High Throughput Microarray Printing and Imaging Methods to Develop new Bioactive Materials for Sensing and Small Molecule Screening

我的nserc支持的研究项目将开发和利用高通量、微阵列和微孔板为基础的方法来合成和表征先进的基于溶胶-凝胶的生物活性材料，这将改变用于诊断和药物发现的固相分析。这些新材料将用于打印生物制品（蛋白质、适体、细胞）作为微阵列，或制备可用于筛选复杂混合物或提取物的整体生物亲和柱。高通量筛选将用于识别具有所需性能的材料（即，高生物活性，低非特异性结合，适当的孔隙率等），并使我们能够更快地研究最佳材料，同时提供丰富的数据，使我们能够更好地了解和控制材料的性能。未来5年的主要目标是：(1)建立和实施自动化方法，以允许高通量合成，筛选和表征具有捕获生物分子的改进溶胶-凝胶材料，包括蛋白质，DNA/RNA适配体和细胞在溶胶-凝胶基材料中的行为的新研究；(2)建立生物界面相互作用（DBI）数据库，协助高温材料数据的编目、挖掘和建模；(3)利用先进的打印方法制备改进的溶胶-凝胶基微阵列，用于蛋白质、细胞和适体的新应用，并采用基于MALDI-MS、XPS、FTIR、SPR和荧光的高通量微阵列成像方法进行表征；(4)深入研究优化生物传感、亲和层析和固定化酶反应器的溶胶-凝胶材料性能。这项研究将提供关键数据，以增强我们对材料的理解，并为特定应用优化材料。它将改变我们对表面和生物物种（特别是细胞）之间界面的理解，并将为如何设计这些材料以优化生物分子特性提供新的见解。它将产生新的“生物活性”界面和新设备，如用于预后和诊断的蛋白质和报告基因细胞微阵列，新的生物分离介质和用于小分子筛选的新工具。

My NSERC-supported research program will develop and utilize high throughput, microarray and microwell plate-based methods to synthesize and characterize advanced sol-gel based bioactive materials that will transform solid-phase assays used in diagnostics and drug discovery. These new materials will be used for printing biologicals (proteins, aptamers, cells) as microarrays, or to prepare monolithic bioaffinity columns that can be used for screening of complex mixtures or extracts. High throughput screening will be used to identify materials with desired properties (i.e., high bioactivity, low non-specific binding, appropriate porosity, etc) and will allow us to hone in on optimal materials more rapidly, while providing an abundance of data that will allow us to better understand and control the properties of our materials. Key objectives over the next 5 years are: (1) establishment and implementation of automated methods to allow high-throughput synthesis, screening and characterization of improved sol-gel materials with entrapped biomolecules, including new studies of how proteins, DNA/RNA aptamers and cells behave within sol-gel based materials; (2) development of a database of biointeface interactions (DBI) to aid in cataloging, mining and modeling of HT materials data; (3) use of advanced printing methods to prepare improved sol-gel based microarrays for new applications utilizing proteins, cells and aptamers, with characterization by high-throughput microarray imaging methods based on MALDI-MS, XPS, FTIR, SPR and fluorescence; and (4) in-depth studies to optimize sol-gel material properties for biosensing, affinity chromatography and immobilized enzyme reactors. This research will provide critical data to enhance our understanding of materials and optimize them for a given application. It will transform our understanding of the interface between surfaces and biological species (particularly cells), and will provide new insights into how to design such materials to optimize biomolecule properties. It will result in novel "bioactive" interfaces and new devices such as protein and reporter-gene cell microarrays for prognostics and diagnostics, new bioseparation media and new tools for small molecule screening.