Center for Cooperative Research in Biomaterials (CIC BiomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastián, Spain.
Department of Analytical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Ankara, Turkey.
ACS Appl Mater Interfaces. 2021 Feb 24;13(7):8823-8831. doi: 10.1021/acsami.0c22203. Epub 2021 Feb 13.
The detection of cancer biomarkers at an early stage of tumor development is vital for effective diagnosis and treatment of cancer. Current diagnostic tools can often detect cancer only when the biomarker levels are already too high, so that the tumors have spread and treatments are less effective. It is urgent therefore to develop highly sensitive assays for the detection of such biomarkers at the lowest possible concentration. In this context, we developed a sandwich immunoassay based on surface-enhanced Raman scattering (SERS) for the ultrasensitive detection of α-fetoprotein (AFP), which is typically present in human serum as a biomarker indicative of early stages of hepatocellular carcinoma. In the immunoassay design, molybdenum disulfide (MoS) modified with a monoclonal antibody was used as a capture probe for AFP. A secondary antibody linked to an SERS-encoded nanoparticle was employed as the Raman signal reporter, that is, the transducer for AFP detection. The sandwich immunocomplex "capture probe/target/SERS tag" was deposited on a silicon wafer and decorated with silver-coated gold nanocubes to increase the density of "hot spots" on the surface of the immunosensor. The developed SERS immunosensor exhibits a wide linear detection range (1 pg mL to 10 ng mL) with a limit of detection as low as 0.03 pg mL toward AFP with good reproducibility (RSD < 6%) and stability. These parameters demonstrate that the proposed immunosensor has the potential to be used as an analytical platform for the detection of early-stage cancer biomarkers in clinical applications.
在肿瘤发展的早期阶段检测癌症生物标志物对于癌症的有效诊断和治疗至关重要。目前的诊断工具通常只能在生物标志物水平已经过高时检测到癌症,此时肿瘤已经扩散,治疗效果较差。因此,迫切需要开发高灵敏度的检测方法,以便在尽可能低的浓度下检测到这些生物标志物。在这种情况下,我们开发了一种基于表面增强拉曼散射(SERS)的夹心免疫测定法,用于超灵敏检测α-胎蛋白(AFP),AFP 通常作为肝癌早期阶段的生物标志物存在于人血清中。在免疫测定设计中,用单克隆抗体修饰的二硫化钼(MoS)被用作 AFP 的捕获探针。与 SERS 编码纳米颗粒相连的二级抗体被用作拉曼信号报告器,即 AFP 检测的换能器。夹心免疫复合物“捕获探针/靶标/SERS 标签”被沉积在硅片上,并通过镀银的金纳米立方体进行修饰,以增加免疫传感器表面上“热点”的密度。所开发的 SERS 免疫传感器在检测 AFP 时具有较宽的线性检测范围(1 pg mL 至 10 ng mL),检测限低至 0.03 pg mL,具有良好的重现性(RSD <6%)和稳定性。这些参数表明,所提出的免疫传感器有可能成为临床应用中早期癌症生物标志物检测的分析平台。