Label-free molecular imaging of the kidney

Prentice, Boone M.; Caprioli, Richard M.; Vuiblet, Vincent

doi:10.1016/j.kint.2017.03.052

Cited by 26 publications

(30 citation statements)

References 186 publications

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“…Of course, cooling can cure these issues, but they have also been partially circumvented by the use of binary matrices, making the sample more stable, and/or enhancing the speed of acquisition . Similar observations have been described by the groups of McEwen, Li, and Caprioli . Obviously, the ‘matrix’ plays a critical role and details are expanded below.…”

Section: Performance Characteristics and Applicationsmentioning

confidence: 70%

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Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

Trimpin

2019

Rapid Comm Mass Spectrometry

110

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Together with my group and collaborators, I have been fortunate to have had a key role in the discovery of new ionization processes that we developed into new flexible, sensitive, rapid, reliable, and robust ionization technologies and methods for use in mass spectrometry (MS). Our current research is focused on how best to understand, improve, and use these novel ionization processes which convert volatile and nonvolatile compounds from solids or liquids into gas-phase ions for analysis by MS using e.g. mass selected fragmentation and ion mobility spectrometry to provide reproducible, accurate, and improved mass and drift time resolution. In my view, the apex was the discovery of vacuum matrix-assisted ionization (vMAI) in 2012 on an intermediate pressure matrix-assisted laser desorption/ionization (MALDI) source without the use of a laser, high voltages, or any other added energy. Only exposure of the matrix:analyte to the sub-atmospheric pressure of the mass spectrometer was necessary to initiate ionization. These findings were initially rejected by three different scientific journals, with comments related to 'how can this work?', 'where do the charges come from?', and 'it is not analytically useful'. Meanwhile, we, and others have demonstrated analytical utility without a complete understanding of the mechanism. In reality, MALDI and electrospray ionization are widely used in science and their mechanisms are still controversially discussed despite use and optimization of now 30 years. This Perspective covers applications, and mechanistic aspects of the novel ionization processes for use in MS that guided us in instrument developments, and provides our perspective on how they relate to traditional ionization processes.

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Section: Performance Characteristics and Applicationsmentioning

confidence: 70%

“…81,101 Similar observations have been described by the groups of McEwen, Li, and Caprioli. [108][109][110]129,130,146 Obviously, the 'matrix' plays a critical role and details are expanded below.…”

Section: Laserspray Ionizationmentioning

confidence: 99%

Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

Trimpin

2019

Rapid Comm Mass Spectrometry

110

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“…Metabolomics. The UTHSA/PNNL group will generate spatial metabolomics measurements by using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), an approach that has been utilized previously for kidney molecular imaging (22,23). Here, freshfrozen tissues are cryosectioned, mounted on optically transparent and electrically conductive slides, coated with an organic matrix that assists in facilitating desorption and ionization of endogenous molecules, and serially probed with a laser to attain mass spectral information at predefined locations.…”

Section: Overview Of Kpmp Technologies: Creating a Molecular And Funcmentioning

confidence: 99%

A Multimodal and Integrated Approach to Interrogate Human Kidney Biopsies with Rigor and Reproducibility: The Kidney Precision Medicine Project

El-Achkar

Eadon

Menon

et al. 2019

Preprint

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Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and therapies tailored to the disease of each patient. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single cell level or in 3-dimensional (3D) space is a significant challenge that can be a futile exercise if not well controlled. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate 3D molecular atlases of healthy and diseased kidney biopsies using multiple state-of-the-art OMICS and imaging technologies across several institutions. We describe a pipeline for generating a reliable and authentic single cell/region 3D molecular atlas of human adult kidney with emphasis on quality assurance, quality control, validation and harmonization across different OMICS and imaging methods. Our “follow the tissue” approach encompasses sample procurement to data generation, analysis, data sharing, while standardizing, and harmonizing procedures at sample collection, processing, storage and shipping. We provide key features of preanalytical parameters, bioassays, post analyses, reference standards and data depositions. A pilot experiment from a common source tissue processed and analyzed at different institutions was executed to identify potential sources of variation, feasibility of multimodal analyses and unique and redundant features of the macromolecules being characterized by each technology. An important outcome was identification of limitations and strengths of the different technologies, and how composite information can be leveraged for clinical application. A peer review system was established to critically review quality control measures and the reproducibility of data generated by each technology before granting approval to work on clinical biopsy specimens. This unique pipeline establishes a process that economizes the use of valuable biopsy tissue for multi-OMICS and imaging analysis with stringent quality control to ensure rigor and reproducibility of results and which can serve as a model for similar personalized medicine projects.Author ContributionsMTE, RM, BBL, TS, TA, AS, SP, CRA, DD, EAO, SW, GZ, MJ and KD performed the ground work for the quality control group, wrote the KPMP TIS manual of procedures and generated figures. HH, JZ, RS, RM, TS, EAO, MTE, TME, PH, SP, MK, ZL and SJ generated the initial working reference marker list. CEA, TME, JBH, JL, MK and SJ led the Pilot 1 protocol. TME, VD, LB, JG, CEA, ZL, SJ and JBH developed the pathology QC tissue qualification and tissue processing criteria. JBH organized and executed the Pilot tissue collection and distribution. JC designed the SpecTrack system. CP prepared and organized the TIS manual of procedures and performed data organization services. YH led ontology development for QC metadata and knowledge standardization. BS and EA organized data integration efforts and data authentication in the data hub. KS and MS led the OMICS discussion group. SJ led the quality control group. TME and CEA led the tissue processing group. MTE and SJ led the Molecular and Pathology Integration group. MTE and SJ conceived and led the TISAC process. RI, OGT KZ, ZL, PH, BR, PCD, KS, MS, JBH, CEA, LB, JG, TME, MK and SJ conceived the integrated TIS pipeline and QC vision. TME and SJ wrote the initial draft of the paper. All authors contributed to the writing and editing of the manuscript.

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“…His opening remarks gave a historical overview of MALDI IMS technology and emphasized its advantages. Dr. Caprioli explained how MALDI IMS employs desorption of molecules by direct laser irradiation to map the location of specific molecules from fresh frozen or formalin-fixed tissue sections without the need to target specific reagents, such as antibodies [ 17 ]. Dr. Caprioli championed the major benefits of the histology-directed approach (that has been developed by his group) over conventional staining and microscopic methods.…”

Section: Maldi Imaging Mass Spectrometry (Ims): Recent Technologicalmentioning

confidence: 99%

“…By integrating microscopy with MALDI IMS, this application is almost limitless and could be used in a variety of biologically and medically relevant research projects. Dr. Caprioli highlighted studies in diabetic nephropathy involving both proteins and lipids and the differentiation of benign skin lesions from melanomas [ 17 , 18 ]. In addition, Dr. Caprioli’s group has applied IMS to drug targeting and metabolic studies in specific organs and in intact whole animal sections following drug administration [ 19 ].…”

Section: Maldi Imaging Mass Spectrometry (Ims): Recent Technologicalmentioning

confidence: 99%

Yale School of Public Health Symposium on tissue imaging mass spectrometry: illuminating phenotypic heterogeneity and drug disposition at the molecular level

et al. 2018

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Label-free molecular imaging of the kidney

Cited by 26 publications

References 186 publications

Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

A Multimodal and Integrated Approach to Interrogate Human Kidney Biopsies with Rigor and Reproducibility: The Kidney Precision Medicine Project

Yale School of Public Health Symposium on tissue imaging mass spectrometry: illuminating phenotypic heterogeneity and drug disposition at the molecular level

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