Laser ablation and ionization for nano-mass cytometry

质谱学是鉴定生物分子最有效的方法之一。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中，并在分子进入真空后将其电离。显微镜对医学科学更是必不可少的。图像分辨率通常被限制在大约一个光波长或~0.5微米。然而，这一限制可以通过“超分辨率成像”来打破，这种成像可以获得10倍小的特征。诺贝尔化学奖因超分辨率显微镜而获奖。令人惊讶的是，超分辨率从未与质谱学相结合。这种结合需要从亚细胞区域--远小于可见光焦点的区域--消融。实现超分辨率质谱学将在生物学最基本的空间尺度上提供化学和生物信息。超分辨率质谱学是一个宏伟的愿景。它极大地影响了我们在3年计划中所做的详细选择，也影响了Fluidigm对支持的选择。Fluidigm与质谱仪一起工作，这是一种质谱学形式，原子标记可以识别生物功能。对于Fluidigm来说，他们开发超分辨率质量细胞术的第一个关键问题是将每个消融区域分解成原子成分并有效地测量它们。我们这个理论和实验联合项目的目标是亚波长消融与高效的全光学材料分解和电离相结合。我们将使用真空紫外辐射将~10^19 cm^-3电子注入到50 nm厚的单元体中。这些电子将作为一种纳米天线，播撒红外线驱动的雪崩电离和烧蚀。我们建议继续用红外线光束照射样品，从而继续加热材料，将其分解为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.