Five Micron High Resolution MALDI Mass Spectrometry Imaging with Simple, Interchangeable, Multi-Resolution Optical System

Feenstra, Adam D.; Dueñas, María Emilia; Lee, Young Jin

doi:10.1007/s13361-016-1577-8

Cited by 81 publications

(84 citation statements)

References 38 publications

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“…Most recently our group has further modified our optics setup to achieve a practical laser spot size of~4 mm which enabled 4-5 mm spatial resolution imaging to be accomplished without the need for oversampling. [16] In the previous work, a home-built Keplerian optical configuration was used as a beam expander, but this work uses a commercially available Galilean configuration beam expander to simplify the optics. In addition, a 1 mm pinhole was utilized instead of the 25 mm pinhole due to the difficulties in optical alignment with such a small pinhole, although the larger pinhole does not remove all the non-Gaussian beam components.…”

Section: Simple Interchangeable Multi-resolution Optical System Witmentioning

confidence: 99%

“…One is the ability to identify unknown compounds directly on tissues without chromatographic separation, and the other is the limited sensitivity in small sampling sizes. We have developed a 'multiplex MS imaging' technique to address the former issue, [14][15][16] and developed various new matrices to address the latter. [17,18] We have divided this review into three major subjects describing our efforts: 1) to achieve small laser spot sizes, 2) to develop multiplex MS imaging, and 3) to expand the variety of currently available matrices.…”

Section: Introductionmentioning

confidence: 99%

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High‐Spatial Resolution Mass Spectrometry Imaging: Toward Single Cell Metabolomics in Plant Tissues

Hansen

Lee

2017

The Chemical Record

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Mass spectrometry imaging (MSI) is a powerful tool that has advanced our understanding of complex biological processes by enabling unprecedented details of metabolic biology to be uncovered. Through the use of high-spatial resolution MSI, metabolite localizations can be obtained with high precision. Here we describe our recent progress to enhance the spatial resolution of matrix-assisted laser desorption/ionization (MALDI) MSI from ∼50 μm with the commercial configuration to ∼5 μm. Additionally, we describe our efforts to develop a 'multiplex MSI' data acquisition method to allow more chemical information to be obtained on a single tissue in a single instrument run, and the development of new matrices to improve the ionization efficiency for a variety of small molecule metabolites. In combination, these contributions, along with the efforts of others, will bring MSI experiments closer to achieving metabolomic scale.

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Section: Simple Interchangeable Multi-resolution Optical System Witmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High‐Spatial Resolution Mass Spectrometry Imaging: Toward Single Cell Metabolomics in Plant Tissues

Hansen

Lee

2017

The Chemical Record

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“…The main limitation of pixel size in MALDI-MSI is the area of desorption/ionisation on the tissue surface, that, in turn, is dependent on the laser spot size. Several groups have reported optical modifications to commercial MALDI-MSI ion sources that have reduced the laser spot size and, thus, achievable pixel sizes, down to < 10 μm and at best~1 μm [11][12][13][14][15]. For example, Kompauer et al recently reported a modified atmospheric pressure MALDI-MSI source capable of reaching 1.4 μm pixel size and imaging lipids within single cells [12].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of lipid coverage and high spatial resolution MALDI-imaging capabilities of oversampling combined with laser post-ionisation

et al. 2019

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Matrix-assisted laser desorption/ionisation-mass spectrometry imaging (MALDI-MSI) is a powerful technique for visualising the spatial locations of lipids in biological tissues. However, a major challenge in interpreting the biological significance of local lipid compositions and distributions detected using MALDI-MSI is the difficulty in associating spectra with cellular lipid metabolism within the tissue. By-and-large this is due to the typically limited spatial resolution of MALDI-MSI (30-100 μm) meaning individual spectra represent the average spectrum acquired from multiple adjacent cells, each potentially possessing a unique lipid composition and biological function. The use of oversampling is one promising approach to decrease the sampling area and improve the spatial resolution in MALDI-MSI, but it can suffer from a dramatically decreased sensitivity. In this work we overcome these challenges through the coupling of oversampling MALDI-MSI with laser post-ionisation (MALDI-2). We demonstrate the ability to acquire rich lipid spectra from pixels as small as 6 μm, equivalent to or smaller than the size of typical mammalian cells. Coupled with an approach for automated lipid identification, it is shown that MALDI-2 combined with oversampling at 6 μm pixel size can detect up to three times more lipids and many more lipid classes than even conventional MALDI at 20 μm resolution in the positive-ion mode. Applying this to mouse kidney and human brain tissue containing active multiple sclerosis lesions, where 74 and 147 unique lipids are identified, respectively, the localisation of lipid signals to individual tubuli within the kidney and lipid droplets with lesion-specific macrophages is demonstrated.

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“…MSI is becoming a powerful analytical tool in biomedical and life sciences . The instrument technologies of MALDI mass spectrometers have greatly advanced in the past decade: for instance, implementing high‐repetition solid‐state lasers, continuous raster sampling, and galvanometer‐based optical scanners for improved throughput; spatially structured laser beam profiles and laser‐induced post‐ionization for improved sensitivity; laser beam shaping, fiber‐optic laser delivery systems, and transmission geometry vacuum MALDI source for improved spatial resolution; stigmatic imaging (microscope mode) instrumentation for both throughput and spatial resolution; and most recently, high‐performance elevated/atmospheric pressure MALDI . It could be argued that MALDI‐MSI applications have led this progress.…”

Section: Introductionmentioning

confidence: 99%

DIUTHAME enables matrix‐free mass spectrometry imaging of frozen tissue sections

Kuwata

Itou

Kotani

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale:A recently developed matrix-free laser desorption/ionization method, DIUTHAME (desorption ionization using through-hole alumina membrane), was examined for the feasibility of mass spectrometry imaging (MSI) applied to frozen tissue sections. The permeation behavior of DIUTHAME is potentially useful for MSI as positional information may not be distorted during the extraction of analytes from a sample. Methods:The through-hole porous alumina membranes used in the DIUTHAME chips were fabricated by wet anodization, were 5 μm thick, and had the desired values of 200 nm through-hole diameter and 50% open aperture ratio. Mouse brain frozen tissue sections on indium tin oxide (ITO)-coated slides were covered using the DIUTHAME chips and were subjected to MSI experiments in commercial time-offlight mass spectrometers equipped with solid-state UV lasers after thawing and drying without matrix application.Result: Mass spectra and mass images were successfully obtained from the frozen tissue sections using DIUTHAME as the ionization method. The mass spectra contained rich peaks in the phospholipid mass range free from the chemical background owing to there being no matrix-derived peaks in that range. DIUTHAME-MSI delivered high-quality mass images that reflected the anatomy of the brain tissue. Conclusions:Analytes can be extracted from frozen tissue by capillary action of the through-holes in DIUTHAME and moisture contained in the tissue without distorting positional information of the analytes. The sample preparation for frozen tissue sections in DIUTHAME-MSI is simple, requiring no specialized skills or dedicated apparatus for matrix application. DIUTHAME can facilitate MSI at a low mass, as there is no interference from matrix-derived peaks, and should provide high-quality, reproducible mass images more easily than MALDI-MSI.

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Five Micron High Resolution MALDI Mass Spectrometry Imaging with Simple, Interchangeable, Multi-Resolution Optical System

Cited by 81 publications

References 38 publications

High‐Spatial Resolution Mass Spectrometry Imaging: Toward Single Cell Metabolomics in Plant Tissues

High‐Spatial Resolution Mass Spectrometry Imaging: Toward Single Cell Metabolomics in Plant Tissues

Evaluation of lipid coverage and high spatial resolution MALDI-imaging capabilities of oversampling combined with laser post-ionisation

DIUTHAME enables matrix‐free mass spectrometry imaging of frozen tissue sections

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