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In some experiments, scientists simply seek the unknown. That can involve exploring samples, even single cells, without hypothetical questions in mind. Some of the most exciting scientific discoveries come from the unexpected.

Omics continually offers new insights into the function of organisms, but tracking the processes in space creates many challenges. With most analytical approaches, it’s impossible to gather spatial and molecular information cell by cell in an exploratory way, but new technological advances promise amazing new opportunities.

“In pure discovery, scientists cast a wide net and see what they get,” says Tarif Awad, PhD, VP for Scientific Affairs at Rebus Biosystems in Santa Clara, CA.

During the past two decades, scientists made countless gene expression discoveries with microarrays, and more recently, with single-cell RNA sequencing. “These techniques produce lots of gene expression information,” Tarif explains, “but you don’t know the locations of the cells within the tissues being analyzed.” He adds that these discovery methods also require “thinking ahead about the next experiments necessary to validate results, prepare for future research, and test new hypotheses.”

The Rebus Esper is already being used in hypothesis-driven research. Here, “scientists must be confident that measurements are precise and quantitative,” Tarif explains. “Our Esper instrument provides that precision.” He adds, “We’ve put a lot of scientific rigor into building those assays and optimizing protocols to make sure we quantify and visualize gene activity as accurately as possible.” Consequently, this platform can be used for
validating discoveries, testing hypotheses, and conducting translational research. “We are adapting our assay to FFPE samples to support translational oncology and other disease areas.”

With the Rebus Esper, scientists can gather high-resolution imaging data that include quantitative single-cell analysis and spatial mapping. The platform generates large datasets across wide fields of view, with precise cell locations and currently 30 transcripts. Soon, the platform will allow discovery with no preconceived expectations or previous information— “you will be able to cast a wider net,” says Tarif.

Hunting with no hypothesis

To expand the platform’s applications, Tarif says, “We are developing novel chemistries for discovery with higher multiplexing to hundreds of transcripts.” That will make the Esper applicable to multiple stages of research.

Instead of using different technologies from one stage of research to another, sticking with one automated platform provides consistency and reproducibility. As Tarif describes it, “We’ve created one instrument that supports multiple chemistries for different stages of biological research.” Those additional capabilities are “in development now,” Tarif says.

The Esper also enables basic research across a wide variety of model organisms. Tarif aims to pursue projects in zebra fish, Drosophila, C. elegans, and plants, demonstrating applications to many experimental scenarios, including “studying development by looking across embryonic stages,” Tarif says. “Esper’s large imageable area allows placing multiple stages on the same slide.”

A fascinating new home

After 20 years of experience in genomics and bioinformatics, Tarif came to Rebus to join what he calls “the spatial omics revolution.” He describes this experience “like coming home—I’ve made a full circle back to my roots, cell biology and microscopy.” But it’s a new home in more ways than one.

“Seeing transcriptomics visualized in the context of cells and tissues is incredibly powerful,” Tarif says. “The first time I saw a sample analyzed with this platform, I got goosebumps.”

In addition to adding new information, spatial omics is art. “Biology is such a beautiful science,” Tarif says. “Biological images at any scale can be so incredibly beautiful, but multiplexing and visualizing molecules in the context of tissues is also extremely useful; the data are so rich and informative—I will undoubtedly focus on this technology and its applications for the rest of my career.” He adds, “That’s how sophisticated and exciting this technology is.”

 

For more information on the Rebus Esper and applications in ​spatial omics, visit: www.rebusbio.com