基于二维阵列多孔硅芯片的低分子量生物标志物分析技术及其在疾病诊断中的应用

项目名称： 基于二维阵列多孔硅芯片的低分子量生物标志物分析技术及其在疾病诊断中的应用

项目编号： No.21275128

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 邬建敏

作者单位： 浙江大学

项目金额： 80万元

中文摘要： 人血清及体液中肽类物质或低分子量蛋白（LMWP）蕴藏着大量与疾病有关的信息，构成了一类潜在的新型疾病标志物。然而低含量的LMWP极易被血清及体液中的高丰度蛋白质掩盖。因此，如何去捕获、富集 、保护及检测血清或体液中的LMWP是摆在我们面前的一个重要问题。本项目拟构建不同孔径与不同表面电荷特征的二维多孔硅（2D-PSi）阵列芯片。研究该阵列芯片的刻蚀与表面修饰方法，在芯片的一向维度上排列孔道直径呈阶梯分布的多孔硅阵列，在另一个维度上赋予多孔硅阵列不同的表面电荷特征及亲疏水性。此外，拟引入微流控技术将血液或体液样品分别通过2D-PSi的各个点阵，研究该2D-PSi 芯片对血液与体液试样中LMWP的捕获与筛分能力，及作为质谱离子化基质的性能。通过MALDI-TOF/TOF质谱检测与成像技术并结合数学统计模型，建立LMWP谱识别及肽生物标志物发现的新方法，为疾病诊断与疾病信息的跟踪提供重要的手段。

中文关键词： 多孔硅；颗粒；质谱芯片；质谱；血清肽谱

英文摘要： Human plasma or serum contains thousands of low molecular weight protein or peptides （LMWP）, which are shed from tissues and cells or derive from proteolytic degradation of larger serum proteins. It has been proposed that the LMWP represents a rich untapped source of disease-specific diagnostic information. However, two major hurdles limit the mining of information from the pool of the LMWP: (1) the extremely low concentration of disease-relevant biomarkers that enter circulation early in the course of a disease may be masked by other proteins, including high-abundance species such as albumin and immunoglobulins. Conventional methods, such as two-dimensional (2-D) gel electrophoresis, do not have the sensitivity and resolution to detect and quantify these low-abundance, low molecular weight proteins. (2) Degradation of protein biomarkers can occur immediately following the collection of blood or other bodily fluids as a result of ex-vivo proteolytic processes. Therefore, It is highly important to develope a practical method to capture,enrich,protect,and detect the low abundant LMWP in the disease information mining and clinical diagnosis.In this poject, we propose to construct a two dimentional Porous Silicon chip (2D-PSi),which have a capability to fractionate, capture, and protect the LMWP from serum, urine an

英文关键词： Porous Silicon；particle；Mass spectrometric chip；Mass spectrometry；Serum peptide profile