论文标题
细胞内药物结合位点的无标签化学纳米成像
Label-Free Chemical Nano-Imaging of Intracellular Drug Binding Sites
论文作者
论文摘要
光学显微镜的衍射有限分辨率约为250 nm。荧光方法（例如，棕榈，暴风雨，st脚）击败了此方法，但它们仍然限制为10 s的NM，并且图像是仅部分对象的一部分的间接点表示。在这里，我们描述了一种结合从组织病理学采集的样品制备技术以及基于探针的纳米成像技术（SNOM）的方法。这使我们能够以光学的方式对亚细胞结构进行图像，并且以比正常显微镜要好约100 x的纳米级分辨率进行图像。通过添加可调激光源，我们还展示了人骨髓瘤细胞中的中红外化学纳米成像（MICHNI），并使用它来绘制抗癌药物硼替佐米的结合位点，以绘制小于10 Zl大小的细胞内成分。 Michni不含标签，可与具有特定功能化学的任何生物材料和药物一起使用。我们认为，它的速度，便宜，简单，安全性和化学对比的结合有望在整个生命科学中产生变革性的影响。
Optical microscopy has a diffraction limited resolution of about 250 nm. Fluorescence methods (e.g. PALM, STORM, STED) beat this, but they are still limited to 10 s of nm, and the images are an indirect pointillist representation of only part of the original object. Here we describe a way of combining a sample preparation technique taken from histopathology, with a probe-based nano-imaging technique, (s SNOM) from the world of Solid State Physics. This allows us to image subcellular structures optically, and at a nanoscale resolution that is about 100 x better than normal microscopes. By adding a tuneable laser source, we also demonstrate mid-infrared chemical nano-imaging (MICHNI) in human myeloma cells and we use it to map the binding sites of the anti cancer drug bortezomib to less than 10 zL sized intracellular components. MICHNI is label free and can be used with any biological material and drugs with specific functional chemistry. We believe that its combination of speed, cheapness, simplicity, safety and chemical contrast promises a transformative impact across the life sciences.
