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

我的NSERC支持的研究计划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溶胶-凝胶为基础的生物活性材料，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。高通量筛选将用于鉴定具有所需性质的材料（即，高生物活性、低非特异性结合、适当的孔隙率等），并将使我们能够更快地找到最佳材料，同时提供丰富的数据，使我们能够更好地了解和控制我们材料的性能。未来5年的主要目标是：（1）建立和实施自动化方法，以高通量合成、筛选和表征具有截留生物分子的改进的溶胶-凝胶材料，包括对蛋白质、DNA/RNA适体和细胞在溶胶-凝胶基材料中的行为的新研究;（2）开发生物界面相互作用数据库（DBI），以辅助HT材料数据的编目、挖掘和建模;（3）使用先进的印刷方法来制备用于利用蛋白质、细胞和适体的新应用的改进的基于溶胶-凝胶的微阵列，通过基于MALDI-MS、XPS、FTIR的高通量微阵列成像方法进行表征，SPR和荧光;以及（4）深入研究优化溶胶-凝胶材料的性能，用于生物传感、亲和色谱和固定化酶反应器。这项研究将提供关键数据，以增强我们对材料的理解，并针对特定应用进行优化。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，并将为如何设计此类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”界面和新的装置，如用于生物学和诊断的蛋白质和生物基因细胞微阵列，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.