Labor-intensive multistep biological tasks, such as the construction and cloning of DNA molecules, are prime candidates for laboratory automation. Flexible and biology-friendly operation of robotic equipment is key to its successful integration in biological laboratories, and the efforts required to operate a robot must be much smaller than the alternative manual lab work. To achieve these goals, a simple high-level biology-friendly robot programming language is needed. We have developed and experimentally validated such a language: Programming a Robot (PaR-PaR). The syntax and compiler for the language are based on computer science principles and a deep understanding of biological workflows. PaR-PaR allows researchers to use liquid-handling robots effectively, enabling experiments that would not have been considered previously. After minimal training, a biologist can independently write complicated protocols for a robot within an hour. Adoption of PaR-PaR as a standard cross-platform language would enable hand-written or software-generated robotic protocols to be shared across laboratories.
To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Golden Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.
BackgroundSynthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening.ResultsHerein, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform’s capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, and proteogenic and metabolic output analysis.ConclusionsTaken together, we demonstrate the microfluidic platform’s potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13036-016-0024-5) contains supplementary material, which is available to authorized users.
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