Single-Cell Mass Spectrometry Imaging of Multiple Drugs and Nanomaterials at Organelle Level.

Mass spectrometry imaging (MSI) techniques make possible the spatial chemical identification of analytes, especially for biological samples. As a universal energy source, laser is one of the most commonly used sampling methods in MSI techniques. However, due to the limitation of laser spot size, subcellular spatial resolution imaging, which is significant for life science researches, always remains a challenge for laser-based MSI. In this research, we designed a laser ablation (LA) system with a microlensed fiber and a "three-way" structure ablation chamber, and achieved nanoscale inductively coupled plasma (ICP) MSI with an adjustable spatial resolution down to 400 nm, which surpasses most existing technologies. With this device, the distribution of various photodynamic therapy drugs in the intestine of mouse can be clearly observed. The comparison imaging results showed that the drug distribution in tissue slice could be identified at the subcellular level with the high-resolution mode. More valuably, gold nanorods (GNRs) and carboplatin in a single cell are able to be visualized at organelle level due to the nanoscale resolution, which is able to reveal the mechanism of cell apoptosis. This reliable and economical MSI technique is expected to be used in understanding the precise chemical composition and transportation in small tissues, microorganisms, and single cells.