Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Anal Chem. 2020 May 5;92(9):6312-6320. doi: 10.1021/acs.analchem.9b05159. Epub 2020 Apr 1.
Imaging mass cytometry (IMC) is an emerging imaging technology that exploits the multiplexed analysis capabilities of the CyTOF mass cytometer to make spatially resolved measurements for tissue sections. In a comprehensive view of tissue composition and marker distribution, recent developments of IMC require highly sensitive, multiplexed assays. Approaching the sensitivity of the IMC technique, we designed a novel type of biocompatible metal-labeled aptamer nanoprobe (MAP), named Er-A10-3.2. The small molecular probe was synthesized by conjugating Er-polymeric pentetic acid (Er-DTPA) with an RNA aptamer A10-3.2. For demonstration, Er-A10-3.2 was applied for observing protein spatial distribution on prostatic epithelium cell of paraffin embedded Prostatic adenocarcinoma (PaC) tissue sections by IMC technology. The Er-A10-3.2 capitalizes on the ability of the aptamer to specifically bind target cancer cells as well as the small size of Er-A10-3.2 can accommodate multiple aptamer binding antigen labeled at high density. The detection signal of Er-A10-3.2 probe was 3-fold higher than that of PSMA antibody probe for a targeted cell under lower temperature epitope retrieval (37 °C) of PaC tissue. Furthermore, we successfully demonstrated the simultaneously staining ability of aptamer probes in IMC analysis. The successful imaging acquisition using aptamers probes in IMC technology may offer opportunity for the diagnosis of malignancies in the future.
成像质谱细胞术(IMC)是一种新兴的成像技术,利用 CyTOF 质谱细胞仪的多重分析能力对组织切片进行空间分辨测量。在组织成分和标记物分布的综合视图中,IMC 的最新发展需要高度敏感的多重分析。为了接近 IMC 技术的灵敏度,我们设计了一种新型的生物相容性金属标记适体纳米探针(MAP),命名为 Er-A10-3.2。小分子探针通过将 Er-聚合戊二酸(Er-DTPA)与 RNA 适体 A10-3.2 偶联而合成。为了进行演示,我们应用 Er-A10-3.2 通过 IMC 技术观察石蜡包埋前列腺腺癌(PaC)组织切片中前列腺上皮细胞上的蛋白质空间分布。Er-A10-3.2 利用适体特异性结合靶癌细胞的能力以及 Er-A10-3.2 的小尺寸可以容纳高密度标记的多个适体结合抗原。在 PaC 组织的较低温度表位检索(37°C)下,Er-A10-3.2 探针的检测信号比 PSMA 抗体探针对靶细胞的检测信号高 3 倍。此外,我们还成功证明了适体探针在 IMC 分析中的同时染色能力。IMC 技术中适体探针的成功成像采集可能为未来恶性肿瘤的诊断提供机会。