S. Ghorai, C.A. Seneviratne, K.K. Murray, “Tip-enhanced laser ablation sample transfer for biomolecule mass spectrometry,” J. Am. Soc. Mass Spectrom.26 (2015) 63–70. doi:10.1007/s13361-014-1005-x.

Abstract: Atomic force microscope (AFM) tip-enhanced laser ablation 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 355 nm Nd:YAG laser. The ablated material was captured on a silver wire that was held 300 μm vertically and 100 μm horizontally from the tip. For the small molecules anthracene and rhodamine 6G, the wire was cut and affixed to a metal target using double-sided conductive tape and analyzed by LDI using a commercial laser desorption time-of-flight mass spectrometer. Approximately 100 fg of material was ablated from each of the 1 μm ablation spots and transferred with approximately 3% efficiency. For larger polypeptide molecules angiotensin II and bovine insulin, the captured material was dissolved in saturated matrix solution and deposited on a target for MALDI analysis.

AFM image of ablation crater of an insulin thin film and MALDI mass spectrum of the collected material
Atomic force microscope with pulsed laser ablation and sample capture
Atomic force microscope stage with capture wire for tip enhanced laser ablation