Tip-Enhanced Laser Ablation Sample Transfer for Mass Spectrometry

Abstract

In this research, atomic force microscope tip-enhanced laser ablation mass spectrometry (AFM TELA-MS), an ambient sub-micrometer scale sampling method for offline MS was developed. AFM TELA was used to transfer molecules from thin films to a suspended silver wire for off-line mass spectrometry using laser desorption ionization (LDI) and matrix-assisted laser desorption ionization (MALDI). An AFM with a 30 nm radius gold-coated silicon tip was used to image the sample and to hold the tip 15 nm from the surface for material removal using a pulsed Nd:YAG laser, which provides output at wavelengths of 532 nm in the visible, 1064 nm in the near IR, or the 355 nm UV wavelength. The laser is mildly focused onto the AFM tip and the fluence is set just below the far-field ablation threshold to irradiate the AFM tip for material removal with a smaller spot size than a laser focused with a conventional lens system. The AFM is used to image ablation craters and place the tip at the area being analyzed. For small molecules, approximately 100 fg of material was ablated from each of the 1 µm ablation spots and transferred with approximately 3% efficiency. AFM-TELA of large biomolecules was also demonstrated at 3% efficiency and a mass range up to 600 Da. AFM-TELA studies with different laser parameters indicated that the tip-enhanced material ejection depends on laser wavelength, polarization, fluence, and number of laser shots used for material ejection, but not on the absorption of the sample itself. The utility of AFM-TELA was applied to sampling of rat brain tissue. The ability of producing sub-micrometer scale craters, capture on a suspended silver wire and detection of lipids were demonstrated using off-line MALDI MS.