Rebus Biosystems Inc. has closed a $20 million series B fundraising round. The financing round was led by Illumina Ventures with participation by Lifecore Partners, Ncore Ventures, Xolon Invest, Ctk Investments, Ray Co. Ltd., Seegene Medical Foundation, Labgenomics Co. Ltd. and Timefolio Asset Management. Rebus builds spatial omics tools, assays and platforms.

The company plans to use the new funding to support commercialization of its spatial omics solution and expansion of its marketing, sales, research, and product development teams, said Rebus CEO Paul Sargeant. Rebus plans to launch its automated, standalone Rebus Biosystems instrument and optimized assay kits for spatial transcriptomics early in 2021.

Rebus is in the midst of officially changing its name from Optical Biosystems Inc. The company chose the new name as a reflection of its technology’s ability to enable “researchers to create ‘big picture’ meaning out of images and data collected by our technology. Sequencing represents data with letters; we use pictures,” Sargeant told BioWorld.

By combining molecular analysis with spatial information, spatial omics enables researchers to study cellular subpopulations and microenvironmental signatures as they relate to neighboring cells and the extracellular matrix surrounding them. Seeing individual cells in their native environment reveals changes in cellular geometry such as position, density, and distribution that might otherwise go unnoticed. Within cells, spatial omics illuminates the relationships between position, environment, and expression levels of different components.

“If you look at how [next generation sequencing] has revolutionized biology and medicine, we think spatial omics is going to do something similar, just on a larger scale,” Sargeant told BioWorld. “It will take our understanding of almost every area of biology to the next level. From neuroscience to oncology to infectious disease, understanding cells in their spatial context is critical to understanding both health and disease. By understanding the function of cells in context, we’ll be able to develop more targeted medicines and understand which medicines are best for which patients.”

Seeing the context

Rebus has built its business largely around its patented Synthetic Aperture Optics (SAO) system. The system offers the resolution and sensitivity of a 100x oil lens with the larger area and greater depth available with a 20x air lens. Typically, a tradeoff is required – the 100x lens has greater magnification of a small field, though with some distortion from the difference in the refractive index between the lens and air. An oil lens eliminates the refractive difference and provides a very crisp image of a small area. The 20x lens enables examination of a larger field, but with much less detail.

Rebus’ SAO illuminates a sample with a series of high-resolution patterns created by the interference of excitation laser beams, Sargeant explained. Proprietary algorithms then assemble a series of low-resolution images to generate a single high-resolution image. The image processing algorithms use computer vision to detect nuclei, segment cells and assign cellular features, resulting in a spatially annotated matrix that researchers can use for further analysis.

That’s fundamentally different from the process used by others in the spatial omics field. “Several other solutions for spatial omics analysis rely on removing biological molecules from fairly large spots in a sample, analyzing it on a sequencer and then mapping back to the tissue,” Sargeant said. “We think that’s a great approach when you’re in discovery mode and trying to get a broad sense of, for example, gene expression patterns across a tissue.”

That process lacks the sensitivity, resolution and speed of Rebus’ SAO, which claims to capture data 100 times faster than imaging-based spatial omics methods which use 100x lenses and z-stacking. Z-stacking, or focus stacking, builds a composite image from multiple images taken at various focal distances. By removing the sample from its environment, researchers lose – or have a much-narrowed view of – the native context.

“Our solution enables researchers to literally see biology, and it does so on a massive scale across tissue sections so that quantitative insights can be gleaned,” added Sargeant.

Rebus is offering early access to the first application the company has developed for the platform through its Spatial Omics as a Service program. The current application focuses on spatial transcriptomics and is already used by academic laboratories and pharmaceutical companies.

"The Rebus Biosystems platform offers a unique solution that combines a fully automated microfluidics setup for sequential labelling of expressed transcripts with sensitive and scalable high-resolution imaging," said Tomasz Nowakowski, assistant professor of anatomy at the University of California-San Francisco, investigator at the Chan-Zuckerberg Biohub, and member of the Allen Institute for Brain Science Next Generation Leaders Council. "Researchers in my lab and several of my colleagues are working with Rebus Biosystems because their technology is unique in enabling them to visualize gene expression profiles across large areas of human brain tissue sections at remarkable speed and without compromising data quality."

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