Founded in 2020, Syncell launched its first products at the beginning of last year. The Microscoop Mint and Synlight photolabeling kit and Synpull protein extraction reagents together offer a subcellular solution for spatial proteomics by utilizing laser nano-pulldown (LNP). In 2024, the company closed a $15 million Series A funding, led by Taiwania Capital. The company has raised $30 million in total.

Syncell’s technology is used to prepare samples for analysis by liquid chromatography-mass spectrometry (LC-MS/MS) by photolabeling proteins within the region of interest, complementing techniques such as laser capture microdissection (LCM). “There are use cases that require subcellular resolution that laser capture cannot answer where we can provide value,” said Nikhil Rao, Ph.D., CCO of Syncell. “We’re not actively trying to replace any technologies. We’re more demonstrating the new potential of our method relative to everything else that exists.”

The Microscoop instrument works with fixed cells or tissue samples, including FFPE. Researchers start with a fluorescently labeled sample that is then imaged and converted into a binary mask, segmenting the region of interest. The region of interest can be based on size, shape, location, distance and intensity. A reagent is added to the entire sample and a laser scan triggers protein photo-biotinylation based on thousands of fields of view.

The whole process is automated, and sample contents are then collected and can be pooled. This is followed by extraction, enrichment, purification and digestion into peptides. The digested dried proteins can then be analyzed using specified MS systems from Bruker, SCIEX or Thermo Fisher Scientific. Finnaly, the photo-labeled unlabeled samples are compared.

“You can unbiasedly, with no predetermined markers of interest like antibody-based methods, understand what proteins exist for selected subcellular features or cells”

As Dr. Rao explained, “[The system] takes your sample and does an automated scan across the sample. You’re shooting laser light in the pre-defined regions of interest, which creates a covalent bond, tagging all the proteins.” He added, “Once the biotinylation is completed, the rest of the workflow is off-instrument. We have another reagent kit that allows you to extract those tagged proteins away from the untagged proteins.”

The Microscoop enables measurements at a resolution of 350 nm in x-y plane and 1.5 µm in z-axis, with a precision of sub-cellular scale compared to a few microns of resolution for LCM. It provides an alternative to proximity labeling or antibody-based techniques. “You can unbiasedly, with no predetermined markers of interest like antibody-based methods, understand what proteins exist for selected subcellular features or cells,” noted Dr. Rao.

Neurology is one of the company’s major application areas, as well as other fields such as cell biology. Syncell allows for cell subtyping. In one study, the system was used to characterize the differences of the proteomes between astrocytes in the cortical and hippocampal regions of mice brains. The cells’ proteomics were profiled, enabling the comparison of the two cell types and their roles, contributing to the future discovery of astrocyte markers.

Sample types for which LNP are well-suited include stress granules, cellular structures made up of RNA and proteins that are involved in RNA metabolism and have been linked to carcinogenesis. An application note from Syncell highlights the use of Microscoop to identify 1,754 consistently enriched stress granule proteins.