Bifrost Biosystems launches with novel optical pooled screening technology to power efficient discovery

Bifrost Biosystems announced its launch with a vision to power efficient drug discovery through its novel automated Optical Pooled Screening (OPS) platform. The Bifrost OPS platform uniquely integrates rich, image-based, single-cell profiling data with genome-wide CRISPR perturbations. Through advanced software analysis and machine learning/artificial intelligence algorithms, the platform provides actionable, high-quality information to direct next steps in the discovery process.

“Drug development is a time-intensive and costly endeavor, and failures can be financially devastating,” said Shawn Marcell, Bifrost co-founder and Executive Chairman. “Bifrost’s cutting-edge technology aims to mitigate these challenges by providing drug developers with significantly more high-quality information in the early stages of drug discovery. By quickly and efficiently identifying drug targets and providing meaningful understanding of gene-drug and gene-gene interactions and networks, our ambition is to provide a tool that not only helps reduce costs but accelerates the delivery of critical new therapies to patients.”

About Optical Pooled Screening

Bifrost’s advanced OPS platform revolutionizes functional genomics through high-speed, microscopy-based pooled single-cell screens of CRISPR-based perturbations. This cutting-edge technology employs high-resolution microscopy, utilizing phase contrast and epi-fluorescent methods, along with in situ sequencing of guide RNA to comprehensively analyze massive cell libraries. Bifrost’s approach, 10-100 times faster than alternative arrayed methods, enables deep single-cell profiling to answer complex biological questions about cellular systems and pathways. The resulting extensive dataset facilitates understanding of complex biological processes, target identification and validation – actionable insights that accelerate discovery pipelines in biological research.

Optical Pooled Genetic Screens

(A) In pooled screens, a library of genetic perturbations is introduced, typically at a single copy per target cell. In existing approaches, cellular phenotypes are evaluated by bulk NGS of enriched cell populations or single-cell molecular profiling (e.g., single-cell RNA-seq). In optical pooled screens, high-content imaging assays are used to extract rich spatiotemporal information from the sample prior to enzymatic amplification and in situ detection of RNA barcodes, enabling linkage between the phenotype and perturbation genotype of each cell. (B) Targeted in situ sequencing is used to read out RNA barcodes expressed from a single genomic integration. Barcode transcripts are fixed in place, reverse transcribed, and hybridized with single-stranded DNA padlock probes, which bind to common sequences flanking the barcode. The 3′ arm of the padlock is extended and ligated, copying the barcode into a circularized ssDNA molecule, which then undergoes rolling circle amplification. The barcode sequence is then read out by multiple rounds of in situ sequencing-by-synthesis

“We are delivering a tool to produce powerful insights with vast therapeutic implications,” Johan Paulsson, PhD, Bifrost co-founder and Professor of Systems Biology. “The platform facilitates deep analysis of a broad range of cell types from bacteria to human cells, with use cases from personalized medicine to combating the global threat of antibiotic resistance.”

Feldman D, Singh A, Schmid-Burgk JL, Carlson RJ, Mezger A, Garrity AJ, Zhang F, Blainey PC. (2019) Optical Pooled Screens in Human Cells. Cell 179(3):787-799.e17. [article]

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