Multiplex Immunochips for High-Accuracy Detection of AFP-L3% Based on Surface-Enhanced Raman Scattering: Implications for Early Liver Cancer Diagnosis

被引:105
作者
Ma, Hao [1 ]
Sun, Xiaoying [2 ]
Chen, Lei [3 ]
Cheng, Weina [1 ]
Han, Xiao Xia [1 ]
Zhao, Bing [1 ]
He, Chengyan [2 ]
机构
[1] Jilin Univ, State Key Lab Supramol Struct & Mat, Changchun 130012, Jilin, Peoples R China
[2] Jilin Univ, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China
[3] Jilin Normal Univ, Minist Educ, Key Lab Preparat & Applicat Environm Friendly Mat, Changchun 130103, Jilin, Peoples R China
关键词
P-MERCAPTOBENZOIC ACID; ALPHA-FETOPROTEIN; HEPATOCELLULAR-CARCINOMA; ULTRASENSITIVE IMMUNOASSAY; FREQUENCY-SHIFT; CHARGE-TRANSFER; SANDWICH ASSAY; TUMOR-MARKER; SERS; NANOPARTICLES;
D O I
10.1021/acs.analchem.7b01349
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
alpha-Fetoprotein (AFP) is an important tumor biomarker. In particular, the overexpression of AFP-L3 is associated with hepatocellular carcinoma (HCC). Accordingly, several hospitals have begun to employ the ratio of AFP-L3 to the total AFP level (AFP-L3%) as new diagnostic evidence for HCC owing to its high diagnostic accuracy. However, current methods of detection for AFP and AFP-L3 are time-consuming, require multiple samples, and lack in sensitivity and specificity. Herein, we, present a novel concept for the early diagnosis of HCC based on the combination of Raman frequency shift and intensity change, and developed surface-enhanced Raman scattering (SERS)-based immunochips via AFP-L3%. In the first step of the study, the frequency shift of 4-mercaptobenzoic acid (MBA) was applied for the quantitative determination of total AFP based on the AFP and anti-AFP interaction on MBA-modified silver chips. 5,5-Dithiobis(succinimidy1-2-nitrobenzoate) (DSNB)-modified immunogold was then incorporated with AFP-L3 antibodies for sandwich immunoreaction on the chips. As a result, we found that a typical Raman band intensity of DSNB presented an exponential linear relationship with the concentration of AFP-L3. Thus, the AFP-L3% can be calculated according to the concentrations of AFP-L3 and total AFP. The most important advantage of the proposed method is the combination of AFP-L3% and frequency shifts Of SERS, which exhibits excellent reproducibility and high accuracy, and significantly simplifies the conventional detection procedure of AFP-L3%. Application of the proposed method with the serum of patients with HCC demonstrated its great potential in early liver cancer diagnosis.
引用
收藏
页码:8877 / 8883
页数:7
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