DNA Strand Displacement-Driven Molecular Additive Manufacturing

Atomically precise manufacturing (APM) is a potential disruptive tech- nology that could have a major impact Schematic depiction of a two-dimensional (2D) printer utilizing the ‘slider’ – ‘rail’ on a variety of emerging energy and – ‘canvas’ “stack’ architecture made from self-assembled DNA origami. This manufacturing issues. APM is the project will develop the ability to spatially position and activate multiple printheads production of materials, structures, simultaneously. Graphic courtesy of the Dana-Farber Cancer Institute. devices, and finished goods in a manner such that every atom is at of atoms and molecules with atomic Benefits for Our Industry and its specified location relative to the precision to create atomically precise Our Nation other atoms, and in which there are products. Successful self-assembly of molecular no defects, missing atoms, extra This project will develop a 2D molecular to atomic-level specifications atoms, or incorrect (impurity) atoms. printer using self-assembled ‘DNA shows great promise to deliver new APM with molecular systems origami,’ which relies on folding long material functionalities and ultra-high is in its very early development stage; strands of DNA, aided by shorter performance. APM can potentially enable tools and processes that may dramatically there are no existing productive ‘staple’ strands, to create scaffolding of specific shapes for use as nanoscale reduce the energy and materials costs of technologies. construction materials. DNA building manufacture by replacing processes that This proof-of-concept project aims blocks will self-assemble into DNA require highly refined starting materials, to design and build a first-of-its-kind origami frameworks, creating molecular high-energy casting processes, and/or molecular two-dimensional (2D) printer; additive manufacturing machines. substantial subtractive processing. APM an initial electro-mechanical integrated Three independently moving layers can potentially offer zero material waste nanosystem for APM. This development of DNA origami will be integrated by building materials from liquid or will leverage the recent progress being with ‘stepper’ positioning capable of soluble feedstocks rather than carving made in two rapidly developing fields. controlling motion in 2D and spatially them from solids. positioning a deposition pattern at Self-assembled deoxyribonucleic multiple sites simultaneously. Chemical- Applications in Our Nation’s acid (DNA) origami is showing a mechanical cycles of catalyzed DNA remarkable capacity for creating a strand displacement will be used to Industry variety of molecular structures, including control the movement and position of This technology is a molecular building assembling synthetic molecular site-specific writing on the DNA canvas. block with broader applicability to further machinery with nanometer (nm) level DNA-based molecular machinery is a APM. Over time as the technology field precision. Additive manufacturing (also promising approach to manufacturing progresses, potential applications may known as 3D printing) is a manufacturing next generation assemblers made from include: photovoltaics; photosynthetic technique that progressively adds other higher-performing materials. It is and fuel cells; thermoelectrics and layers of material to build up products extremely ambitious and represents a anisotropic heat spreaders; solid-state with more refined geometries while radically new direction for scaling up lighting; molecular electronic and avoiding material waste. Molecular-scale fabrication. plasmonic circuits; selectively permeable additive manufacturing could enable membranes; and self-repairing materials the controlled placement and bonding with high strength-to-weight and fracture resistance.

ADVANCED MANUFACTURING OFFICE ADVANCED MANUFACTURING OFFICE

Project Description Milestones First-generation molecular printers The project objective is to self-assemble This three-year project began in June may prove popular in the research three independently moving layers of 2018. community where related methods such DNA origami and control motion in two as single-molecule optical trapping and dimensions (2D) with stepper motor • Demonstrate assembly and already have positioning while printing a pattern at transmission electron microscopy gained traction. Once the concept is multiple sites simultaneously. (TEM) validation of 1D stepper experimentally validated, it is envisioned with two different that funds will be raised for a start-up architectures (‘stack’ and ‘wrap’); company to assist with subsequent Barriers with the expectation that at least one commercialization, with supplemental • Ability to control multisite interactions architecture can be actuated in 1D with support provided by Harvard. Initially, at interfaces between DNA origami >95% yield per driven step (2019) molecular printers may be distributed to surfaces in the ‘stack’ and ‘wrap’ a set of selected pilot users for testing. designs • Demonstrate assembly and TEM Later, distribution may ramp up through validation of 2D stepper nanomotors a web-based sales interface. Distribution • Overcoming failure and low- with ‘stack’ and ‘wrap’ architectures; may also be considered through licensing performance modes for the sliders (e.g., with the expectation that at least one to existing companies in the U.S. that sliders that fail to move for one or more architecture can be actuated in 2D with already offer DNA origami as products. cycles, or sliders that fall off the rails) >95% yield per driven step (2020)

• Overcoming high positional variance of • Demonstrate 2D printing on the Project Partners sliders at each register canvases, catalyzed by positional Dana-Farber Cancer Institute control of the writehead; with Harvard University • Overcoming pixel-writing failures the expectation that at least one Boston, MA (e.g., missing pixels, unwanted architecture can be patterned with Principal Investigator: Dr. William Shih pixels) at multiple printheads, despite >80% occupancy per designed site, as Email: [email protected] positioning within specifications, by assessed by TEM (2021) better control of chemical reactions University of Oxford • Demonstrate surface immobilization Oxford, United Kingdom Pathways and microfluidic actuation of 1D and 2D stepper nanomotors; using super- Development pathways include strategies resolution fluorescence microscopy to For additional information, for minimizing the fraction of DNA monitor stepping of the nanomotors in please contact strand displacement-driven movement real-time (2021) David Forrest, Sc.D., PE, FASM that exhibits sub-optimal performances. Technology Manager The project will develop DNA-based 2D U.S. Department of Energy printers using two architecture designs: Technology Transition Advanced Manufacturing Office ‘stack’ and ‘wrap.’ Initially, efforts will This project will develop a prototype Phone: (202) 586-5725 be focused on actuating a self-assembled programmable nanoscale printer cable Email: [email protected]  stepper in one dimension of writing a pattern on a DNA origami (1D). Subsequently, efforts will focus on canvas. This molecular additive validating actuation in 2D. manufacturing process could be a promising approach for atomically Following successful 2D actuation, precise manufacturing by demonstrating efforts will focus on advancing a self- massively parallel operation of assembled, programmed, and externally synthetic molecular machinery. The controlled 2D printer that can write use of self-assembly based methods a pattern on a DNA origami canvas could make this a scalable approach. (the workpiece) with high levels of The first-generation molecular 2D patterning and site occupancy on the printer will offer many advantages over canvas. While external control has been conventional DNA origami patterning, shown previously, this project aims to such as faster prototyping, faster dynamic demonstrate control over printing at rearrangement of patterns, and the ability multiple locations. to respond with feedback. Multi-head molecular printers will offer far greater throughput than these previous methods.

For more information, visit: energy.gov/eere/amo

DOE/EE-1840 • February 2019