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基于智能手机的电化学发光法用于甲状腺癌患者血浆中 和 肿瘤抑制基因甲基化的可视化同时检测。

Smartphone-Based Electrochemiluminescence for Visual Simultaneous Detection of and Tumor Suppressor Gene Methylation in Thyroid Cancer Patient Plasma.

机构信息

Department of Chemistry, Faculty of Basic Science, Ayatollah Boroujerdi University, Boroujerd 6869199-69737, Iran.

Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, P.O. Box 1411713137, Islamic Republic of Iran.

出版信息

Anal Chem. 2022 Jun 7;94(22):8005-8013. doi: 10.1021/acs.analchem.2c01132. Epub 2022 May 26.

Abstract

Visual one-step simultaneous detection of low-abundance methylation is a crucial challenge in early cancer diagnosis in a simple manner. Through the design of a closed split bipolar electrochemistry system (BE), detection of promoter methylation of tumor suppressor genes in papillary thyroid cancer, and , was achieved using electrochemiluminescence. For this purpose, electrochemiluminescence of luminol loaded into the FeO@UiO-66 and gold nanorod-functionalized graphite-like carbon nitride nanosheet (AuNRs@CN NS), separately, on the anodic and cathodic pole bipolar electrodes (BPEs) in two different chambers of a bipolar cell were recorded on a smartphone camera. To provide the same electric potential (Δ) through the BPEs to conduct simultaneous light emission, as well as to achieve higher sensitivity, anodic and cathodic poles BPEs were separately connected to ruthenium nanoparticles electrodeposited on nitrogen-doped graphene-coated Cu foam (fCu/N-GN/RuNPs) to provide a hydrogen evolution reaction (HER) and polycatechol-modified reduced graphene oxide/pencil graphite electrode (PC-rGO/PGE) to provide electrooxidation of hydrazine. Moreover, taking advantages of the strong cathodic ECL activity due to the roles of AuNRs, as well as the high density of capture probes on the UiO-66 and FeO roles in improving the signal-to-background ratio (S/B) in complicated plasma media, a sensitive visual ECL immunosensor was developed to detect two different genes as model target analytes in patient plasma samples. The ability of discrimination of methylation levels as low as 0.01% and above 90% clinical sensitivity in thyroid cancer patient plasma implies that the present strategy is able to diagnose cancer early, as well as monitor responses of patients to therapeutic agents.

摘要

可视化一步同时检测低丰度甲基化是一种简单的方法,在早期癌症诊断中具有重要的挑战。通过设计一个封闭的分裂双极电化学系统(BE),实现了对甲状腺乳头状癌中肿瘤抑制基因启动子甲基化的电化学发光检测, 和 。为此,在双极电池的两个不同腔室中的阳极和阴极双极电极(BPE)上分别记录了负载在 FeO@UiO-66 和金纳米棒功能化石墨状碳氮纳米片(AuNRs@CN NS)中的鲁米诺的电致化学发光,使用智能手机相机。为了通过 BPE 提供相同的电势(Δ)以进行同时发光,并实现更高的灵敏度,阳极和阴极 BPE 分别连接到氮掺杂石墨烯涂覆的 Cu 泡沫上沉积的钌纳米颗粒(fCu/N-GN/RuNPs)以提供析氢反应(HER)和聚儿茶酚修饰的还原氧化石墨烯/铅笔石墨电极(PC-rGO/PGE)以提供肼的电氧化。此外,利用 AuNRs 的强阴极 ECL 活性以及在 UiO-66 和 FeO 中捕获探针的高密度在复杂的等离子体介质中提高信号背景比(S/B)的作用,开发了一种灵敏的可视化 ECL 免疫传感器来检测两种不同的基因作为患者血浆样本中的模型靶分析物。在甲状腺癌患者血浆中检测到低至 0.01%和高于 90%临床灵敏度的甲基化水平的区分能力表明,该策略能够早期诊断癌症,并监测患者对治疗剂的反应。

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