Development of Biosensor-type-DNA Chip for the Diagnosis of Cancer

开发一种用于癌症诊断的生物传感器类型的DNA芯片是本研究的目标。为了达到这一目标，我们设计了两个研究项目。对于第一个项目，我们系统地检测了包括肝细胞癌在内的各种疾病的肝脏的表达谱。用自制的DNA芯片分析了100多份临床资料，并展示了每种疾病的表达谱。这项研究揭示了DNA芯片分析提供了常规生化和病理检查无法获得的新信息，使DNA芯片成为一种新的诊断技术，或一种新的肿瘤标志物。利用基因表达序列分析(SAGE)，获得了30多万个肝脏表达标签，并将其存入数据库。一种预测慢性丙型肝炎药物疗效的DNA芯片已经上市。该项目的另一条线路是制造一种生物传感器类型的DNA芯片，可以在现场的常规临床环境中使用。使用芯片上的微电极，可以在液体中测量目标核酸(2001年申请了一项专利)。研制了一种用于微电极测量的小型热循环仪(2000年申请专利)。还开发了一种微电极上的DNA观察器(正在申请专利)。利用这些相继发展的成果，研制出了一种体积小、价格低、临床诊断速度快的生物传感器型DNA芯片。

Development of a biosensor-type-DNA chip for the diagnosis of cancer is an objective of this research. To attain this objective, two lines of research projects were designed.For the first line of the project, we systematically examined expression profiles in the liver with various diseases including hepatocellular carcinoma. Over one hundred clinical materials were analyzed with home-made DNA chips, and the expression profile in each disease was demonstrated. This study revealed that a DNA chip analysis gives new information that cannot be obtained by routine biochemical and pathological examinations, and made the DNA chip be a new diagnostic technique, or a new tumor marker. Using serial analysis of gene expression (SAGE), over 300,000 expressed tags in the liver were obtained and deposited into databases. A DNA chip, which predicts the efficacy of drugs against chronic hepatitis C, was put on the market.Another line of the project is to make a biosensor-type-DNA chip, which can be used in routine clinical settings on site. Using microelectrodes on a chip, target nucleic acids can be measured in liquid (applied for a patent in 2001). A small-size thermal cycler for the introduction of measurement on microelectrodes was developed (applied for a patent in 2000). A DNA spotter on a microelectrode was also developed (pending for a patent). Using these successive developments, a biosensor-type-DNA chip, which is small-size, less expensive compared with former laser-detection-type DNA chips, and faster for the clinical diagnosis, was made.