Functionalized Thiophene-Based Aptasensors for the Electrochemical Detection of Mucin-1
Functionalized Thiophene-Based Aptasensors for the Electrochemical Detection of Mucin-1
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DOI：
10.1021/acsapm.2c01739
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发表时间：
2023-01-20
影响因子：
5
通讯作者：
Irvin，Jennifer A.
中科院分区：
文献类型：
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作者：
Haya，Grace;Runsewe，Damilola O.;Irvin，Jennifer A.
粘蛋白-1（MUC 1）是一种在上皮组织中发现的糖蛋白;其功能是通过阻止病原体到达细胞来保护身体。在乳腺癌、肺癌、胃癌、卵巢癌和许多其他类型的恶性肿瘤中观察到这种蛋白的过表达和血清水平升高。目前用于检测癌症的方法价格昂贵，因此不易获得;有些方法也是侵入性的。检测MUC 1的能力可以允许早期检测癌症，从而获得更成功的结果。这项研究的重点是开发一个强大的生物传感器平台的基础上适配体功能化的电活性聚合物（EAP），可用于检测癌症。为了实现这一点，对氧化铟锡载玻片表面进行改性以使得能够电化学生长3，4-亚乙基二氧噻吩（EDOT）和2，2-（3，4-二氢-2H-噻吩并[3，4-B][1，4]二氧杂环庚三烯-3，3-二基）二乙酸（ProDOT（COOH）2）的电活性共聚物，其中添加羧酸官能团以引入MUC 1特异性适体的结合位点。研究了三种共聚物比率以最大化性能。然后将适体连接至EAP以产生可用于MUC 1多肽的电化学检测的适体传感器。对传感器的检测限和稳定性进行了评价。当储存在0.1 M磷酸盐缓冲盐水中时，MUC 1适体传感器显示出至少6天的稳定性，这取决于共聚物的比例。发现1：2的EDOT/ProDOT（COOH）2共聚物随时间推移是最稳定的，并且提供最小的检测限之一，使其成为适体传感器优化的最有利比率。具体来说，1：2 EDOT/ProDOT（COOH）2生物传感器对MUC 1肽APDTRPAPG的检测限为369 fg/mL（418 fM），线性范围为625 fg/mL至6.25 ng/mL（709 fM至7.09 nM）。该传感器还显示出选择性，当测试与竞争剂，包括IgG和细胞培养基。适体传感器的性能证明了其作为MUC 1检测的高灵敏度和选择性生物传感器的潜力。
Mucin-1 (MUC1) is a glycoprotein found in epithelial tissues; its function is to protect the body by blocking pathogens from reaching the cells. Overexpression and elevated serum levels of this protein are observed in breast cancer, lung cancer, stomach cancer, ovarian cancer, and many other types of malignancies. Current methods used to detect cancer are expensive and therefore not readily accessible; some methods are also invasive. The ability to detect MUC1 could allow for early detection of cancer, leading to more successful outcomes. This research focuses on the development of a robust biosensor platform based on aptamer-functionalized electroactive polymers (EAPs) that can be used for the detection of cancer. To achieve this, indium tin oxide slide surfaces were modified to enable the electrochemical growth of an electroactive copolymer of 3,4-ethylenedioxythiophene (EDOT) and 2,2-(3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepine-3,3-diyl)diacetic acid (ProDOT(COOH)2), with the carboxylic acid functionalities added to introduce bonding sites for a MUC1-specific aptamer. Three copolymer ratios were investigated to maximize the performance. The aptamer was then attached to the EAPs to create aptasensors that could be used for the electrochemical detection of a MUC1 polypeptide. The limits of detection of the biosensors and their stabilities were evaluated. The MUC1 aptasensor showed stability for at least 6 days, depending on the ratio of the copolymer, when stored in 0.1 M phosphate-buffered saline. The 1:2 EDOT/ProDOT(COOH)2copolymer was found to be the most stable over time and to offer one of the smallest limits of detection, making it the most favorable ratio for aptasensor optimization. Specifically, the 1:2 EDOT/ProDOT(COOH)2biosensor provided a limit of detection of 369 fg/mL (418 fM) and a linear range of 625 fg/mL to 6.25 ng/mL (709 fM to 7.09 nM) with the MUC1 peptide APDTRPAPG. The sensor also showed selectivity when tested with competing agents including IgG and cell media. The performance of the aptasensor demonstrated its potential as a highly sensitive and selective biosensor for MUC1 detection.