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采用阻抗谱技术的用于检测胰腺癌生物标志物的可控薄膜结构。

Controlled Film Architectures to Detect a Biomarker for Pancreatic Cancer Using Impedance Spectroscopy.

机构信息

São Carlos Institute of Physics, University of São Paulo , 13560-970 São Carlos, São Paulo Brazil.

São Carlos School of Engineering, University of São Paulo , 13560-000 São Carlos, São Paulo, Brazil.

出版信息

ACS Appl Mater Interfaces. 2015 Nov 25;7(46):25930-7. doi: 10.1021/acsami.5b08666. Epub 2015 Nov 11.

Abstract

The need for analytical devices for detecting cancer at early stages has motivated research into nanomaterials where synergy is sought to achieve high sensitivity and selectivity in low-cost biosensors. In this study, we developed a film architecture combining self-assembled monolayer (SAM) and layer-by-layer (LbL) films of polysaccharide chitosan and the protein concanavalin A, on which a layer of anti-CA19-9 antibody was adsorbed. Using impedance spectroscopy with this biosensor, we were capable of detecting low concentrations of the antigen CA19-9, an important biomarker for pancreatic cancer. The limit of detection of 0.69U/mL reached is sufficient for detecting pancreatic cancer at very early stages. The selectivity of the biosensor was inferred from a series of control experiments with samples of cell lines that were tested positive (HT29) and negative (SW620) for the biomarker CA19-9, in addition to the lack of changes in the capacitance value for other analytes and antigen that are not related to this type of cancer. The high sensitivity and selectivity are ascribed to the very specific antigen-antibody interaction, which was confirmed with PM-IRRAS and atomic force microscopy. Also significant is that used information visualization methods to show that different cell lines and commercial samples containing distinct concentrations of CA19-9 and other analytes can be easily distinguished from each other. These computational methods are generic and may be used in optimization procedures to tailor biosensors for specific purposes, as we demonstrated here by comparing the performance of two film architectures in which the concentration of chitosan was varied.

摘要

对用于早期癌症检测的分析设备的需求促使人们研究纳米材料,以寻求协同作用,从而在低成本生物传感器中实现高灵敏度和选择性。在这项研究中,我们开发了一种薄膜结构,将多糖壳聚糖的自组装单层 (SAM) 和层层 (LbL) 薄膜与蛋白伴刀豆球蛋白 A 结合,在其上吸附了一层抗 CA19-9 抗体。使用这种生物传感器的阻抗谱,我们能够检测到低浓度的抗原 CA19-9,CA19-9 是胰腺癌的一个重要生物标志物。达到的 0.69U/mL 的检测限足以用于检测非常早期的胰腺癌。生物传感器的选择性是从一系列对照实验推断出来的,这些对照实验使用了对生物标志物 CA19-9 呈阳性(HT29)和阴性(SW620)的细胞系样本,此外,对于其他与这种癌症无关的分析物和抗原,电容值没有变化。高灵敏度和选择性归因于非常特异的抗原-抗体相互作用,这通过 PM-IRRAS 和原子力显微镜得到了证实。同样重要的是,我们使用信息可视化方法表明,不同的细胞系和包含不同浓度 CA19-9 和其他分析物的商业样本可以很容易地彼此区分开来。这些计算方法是通用的,可以用于优化程序,以针对特定目的定制生物传感器,正如我们在这里通过比较两种薄膜结构的性能所展示的那样,其中壳聚糖的浓度有所不同。

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