We present a surface sampling method for the chemical analysis of liquid-immersed solid samples. Liquid immersion allows samples to be kept in a hydrated state. We employed cavitation generated by high-intensity focused ultrasound for localized material removal. The appropriate transducer–sample distance was determined using the actuating ultrasound transducer prior to sampling, allowing sonication in focus despite surface height variation. We demonstrate the proposed surface sampling method on water-submerged glass cover slides painted with permanent markers, achieving sampling with tunable spot size down to 500  μm. The removed and collected material was transferred for chemical analysis by electrospray ionization mass spectrometry, which showed mass peaks characteristic to the permanent markers.

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