Department of Applied Physics, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
RIKEN Cluster for Pioneering Research and RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Sci Rep. 2021 Aug 3;11(1):15742. doi: 10.1038/s41598-021-95139-8.
Although Raman spectroscopy has been used for the quantitative analysis of samples in many fields, including material science, biomedical, and pharmaceutical research, its low sensitivity hindered the application of the analytical capability for high-throughput screening. Here, we developed a high-throughput Raman screening system that can analyze hundreds of specimens in a multiwell plate simultaneously. Multiple high numerical aperture (NA) lenses are assembled under each well in the multiwell plate to detect Raman scattering simultaneously with high sensitivity. The Raman spectrum of 192 samples loaded on a standard 384-well plate can be analyzed simultaneously. With the developed system, the throughput of Raman measurement was significantly improved (about 100 times) compared to conventional Raman instruments based on a single-point measurement. By using the developed system, we demonstrated high-throughput Raman screening to investigate drug polymorphism and identify a small-molecule binding site in a protein. Furthermore, the same system was used to demonstrate high-speed chemical mapping of a centimeter-sized pork slice.
尽管拉曼光谱已被用于许多领域（包括材料科学、生物医学和药物研究）的样品定量分析，但由于其灵敏度低，限制了其在高通量筛选中的分析能力的应用。在这里，我们开发了一种高通量拉曼筛选系统，该系统可以同时分析多微孔板中的数百个标本。在多微孔板的每个孔下都组装了多个高数值孔径（NA）透镜，以同时进行高灵敏度的拉曼散射检测。可以同时分析加载在标准 384 孔板上的 192 个样本的拉曼光谱。与基于单点测量的传统拉曼仪器相比，该开发系统显著提高了拉曼测量的通量（约 100 倍）。通过使用该系统，我们展示了高通量拉曼筛选，以研究药物多晶型和鉴定蛋白质中的小分子结合位点。此外，还使用相同的系统对厘米大小的猪肉切片进行了高速化学映射。
