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基于多功能纳米牛血清白蛋白功能化的新型石墨烯生物传感器用于癌症生物标志物的高灵敏度检测

Novel Graphene Biosensor Based on the Functionalization of Multifunctional Nano-bovine Serum Albumin for the Highly Sensitive Detection of Cancer Biomarkers.

作者信息

Zhou Lin, Wang Kun, Sun Hao, Zhao Simin, Chen Xianfeng, Qian Dahong, Mao Hongju, Zhao Jianlong

机构信息

State Key Laboratory of Transducer Technology; Key Laboratory of Terahertz Solid-State Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

出版信息

Nanomicro Lett. 2019 Mar 9;11(1):20. doi: 10.1007/s40820-019-0250-8.

DOI:10.1007/s40820-019-0250-8
PMID:34137997
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7770693/
Abstract

A simple, convenient, and highly sensitive bio-interface for graphene field-effect transistors (GFETs) based on multifunctional nano-denatured bovine serum albumin (nano-dBSA) functionalization was developed to target cancer biomarkers. The novel graphene-protein bioelectronic interface was constructed by heating to denature native BSA on the graphene substrate surface. The formed nano-dBSA film served as the cross-linker to immobilize monoclonal antibody against carcinoembryonic antigen (anti-CEA mAb) on the graphene channel activated by EDC and Sulfo-NHS. The nano-dBSA film worked as a self-protecting layer of graphene to prevent surface contamination by lithographic processing. The improved GFET biosensor exhibited good specificity and high sensitivity toward the target at an ultralow concentration of 337.58 fg mL. The electrical detection of the binding of CEA followed the Hill model for ligand-receptor interaction, indicating the negative binding cooperativity between CEA and anti-CEA mAb with a dissociation constant of 6.82 × 10 M. The multifunctional nano-dBSA functionalization can confer a new function to graphene-like 2D nanomaterials and provide a promising bio-functionalization method for clinical application in biosensing, nanomedicine, and drug delivery.

摘要

基于多功能纳米变性牛血清白蛋白(nano-dBSA)功能化开发了一种简单、便捷且高灵敏度的用于石墨烯场效应晶体管(GFET)的生物界面,以靶向癌症生物标志物。通过加热使石墨烯基底表面的天然牛血清白蛋白变性,构建了新型的石墨烯-蛋白质生物电子界面。形成的纳米dBSA膜作为交联剂,将抗癌胚抗原单克隆抗体(anti-CEA mAb)固定在由1-乙基-3-(3-二甲氨基丙基)碳二亚胺(EDC)和磺基-N-羟基琥珀酰亚胺(Sulfo-NHS)活化的石墨烯通道上。纳米dBSA膜作为石墨烯的自保护层,可防止光刻过程中的表面污染。改进后的GFET生物传感器在超低浓度337.58 fg/mL下对目标物表现出良好的特异性和高灵敏度。癌胚抗原(CEA)结合的电学检测遵循配体-受体相互作用的希尔模型,表明CEA与anti-CEA mAb之间存在负协同结合,解离常数为6.82×10⁻⁸ M。多功能纳米dBSA功能化可为类石墨烯二维纳米材料赋予新功能,并为生物传感、纳米医学和药物递送等临床应用提供一种有前景的生物功能化方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/c605816003ce/40820_2019_250_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/8bcb8ecc828a/40820_2019_250_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/4d990c5a9462/40820_2019_250_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/cea1db631d8f/40820_2019_250_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/a5a693080438/40820_2019_250_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/c605816003ce/40820_2019_250_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/8bcb8ecc828a/40820_2019_250_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/4d990c5a9462/40820_2019_250_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/cea1db631d8f/40820_2019_250_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/a5a693080438/40820_2019_250_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ba/7770693/c605816003ce/40820_2019_250_Fig5_HTML.jpg

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