Sensitive Microarray Slides Using Silica Colloidal Crystals

描述（由申请人提供）：微阵列已成为研究和医学中不可或缺的工具。DNA微阵列是作为研究工具建立的，它们有望发展成为临床诊断。更高的灵敏度将促进这一转变，同时也有利于研究。蛋白质比DNA或mRNA更直接地报告生物学，蛋白质微阵列现在已经商业化。蛋白质微阵列在基底设计方面提出了新的挑战，因为蛋白质必须在附着到表面后保持功能。此外，由于蛋白质不能通过PCR扩增，因此迫切需要更高的灵敏度。申报产品是一种创新的显微镜载玻片，带有一层薄的光学透射二氧化硅胶体晶体，可使灵敏度提高10倍以上。仅此功能就使幻灯片优于当今任何现有的幻灯片。此外，硅烷化学允许设计用于附着DNA、蛋白质、肽、凝集素或适体作为捕获剂的表面，并且这种多功能性在高表面积载玻片中是独特的。该提案的重点是蛋白质微阵列，这是最迫切的需求。我们的目标是将这种更高的表面积转化为大于10倍的灵敏度增加。有三个具体目标。第一个将测试灵敏度如何随颗粒大小和生物分子大小变化的模型。第二个将测试硅烷涂层的共价连接，功能损失最小。第三个将通过确定最佳的硅烷组合物来最小化斑点大小和芯吸。这里提出的第一阶段研究将确定第二阶段研究的可行性，第二阶段研究将比较bioVidria的玻片与商业玻片的两个重要应用：生物标志物发现和临床诊断。公共卫生相关性：纳米技术被提议用于推进医学研究和医学诊断。这项技术将允许对生物标志物和肿瘤进行更敏感的研究。

DESCRIPTION (provided by applicant): Microarrays have become indispensable tools in research and medicine. DNA microarrays are established as research tools, and they are expected to grow into clinical diagnostics. Higher sensitivity would advance this transition, while also benefiting research. Proteins report more directly on the biology than does DNA or mRNA, protein microarrays have now become commercially available. Protein microarrays present new challenges in design of the substrate because the protein has to remain functional after it is attached to the surface. In addition, higher sensitivity is urgently needed because proteins cannot be amplified by PCR. The proposed product is an innovative microscope slide bearing a thin layer of optically transmissive silica colloidal crystal to impart higher sensitivity by more than 10 fold. This feature alone makes the slide advantageous over any existing slide today. In addition, the silane chemistry allows design of the surface for attachment of DNA, proteins, peptides, lectins, or aptamers as capture agents, and this versatility is unique among high surface-area slides. The proposal focuses on protein microarrays, for which the need is most urgent. The goal is to translate this higher surface area into a sensitivity increase of greater than 10 fold. There are three specific aims. The first will test a model of how sensitivity varies with particle size and biomolecule size. The second will test silane coatings for covalent attachment with minimal loss of function. The third will minimize spot size and wicking by identifying the optimal silane composition. The Phase I research proposed here will establish the feasibility of Phase II research, which will compare bioVidria's slides with commercial slides for two important applications: biomarker discovery and clinical diagnostics. PUBLIC HEALTH RELEVANCE: Nanotechnology is proposed to be used to advance medical research and medical diagnostics. The proposed technology will allow for more sensitive studies of biomarkers and tumors.