Breaking Down Barriers in Multiomic Imaging
An early user of the neofleX MALDI-TOF instrument discusses how the technology adds new capabilities to MSI workflows.
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The next evolution of spatial biology: Multiomic imaging
Spatial biology enables researchers to untangle the complex cellular interactions that determine the formation, structure and function of tissues. The human body is a dynamic ecosystem, and mapping the architecture of tissue significantly enhances our understanding of healthy physiology and disease pathogenesis.
Initially, spatial biology was limited to the analysis of DNA, RNA and proteins. The evolution of mass spectrometry (MS) technologies now means that other constituents of the multiomics cascade can be localized in tissue using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry-based imaging (MSI).
A recent development in the spatial biology arena is Bruker’s neofleXTM MALDI-TOF system. The neofleX is a multiomics MSI system that enables the analysis of proteins, glycans, lipids, peptides and pharmaceuticals within tissue samples.
“I don’t think there is any other existing platform that analyzes RNA, proteins, glycans and lipids – so it’s exciting to expand those barriers,” Rohan Thakur, president of Bruker Daltonics, told Technology Networks. “This system really is the definition of ‘multiomic’.”
Professor Carsten Hopf, head of CeMOS (Center of Mass Spectrometry and Optical Spectroscopy) at Mannheim Technical University, is an early user of the neofleX system.
Hopf’s laboratory currently has two key application areas for the neofleX technology: “We are analyzing tumor microarrays together with pathology partners, making use of the multiple markers that we can see in a single experiment. To do this using other platforms you would need more iterations. We are focusing on the protein capabilities of the neofleX together with the MALDI HiPLEX-immuno-histochemistry (IHC) approach,” he said.
Hopf is also using the neofleX to study neurodegenerative diseases, such as Alzheimer’s, where there is a critical unmet need for effective diagnostics and treatments.
“We are studying animal models of Alzheimer’s disease and will be moving to human tissue soon. We are interested in creating overlays of histology annotations, lipid imaging – a difference maker in Alzheimer’s studies – and protein marker imaging as in MALDI HiPLEX-IHC. Using a real spatial multiomics approach, you get three modalities: classic histology staining, MALDI HiPLEX-IHC and lipid MALDI imaging together,” Hopf added.
“We can then look at pathology lesions in the animal brains and ultimately patient’s brains.”
Small in size, mighty in capability
Many imaging mass spectrometers are large, complex imposing pieces of equipment, which can intimidate researchers that are not accustomed to the technology, ultimately limiting its use. The neofleX is a benchtop instrument, enhancing accessibility to MSI equipment across various types of laboratories.
“The neofleX features all of the capabilities and natural evolution of MSI technology, it’s just smaller,” Thakur said. “We have taken high-performance and put it into a benchtop piece of equipment, which enables increased lab space, more automated features and ease-of-use.”
“Given that the neofleX is a benchtop instrument, we are very pleased with what it can do and the quality it delivers. It’s a unique device,” Hopf emphasized.
The system’s accessibility appeals to researchers like Hopf, whose laboratory is actively working to make MALDI imaging more widely available.
“I believe that MALDI imaging can enhance research for everybody,” Hopf said. “We need to make MALDI imaging more accessible, for example, for people who do not have a post-doc in analytical chemistry.”
“We work with partners in the pharmaceutical industry and clinical research who simply want to visualize multiple molecules of interest and biomarkers in parallel, and to colocalize multiple protein biomarkers with lipids, drugs and transcripts to create a visualization of a wide mix of biomolecules that have either pharma or clinical relevance but who don't want to look at mass spectra. This ‘routine-ification’ of MALDI imaging is driven by the neofleX,” Hopf continued.
“Another focus [for us] is to improve the type of molecules we can see with MALDI imaging on more sophisticated machines. We think this would also be applicable with the neofleX.”
The neofleX is also designed to integrate with SCiLS™ Scope, Bruker’s new MALDI imaging software which enables more insights per pixel, and consumables such as IntelliSlides™ and SCiLS autopilot, helping to streamline tasks such as sample preparation, tracking and analysis. This integration minimizes user input, enabling efficient and automated MSI workflows.
Bruker told Technology Networks that its plan to continue the evolution of this technology will lead to additional analytical features that appeal to the spatial biology community.
