PI: John Reif PI: John Reif, Duke University , Duke University Subcontractors: Subcontractors: Nadrian C. C. Seeman Seeman, NYU , NYU Nadrian DARPA BIOCOMP Contract: DARPA BIOCOMP Contract: & Erik Winfree & Erik Winfree, Caltech , Caltech Programmable DNA Lattices: Design, Synthesis and Applications Programmable DNA Lattices: Design, Synthesis and Applications • • Key Technology: The Programmed Self-Assembly of Patterned 2D Lattices Key Technology: The Programmed Self-Assembly of Patterned 2D Lattices A New, Powerful Technology for Rendering Patterns at the Molecular Level A New, Powerful Technology for Rendering Patterns at the Molecular Level A 2D DNA lattice is constructed by a self-assembly process: A 2D DNA lattice is constructed by a self-assembly process: - --Begins with the assembly of -Begins with the assembly of DNA tile nanostructures DNA tile nanostructures: : - DNA tiles of size - DNA tiles of size 14 x 7 nanometers 14 x 7 nanometers - Composed of short DNA strands with Holliday junctions - Composed of short DNA strands with Holliday junctions - These DNA tiles self-assemble DNA tiles self-assemble to form a to form a 2D lattice: 2D lattice: - These -The Assembly is Programmable: Programmable: -The Assembly is -Tiles have sticky ends that provide programming for the patterns to be formed. -Tiles have sticky ends that provide programming for the patterns to be formed. -Or tiles self-assemble around segments of a DNA strand encoding a 2D pattern. tiles self-assemble around segments of a DNA strand encoding a 2D pattern. -Or - Patterning: Patterning: Each of these tiles has a surface perturbation depending on the pixel intensity. Each of these tiles has a surface perturbation depending on the pixel intensity. - -pixel distances 7 to 14 nanometers -pixel distances 7 to 14 nanometers -not diffraction limited -not diffraction limited Key Applications: Assembly of molecular electronic components & Assembly of molecular electronic components & circuits circuits, , Key Applications: molecular robotic components, image rendering molecular robotic components, image rendering, , cryptography, mutation detection. cryptography, mutation detection.
PI: John Reif PI: John Reif, Duke University , Duke University Sucontractors: : Sucontractors Nadrian C. C. Seeman Seeman, NYU , NYU Nadrian DARPA BIOCOMP Contract: DARPA BIOCOMP Contract: & Erik Winfree & Erik Winfree, Caltech , Caltech Programmable DNA Lattices: Design, Synthesis and Applications Programmable DNA Lattices: Design, Synthesis and Applications Tasks and Goals: • Tasks and Goals: • 1) Patterned DNA Arrays. 1) Patterned DNA Arrays. • Set of specific tiles which form patterns. • Set of specific tiles which form patterns. • Assembly around scaffold strands. Assembly around scaffold strands. • • Molecular fabric. Molecular fabric. • 2) Computation via DNA Self-Assembly 2) Computation via DNA Self-Assembly • Reporter strand output (requires • Reporter strand output (requires ligation ligation). ). • Microscopic readout Microscopic readout • (via AFM, TEM, SEM, etc.). (via AFM, TEM, SEM, etc.). 3) Applications of DNA-Based Assemblies. 3) Applications of DNA-Based Assemblies. Molecular motors & actuators: Molecular Electronics: Molecular motors & actuators: Molecular Electronics: WIR E Motor Ab Oligonucleotides. Annealed Lattice. Bound Nanoparticles. Metal Deposition. Fused Wire. DNA tile 4) Software for Design and Simulation of DNA Assemblies. 4) Software for Design and Simulation of DNA Assemblies.
Programmable DNA Lattices: Design Synthesis & Applications Duke University (PI John Reif) Subcontracts: NYU (Nadrian Seeman), Caltech (Erik Winfree & Niles Pierce) New Ideas: Molecular Self-assembly: Scientific Objectives: -DNA strands self-assemble into DNA tile nanostructures. Programmable construction of complex nanostructures of -DNA tiles self-assemble into periodic and aperiodic lattices. supramolecular (10-100 nm) scale. - DNA lattices with complex 2D patterning, and Algorithmic Self-assembly: - periodic 3D DNA lattices. -DNA tiles form DNA lattices with complex patterning. -Methodology is programmable by choice of DNA tiles . Nanostructure Templating and Patterning: -DNA lattice superstructure for other complex nanostructures. -Other molecular nanostructures attach to specific DNA strands within DNA lattices. Tiling Design for Binary Counter Impact to US defense: Schedule: Protein structure determination via host-lattice crystals: Design of novel DNA tiles & lattices and support software -Periodic 3D DNA lattices capture proteins for X-ray Optimization algorithms for DNA design implemented. diffraction. Key spin-off: Structural characterization of Patterned 2D DNA lattice: modest size (64 tiles) antigens from pathogens. Periodic 3D DNA lattices: diffracting to 2.5 Å Characterization of error rates of self-assemblies Patterned DNA Lattice Technology: Patterned 2D DNA lattices: moderate size(512 tiles) -DNA nanostructures can serve as scaffolds for molecular Periodic 3D DNA lattice: diffracting to 2.5 Å sensors and actuators. Self-assembly of 4-bit demultiplexing RAM Key Spin-off: identifying pathogens (e.g., bacteria). Patterned 2D DNA lattices: thousands of tiles -DNA lattices can be used as scaffolds for positioning Periodic 3D DNA lattices: diffracting to 2.5 Å molecular electronics components into complex circuits. Key Spin-off: Molecular Nanoelectronics. 2001 2002 2003 2004
DUKE PERSONNEL on PROJECT DUKE PERSONNEL on PROJECT John H. Reif John H. Reif • • Professor (PI) Professor (PI) • • 25% Effort 25% Effort • • Thomas H. LaBean LaBean Thomas H. • • Assistant Research Professor Assistant Research Professor • • 25% Effort 25% Effort • • Hao Yan Hao Yan • • Assistant Research Professor Assistant Research Professor • • 50% Effort 50% Effort • • Liping Feng Liping Feng • • Research Technician Research Technician • • 75% Effort 75% Effort • • Dage Liu Liu Dage • • Postdoctoral Research Associate Postdoctoral Research Associate • • 25% Effort 25% Effort • •
Major Goals of Duke Group Major Goals of Duke Group 1) Patterned DNA Arrays. 1) Patterned DNA Arrays. • Set of specific tiles which form patterns. Set of specific tiles which form patterns. • • Assembly around scaffold strands. Assembly around scaffold strands. • • Molecular fabric. Molecular fabric. • 2) Computation via DNA Self-Assembly 2) Computation via DNA Self-Assembly • Reporter strand output (requires ligation). Reporter strand output (requires ligation). • • Microscopic readout (via AFM, TEM, SEM, etc.). Microscopic readout (via AFM, TEM, SEM, etc.). • 3) Applications of DNA-Based Assemblies. 3) Applications of DNA-Based Assemblies. • Molecular and nano-scale electronics. Molecular and nano-scale electronics. • • Molecular motors and actuators. Molecular motors and actuators. • 4) Software for Design and Simulation of DNA 4) Software for Design and Simulation of DNA Assemblies. Assemblies.
NYU SUBCONTRACT DIRECTED ASSEMBLY OF 3D NANOSTRUCTURE ARRAYS NADRIAN C. SEEMAN, NEW YORK UNIVERSITY SCIENTIFIC OBJECTIVES: NEW IDEAS: DESIGN 3D CRYSTALLINE ARRAYS FROM DNA. SELF-ASSEMBLY OF DNA FOR CONTROL OF NANOSTRUCTURE. DESIGNED CONNECTION BETWEEN THE MOLECULAR AND MACROSCOPIC SCALES. A B C C D D ' ' DIRECTING THE ASSEMBLY OF BIOLOGICAL ABC'D' Array AND NANOELECTRONIC MOLECULES BY DNA SCAFFOLDING. IMPACT: SCHEDULE ELIMINATION OF THE MACROMOLECULE DESIGN 3D MOTIFS CRYSTALLIZATION PROBLEM -- RATIONAL CONSTRUCTION OF CRYSTALS TO SOLVE CHARACTERIZE MELTING PATHOGEN PROTEIN 3D STRUCTURES. OPTIMIZE PROTOCOLS FACILITATION OF NANOELECTRONICS THROUGH DNA-DIRECTED SCAFFOLDING. DEMONSTRATE DIFFRACTION IMPLEMENTATION OF NANOROBOTICS. 0 1 2 3
CALTECH SUBCONTRACT Computational and Experimental Design of DNA Devices Erik Winfree and Niles Pierce Scientific Objectives: New Ideas: DNA sequence design of self-assembled devices for Reliable lattice assembly & patterned nanostructures Algorithmic self-assembly of DNA tiles forming templates for electronic circuits Thermodynamic partition functions and dynamic simulation for multi-stranded DNA systems Algorithms for positive and negative DNA sequence design Binary Counter AFM image of striped lattice Impact: Schedule : Reliable automated design of complex molecular systems Formulate DNA design problem Implement DNA design algorithms Ability to pattern nanostructures using self-assembled DNA lattice Binary counter demonstration Self-assembled Nanoelectronics, nanorobotics, nanosensors, RAM circuit pattern nanoactuators 0 1 2 3
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