How Berkeley Lights Enables Synthetic Biology

The human body is such an incredibly complex system that in order to truly understand it, we’ll need to emulate it by creating a digital twin. Last summer, we met with a Hungarian startup called Turbine that’s building digital cells that are so accurate they can mimic wet lab experiments. The next step is to emulate the estimated 10 quadrillion cells found in the human body. In order to perform that task, we need the ability to control cells at an individual level. One company called Berkeley Lights is working to dramatically advance how scientists study the interaction of cells by using light to sort cells into tiny little chambers.

About Berkeley Lights

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Founded in 2011, San Francisco startup Berkeley Lights has raised $191.5 million in funding so far from names like Sequoia, Nikon, and Varian Medical Systems (VAR). Their flagship technology is a combination of optics and nanofluidics called optofluidics. In short, they use light and semiconductor technology to corral cells into tiny chambers, working with thousands of cells in parallel. Called NanoPens, these chambers are 100,000 times smaller in volume than a traditional microwell, meaning a single cell can be isolated and assayed in its own discrete chamber. These NanoPens are all housed within a line of chips called OptoSelect which present various configurations depending on your needs.

An OptoSelect chip containing NanoPen chambers for sorting cells
An OptoSelect chip containing NanoPen chambers for sorting cells – Credit: Berkeley Lights

These chips are the foundation of the company’s flagship product, the Beacon optofluidic platform.

The Beacon Optofluidic Platform

While the form factor of the Beacon is a nearly six-foot-tall machine that weighs around 1,200 lbs, the breadth of functionality encompassed allows scientists to replace an entire roomful of equipment. Equally impressive are the software workflows that automatically identify single cells and direct them into NanoPens in less than 30 minutes.

The Beacon optofluidics platform
The Beacon optofluidics platform – Credit: Berkeley Lights

While the Beacon may not be cheap (we weren’t able to come across a price tag), it costs a fraction of what it would take to outfit a laboratory that’s capable of manipulating cells the old way. It also lets you do things a whole lot quicker. For example, discovering an antibody is a process that would typically take about three months. Using the Beacon, that same process takes just a single day, something that Pfizer talked about in a two-pager they published late last year.

Traditional methods of antibody discovery, including hybridoma, phage display, and EBV-transformed clones, are often labor-intensive, require months of work, and have inherent inefficiencies. The Beacon platform’s one-day antibody discovery workflow enables scientists to bypass these traditional methods by directly screening primary ASCs.

Credit: Pfizer paper titled ” Rapid Antibody Discovery on the Beacon® Platform”

Instead of the typical 5-7 week antibody-discovery process Pfizer has used historically, they’re now able to accomplish the same thing in a single day.

It’s not just about speed and cost but insights. The Beacon platform measures all kinds of data points.

What the Beacon platform measures – Credit: Berkeley Lights

Being able to measure these attributes is appealing to biopharmaceutical companies like Sanofi, Novo Nordisk, Samsung Biologics, and Takeda that have purchased the Beacon platform to accelerate their cell line development (CLD) processes. In laboratories around the globe, scientists are working to develop “stable cell lines” that are able to reproduce over multiple generations while maintaining the same genetic characteristics. The Beacon platform allows researchers to set up a cell line development workflow using a simple touchscreen.

Setup of a cell line development workflow using a simple touchscreen
Setup of a cell line development workflow using a simple touchscreen – Credit: Berkeley Lights

What used to be an error-prone manual process that took up to two months is now fully automated and takes just five days. Berkeley Lights has also produced a desktop version of the beacon called the Lightning optofluidic platform which lets you manipulate live cells in a similar manner.

Berkeley Lights and Ginkgo Bioworks

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The last time we came across Berkeley Lights was in an article we published titled “Most Funded Synthetic Biology Companies in 2018.” While optofluidics technology can be used for a broad number of uses cases, we’re most excited about the impact it can have on synthetic biology applications that depend on selecting from hundreds of thousands of cells to find the right cell or clone. What used to require intensive, expensive, manual manipulation is now fully automated.

For proof of how disruptive optofluidics technology is, look no further than synthetic biology’s first unicorn, Ginkgo Bioworks, which now commands a valuation of $4.2 billion having taken in $719 million in funding. Ginkgo’s latest round of $290 million – the largest yet – closed in September of last year. The following month, Ginkgo Bioworks and Berkeley Lights announced a $150 million collaboration.

Cells are programmable similar to computers because they run on digital code in the form of DNA. We believe Ginkgo has the best compiler and debugger for writing genetic code and we use it to program cells for customers in a range of industries.

Jason Kelly, CEO and co-founder of Ginkgo Bioworks.

Cells are little machines that operate based on directions provided by DNA strings. We can read the strings using machines from Illumina, and we can use gene-editing technologies like CRISPR to re-write the instructions. The final step is to write the new strings of edited DNA and use them to turn cells into little machines that do useful things. What Ginkgo has created is a factory for producing organisms in an automated fashion. They recently announced a $350 million fund to invest in all companies that are being created using their platform. The nanobots are finally here, and all these organisms being created are using the most efficient means of manufacturing known to mankind – biology. What Ginkgo Bioworks is doing could lead us to a world where we stop manufacturing everything and grow everything.

Biology is the most advanced manufacturing technology on the planet. Self-assembling, self-replicating, and self-repairing, biology builds renewably—from the molecular machines inside of cells to global ecosystems.

Credit: Ginkgo Bioworks

In an interview with Bloomberg, CEO of Ginkgo Bioworks, Jason Kelly, talked about how for the past five years the company has been roughly tripling output and halving costs every year. By using Berkeley Lights technology, Ginkgo’s capacity to measure the performance of cells is expected to more than triple, increasing the speed and efficiency at which they can deliver new organisms to customers. Additionally, the collaboration will bring new development workflows for organisms including yeast, and bacterial and fungal cells that will allow the technology platform to be used for a wider range of synthetic biology applications.

Conclusion

Saint Steve Jobs once said that “the biggest innovations of the twenty-first century will be at the intersection of biology and technology.” Berkeley Lights describes what they do as “digital cell biology,” an appropriate name that describes the marriage of computing technology and biology. One of the world’s largest and most exciting synthetic biology companies expects to triple output as a result of using optofluidics technology. The technology Berkeley Lights has developed is not a nice-to-have, it’s a must-have for any company that wants to work with individual cells quickly, and at scale.

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