Grant Number:	5UH3CA255132-04 Interpret this number
Primary Investigator:	Laskin, Julia
Organization:	Purdue University
Project Title:	Novel Platform for Quantitative Subcellular Resolution Imaging of Human Tissues Using Mass Spectrometry
Fiscal Year:	2021

Novel Platform for Quantitative Subcellular Resolution Imaging of Human Tissues Using Mass Spectrometry Mass spectrometry imaging (MSI) is a powerful technique that enables label-free spatial mapping of different classes of biomolecules in biological systems. Because it does not require any special sample pretreatment, ambient MSI is particularly attractive for high throughput automated imaging applications. The throughput of ambient MSI experiments is typically limited by the inherently slow microprobe-type sampling from surfaces, which is a characteristic shortcoming of many chemical imaging modalities. This project will combine several highly innovative approaches to address challenges associated with the high-throughput high- resolution ambient MSI of lipids and metabolites using nanospray desorption electrospray ionization (nano-DESI). Nano-DESI is an ambient ionization technique, which relies on gentle localized liquid extraction of molecules from tissue sections into a flowing solvent confined between two glass capillaries. The extracted molecules are efficiently delivered to a mass spectrometer inlet and ionized by soft electrospray ionization. Nano-DESI MSI enables detection of hundreds of metabolites, lipids, and peptides in tissue sections with high sensitivity, high spatial resolution, and without special sample pretreatment. Furthermore, on-the-fly quantification of lipids and metabolites in tissue sections during nano-DESI imaging experiments is achieved by doping the working solvent with appropriate standards of known concentration. This project will extend these powerful capabilities of nano-DESI MSI to enable high-throughput imaging of large tissue sections of interest to the HubMAP Consortium. This will be achieved using a combination of a conceptually different nano-DESI probe design optimized for robustness, ease of fabrication, and spatial resolution and a suite of advanced machine learning and compressed sensing computational approaches. These developments will be applicable to different types of human tissues and will transform quantitative molecular imaging of multiple classes of biomolecules in tissue sections. Although the capabilities of the new imaging platform will be demonstrated using non-diseased tissue, these developments will be broadly applicable to scientific problems associated with understanding health and disease




Coupling Microdroplet-Based Sample Preparation, Multiplexed Isobaric Labeling, and Nanoflow Peptide Fractionation for Deep Proteome Profiling of the Tissue Microenvironment.
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EPub date: 2024-08-01 00:00:00.0.
PMID: 39089681
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Hardware and software solutions for implementing nanospray desorption electrospray ionization (nano-DESI) sources on commercial mass spectrometers.
Authors: Jiang L.X. , Hilger R.T. , Laskin J. .
Source: Journal Of Mass Spectrometry : Jms, 2024 Jul; 59(7), p. e5065.
PMID: 38866597
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A monolithic microfluidic probe for ambient mass spectrometry imaging of biological tissues.
Authors: Jiang L.X. , Polack M. , Li X. , Yang M. , Belder D. , Laskin J. .
Source: Lab On A Chip, 2023-10-24 00:00:00.0; 23(21), p. 4664-4673.
EPub date: 2023-10-24 00:00:00.0.
PMID: 37782224
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High-resolution integrated microfluidic probe for mass spectrometry imaging of biological tissues.
Authors: Li X. , Hu H. , Laskin J. .
Source: Analytica Chimica Acta, 2023-10-23 00:00:00.0; 1279, p. 341830.
EPub date: 2023-09-17 00:00:00.0.
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Nanospray Desorption Electrospray Ionization (Nano-DESI) Mass Spectrometry Imaging with High Ion Mobility Resolution.
Authors: Jiang L.X. , Hernly E. , Hu H. , Hilger R.T. , Neuweger H. , Yang M. , Laskin J. .
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EPub date: 2023-07-18 00:00:00.0.
PMID: 37463098
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Proteome Mapping of the Human Pancreatic Islet Microenvironment Reveals Endocrine-Exocrine Signaling Sphere of Influence.
Authors: Gosline S.J.C. , Veličković M. , Pino J.C. , Day L.Z. , Attah I.K. , Swensen A.C. , Danna V. , Posso C. , Rodland K.D. , Chen J. , et al. .
Source: Molecular & Cellular Proteomics : Mcp, 2023 Aug; 22(8), p. 100592.
EPub date: 2023-06-15 00:00:00.0.
PMID: 37328065
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Proteome Landscapes of Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.
Authors: Yi X. , Zhu J. , Liu W. , Peng L. , Lu C. , Sun P. , Huang L. , Nie X. , Huang S. , Guo T. , et al. .
Source: Molecular & Cellular Proteomics : Mcp, 2023 Aug; 22(8), p. 100604.
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PMID: 37353004
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High-Throughput Mass Spectrometry Imaging of Biological Systems: Current Approaches and Future Directions.
Authors: Jiang L.X. , Yang M. , Wali S.N. , Laskin J. .
Source: Trends In Analytical Chemistry : Trac, 2023 Jun; 163, .
EPub date: 2023-04-13 00:00:00.0.
PMID: 37206615
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Nano-DESI Mass Spectrometry Imaging of Proteoforms in Biological Tissues with High Spatial Resolution.
Authors: Yang M. , Unsihuay D. , Hu H. , Nguele Meke F. , Qu Z. , Zhang Z.Y. , Laskin J. .
Source: Analytical Chemistry, 2023-03-28 00:00:00.0; 95(12), p. 5214-5222.
EPub date: 2023-03-14 00:00:00.0.
PMID: 36917636
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Deep Learning Approach for Dynamic Sampling for Multichannel Mass Spectrometry Imaging.
Authors: Helminiak D. , Hu H. , Laskin J. , Hye Ye D. .
Source: Ieee Transactions On Computational Imaging, 2023; 9, p. 250-259.
EPub date: 2023-02-24 00:00:00.0.
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Revving an Engine of Human Metabolism: Activity Enhancement of Triosephosphate Isomerase via Hemi-Phosphorylation.
Authors: Schachner L.F. , Soye B.D. , Ro S. , Kenney G.E. , Ives A.N. , Su T. , Goo Y.A. , Jewett M.C. , Rosenzweig A.C. , Kelleher N.L. .
Source: Acs Chemical Biology, 2022-10-21 00:00:00.0; 17(10), p. 2769-2780.
EPub date: 2022-08-11 00:00:00.0.
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High-Throughput Mass Spectrometry Imaging with Dynamic Sparse Sampling.
Authors: Hu H. , Helminiak D. , Yang M. , Unsihuay D. , Hilger R.T. , Ye D.H. , Laskin J. .
Source: Acs Measurement Science Au, 2022-10-19 00:00:00.0; 2(5), p. 466-474.
EPub date: 2022-08-15 00:00:00.0.
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Emerging Computational Methods in Mass Spectrometry Imaging.
Authors: Hu H. , Laskin J. .
Source: Advanced Science (weinheim, Baden-wurttemberg, Germany), 2022-10-17 00:00:00.0; , p. e2203339.
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Source: Science Advances, 2022-08-12 00:00:00.0; 8(32), p. eabp9929.
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Authors: Yang M. , Hu H. , Su P. , Thomas P.M. , Camarillo J.M. , Greer J.B. , Early B.P. , Fellers R.T. , Kelleher N.L. , Laskin J. .
Source: Angewandte Chemie (international Ed. In English), 2022-07-18 00:00:00.0; 61(29), p. e202200721.
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High-Throughput Nano-DESI Mass Spectrometry Imaging of Biological Tissues Using an Integrated Microfluidic Probe.
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Source: Analytical Chemistry, 2022-07-12 00:00:00.0; 94(27), p. 9690-9696.
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New Views of Old Proteins: Clarifying the Enigmatic Proteome.
Authors: Burnum-Johnson K.E. , Conrads T.P. , Drake R.R. , Herr A.E. , Iyengar R. , Kelly R.T. , Lundberg E. , MacCoss M.J. , Naba A. , Nolan G.P. , et al. .
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Self-supervised clustering of mass spectrometry imaging data using contrastive learning.
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Source: Chemical Science, 2021-12-22 00:00:00.0; 13(1), p. 90-98.
EPub date: 2021-11-26 00:00:00.0.
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Authors: Unsihuay D. , Mesa Sanchez D. , Laskin J. .
Source: Annual Review Of Physical Chemistry, 2021-04-20 00:00:00.0; 72, p. 307-329.
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