Digital-to-biological converter for on-demand production of biologics

[Note:  This item comes from friend Judi Clark.  DLH]

Digital-to-biological converter for on-demand production of biologics
By Kent S Boles, et al
May 29 2017

Manufacturing processes for biological molecules in the research laboratory have failed to keep pace with the rapid advances in automization and parellelization1, 2, 3. We report the development of a digital-to-biological converter for fully automated, versatile and demand-based production of functional biologics starting from DNA sequence information. Specifically, DNA templates, RNA molecules, proteins and viral particles were produced in an automated fashion from digitally transmitted DNA sequences without human intervention.

The manufacturing industry has continuously evolved new business models. A principal example is distributed manufacturing, which decentralizes the manufacturing process such that a robust supply chain coordinates production of a final product from intermediates manufactured at geographically distant locations1, 2, 3. Distributed manufacturing also refers to on-demand, small-scale production by consumers (close to the intended destination), such as the RepRap initiative for 3D printing of 3D printers4, 5. Rapid progress in synthetic biology and biotechnology methods to synthesize biologics has, however, outpaced development of improved manufacturing technologies.

Approaches that reduce production timelines and simplify manufacturing processes for biological material are needed6. For example, demand-based synthesis of biological materials, including higher-order assemblies such as synthetic chromosomes7, 8 and viral particles9, could accelerate the design–build–test cycle for research. In biomedical applications, emergency responses to disease outbreaks in areas lacking robust infrastructures could be achieved by need-based manufacturing of therapeutics at the site of use10, 11, 12. Reliable, portable manufacturing units could also facilitate the delivery of personalized medicine and vaccines10, 11, 12, 13.

We present a scalable bio-manufacturing unit, called a digital-to-biological converter (DBC), that receives digitally transmitted DNA sequence information and converts it into biopolymers, such as DNA, RNA and proteins, as well as complex entities such as viral particles, without any human intervention (Fig. 1, Supplementary Figs. 1 and 2 and Supplementary Videos 1,2,3,4). The DBC integrates multiple software and instruments through a system controller (Hudson Robotics). This includes Archetype, a proprietary software (Synthetic Genomics, Inc.) that designs an optimized assembly strategy for input DNA sequence and splits it into overlapping oligonucleotides (Supplementary Code); SoftLinks V (Hudson Robotics) for the underlying workcell automation; an oligonucleotide synthesizer operated by Poseidon software (BioAutomation) that initiates the synthesis of oligonucleotides automatically; robotic parts for oligonucleotide post-synthesis processing and accurate liquid handling, orchestrated by SoloSoft software (Hudson Robotics); and an automated thermocycler that functions as a DNA assembly module and production platform for biopolymers synthesis.



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