Micro‐Lensed Fiber Laser Desorption Mass Spectrometry Imaging Reveals Subcellular Distribution of Drugs within Single Cells

Abstract

The visualization of temporal and spatial changes in the intracellular environment has great significance for chemistry and bioscience research. Mass spectrometry imaging (MSI) plays an important role because of its unique advantages, such as being label‐free and high throughput, yet it is a challenge for laser‐based techniques due to limited lateral resolution. Here, we develop a simple, reliable, and economic nanoscale MSI approach by introducing desorption laser with a micro‐lensed fiber. Using this integrated platform, we achieved 300 nm resolution MSI and successfully visualized the distribution of various small‐molecule drugs in subcellular locations. Exhaustive dynamic processes of anticancer drugs, including releasing from nanoparticle carriers entering nucleus of cells, can be readily acquired on an organelle scale. Considering the simplicity and universality of this nanoscale desorption device, it could be easily adapted to most of laser‐based mass spectrometry applications.

Native Mass Spectrometry Imaging of Proteins and Protein Complexes by Nano-DESI

“…Substantial improvement of spatial resolution is therefore a key focus to make native MSI a more powerful tool for biology, particularly as MSI of small molecules is now routinely achievable at cellular resolutions. 17 , 18 Alternative ambient ionization techniques were considered for adaption for native MSI: desorption electrospray ionization (DESI) has been successfully applied to protein imaging under denaturing conditions with the assistance of ion mobility separation, 9 , 10 and is capable of native analysis of purified proteins applied to a glass slide, 19 but requires harsh desolvation conditions. Nanospray-desorption electrospray ionization (nano-DESI), 20 , 21 which employs direct contact of a flowing solvent bridge with the sample to dissolve molecules prior to ionization, has also been applied to denatured protein MSI.…”

Chemical Analysis of Single Cells and Organelles

“…2020 , 18020–18027. Copyright 2020 Angewandte Chemie (ref ( 127 )). (C) (a) Thermal imaging of the hydrogen flame (VH2/VCO2 = 1:1), (b, c) SEM images of the tip of the probe, (d) microscope image of the probe postsampling, and (e) photograph of the thermal desorption spray plume.…”

“…Meng et al considered the matter of high costs and complexity of modern, ever-advancing MS methods; they introduced a nano laser probe-based LDI-MS that only requires an existing LDI-MS apparatus to be fitted with a microlensed fiber and a submicron precision positioner, making the upgrade approachable. 127 Here, the microlensed fiber was used to focus the beam, producing a lateral resolution of 300 nm in HeLa cells cultured with the drugs acriflavine and azure B. A schematic of the setup is shown in Figure 7 B.…”

“…127 NPs receive considerable attention particularly in the biomedical field due to their applications in areas such as targeted drug delivery and toxicology assays; these innovative NDPI-MS approaches reportedly bridge the gap between LDI-MS and multimodal single-cell imaging and open the door to novel tools for drug monitoring via laser-based, high resolution single-cell MS. Meng et al considered the matter of high costs and complexity of modern, ever-advancing MS methods; they introduced a nano laser probe-based LDI-MS that only requires an existing LDI-MS apparatus to be fitted with a microlensed fiber and a submicron precision positioner, making the upgrade approachable. 128 Here, the microlensed fiber was used to focus the beam, producing a lateral resolution of 300 nm in HeLa cells cultured with the drugs acriflavine and azure B. A schematic of the setup is shown in Figure 7B.…”

Airborne fine particulate matter induces cognitive and emotional disorders in offspring mice exposed during pregnancy

“…In order to improve the lateral resolution of MSI, Hang group [28] proposed the high-resolution MSI strategy to identify the exogenous and endogenous compounds from the micro-scale to nano-scale in the homogenous and heterogeneous tissues. Subsequently, Hang and co-workers [29] designed a micro-lensed fiber laser desorption MSI to obtain 300 nm resolution. They successfully investigated the spatial distribution of drugs in single cells.…”