改性聚二甲基硅氧烷 (iPDMS) 蛋白芯片在肿瘤相关抗原自身抗体筛查中的应用

Application of iPDMS protein microarray in screening of tumor-associated antigen autoantibodies

摘要:

肿瘤标记的快速筛查是临床早期诊断的难题。利用化学发光蛋白质芯片技术，对低丰度的肿瘤相关抗原的自身抗体进行高灵敏度的筛选，是一种有益的尝试。本研究首先将带烯烃末端的、引发聚合反应的表面引发剂加入到常规聚二甲基硅氧烷材料中，再通过热交联反应固定到聚二甲基硅氧烷的三维结构中，形成改性聚二甲基硅氧烷 (iPDMS)。为了使iPDMS材料具有抗蛋白质非特异性吸附的特性，在活性引发位点处通过表面引发的原子转移自由基聚合反应合成poly(OEGMA) 高分子刷。最后将20种肿瘤相关的抗原利用高通量喷点打印技术打印到芯片的特定区域，并组装成iPDMS芯片的48孔检测微孔板。对临床上常见的8种肿瘤患者血清进行分析，发现VEGFR1和VEGF121自身抗体对常见的8种肿瘤具有检测价值，有望成为肿瘤快速筛查的检测指标。

Abstract:

The rapid screening of tumor markers is a challenging task for early diagnosis of cancer. This study aims to use highly sensitive chemiluminescent protein microarray technology to efficiently screen a variety of low abundance tumor related markers. A new material, termed integrated polydimethylsiloxane modified silica gel (iPDMS), was obtained by adding a surface polymerization initiator with olefin end to the conventional polydimethylsiloxane, and fixing into the three-dimensional structure of polydimethylsiloxane by thermal crosslinking through silicon hydrogen bonding. In order to make the iPDMS material resistant to non-specific protein adsorption, a poly(OEGMA) polymer brush was synthesized by surface-initiated atom transfer radical polymerization at the active initiation site. Finally, 20 tumor-related antigens were printed into the specific areas of the microarray by high-throughput spray printing technology, and assembled into 48-well detection microtiterplates of the iPDMS microarray. It was found the VEGFR and VEGF121 autoantibodies that obtained from 8 common tumors (breast cancer, lung cancer, colon cancer, gastric cancer, liver cancer, leukemia, lymphoma and ovarian cancer) can be used as potential tumor markers. The chemiluminescence labeled iPDMS protein microarray can be used for the screening of tumor autoantibodies at early stage.