Proteins are the primary effectors of biological function and the main targets of therapeutic intervention. However, despite their central role in disease and drug response, system-wide approaches to profile proteins in situ remain underutilized in early-stage drug discovery. While mass spectrometry-based proteomics has evolved rapidly — with advances in instrumentation, data analysis, and chemoproteomics — limitations in sample preparation still constrain its full potential.
Traditional methods often lack the spatial resolution, flexibility, or sample compatibility required to interrogate complex tissue microenvironments or discover novel targets without prior assumptions. These gaps hinder researchers’ ability to dissect disease phenotypes, monitor drug effects at the molecular level, and identify safety liabilities early.
Microscoop® Mint, a high-resolution, imaging-guided sample preparation platform developed by Syncell, is tackling this problem head-on. By enabling unbiased, subcellular proteomic profiling across a wide range of tissues, this technology is helping researchers generate new insights into disease mechanisms, drug activity, and biomarker discovery. At the 2025 ASMS conference, Drug Discovery News spoke with Nikhil Rao, Chief Commercial Officer at Syncell, to learn how this innovation is expanding what’s possible in target identification and validation.
A new way to map proteins
Microscoop Mint is a high-resolution, imaging-guided sample preparation system that allows researchers to isolate and analyze all proteins from precisely defined regions of interest (ROIs) — without requiring prior knowledge of what proteins are present. This makes it especially powerful in drug discovery workflows, where understanding the localized proteome is key to identifying novel therapeutic targets or elucidating drug mechanisms.
Unlike proximity labeling, which typically requires transfection and is often limited to mouse or rat models, Microscoop Mint can be applied to a wide range of human samples, including archival FFPE tissue. And unlike laser capture microdissection, which has limited spatial resolution, Microscoop Mint can isolate structures as small as 350 nm in the x–y plane and 1.5 µm in the z-axis — small enough to target individual organelles.
“We’re essentially scooping up proteins from specific cellular or subcellular regions,” said Rao. “And because we’re guided by microscopy in combination with mass spectrometry, we can do this in a hypothesis-free way. That means discovering protein constituents of organelles, structures, or cell types that were previously inaccessible.”
How it works: Microscopy-guided biotinylation
The system starts with a simple fluorescent marker, often a single antibody, to identify the structure of interest, such as mitochondria, plaques, or nuclear bodies. An image mask is created to define the ROIs, which is then aligned with the physical sample. A laser is used to activate a biotinylation reagent at the ROI, covalently tagging all proteins within that region. These biotin-tagged proteins are later extracted and analyzed via mass spectrometry.
The result is a highly specific proteomic dataset from just the selected substructures. Researchers can obtain proteomic profiles of individual organelles, specific cell types, or even pathological features such as amyloid plaques, with minimal background signal.
The idea behind Microscoop Mint was born from a common frustration. While studying primary cilia as a faculty member at Columbia University, Syncell’s founder Jung-Chi Liao, found himself unable to isolate their proteome. “He had his postdocs trying to cut out one-micron-wide structures with lasers,” Rao recalled. “It didn’t work. So, he started developing a solution for himself. After a decade of work, he realized this wasn’t just his problem — it was a shared bottleneck in the field.”
A tool for the drug discovery toolkit
Microscoop Mint is already being used in neuroscience and oncology applications, with growing relevance for drug discovery.
“One of the biggest themes at this year’s ASMS was using Microscoop Mint for drug target identification,” Rao said. “Scientists are asking: Can we identify a druggable biomarker in a specific subcellular context? Or, if we tag a drug with a fluorescent marker, can we track its movement through the cell and identify the proteins involved in trafficking?”
These insights are particularly valuable in complex tissue environments, such as tumors or neurodegenerative lesions, where conventional sample prep often falls short.
“Researchers studying Alzheimer’s, ALS, and Parkinson’s are some of our earliest adopters,” he noted. “Plaques are notoriously hard to isolate. Laser capture doesn’t work well and proximity labeling isn’t viable. Our method fills a real gap.”
In cancer research, scientists are using Microscoop Mint to compare metastatic versus non-metastatic cells and interrogate the tumor microenvironment at high resolution. These are crucial steps in understanding disease progression and response to therapy.
Compatible, flexible, hypothesis-free
A major strength of Microscoop Mint is its compatibility with various sample types, including fresh, frozen, PFA-fixed, methanol-fixed, and FFPE tissue. This opens up access to a wide range of preclinical and clinical specimens, including rare or archived samples.
“With antibody-based techniques, you have to ask: Does the antibody work on FFPE? Frozen? Human? Mouse? That narrows the scope quickly,” Rao noted. “We sidestep that. Our method is non-specific post-labeling. Once the image is captured and ROIs are defined, we apply light-activated chemistry to tag all proteins in the area — no need for prior assumptions.”
This flexibility opens the door to exploratory, hypothesis-free workflows ideal for target discovery, particularly when working with clinical or archival tissue. “We’re routinely detecting thousands of proteins per individual cell,” he added.
While the current platform is focused on proteomics, Rao suggested that future iterations could support additional omics layers such as metabolomics, lipidomics, and RNA profiling. This could further enhance drug discovery workflows by enabling integrated, spatially resolved multi-omics analyses.
Designed by scientists, for scientists
Microscoop Mint could significantly transform how researchers prepare samples for mass spectrometry, eliminating the need for prior target knowledge, enabling subcellular specificity and expanding access to diverse tissue types. For drug discovery scientists, it opens new possibilities for identifying disease-relevant proteins, understanding drug behavior in tissue, and designing more targeted, effective therapies.
“In the end, what researchers want to know is: What are the protein constituents of this organelle in that cell type, under those conditions,” Rao said. “Microscoop Mint gives them the tools to finally answer that question.”
