NEW YORK – Backed by $15 million in Series A funding, Taiwanese life science firm Syncell is looking to drive commercialization of its spatial proteomics platform.
Called Microscoop, the company's technology lets users extract proteins from specific cellular regions of interest and measure them via methods like mass spectrometry, an approach that enables untargeted spatial proteomic analyses.
Spatial proteomics has drawn significant commercial and research interest in recent years. A number of firms, including Akoya Biosciences, Standard BioTools, Bruker, Ionpath, and 10x Genomics have brought spatial proteomics tools to market. This month, the journal Nature Methods also named spatial proteomics its "method of the year" for 2024.
Most spatial proteomics methods are antibody-based, meaning researchers "have to know what they are looking for," said Nikhil Rao, senior VP of commercial for Syncell. The company's Microscoop technology, on the other hand, extracts all the proteins present in a particular subcellular region, allowing researchers to perform unbiased spatial proteomics experiments.
At the beginning of the workflow, researchers identify a cellular region of interest, either by tagging a molecular marker of that region via immunofluorescence or by identifying an anatomical marker located in that region. The Microscoop platform then images the tagged sample and creates an image mask defining the specific region to be targeted for protein extraction.
Users then apply to the sample what Syncell calls its Synlight Rich kit, which consists of a photobiotinylation reagent that binds to proteins when exposed to light. Following application of this reagent, the platform uses a laser to expose the region of interest defined by the image mask to light, binding the photobiotinylation reagent to the proteins in this portion of the sample. Those proteins can then be extracted using a streptavidin-biotin pull-down workflow and analyzed by mass spectrometry or another protein measurement technology.
Rao said the laser used in the instrument allows researchers to select regions with subcellular resolution — down to around 250 nanometers. The company's imaging software lets users choose regions of interest with high specificity and flexibility, he added.
The approach is somewhat similar to the deep visual proteomics method developed by researchers at the University of Copenhagen and the Max Planck Institute of Biochemistry, which uses AI-based image analysis to identify cells and regions of interest. These regions are then isolated via laser capture microdissection (LCM) for proteomic profiling using mass spec.
Initially, Syncell sees two main groups of customers for the platform, Rao said — researchers currently using mass spectrometry for LCM and proximity labeling experiments and researchers doing antibody-based spatial proteomics who might be interested in exploring an untargeted spatial approach.
He considers the first group as "lower hanging fruit," as these researchers are typically comfortable with mass spec-based proteomics. "They already do a lot of mass spec, and it's a bit of a more mature customer base," he said.
Among researchers using LCM, "there is a lot of interest to get down to the cellular or subcellular level," he said, but at that level, the amount of protein material available for analysis becomes limiting.
The Microscoop platform allows researchers to tag and select identical regions of interest across multiple cells, which can be pooled to provide a sufficiently large sample.
"We're surveying all the anatomically interesting and similar features and pooling it all to run on the mass spec," he said. "And because we have such high resolution, your specificity [for the region of interest] is super high. If you're interested in a receptor, for instance, you're not also getting cytoplasm."
This approach allows researcher to address questions such as "the proteome of organelle X within cell type Y," Rao added.
Overall, Syncell sees its technology as bridging the distance between traditional mass spec-based proteomics and more recently developed spatial approaches, he said.
Wilfried Rossoll, associate professor of neuroscience and director of the new multiomics mass spectrometry core facility at the Mayo Clinic in Florida, has been using the system to analyze the proteome of phosphorylated TDP-43 aggregates in human brain samples, which are characteristic of neurodegenerative conditions including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
He initially began working with the Microscoop platform in 2022, when his lab’s proposal was selected as a winner of Syncell's Microscoop Spatial Proteomics Grant Opportunity Award, along with that of Bruno Silva-Santos at the University of Lisbon's Institute of Molecular Medicine. Each winner received $50,000 in sample-to-results services from Syncell. Rossoll said that based on the data generated through this program, his core facility purchased the system.
In his experience, the Microscoop platform provides higher resolution and greater control over the region being sampled than approaches like LCM, he said..
This advantage is particularly critical for studying protein aggregates that are the hallmarks of many neurodegenerative diseases, he added, which are often not amenable to biochemical isolation because they are highly insoluble.
Rossoll said the method's untargeted nature could help address questions that are difficult to tackle with affinity-based spatial proteomics. "Currently, spatial proteomics is often just glorified multiplexed immunohistochemistry," he said.
"I think what is very exciting [about the Microscoop platform] is that it offers the ability for true unbiased discovery, which can then be the basis for following up with antibodies or other methods," he added.
Syncell recently signed a memorandum of understanding with Thermo Fisher Scientific for the use of its workflow with the company's Orbitrap Astral instrument, Rao said, noting that the vendor "has shown some interest" in applying that instrument to spatial biology. He added that Syncell "is open" to similar relationships with other vendors.
Among mass spec firms, Bruker has been perhaps the most active in assembling a spatial biology portfolio, acquiring companies including Canopy Biosciences and NanoString Technologies and partnering with AmberGen on affinity reagents for mass spec-based spatial biology workflows.
Rao said Syncell expects it will take the company more time to develop the market for its platform among groups focused on targeted, affinity-based spatial proteomics.
"I think it's going to take some time for them to kind of understand mass spec because a lot of them have been doing NGS-based readouts or imaging-based readouts," he said. "But they do have this desire for proteome discovery, and there's not really a discovery solution for spatial proteomics. That's what we're bringing."
Syncell launched the Microscoop platform in 2023, which is currently available in the US, Europe, and Asia. Rao declined to disclose how many instruments the company has placed so far but said it has had sales in each of those three regions.