Karlsruhe Institute of Technology (KIT), Institute of Biological and Chemical Systems-Functional Molecular Systems (IBCS-FMS), Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
Bruker Daltonik GmbH, Fahrenheitstraße 4, 28359, Bremen, Germany.
Nat Commun. 2020 Oct 26;11(1):5391. doi: 10.1038/s41467-020-19040-0.
Acceleration and unification of drug discovery is important to reduce the effort and cost of new drug development. Diverse chemical and biological conditions, specialized infrastructure and incompatibility between existing analytical methods with high-throughput, nanoliter scale chemistry make the whole drug discovery process lengthy and expensive. Here, we demonstrate a chemBIOS platform combining on-chip chemical synthesis, characterization and biological screening. We developed a dendrimer-based surface patterning that enables the generation of high-density nanodroplet arrays for both organic and aqueous liquids. Each droplet (among > 50,000 droplets per plate) functions as an individual, spatially separated nanovessel, that can be used for solution-based synthesis or analytical assays. An additional indium-tin oxide coating enables ultra-fast on-chip detection down to the attomole per droplet by matrix-assisted laser desorption/ionization mass spectrometry. The excellent optical properties of the chemBIOS platform allow for on-chip characterization and in-situ reaction monitoring in the ultraviolet, visible (on-chip UV-Vis spectroscopy and optical microscopy) and infrared (on-chip IR spectroscopy) regions. The platform is compatible with various cell-biological screenings, which opens new avenues in the fields of high-throughput synthesis and drug discovery.
加速和统一药物发现对于降低新药开发的努力和成本非常重要。多样化的化学和生物条件、专门的基础设施以及高通量、纳升级别化学与现有分析方法之间的不兼容性，使得整个药物发现过程漫长而昂贵。在这里，我们展示了一个结合了芯片上化学合成、表征和生物筛选的 chemBIOS 平台。我们开发了一种基于树状大分子的表面图案化技术，能够生成用于有机和水溶液的高密度纳米液滴阵列。每个液滴（每个平板上超过 50000 个液滴中的一个）都作为一个单独的、空间分离的纳米容器发挥作用，可用于基于溶液的合成或分析测定。另外一层氧化铟锡涂层能够通过基质辅助激光解吸/电离质谱法实现超快速的芯片上检测，达到每个液滴低至飞摩尔的检测限。chemBIOS 平台具有出色的光学性能，允许在芯片上进行紫外、可见（芯片上的紫外-可见光谱和光学显微镜）和红外（芯片上的红外光谱）区域的实时在线表征和原位反应监测。该平台与各种细胞生物学筛选兼容，为高通量合成和药物发现开辟了新途径。
