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电化学肽传感器用于诊断结肠癌的腺瘤-癌转变。

Electrochemical peptide sensor for diagnosing adenoma-carcinoma transition in colon cancer.

机构信息

Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan 38610, Republic of Korea.

Department of Biotechnology, Daegu University, Gyeongsan 38453, Republic of Korea.

出版信息

Biosens Bioelectron. 2017 Dec 15;98:330-337. doi: 10.1016/j.bios.2017.07.013. Epub 2017 Jul 6.

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Therefore, more sensitive and early diagnostic methods for CRC are urgently needed. In this study, an efficient electrochemical biosensor for early diagnosis of adenoma-to-carcinoma progression that employs a series of chemically modified affinity peptides was developed. A series of amino acid-substituted and cysteine-incorporated synthetic peptides with flexible linkers was chemically synthesized and immobilized to a gold sensor layer; performance of the sensor was monitored using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Potential affinity peptides (LRG1 BP1-BP4) specific for the LRG1 biomarker as a target protein were chosen according to a quantitative current decrease and dynamic impedance increase by CV and EIS, respectively. Using EIS, the K value of the LRG1 BP3 peptide was found to be 8.3 ± 2.7nM. The applicability of the sensor to detect LRG1 proteins was confirmed in human plasma from colorectal adenomas and carcinomas (n = 20 in each group). The detection of LRG1 in accordance with the ΔR value (electron-transfer resistance at the electrode surface) of the sensor layer incorporating LRG1 BP3 peptides showed a statistically significant difference (p < 0.001) between adenomas and carcinomas, indicating that the potential use of this biosensing platform for detecting the CRC biomarker, as well as for monitoring the colorectal adenoma-to-carcinoma transition in an electrochemically miniaturized biosensor (e-chem biosensor) in point-of-care testing, is possible.

摘要

结直肠癌(CRC)是癌症相关死亡的主要原因之一。因此,迫切需要更敏感和早期的 CRC 诊断方法。在这项研究中,开发了一种基于一系列化学修饰亲和肽的用于早期诊断腺瘤癌变进展的高效电化学生物传感器。一系列带有柔性接头的氨基酸取代和半胱氨酸掺入的合成肽被化学合成并固定在金传感器层上;使用循环伏安法(CV)和电化学阻抗谱(EIS)监测传感器的性能。根据 CV 和 EIS 分别定量电流减少和动态阻抗增加,选择了针对 LRG1 生物标志物作为靶蛋白的潜在亲和肽(LRG1 BP1-BP4)。使用 EIS,发现 LRG1 BP3 肽的 K 值为 8.3 ± 2.7 nM。该传感器在结直肠腺瘤和癌患者的人血浆中检测 LRG1 蛋白的适用性得到了证实(每组 20 例)。根据包含 LRG1 BP3 肽的传感器层的 ΔR 值(电极表面的电子转移电阻)检测 LRG1,在腺瘤和癌之间表现出统计学上的显著差异(p < 0.001),表明该生物传感平台有可能用于检测 CRC 生物标志物,以及在电化学微型化生物传感器(e-chem 生物传感器)中监测结直肠腺瘤癌变过渡,以实现即时检测。

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