The rapid growth, innovation, and applications stemming from synthetic biology have been making an indelible mark across a multitude of disciplines -- from apparel and agriculture to data storage and economics. The field has become incredibly sophisticated. Our ability to generate massive libraries with unprecedented diversity has facilitated the transfer of entire metabolic pathways from one organism to another while selecting against those that do not benefit the production of target molecules.However, the very diversity that can be so empowering also causes one of the most significant bottlenecks in design-build-test cycles: analyzing the search space to reveal the “best” cell or strain is a complex problem that can significantly slow down production pipelines. Berkeley Lights is a company whose technology has an unprecedented ability to find and recover rare cells that has allowed them to disrupt therapeutic antibody discovery and cell line development by compressing timelines and increasing the quality of results. A powerful combination of single cell manipulation and microfluidics, their optofluidic-based technology enables real-time, non-destructive, and manufacturing-relevant analysis with optimized multiple serial assays across thousands of clonal populations in a single experiment, allowing for the efficient capture of cells with phenotypes of interest.

Elucidating the industry-standard Berkeley Lights workflow

Most of Berkeley Lights’ success has been in biopharmaceuticals; a majority of the top 25 biopharma companies and top contract research organizations (CROs) have adopted its technology. However, this same technology is transferable to a wide range of industries leveraging synthetic biology tools and techniques.The Berkeley Lights workflow is currently the gold standard for cell line development, particularly at AMGEN where the time for antibody discovery has been decreased by four months. The workflow consists of four stages -- Import, Culture, Assay, and Export/Recovery -- that are operated seamlessly together in one, end-to-end automated workflow that can retrieve multiple high-quality clones of interest.

Import, culture, assay, and recover clones of interest in a single, automated experiment. Credit: Berkeley LightsThe import stage utilizes OptoSelect™ chips that use optical tools to move thousands of individual cells in parallel into NanoPen™ reaction chambers that are 100,000 times smaller than a microwell. Inside these chambers, live cells are isolated for on-chip culture and analysis, and these cells can be sorted based on phenotype or fluorescence, for example.

Culturing yeast clones in NanoPen chamber. Credit: Berkeley Lights and AmyrisThe culture stage allows for the precise control and cultivation of cellular environments, including media and gas conditions, to support cell growth. This feeds directly into the assay phase, where working at nanoliter volumes allows Berkeley Lights to take extremely sensitive measurements, test over thousands of clones on a single chip immediately (without the need to wait for cells to reach a specific density to detect desired target molecules), and flow in and out specific components to run multiple assays on the exact same set of cells -- regardless of whether the assays are for cell growth, morphology, or a variety of fluorescence-based protocols.

Assaying secretion of a small biomolecule using fluorescence-based assay across thousands of NanoPens. Credit: Berkeley Lights and Amyris The final step, export and recovery, allows for the selective and clonal picking of high-productivity strains, completing a highly customizable and streamlined workflow powered by its graphical user interface and efficiency in experiments.

Implementing optimized technology specifically for synthetic biology

Although these techniques have been primarily employed by biopharma thus far, Berkeley Lights is also making its impact in the world of pure synthetic biology. "We are excited to have been developing early partnerships in synthetic biology to help transfer these capabilities to applications ranging from food to industrial chemical production," says Troy Lionberger, Associate Director of Technology Development at Berkeley Lights.In particular, there is a promising partnership with Amyris to adapt and transfer this technology to increase throughput and improve predictive quality of strain testing with their yeast library for small molecule development.“Our early partnerships show that Berkeley Lights technology has the potential to push the envelope and accelerate design-build-test cycles across a wide range of synthetic biology applications," says Eric Hobbs, CEO of Berkeley Lights. “We’re constantly working with our customers and are actively seeking partners to help us adapt and extend our technology to support the broad synthetic biology market.”With production timelines dropping due to the workflows of companies like Berkeley Lights coupled with our advances in computer science and biology overall, DNA reading and writing, and more, the future is certainly bright for the field of synthetic biology -- stay tuned to see what exciting developments occur next.Berkeley Lights is a Gold sponsor of SynBioBeta 2019 October 1-3 in San Francisco, CA. Meet Troy Lionberger and Eric Hobbs during a Benchmarking session held Wednesday, October 2, at 1:30pm.