An open-source advanced maskless synthesizer for light-directed chemical synthesis of large nucleic acid libraries and microarrays

22 February 2024, Version 1

Abstract

Large- to ultra-large-scale synthesis of nucleic acids is becoming an increasingly important tool for understanding and manipulating biological systems, as well as for developing new technologies based on engineered biological materials, including DNA-based nanofabrication, aptamers and writing digital data at the molecular level. Several technologies for large-scale synthesis have been developed over the years, but all of them remain inaccessible to most researchers due to their complexity and/or use of proprietary technologies. Here, we present a fully open source, benchtop device for ultra-large scale nucleic acid synthesis that is also highly flexible and adaptable, able to accommodate a wide range of monomers and chemistries, while providing unrestricted access to synthesis parameter space.

Keywords

Nucleic acid chemistry
DNA
RNA
Photochemistry
Microarray
Phosphoramidite chemistry
Oligonucleotides
maskless array synthesis
Digital micromirror device

Supplementary materials

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Mechanical drawings MAS 2.0
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Mechanical drawings of all of the components of the MAS 2.0 in pdf format (82 files)
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Optical drawings MAS 2.0
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Optical drawings for MAS 2.0 in pdf format (6 files)
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Step files of all the mechanical components of the MAS 2.0 (86 files))
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CAD files of all the mechanical components of the MAS 2.0 in step format (.stp). Includes assembly tools. 87 files.
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STL files for components of the MAS 2.0 to be 3D printed (3 files)
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STL files for components to be 3D printed
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Component list spreadsheet MAS 2.0
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Spreadsheet with a list components for MAS 2.0. Tab 1. Machined metal components (including cost estimate) Tab 2. Plastic 3D components Tab 3. List of fasteners and other hardware parts
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MAS 2.0 Photolithographic Synthesis of Nucleic Acids Process and Reference Manual
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A detailed manual on the use of MAS 2.0 for the large-scale synthesis of nucleic acids. Incudes background material on the chemistry and photochemistry as well as usage instructions, procedures and protocols for nucleic acid synthesis and post-processing. Also includes list of reagents, solvents and other materials (electronics, optics, optomechanics, fluidics, and their commercial sources. Includes information on fluidics protocols and software usage instructions. References to relevant background publications in the scientific literature are also included.
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CAD files for MAS 2.0 assembly
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Fusion 360 archive file of MAS 2.0 assembly Step file of MAS 2.0 assembly exported from Fusion 360
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Python software for MAS 2.0
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Software for running the MAS 2.0 device with either a XGA or 1080p DLP modules (current hardware versions, as well as DLLs from Vialux). The software is also configured for use with a LabJack U12 DAQ, an Expedite 8909 nucleic acid synthesizer, and with temperature and humidity logging with a W&T Web-Thermo-Hygrometer. User interface instruction are provided in the MAS 2.0 Photolithographic Synthesis of Nucleic Acids Process and Reference Manual.
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Supplementary weblinks

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