Synthetic biology is poised to find answers to some of the world’s most pressing problems, like feeding the planet and developing sustainable manufacturing processes. The synthetic biology stack -- an ecosystem of technologies that will help us build biotechnology solutions one-hundred or even one-thousand fold faster -- is a critical component of our eventual success in meeting these goals.The concept is already well established in the technology world through the tech stack. In synthetic biology, the analogous stack is a combination of technologies that separate parts of huge, complicated systems into categories of layers: the application layer, the Bio CAD/CAM layer, the process execution layer, and the biological reagents layer -- each of which can be further broken down into sub-layers. Companies, organizations, and research labs may specialize in one or two layers of the stack, making their work easier because they can focus on their specific technology without the need to think about how other technologies will support or use theirs.This is the story of how one organization -- the DAMP (Design, Automation, Manufacturing, and Prototyping) Laboratory -- is utilizing the stack to move synthetic biology research forward.The DAMP Lab is a fledgling biofoundry that is taking shape within the new Biological Design Center at Boston University. Its mission is to develop novel biological systems using formal representations of protocols and experiments for the specify-design-build-test cycle -- ultimately producing faster, more scalable, and reproducible research results.Spearheaded by Dr. Douglas Densmore, an associate professor in the Department of Electrical and Computer Engineering, the facility -- housed on the 4th floor of the USD$150 million Rajen Kilachand Center for Integrated Life Sciences and Engineering -- is uniquely software-focused, and plans to integrate high-throughput robotics with software for biological design and experimental planning. This approach is designed to meet the growing demand for standards and scalability across both academia and industry in the field of synthetic biology.

The Rajen Kilachand Center for Integrated Life Sciences & Engineering is named in honor of Rajen Kilachand, a visionary Boston University alumnus and trustee.

“The DAMP lab relies on the separation of distinct technical areas which form a coherent top-down workflow. This begins with a design layer where software will be used to create designs from modular DNA elements. This then is transferred to a planning layer which takes this design along with other designs and holistically plans how these can be physically assembled. The following layer decomposes these plans into laboratory specific protocols. The execution layer distributes these protocols to laboratory hardware like liquid handling robotics. Finally, this is all supported by laboratory reagents, labware, and other consumables”, says Prof. Dr. Douglas Densmore, Principal Investigator at the DAMP Lab.

A LIMS-based process facilitates protocol execution

So how does the DAMP Lab do it? The entire process is based on an open-source LIMS system (Aquarium, developed by Eric Klavins’ lab at the University of Washington), which serves as a general framework for organizing protocols, jobs, and inventory. Today, the DAMP Lab offers about 30 synthetic biology protocols (such as cloning, transformation, sequencing, and DNA purification, among others) as a fee-for-service to the scientific community. Users specify an experimental plan remotely, either through the DAMP Lab web interface or using some external planning software that can interact with the LIMS API. Researchers can also introduce information about their samples, and as soon as the technicians at the DAMP Lab receive the physical samples, they store and document their location in the lab using the information provided by the LIMS system.The protocols are specified and designed to capture all necessary steps to execute the protocol successfully by any technician working in the lab, for any allowed input. The jobs are queued manually by a Lab Manager who decides, based on the time to execute a protocol and available resources, the order of the experiments that makes the most sense. Researchers have real-time access to experiment updates, results, and costs.Real-time data collection (sample quality and concentration, bacterial transformation efficiency, etc.) is one of the most important functionalities of the DAMP Lab’s LIMS system. The DAMP Lab uses these data to continuously improve their protocols and pipeline.

The DAMP Lab Process. Picture courtesy of Nick Emery.

Creating a complete synbio stack

The ability to integrate the LIMS system with several other tools is allowing the DAMP Lab team to build a complete synthetic biology stack containing layers with bioCAD tools, LIMS, Hardware, and Experimental Biology. To achieve this goal, the team has been working to connect software tools they’ve developed, like Puppeteer and Cello, to the LIMS software. They have also been working together with Opentrons to integrate the new OT-2 (small scale liquid handlers) into the LIMS software to increase throughput while maintaining consistency. The decision to execute a plan manually or via automation might come from the number of jobs available, the resources available, and the feasibility to automate a determined protocol using the available hardware. This will allow for more standardized and reproducible research results that can be transferred faster from academia to society.

Building a collaborative synthetic biology community

Building a functioning stack is a lot easier when organizations providing different stack layers work together. The DAMP Lab is focused on making synthetic biology protocols and tools available to the broader community to facilitate faster, better, research. It is a member of the Global Biofoundry Alliance, led by Profs. Paul Freemont and Richard Kitney among others, which aims to improve the efficiency of biological experimentation by creating shared resources, including libraries of genetic components that are tested and standardized, software, and standardized experimental protocols between Biofoundries around the world, for accelerated biological engineering and fundamental research. Labs can also purchase their own OT-2 and, in the near future, download the open-source software the DAMP Lab has been developing -- and, for under $10,000, have their own automated synbio foundry.

A critical component of the DAMP Lab automation station is the Opentrons robot. Photo credit: DAMP Lab.

https://vimeo.com/303374891In October 2018, the DAMP Lab hosted the 1st IWBMA (International Workshop in Bio-Manufacturing Automation), focused on the manufacturing aspect of synthetic biology automation. It gathered key members of the scientific community, both from academia and industry, as well as commercial partners. An important outcome of this event will be the creation of a Biomanufacturing Consortium to continue to promote collaboration and partnerships to advance this field.In a landscape where a number of cloud-based, automated synthetic biology laboratories are emerging, the DAMP Lab is a unique academic-located environment where in-house software tools being developed to rapidly generate a large number of designs that implement desired functionality can be tested and integrated to the pipeline.