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Spatial proteomics with mass spectrometry
If most drugs target proteins, why not study what you’re targeting? Spatial proteomics offers a direct readout of phenotype that complements RNA-based methods. Proteins are functionally active, can be more spatially and temporally stable than transcripts, and often reveal biology that transcript-level analysis alone may not capture. The proteome reflects real-time regulatory states and actionable biology, especially in disease contexts.
Spatial proteomics powered by mass spectrometry offers the deepest and most unbiased approach to understanding spatial biology. By combining the depth of modern proteomics with the ability to maintain tissue architecture, researchers can map protein expression across multicellular regions, microenvironments, and single-cell equivalents. The deeper view of the proteome reveals more biology by showing how proteins are organized in space and how they contribute to function in systems such as cancer, immunology, neuroscience, and precision medicine.
Benefits and pillars of a successful spatial proteomics solution
Uncover the full biological story within tissue. Spatial proteomics brings protein-level insights into the spatial biology toolkit.
By enabling direct, untargeted protein measurements with Thermo Scientific Orbitrap mass spectrometers, you can complement imaging and transcriptomics with deep functional information.
Achieve unbiased proteomics, biological significance, post-translational modification analysis, and spatial specificity with our deep protein profiling solutions.
Unbiased proteomics
Move beyond the limits of predefined panels. Benefit from untargeted, label-free identification of thousands of proteins from intact tissue, including low-abundance regulatory proteins. This enables expansion of existing spatial data and discovery of novel biology without restriction.
Simultaneously detect high- and low-abundance proteins from limited tissue input with Orbitrap mass spectrometers, including the Thermo Scientific Orbitrap Astral Mass Spectrometers, which deliver exceptional sensitivity and dynamic range. The broad coverage supports truly unbiased proteomic discovery, capturing signaling molecules, structural proteins, and novel biomarkers in a single experiment.
Biological significance
Bridge the gap between expression and biological function. Functional proteins ultimately drive cell behavior. To connect molecular patterns to phenotypes, disease states, or therapeutic outcomes, Orbitrap mass spectrometers deliver high-resolution, quantitative protein measurements across spatial regions.
Experience high-resolution, quantitative analysis of over 5,000 proteins across spatially defined tissue regions with Orbitrap mass spectrometers. Accurate mass detection and robust spectral quality reveal biologically significant up- and downregulated proteins, empowering confident differential expression analysis and pathway discovery in complex tissue environments, including tumor microenvironments and subcellular domains.
Post-translational modifications
Critical biological processes are regulated after transcription. Our deep protein profiling workflows detect thousands of Post-Translational Modifications (PTMs) - including phosphorylation, acetylation, and ubiquitination- simultaneously and in spatial context.
Full MS/MS ion transmission and robust spectral quality enable discovery of novel modification sites, providing functional insight into protein activity, signaling, and disease mechanisms critical to understanding the full spatial biology story.
Spatial specificity
Spatial proteomics begins with the right regions and ends with the sensitivity to measure them. To enable proteomic analysis of precisely defined tissue compartments, cellular niches, or subcellular structures, Orbitrap mass spectrometers are compatible with upstream workflows, including laser capture microdissection and targeted extraction.
From formalin-fixed, paraffin-embedded (FFPE) tumor margins to rare cell types, achieve spatial resolution with molecular depth. Experience high-confidence protein identification from precisely defined regions of interest with spatial proteomics powered by Orbitrap mass spectrometers.
Pair with high sensitivity Orbitrap mass spectrometers to support high spatial resolution, preserve proteome depth, and reduce background across complex tissue samples.
Region selection workflows, including cellular contouring
Subcellular targeting
Deep protein profiling workflows
Discover workflows and technologies that support the critical steps required for high-sensitivity protein profiling from spatially defined tissue regions. Spatial sample preparation can take many forms- from laser capture microdissection to antibody-guided extraction- but the challenge is turning those regions into deep, reproducible proteomic data.
Workflow steps
- Tissue preparation – Preserving biological context through optimal sample handling and sectioning. FFPE and fresh froze tissue is compatible with deep protein profiling.
- Isolation of regions of interest – Using techniques such as deep visual proteomics with laser capture microdissection (LCM or LMD) or targeted extraction to define precise tissue compartments or cell populations.
- Bottom-up proteomics
- Sample preparation: Digestion of proteins into peptides for analysis.
- High-sensitivity LC-MS/MS analysis – Leveraging Orbitrap and linear ion trap technologies to achieve deep proteome coverage with quantitative accuracy.
- Data analysis and integration – Converting spectral data into protein identifications and quantitation aligned with spatial location.
- Biological and therapeutic insights – Linking protein signatures to tissue architecture for applications in biomarker discovery, disease progression studies, and therapy development.
Deep visual proteomics workflow
What customers are saying about Orbitrap Astral MS
"Deep Visual Proteomics enables single-cell resolved analysis of tissue architecture and molecular pathology. In our recent work, we combined high sensitivity tip-based liquid chromatography methods with the Orbitrap Astral mass spectrometer to achieve unprecedented depth and precision in spatial proteomics. This was key to shed light and even curing one of two very serious diseases."
Mathias Mann, PhD, Professor
Proteomics and signal Transduction. Max Planck Institute of BioChemistry and Director, Novo Nordisk Foundation Center for Protein Research
Targeted extraction workflow
With targeted extraction, you can label and enrich proteins from subcellular or cellular regions across an entire tissue slide. Using antibody-guided masks and in situ photolabeling, this workflow generates high-resolution proteomic input from diverse microenvironments. Orbitrap mass spectrometers then deliver deep, unbiased protein profiles to help distinguish fine-grained biological patterns across complex tissues.
What customers are saying about the workflow
"The Syncell Microscoop paired with the Thermo Scientific Orbitrap MS was both efficient and highly informative.
It allowed us to pinpoint developmental proteomic changes in mossy fiber boutons that would have been very difficult to capture otherwise."
Hwai-Jong Cheng, MD, PhD, Professor
Institute of Molecular Biology, Academia Sinica, Taiwan
FFPE workflow
Extract meaningful proteomic insights from FFPE tissue, including archived clinical samples with our deep protein profiling workflow. Starting with streamlined protein preparation, the workflow enables mass spectrometry-based identification of thousands of proteins while preserving tissue context. FFPE proteomics is now practical, scalable, and deeply informative, whether you are working with limited clinical material or looking to complement spatial transcriptomics.
What customers are saying about the FFPE workflow
"We developed and partially automated a plate-based workflow for FFPE proteomics. Our optimized method combines pathology-guided macrodissection, Adaptive Focused Acoustics (AFA) sonication for lysis and decrosslinking, S-Trap digestion and cleanup of peptides, and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Using the Orbitrap Astral with short, 24-minute gradients, the workflow identifies up to 10,000 unique proteins and 11,000 fully localized phosphosites in LUAD FFPE tissue, demonstrating the ability to derive biologically relevant phosphoprotein/peptide results from clinically derived FFPE tumor samples.
Our high-throughput, scalable workflow advances biomarker discovery and proteomic research in archival tissue samples."
Steven A. Carr, PhD, Michael Gillette, MD, PhD and Moe Haines (pictured)
LC-MS/MS method optimization
FFPE workflow developed at the Broad Institute can analyze 60 samples per day, with over 10,000 protein identifications and over 11,000 class I phosphosites from FFPE tissue. (Haines, Satpathy et al 2025).
MASP workflow
Map protein localization across whole tissue sections without the need for dissection with the micro-scaffold assisted spatial proteomics (MASP) workflow. This method uses scaffold-assisted sectioning to preserve spatial integrity while enabling deep proteome coverage using Orbitrap mass spectrometers. MASP is ideal for uncovering protein gradients and distribution patterns, PTM patterns, and region-specific signatures in complex tissues.
Spatial brain maps highlighting regional variation in both protein and phosphoprotein abundance
Developed by the Jun Qu lab at the University at Buffalo, the MASP workflow enables parallel, whole-tissue mapping of more than 10,000 proteins and 30,000 phosphosites.
What customers are saying about Orbitrap Astral MS
"Orbitrap Astral MS powers our invention of spatial phosphoproteomics and spatial proteomics. Its exceptional sensitivity, speed, and dynamic range enable high‑throughput quantification of proteins and phosphosites from trace‑level inputs, making possible, for the first time, whole‑tissue spatial phosphoproteomics performed in parallel with spatial proteomics. Applied to Alzheimer’s disease, this spatial platform revealed tissue‑scale signaling biology that simply wasn’t accessible before."
Jun Qu, PhD, Professor
University of Buffalo, Department of Pharmaceutical Sciences
Director, Pharmaceutical and Proteomic Analysis Core, New York State Center of Excellence in Bioinformatics and Life Sciences (NYS-COE)
Targeted spatial proteomics workflow
For researchers translating spatial discoveries into actionable insights, the Thermo Scientific Stellar MS delivers robust, targeted quantitation across tissue compartments, supporting biomarker verification and method standardization for thousands of targets.
Stellar MS provides the flexibility needed for spatial proteomics studies that require high sensitivity (A), advanced selectivity (B), and simplified method development (C).
Bridging discovery spatial proteomics and translational multiplex mapping for spatial imaging
Connect protein discovery to spatial visualization using mass spectrometry insights to inform spatial imaging system panels, whether you start with deep spatial proteomics or targeted imaging.
To reveal insights into cellular neighborhoods, interactions, and spatial relationships, the Invitrogen EVOS S1000 Spatial Imaging System enables high-resolution visualization of up to 9 markers in a single round, with high confidence and simplicity, and at a fraction of the time.
Learn more about Spatial OMICS
For Research Use Only. Not for use in diagnostic procedures.