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

Abstract

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.

Image to insight: exploring natural products through mass spectrometry imaging

“…MIBI, a reporter-based method using heavy metal tags coupled with SIMS, has allowed for targeted imaging analysis of proteins at the subcellular level. 5,118 The development of optical ber-based laser ablation electrospray ionization mass spectrometry (f-LAESI-MS), [119][120][121] Nano-DESI, 122 and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) 123,124 have enabled MSI analysis of single cells under ambient conditions. Recent methodological and technological advances in MALDI imaging have improved its spatial resolution to 1-10 mm, making MALDI imaging at cellular and subcellular possible.…”

Mass Spectrometry Imaging Spatial Tissue Analysis toward Personalized Medicine

“…The high sensitivity of MSI approaches was also explored for single-cell analysis [ 70 , 71 , 72 , 73 ]. While most of the ongoing single-cell studies could provide more information about disease progression, intracellular mechanisms, and novel treatment targets, we can foresee that this level of detail could also be useful in the clinic, especially for early on-set diagnosis, treatment choice, and disease prognosis, for example, to further assess the response of immune cells to a specific treatment, or in the diagnosis of small sections or sections with a low number of tumor cells present, e.g., in small precursor lesions.…”

Desorption Electrospray Ionization Mass Spectrometry Imaging Illustrates the Quality Characters of Isatidis Radix

“…In recent years, the new technique of mass spectrometry imaging (MSI) has been proven as a powerful tool to explore the spatial distribution of molecules in biomaterials including cell (Mcmahon and Lechene, 2021 ; Meng et al, 2021 ), plant (Hu et al, 2021 ; Tong et al, 2021 ), animal (Yang et al, 2020 ; Sisley Emma et al, 2022 ), and human being (Kip et al, 2021 ). Thanks to its in situ , label-free, and untargeted capabilities, MSI offers the unprecedented spatio-chemical information, which is lost in routine homogenization-based approaches.…”