Building a biofoundry

Abstract

A biofoundry provides automation and analytics infrastructure to support the engineering of biological systems. It allows scientists to perform synthetic biology and aligned experimentation on a high-throughput scale, massively increasing the solution space that can be examined for any given problem or question. However, establishing a biofoundry is a challenging undertaking, with numerous technical and operational considerations that must be addressed. Using collated learnings, here we outline several considerations that should be addressed prior to and during establishment. These include drivers for establishment, institutional models, funding and revenue models, personnel, hardware and software, data management, interoperability, client engagement and biosecurity issues. The high cost of establishment and operation means that developing a long-term business model for biofoundry sustainability in the context of funding frameworks, actual and potential client base, and costing structure is critical. Moreover, since biofoundries are leading a conceptual shift in experimental design for bioengineering, sustained outreach and engagement with the research community are needed to grow the client base. Recognition of the significant, long-term financial investment required and an understanding of the complexities of operationalization is critical for a sustainable biofoundry venture. To ensure state-of-the-art technology is integrated into planning, extensive engagement with existing facilities and community groups, such as the Global Biofoundries Alliance, is recommended.

Keywords: biofoundry; high-throughput; synthetic biology.

Figure 1.

The Design-Build-Learn-Test cycle. Biofoundries typically focus on the BUILD and TEST aspects of the cycle, but this is not a firm rule; a facility might, for example, focus more on LEARN capabilities by developing data analysis and machine learning methods.

Figure 2.

Modular nature of biofoundry services. Services offered by a given biofoundry can be easily grouped into functional modules and clients may be allowed to mix and match modules and/or services to fit their needs better.

Figure 3.

Mapping of a manual workflow onto an automated one. This figure depicts a typical mapping exercise where a DNA assembly and subsequent bacterial transformation is being considered for automation. In the first step, the reagents used in tubes are mapped to a microplate layout. Next, instead of manual pipetting automated dispensing is implemented. For the small volumes of a PCR reaction or DNA assembly, an acoustic liquid handler would be good choice. Next, a thermal cycler with 96-well or 384-well plate format is required. For workflows that include DNA amplification by PCR, a quality control step to assess amplified fragments is included. In low-throughput, manual methods this would be done using standard gel electrophoresis. In an automated setup, this can be done in an automated DNA analyzer in 96-well format. Next, the heat shock reaction is be setup and executed using pipettes in manual workflow, whereas this can be executed by an automated liquid handler. Finally, after transformation and overnight growth colonies are picked—using your tool of choice out of a petri dish or using an automated colony picker in the automated alternative.

Figure 4.

The biofoundry funnel. This diagram outlines how different elements discussed in this guide interact with each other. They have been listed in the two central columns, reflecting early- (left) and mid- to late-stage (right) activities, noting that there is often need to parallelize and prioritize different parts of the funnel to match the developing situation.