Laser ablation and ionization for nano-mass cytometry

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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.