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Portfolio Company Spotlight

Rebus Biosystems Brings Spatial Context to Genomics

June 2021 – A holistic understanding of cells in their native tissues is key to unlocking new discoveries in neuroscience, cancer, infectious disease, immunology and developmental biology. Researchers moved a step closer to this crucial understanding when Rebus Biosystems launched its Rebus Esper    spatial omics platform at AGBT 2021.


The Rebus Esper platform rapidly analyzes biological molecules, with subcellular resolution, in and across large tissue sections. Scientists can now see the big picture view of cellular interactions, spatially combined with quantitative single-molecule, single-cell data.


“Single-cell sequencing has reached its limit to resolve biological complexity, the next frontier is spatial,” said Rebus Bio CEO, Paul Sargeant, PhD. “The Rebus Esper puts gene expression, cellular interactions and molecular pathways in their true biological spatial context -- the only way to reveal the nuances of biological heterogeneity and lead to an accurate understanding of biology.”


The technology has far-reaching implications. For example, sequencing can show immune cells have infiltrated a tumor but can’t identify where they are located within the tumor. With spatial analysis, researchers can illuminate how those immune cell locations impact tumor aggressiveness and treatment response.


“This technology is an incredible tool,” said Illumina Ventures partner, Tom Willis, PhD. “By enabling researchers to study cellular and molecular interactions in their native contexts while delivering tens of millions of data points from hundreds of thousands of cells in a matter of days, the Rebus Esper spatial omics platform is ushering in a new era of biology.”

Multiple Innovations in a Single Integrated System

Rebus Biosystems was founded on the strength of its patented Synthetic Aperture Optics (SAO) technology. SAO uses a 20X air objective, with a wide field of view, to capture a series of low-resolution images and reconstruct them into a single high-resolution image equivalent to a 100X oil immersion lens.


As a result, the Rebus Esper produces rapid, ultra-high-resolution analyses of full tissue sections in a fraction of the time it would take with high-resolution microscopy using traditional optics.


“SAO overcomes a fundamental limitation of lens physics, the inherent trade-off between resolution and field of view,” said Sargeant. “The result is an unprecedented combination of resolution, scale and speed in a fully integrated, automated platform.”


The Rebus Esper combines the company’s advanced imaging technology with on-system chemistry, delivered through a finely-tuned fluidics system, and intuitive software for data processing and visualization.  The platform is built for flexibility.


“With the Rebus Esper, we’ve developed a single instrument that will run multiple optimized assays allowing for discovery to translational research and everything in between,” said Sargeant.


The first assay to be released is the Esper    High Fidelity assay, which empowers scientists to detect and quantify individual transcripts in their native locations with high sensitivity and specificity. This approach is based on smFISH, the gold standard for gene expression analysis.


The Rebus Esper makes smFISH, which has been a challenging and labor-intensive technique, plug and play for all researchers. By integrating and automating the process, Rebus Bio has streamlined the workflow to minimize hands-on time to less than an hour and provide truly walk-away operation.


“We’re delivering high fidelity spatial omics, which is so critical for researchers looking to validate and extend their early discovery-focused work,” said Sargeant. “Scientists can now do studies in a matter of days that otherwise might have taken weeks or months.”


Spatial omics has virtually endless applications. All biologists need context to understand what is happening in real life tissues. The Rebus Esper platform is being used to investigate structural changes in liver disease, human brain development dynamics, immune processes associated with cardiovascular disease and cell types linked to neurodegeneration and therapy response.


Researchers are also using this data to create cell atlases across multiple organs to enable further spatial biology explorations.

On Market and Making an Impact

The Rebus Esper was launched in March 2021, and four instruments have been sold to leading academic institutions, including the Karolinska Institutet, UC San Diego and EPFL. The company is on track for 8 to 10 system sales by the end of the year. To meet demand, Rebus Bio is hiring at all levels and has recently added a Vice President of Scientific Affairs to drive collaborations that will expand applications.


A robust roadmap for product extensions is already in the works. The Esper High Fidelity assay menu will be augmented later this year, with increased plex, protein and RNA co-analysis and the ability to analyze formalin-fixed paraffin-embedded (FFPE) samples.


The Esper High Plex assay, also coming in 2021, will enable analysis of more than 400 gene targets in the same experiment. New, complementary hardware will also be introduced, allowing researchers to further increase throughput by parallelizing sample preparation and analysis.


For Sargeant, the most important thing is data. “We’re the first high-resolution spatial omics company to put instruments into customers’ hands, and what we’re seeing is amazing,” he said. “Researchers are unlocking new biological insights they could not even fathom a year ago and they are doing it at a rapid pace. The unrivalled combination of resolution, scale and speed are challenging to achieve with other technology combinations. The Rebus Esper platform is truly delivering on our mission of enabling spatial omics without compromise.”


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