High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry

Yin, Ruichuan; Burnum-Johnson, Kristin; Sun, Xiaofei; Dey, Sudhansu K.; Laskin, Julia

doi:10.1038/s41596-019-0237-4

Cited by 143 publications

(185 citation statements)

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“…Tissue sections were prepared according to the previously described methods. [1] Briefly, one uterine horn was collected from a 4 days pregnant mouse, frozen in freezing media (Super Friendly Freeze`It TM , Fisher), and sliced to a series of sections with a thickness of 12 µm using a Leica CM 3050 cryostat. Brain tissue was collected from a healthy adult mouse.…”

Section: S-2mentioning

confidence: 99%

“…Mass spectrometry imaging (MSI) [1] is a powerful analytical tool, which enables both targeted and untargeted label-free detection of molecules in biological samples with high sensitivity and chemical specificity. Although matrix-assisted laser desorption ionization (MALDI) MSI [1a,2] is by far the most widely used technique, substantial effort has been dedicated to the development of ambient MSI approaches.…”

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confidence: 99%

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An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples**

Yin

et al. 2020

Angew Chem Int Ed

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Ambient ionization based on liquid extraction is widely used in mass spectrometry imaging (MSI) of molecules in biological samples. The development of nanospray desorption electrospray ionization (nano-DESI) has enabled the robust imaging of tissue sections with high spatial resolution. However, the fabrication of the nano-DESI probe is challenging, which limits its dissemination to the broader scientific community. Herein, we describe the design and performance of an integrated microfluidic probe (iMFP) for nano-DESI MSI. The glass iMFP fabricated using photolithography, wet etching, and polishing shows comparable performance to the capillary-based nano-DESI MSI in terms of stability and sensitivity; the spatial resolution of better than 25 μm was obtained in these first proof-of-principle experiments. The iMFP is easy to operate and align in front of a mass spectrometer, which will facilitate broader use of liquid extraction-based MSI in biological research, drug discovery, and clinical studies. File list (3) download file view on ChemRxiv Manuscript-An Integrated Microfluidic Probe-ChemRxiv.... (733.76 KiB) download file view on ChemRxiv Manuscript-An Integrated Microfluidic Probe-ChemRxiv.... (466.01 KiB) download file view on ChemRxiv Supporting Information-An Integrated Microfluidic Probe... (492.35 KiB)

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Section: S-2mentioning

confidence: 99%

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confidence: 99%

An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples**

Yin

et al. 2020

Angew Chem Int Ed

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“…We evaluate the performance of nano-DESI-QTOF MSI by comparing the results obtained using the IM-QTOF system operated in the MS mode with the results obtained using the nano-DESI-Orbitrap system described in our previous studies. 43,49 Furthermore, we demonstrate the capabilities of nano-DESI MSI in combination with IM separation, which enables both m/z-and ion mobility-selected imaging of molecules in tissues. Recently, it has been demonstrated that separation of the isobaric species can be improved using a Fourier transform ion cyclotron resonance mass spectrometer, an instrument, which has mass resolution far superior to the mass spectrometers employed in this work.…”

Section: ■ Results and Discussionmentioning

confidence: 97%

Nanospray Desorption Electrospray Ionization (nano-DESI) Mass Spectrometry Imaging of Drift Time-Separated Ions

Unsihuay¹,

Yin²,

Sanchez³

et al. 2020

Preprint

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Simultaneous spatial localization and structural characterization of molecules in complex biological samples currently represents an analytical challenge for mass spectrometry imaging (MSI) techniques. In this study, we describe a novel experimental platform, which substantially expands the capabilities and enhances the depth of chemical information obtained in high spatial resolution MSI experiments performed using nanospray desorption electrospray ionization (nano-DESI). Specifically, we designed and constructed a portable nano-DESI MSI platform and coupled it with a drift tube ion mobility spectrometer-mass spectrometer (IM-MS). Separation of biomolecules observed in MSI experiments based on their drift times provides unique molecular descriptors necessary for their identification by comparison with databases. Furthermore, it enables isomer-specific imaging, which is particularly important for unraveling the complexity of biological systems. Imaging of day 4 pregnant mouse uterine sections using the newly developed nano-DESI-IM-MSI system demonstrates rapid isobaric and isomeric separation and reduced chemical noise in MSI experiments. A direct comparison of the performance of the new nano-DESI-MSI platform operated in the MS mode with the more established nano-DESI-Orbitrap platform indicates a comparable performance of these two systems. A spatial resolution of better than ~16 µm and similar molecular coverage was obtained using both platforms. The structural information provided by the ion mobility separation expands the molecular specificity of high-resolution MSI necessary for the detailed understanding of biological systems.

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“…[10] This configuration generates high-quality ion images with a spatial resolution of better than 10 µm. [11] Despite the advances in the development of this technique, the fabrication and alignment of the finely pulled capillaries are still challenging. The ability to fabricate an integrated probe for the robust nano-DESI imaging with high spatial resolution will allow the broader scientific community to adapt this technique to a wide range of applications.…”

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confidence: 99%

“…This comparison indicates that iMFP provides ion images, which are in good agreement with the best-performing capillarybased nano-DESI probe. [11] Figure 2. Representative positive ion images of [M+Na] + ions of molecules in mouse uterine tissues obtained using iMFP (A) and capillary-based nano-DESI probe (B).…”

mentioning

confidence: 99%

An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples

Yin

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Ambient ionization based on liquid extraction is widely used in mass spectrometry<br>imaging (MSI) of molecules in biological samples. The development of nanospray desorption electrospray ionization (nano-DESI) has enabled the robust imaging of tissue sections with high spatial resolution. However, the fabrication of the nano-DESI probe is challenging, which limits its dissemination to the broader scientific community. Herein, we describe the design and performance of an integrated microfluidic probe (iMFP) for nano-DESI MSI. The glass iMFP fabricated using photolithography, wet etching, and polishing shows comparable performance to the capillary-based nano-DESI MSI in terms of stability and sensitivity; the spatial resolution of better than 25 μm was obtained in these first proof-of-principle experiments. The iMFP is easy to operate and align in front of a mass spectrometer, which will facilitate broader use of liquid extraction-based MSI in biological research, drug discovery, and clinical studies.

show abstract

High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry

Cited by 143 publications

References 51 publications

An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples**

An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples**

Nanospray Desorption Electrospray Ionization (nano-DESI) Mass Spectrometry Imaging of Drift Time-Separated Ions

An Integrated Microfluidic Probe for Mass Spectrometry Imaging of Biological Samples

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