Institute of Nanotechnology (INT) and Karlsruhe Nano Micro Facility (KNMF), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
Department of Chemistry Doane University, 014 Boswell Ave, Crete, NE, 68333, USA.
Adv Mater. 2018 Aug;30(31):e1801632. doi: 10.1002/adma.201801632. Epub 2018 Jun 25.
Surface-bound microarrays of multiple oligo- and macromolecules (e.g., peptides, DNA) offer versatile options in biomedical applications like drug screening, DNA analysis, or medical diagnostics. Combinatorial syntheses of these molecules in situ can save significant resources in regard to processing time and material use. Furthermore, high feature densities are needed to enable high-throughput and low sample volumes as generally regarded in combinatorial chemistry. Here, a scanning-probe-lithography-based approach for the combinatorial in situ synthesis of macromolecules is presented in microarray format. Feature sizes below 40 µm allow for the creation of high-density arrays with feature densities of 62 500 features per cm . To demonstrate feasibility of this approach for biomedical applications, a multiplexed array of functional protein tags (HA- and FLAG-tag) is synthesized, and selective binding of respective epitope recognizing antibodies is shown. This approach uses only small amounts of base chemicals for synthesis and can be further parallelized, therefore, opening up a route to flexible, highly dense, and cost-effective microarrays.
表面结合的多种寡聚和多聚物（例如，肽，DNA）的微阵列在药物筛选、DNA 分析或医学诊断等生物医学应用中提供了多种选择。这些分子的原位组合合成可以节省大量的处理时间和材料使用。此外，为了实现高通量和低样品量，需要高特征密度，这是组合化学中普遍认为的。在这里，提出了一种基于扫描探针光刻的用于大分子原位组合合成的微阵列格式。特征尺寸小于 40 µm，允许创建具有每平方厘米 62500 个特征的高密度阵列。为了证明这种方法在生物医学应用中的可行性，合成了功能蛋白标签（HA 和 FLAG 标签）的多重阵列，并显示了各自识别表位的抗体的选择性结合。这种方法仅使用少量的基础化学物质进行合成，并且可以进一步并行化，因此为灵活、高密度和具有成本效益的微阵列开辟了道路。
