 Jun 25;96(25):10332-10340. doi: 10.1021/acs.analchem.4c01278. Epub 2024 Jun 12.

DOI:10.1021/acs.analchem.4c01278
PMID:38865206
Abstract

The neurofilament protein light chain (NEFL) is a potential biomarker of neurodegenerative diseases, and interleukin-6 (IL-6) is also closely related to neuroinflammation. Especially, NEFL and IL-6 are the two most low-abundance known protein markers of neurological diseases, making their detection very important for the early diagnosis and prognosis prediction of such kinds of diseases. Nevertheless, quantitative detection of low concentrations of NEFL and IL-6 in serum remains quite difficult, especially in the point-of-care test (POCT). Herein, we developed a portable, sensitive electrochemical biosensor combined with smartphones that can be applied to multiple scenarios for the quantitative detection of NEFL and IL-6, meeting the need of the POCT. We used a double-antibody sandwich configuration combined with polyenzyme-catalyzed signal amplification to improve the sensitivity of the biosensor for the detection of NEFL and IL-6 in sera. We could detect NEFL as low as 5.22 pg/mL and IL-6 as low as 3.69 pg/mL of 6 μL of serum within 2 h, demonstrating that this electrochemical biosensor worked well with serum systems. Results also showed its superior detection capabilities over those of high-sensitivity ELISA for serum samples. Importantly, by detecting NEFL and IL-6 in sera, the biosensor showed its potential for the POCT model detection of all known biomarkers of neurological diseases, making it possible for the mass screening of patients with neurodegenerative diseases.

摘要

神经丝轻链蛋白(NEFL)是神经退行性疾病的潜在生物标志物,白细胞介素 6(IL-6)也与神经炎症密切相关。特别是,NEFL 和 IL-6 是神经系统疾病中两个已知含量最低的蛋白标志物,因此它们的检测对于这些疾病的早期诊断和预后预测非常重要。然而,在血清中定量检测低浓度的 NEFL 和 IL-6 仍然非常困难,特别是在即时检测(POCT)中。在此,我们开发了一种便携式、灵敏的电化学生物传感器,结合智能手机,可以应用于多种场景,用于定量检测 NEFL 和 IL-6,满足 POCT 的需求。我们使用双抗体夹心构型结合多酶催化信号放大来提高生物传感器对血清中 NEFL 和 IL-6 的检测灵敏度。我们可以在 2 小时内检测到 6μL 血清中低至 5.22pg/mL 的 NEFL 和低至 3.69pg/mL 的 IL-6,表明该电化学生物传感器在血清系统中运行良好。结果还表明,该生物传感器对血清样本的检测能力优于高灵敏度 ELISA。重要的是,通过检测血清中的 NEFL 和 IL-6,该生物传感器显示出在 POCT 模型中检测所有已知神经疾病生物标志物的潜力,使对神经退行性疾病患者进行大规模筛查成为可能。

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