Proteomics researchers have long faced a fundamental problem: how to accurately profile the molecular makeup of tiny or complex regions within cells and tissues without contamination or loss of resolution.
Traditional approaches, such as proximity labeling or laser capture microdissection, have advanced the field, but each comes with trade-offs in sample compatibility, resolution, and scope.
At ASMS 2025, Nikhil Rao, Chief Commercial Officer (CCO) of Syncell, introduced Microscoop Mint. This platform combines microscopy-guided photo-biotinylation with high-resolution targeting to isolate and analyze proteins from precisely defined cellular or subcellular regions.
“We can go back to a 10-year-old human brain sample and precisely capture proteins from a single organelle,” says Rao. “That’s simply not possible with proximity labeling or laser capture.”
He likens the precision to focusing on "just the ham in a sandwich".
This capability underscores Microscoop Mint’s role in unlocking new possibilities for retrospective studies and rare sample analysis, where preserving and extracting spatially precise proteomic data is critical.
“It’s a very multidisciplinary system,” Rao adds. “You kind of have to know the sample prep as well as understand proteomics,” highlighting the operational learning curve for adoption and the need for cross-disciplinary collaboration.
Microscopy-Guided Photo-Biotinylation: How It Works
The Microscoop Mint workflow begins with researchers labeling the region of interest, such as mitochondria, with a single antibody or fluorescent marker. The system images the sample and generates a binary mask that identifies the exact locations to be analyzed.
A focused laser then triggers a photo-biotinylation reaction at those regions. Proteins within the targeted zones are tagged with biotin, extracted using streptavidin-based kits, and analyzed by mass spectrometry.
“When this laser shoots at those regions of interest, we have a reagent that sits on the sample. It creates a biotinylation reaction with all the proteins that co-localize with that laser,” Rao explains. “It’s a photo-activated biotinylation, meaning the laser activates a chemical reaction between biotin and the amino acid sequences, and it creates a non-specific binding of biotin to all the proteins within it.”
This approach offers several performance advantages over traditional workflows:
- Resolution: ~350 nm in X/Y, 1.5 μm in Z; orders of magnitude finer than laser microdissection.
- Specificity: Selects only the regions of interest, avoiding surrounding tissue.
- Sensitivity: Higher dynamic range and protein detection rates due to cleaner, more concentrated inputs.
These strengths collectively help researchers push the boundaries of what is possible in proteomic analysis, enabling discoveries that were previously out of reach with conventional methods.
Broad Sample Compatibility
Unlike proximity labeling, which often requires genetic manipulation and is limited to certain model organisms, Microscoop Mint can analyze a wide variety of fixed samples, including:
- Primary cells and established cell lines
- Formalin-fixed, paraffin-embedded (FFPE) tissue samples
- Fresh frozen samples
- Paraformaldehyde (PFA)- or methanol-fixed tissues
- Archival human specimens
Because the biotinylation chemistry is non-specific to protein type, researchers are not constrained by antibody availability beyond the initial targeting step.
This expands the range of potential research questions and simplifies method development. This sample-type agnosticism also enables integration into a broad spectrum of separation science workflows, supporting cross-disciplinary studies from clinical diagnostics to environmental proteomics, and allowing laboratories to unlock insights from existing sample archives without compromising analytical rigor.
Applications Across Biology and Medicine
Microscoop Mint’s versatility has led to applications in:
- Neuroscience: Profiling proteins in ALS plaques, Alzheimer’s tangles, and Parkinson’s Lewy bodies, structures difficult to isolate with other methods.
- Cancer research: Comparing proteomes of metastatic vs. normal cells, and mapping tumor microenvironments.
- Cell biology: Studying organelle interfaces, cell-cell interactions, and biomolecular condensates.
- Drug discovery: Tracking drug-tagged fluorescence through cells and identifying proteins involved in drug trafficking and metabolism.
“We’ve seen tremendous interest from neuroscientists, cancer biologists, and pharmaceutical researchers,” Rao notes. “In many cases, this is the only technology that can give them the specificity they need.”
“It’s been exciting to see how adaptable the workflow is across different research questions,” he adds. “Whether it’s a neurodegenerative disease study or a drug discovery program, the same core process delivers high-quality, high-specificity results.”
Future Directions
While currently validated for proteomics, Syncell is developing an even higher-resolution photo-biotinylation kit capable of tagging proteins with diameters less than 100 nm. This next-generation enhancement reflects the company’s continued focus on expanding the limits of spatial proteomics while accelerating adoption of the current platform for immediate impact.
Conclusion
With its ability to deliver nanometer-scale resolution, accommodate a wide range of sample types, and integrate seamlessly into diverse analytical workflows, Microscoop Mint stands poised to influence the future of separation science. Its unique blend of precision, versatility, and compatibility not only addresses long-standing challenges in proteomics but also opens the door to transformative applications across the broader analytical sciences.