Yamamichi Akane, Kasama Toshihiro, Ohka Fumiharu, Suzuki Hiromichi, Kato Akira, Motomura Kazuya, Hirano Masaki, Ranjit Melissa, Chalise Lushun, Kurimoto Michihiro, Kondo Goro, Aoki Kosuke, Kaji Noritada, Tokeshi Manabu, Matsubara Toshio, Senga Takeshi, Kaneko Mika K, Suzuki Hidenori, Hara Masahito, Wakabayashi Toshihiko, Baba Yoshinobu, Kato Yukinari, Natsume Atsushi
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University , Nagoya , Japan.
Sci Technol Adv Mater. 2016 Oct 4;17(1):618-625. doi: 10.1080/14686996.2016.1227222. eCollection 2016.
World Health Organization grade II and III gliomas most frequently occur in the central nervous system (CNS) in adults. Gliomas are not circumscribed; tumor edges are irregular and consist of tumor cells, normal brain tissue, and hyperplastic reactive glial cells. Therefore, the tumors are not fully resectable, resulting in recurrence, malignant progression, and eventual death. Approximately 69-80% of grade II and III gliomas harbor mutations in the isocitrate dehydrogenase 1 gene (), of which 83-90% are found to be the mutation. Detection of the mutation should help in the differential diagnosis of grade II and III gliomas from other types of CNS tumors and help determine the boundary between the tumor and normal brain tissue. In this study, we established a highly sensitive antibody-based device, referred to as the immuno-wall, to detect the mutation in gliomas. The immuno-wall causes an immunoreaction in microchannels fabricated using a photo-polymerizing polymer. This microdevice enables the analysis of the status with a small sample within 15 min with substantially high sensitivity. Our results suggested that 10% content of the mutation in a sample of 0.33 μl volume, with 500 ng protein, or from 500 cells is theoretically sufficient for the analysis. The immuno-wall device will enable the rapid and highly sensitive detection of the mutation in routine clinical practice.
世界卫生组织二级和三级胶质瘤最常发生于成人的中枢神经系统（CNS）。胶质瘤无包膜；肿瘤边缘不规则，由肿瘤细胞、正常脑组织和增生的反应性胶质细胞组成。因此，这些肿瘤无法完全切除，会导致复发、恶性进展并最终导致死亡。大约69 - 80%的二级和三级胶质瘤存在异柠檬酸脱氢酶1基因（）突变，其中83 - 90%被发现是突变。检测该突变应有助于二级和三级胶质瘤与其他类型中枢神经系统肿瘤的鉴别诊断，并有助于确定肿瘤与正常脑组织之间的边界。在本研究中，我们建立了一种基于抗体的高灵敏度检测装置，称为免疫壁，用于检测胶质瘤中的突变。免疫壁在使用光聚合聚合物制造的微通道中引发免疫反应。这种微装置能够在15分钟内用少量样本以相当高的灵敏度分析状态。我们的结果表明，理论上，体积为0.33μl、含有500 ng蛋白质或来自500个细胞的样本中10%的突变含量就足以进行分析。免疫壁装置将能够在常规临床实践中快速、高灵敏度地检测突变。
