Atmospheric pressure mass spectrometric imaging of live hippocampal tissue slices with subcellular spatial resolution

Kim, Jae Young; Seo, Eunseok; Kim, Hyunmin; Park, Ji Won; Lim, Dong Kwon; Moon, Dae Won

doi:10.1038/s41467-017-02216-6

Cited by 51 publications

(53 citation statements)

References 74 publications

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“…Thus, plasma jets have a high applicability and flexibility for various applications, including in vivo single-cell cancer therapy [58] as well as plasma-assisted quantum dot synthesis [59]. Most recently, plasma jets were specifically used as a weakly ionized plasma source in experiments for a case study on electric wind [60], etching biological samples [61], and electron solvation [62], based on the unique features of this type, such as a preference for guiding and releasing plasma species into the ambient air. Along with the use of plasma jets on biological samples for such purposes as wound healing [63][64][65] and cancer therapy [66,67], intensive investigations on the physical and chemical properties of the plasma jet have been conducted.…”

Section: Plasma Jetmentioning

confidence: 99%

Electron characterization in weakly ionized collisional plasmas: from principles to techniques

Park

Choe

Moon

et al. 2018

Advances in Physics: X

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Weakly ionized plasmas at or near 1 atm pressure, or atmospheric-pressure plasmas, have received increasing attention due to their scientific significance and potential for use in a variety of applications, particularly for medicine, agriculture, and food. However, there is a large imbalance between scientific research on plasma physics and applications, which is partly due to the considerable differences in the characteristics of these plasmas compared with those of low-pressure plasmas. This discrepancy is particularly related to the difficulty in performing plasma diagnostics for highly collisional plasmas. Information on electrons (such as the electron density and temperature) is essential since electrons play a dominant role in the generation of active species related to the physical and chemical processes inside the plasma. So far, limited diagnostics have been available for electrons such as Thomson scattering and optical emission diagnostics based on equilibrium models. Here, we review the available diagnostic methods along with their merits and limitations for characterizing electrons in weakly ionized collisional plasmas. Particular attention is paid to continuum radiation-based spectroscopy, which facilitates multidimensional imaging of electron density and temperature. The future impact of these plasmas on relevant fields (i.e. laboratory and industrial plasmas and their applications) is also addressed.

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Section: Plasma Jetmentioning

confidence: 99%

Electron characterization in weakly ionized collisional plasmas: from principles to techniques

Park

Choe

Moon

et al. 2018

Advances in Physics: X

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“…The diameters of the ablated craters determined the pixel size of the images, which were typically between 200-400 µm, while pixel size of 20 µm was achieved with additional focus lens 57 . Recently, another laser ablation based mass spectrometry imaging technique were reported to accomplish mapping images with 2.9µm spatial resolution from special treated live tissue and with plasma ionization 33 . However, the m/z ranges these techniques were able to detect were limited.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, laser desorption/ablation-based methods allow imaging at subcellular level 33,34 . DESI is currently the most widely recognized ambient ionization methods for MSI.…”

Section: Introductionmentioning

confidence: 99%

“…Several instrumental approaches to increase the spatial resolution of ambient ionization MSI have been reported. For example, a hybrid atomic force microscopy mass spectrometer was applied for mapping bacterial colonies at sub-micrometer level under atmospheric pressure 33 .On the other hand, laser desorption/ablation-based methods allow imaging at subcellular level 34,35 . DESI is currently the most widely recognized ambient ionization methods for MSI.…”

mentioning

confidence: 99%

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High Spatial Resolution Ambient Ionization Mass Spectrometry Imaging Using Microscopy Image Fusion Determines Tumor Margins

Lin

Chen

Huang

et al. 2019

Preprint

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Mass spectrometry imaging (MSI) using ambient ionization technique enables a direct chemical investigation of biological samples with minimal sample pretreatment. However, detailed morphological information of the sample is often lost due to its limited spatial resolution. We demonstrated that the fusion of ambient ionization MSI with optical microscopy of routine hematoxylin and eosin (H&E) staining produces predictive, high-resolution molecular imaging. In this study, desorption electrospray ionization (DESI) and nanospray desorption electrospray ionization (nanoDESI) mass spectrometry were emplo yed to visualize lipid and protein species on mouse tissue sections. The resulting molecular distributions obtained by ambient ionization MSI-microscopy fusion were verified with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI and routine immunohistochemistry (IHC) staining on the adjacent sections. Label-free molecular imaging with 5-µm spatial resolution can be achieved using DESI and nanoDESI, whereas the typical spatial resolution of ambient ionization MSI is ~100 µm. In this regard, sharpened molecular histology of tissue sections was achieved, providing complementary references to the pathology. Such multi-modality integration enabled the discovery of potential tumor biomarkers. After image fusion, we identified about 70% more potential biomarkers that could be used to determine the tumor margins on a lung tissue section with metastatic tumors. spectrometry (SIMS) MSI, were reported to achieve sharpened molecular imaging with spatial resolution at cellular level on tissue sections 36,37 . approach for image fusion was reported to be broadly applicable to different tissue type. The distribution of ions was clear at the sub-cellular level. Sharped ion images of MALDI mass spectrometry fused with microscopy of mouse tissue sections were shown in their study 37 . In addition, fusion of SIMS and electron microscopy images were also reported 38 . Although high resolution molecular distribution were revealed, these mass spectrometry methods operated under high vacuum, which limits the compatibility with conventional imaging methods for pathological examinations.In our study, an optical microscope was applied to obtain images containing meticulous details of H&E stained tissue sections. Using multivariate regression algorithm, we fused MSI with optical microscopy and generated predictive fine-grained MSI. This method was applied in different tissue types and demonstrated as a tool for cancer diagnosis. By combining optical microscopy with ambient ionization methods, DESI, and nanoDESI, for tissue mapping with image fusion, both the image resolution and image quality were greatly improved. The workflow of our study is shown in Fig. 1. ResultsElevating spatial resolution of lipid species mapping in DESI MSI. The results for fusion of DESI MSI for mouse brain and cerebellum coronal sections were shown in Fig. 2, whereas the results for mouse kidney sections were shown in Fig. 3. In Fig. 2, the dis...

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“…Moreover, the proposed power delivery design and implementation can also be used in other type of electric propulsion systems for various types of spacecraft, as well as other emerging applications that value size and weight reduction and portability of power electronics systems: it can be directly applied to microelectronics RF plasma systems or to the use of atmospheric plasma jets for biomedical or imaging applications of atmospheric plasma jets [15,16].…”

Section: Introductionmentioning

confidence: 99%

An Integrated RF Power Delivery and Plasma Micro-Thruster System for Nano-Satellites

et al. 2018

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Progress in satellite technologies is ongoing and eventually finds applications back on Earth. Electric propulsion systems have been proven effective on large scale satellites (NASA DAWN) with better propellant efficiency than chemical or cold gas propulsion, and if miniaturized can be promising for long term operation of nano-satellites (e.g., CubeSats) in low Earth orbit or in deep space (NASA MarCO). However, the power supplies often used to power these electric thrusters, particularly those involving radiofrequency (RF) plasma, typically comprise power inefficient linear mode RF power amplifiers (e.g., class AB). These are simple systems designed to operate reliably under a wide range of loads for versatility, but they suffer low power efficiencies when operating at conditions significantly different from the nominal operating point. The required bulky and heavy thermal management components deem these electric propulsion systems impossible to fit on board nano-satellites. Here we present a compact and efficient switched mode dc-RF power inverter integrated with an electro-thermal plasma micro-thruster for nano-satellite (e.g., Cubesats) propulsion. The integrated system can serve as side panels and structural support of CubeSats, saving precious on-board volume for propellant and/or payloads. A complete assembly has been operationally tested in a space simulation system. This development opens a route for a new generation of power supplies applicable to the space sector, the microelectronics industry as well as the field of bioengineering.

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Atmospheric pressure mass spectrometric imaging of live hippocampal tissue slices with subcellular spatial resolution

Cited by 51 publications

References 74 publications

Electron characterization in weakly ionized collisional plasmas: from principles to techniques

Electron characterization in weakly ionized collisional plasmas: from principles to techniques

High Spatial Resolution Ambient Ionization Mass Spectrometry Imaging Using Microscopy Image Fusion Determines Tumor Margins

An Integrated RF Power Delivery and Plasma Micro-Thruster System for Nano-Satellites

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