Laser ablation and ionization for nano-mass cytometry

质谱法是鉴定生物分子最有力的方法之一。它的重要性得到了诺贝尔奖的认可，因为它将分子注入真空并在真空中电离它们。显微术对医学科学更是必不可少。图像分辨率通常限制在大约一个波长的光或~ 0.5微米。然而，这个限制可以通过“超分辨率成像”来打破，它可以实现10倍小的特征。诺贝尔化学奖授予了超分辨率显微镜。令人惊讶的是，超分辨率技术从未与质谱技术相结合。这种组合需要从亚细胞区域（远小于可见光焦点的区域）进行消融。实现超分辨率质谱分析将在最基本的空间尺度上为生物学提供化学和生物信息。超分辨率质谱分析是一个宏伟的愿景。它强烈影响了我们在3年提案中做出的详细选择，也影响了Fluidigm对支持的选择。Fluidigm与质谱仪一起工作，质谱仪是一种原子标记物识别生物功能的质谱法。Fluidigm开发超分辨率细胞计数技术的第一个关键问题是将每个消融区域分解为其原子组成部分并有效地测量它们。我们的这个联合理论和实验项目的目标是亚波长烧蚀结合高效的全光材料分解和电离。我们将使用紫外辐射将~10^19 cm^ 3的电子注入到50 nm厚的细胞切片中。这些电子将作为纳米天线播种红外驱动的雪崩电离和烧蚀。我们建议继续用红外光束照射样品，从而继续加热材料，将其分解成原子碎片并使其电离。

Mass spectrometry is one of the most powerful methods for identifying biological molecules. Its importance was recognized by a Nobel Prize for injecting molecules into a vacuum and ionizing them once they are there. Microscopy is even more essential to medical science. Image resolution is often limited to approximately a wavelength of light or ~ 0.5 microns. This limit, however, can be broken by "super-resolution imaging," where 10 times smaller features are achieved. The Nobel Prize for Chemistry was awarded for super-resolution microscopy. Surprisingly, super-resolution has never been combined with mass spectrometry. The combination requires ablation from sub-cellular regions - regions far smaller than a visible light focal spot. Achieving super-resolution mass spectrometry would offer chemical and biological information at the most fundamental spatial scale for biology. Super-resolution mass spectrometry is a grand vision. It strongly influences the detailed choice we make in our 3-year proposal and it influences Fluidigm's choice of support. Fluidigm works with mass cytometry, a form of mass spectrometry where atomic markers identify biological function. The first critical issue for Fluidigm as they develop super-resolution mass cytometry is to break each ablated region into its atomic components and measure them efficiently. Our aim for this joint theoretical and experimental project is sub-wavelength ablation combined with efficient all-optical material breakup and ionization. We will use VUV radiation to inject ~10^19 cm^-3 electrons into a 50 nm thick cell section. These electrons will serve as a nano-antenna seeding infrared driven avalanche ionization and ablation. We propose to continuing to irradiate the sample with an infrared beam and thereby continue to heat the material, breaking it into atomic fragments and ionizing it.