The single-probe mass spectrometry for single cell analysis and biological tissue imaging

Mass spectrometry (MS) is commonly used to analyze the molecular composition of prepared gas-phase or solution samples. With the recent development, MS has been used to obtain the cellular composition of single cell (i.e. single cell MS) and map the spatial distribution of species on biological tissues (i.e. MS imaging). We have developed a multifunctional device, named as the Single-probe. This device can be coupled with MS for multiple applications, including single cell MS and MS imaging.

To fabricate a Single-probe, a fused silica capillary and a nano-ESI emitter were glued into a dual-bore quartz needle (tip size < 10 µm). The Single-probe has been coupled with a X,Y,Z -stage system, digital microscopes, and a LTQ Orbitrap XL mass spectrometer. Single cell MS. We have cultured cancer cells were cultured and treated them with anticancer compounds. Cells were placed on a glass slide that is attached to the stage system. Using microscopes as the visual guide, the tip of the Single-probe was inserted into a cell by precisely lifting z-translation stage. The corresponding anticancer compounds and cellular metabolites were observed. MS imaging. Mouse brain and kidney slices were prepared using a cryomicrotome, and placed on the stage system. We closely approached the Single-probe tip to the tissue surface, and analytes on the corresponding spot were sampled by the Single-probe followed by MS analysis. We performed point-by-point analysis of the whole tissue slice to reconstruct the spatial distribution of compounds of interest using visualization software. We have obtained high-spatial resolution (8.5 µm) under ambient conditions without sample preparation.