Skip to main content
TECHNOLOGY

Optical pooled screening:
a powerful tool for early drug discovery.

The missing microscopy-based bridge from phenotype to genotype

 

 

 

Genetic perturbation screens of massive pooled libraries enable systematic analysis of a range of spatially and temporally defined cellular phenotypes, including morphology, subcellular protein and enzyme localization, and live-cell dynamics.

Genetic perturbation screens of massive, pooled libraries enable systematic analysis of a wide range of spatially and temporally defined cellular phenotypes, including morphology, subcellular protein and enzyme localization, and live-cell dynamics.

Link cellular profiles to genomic perturbations at massive scale

20,000

genes

x5

guides per gene

x500

replicates per gene & vector

= 50 million

cells deeply interrogated in less than 1 week to reveal actionable insights

About Bifrost

Large-scale genomic perturbation by CRISPR and high-content cellular profiling are each well-established, but approaches to integrate the two have not been accessible until now. Cell by cell, Bifrost’s optical pooled screening platform matches rich image-based profiling data with thousands of CRISPR perturbations across millions of individual cells. These data enable deep genomic interpretation and integration with other available data, all without breaking the bank.”

– Paul Blainey, PhD
    Scientific Founder.

Genome-scale Functional Genomics to Advance Discovery


1. Screen and analyze massive cell libraries

Our next-generation, high-speed, microscopy-based platform performs genome-wide pooled screens of CRISPR-based perturbation libraries, dramatically expanding the depth and scope of current functional genomics approaches. Cells are interrogated phenotypically with high resolution microscopy using phase contrast and epi-fluorescent methods, followed by in situ sequencing of the guide RNA.

2. Answer complex biological questions

Bifrost’s unique combination of deep single-cell profiling via microscopy, chemistry and compute is 10-100 times faster than other methods. With this platform, scientists can understand how cellular systems and pathways work and interact with the many different genes that influence and regulate their behavior. This rich and enormous data set can be used to:

  • Map disease pathways
  • Identify novel drug targets
  • Validate drug targets
  • Reveal hidden gene functions
  • Identify and explore drug candidate MOA
  • Understand dependency of drug responses on genetic variants
  • Uncover variation in cellular effects of competing drug candidates
  • Explore efficacy of drug combinations
3. Propel discovery pipelines
Results from multiparameter genome-wide optical pooled screens provide actionable, high-quality information to. direct next steps in the discovery process.

Large-scale genomic perturbation by CRISPR and high-content cellular profiling are each well-established, but approaches to integrate the two have not been accessible until now. Cell by cell, Bifrost’s optical pooled screening platform matches rich image-based profiling data with thousands of CRISPR perturbations across millions of individual cells. These data enable deep genomic interpretation and integration with other available data, all without breaking the bank.”

– Paul Blainey, PhD,
   Scientific Founder

Genome-scale Functional Genomics to Advance Discovery

1. Screen and analyze massive cell libraries

Our next-generation, high-speed, microscopy-based platform performs genome-wide pooled screens of CRISPR-based perturbation libraries, dramatically expanding the depth and scope of current functional genomics approaches. Cells are interrogated phenotypically with high resolution microscopy using phase contrast and epi-fluorescent methods, followed by in situ sequencing of the guide RNA.

2. Answer complex biological questions

Our next-generation, high-speed, microscopy-based platform performs genome-wide pooled screens of CRISPR-based perturbation libraries, dramatically expanding the depth and scope of current functional genomics approaches. Cells are interrogated phenotypically with high resolution microscopy using phase contrast and epi-fluorescent methods, followed by in situ sequencing of the guide RNA.

3. Propel discovery pipelines

Our next-generation, high-speed, microscopy-based platform performs genome-wide pooled screens of CRISPR-based perturbation libraries, dramatically expanding the depth and scope of current functional genomics approaches. Cells are interrogated phenotypically with high resolution microscopy using phase contrast and epi-fluorescent methods, followed by in situ sequencing of the guide RNA.

  • 1/16

    Ramezani M et al. A genome-wide atlas of human cell morphology. bioRxiv preprint doi: https://doi.org/10.1101/2023.08.06.552164

  • 2/16

    Carlson RJ et al. A genome-wide optical pooled screen reveals regulators of cellular antiviral responses. Proc Natl Acad Sci U S A. 2023 Apr 18;120(16):e2210623120.

  • 3/16

    Karempudi P et al. Real-time pooled optical screening with single-cell isolation capability. bioRxiv preprint doi: https://doi.org/10.1101/2023.09.21.558600.

  • 4/16

    Walton R et al. Pooled genetic screens with image-based profiling. Mol Syst Biol. 2022 Nov;18(11):e10768.

  • 5/16

    Funk L et al. The phenotypic landscape of essential human genes. Cell. 2022 Nov 23;185(24):4634-4653.e22.

  • 6/16

    Wiktor J et al. RecA finds homologous DNA by reduced dimensionality search. Nature. 2021 Sep;597(7876):426-429.

  • 7/16

    Lawson M, Elf J. Imaging-based screens of pool-synthesized cell libraries. Nat Methods. 2021 Apr;18(4):358-365.

  • 8/16

    Bakshi S et al. Tracking bacterial lineages in complex and dynamic environments with applications for growth control and persistence. Nat Microbiol. 2021 Jun;6(6):783-791.

  • 9/16

    Marklund E et al. DNA surface exploration and operator bypassing during target search. Nature. 2020 Jul;583(7818):858-861.

  • 10/16

    Luro S et al. Isolating live cells after high-throughput, long-term, time-lapse microscopy. Nat Methods. 2020 Jan;17(1):93-100.

  • 11/16

    Camsund D et al. Time-resolved imaging-based CRISPRi screening. Nat Methods. 2020 Jan;17(1):86-92.

  • 12/16

    Lord ND et al. Stochastic antagonism between two proteins governs a bacterial cell fate switch. Science. 2019 Oct 4;366(6461):116-120.

  • 13/16

    Feldman D et al. Optical Pooled Screens in Human Cells. Cell. 2019 Oct 17;179(3):787-799.e17.

  • 14/16

    Lawson MJ, Camsund D, Larsson J, Baltekin Ö, Fange D, Elf J. In situ genotyping of a pooled strain library after characterizing complex phenotypes. Mol Syst Biol. 2017 Oct 17;13(10):947.

  • 15/16

    Potvin-Trottier L, Lord ND, Vinnicombe G, Paulsson J. Synchronous long-term oscillations in a synthetic gene circuit. Nature. 2016 Oct 27;538(7626):514-517.

  • 16/16

    Norman TM, Lord ND, Paulsson J, Losick R. Memory and modularity in cell-fate decision making. Nature. 2013 Nov 28;503(7477):481-486.