Computer-Aided Design for DNA Self-Assembly: Process and Applications

Chris Dwyer Assistant Professor Dept. of Electrical and Computer Engineering Dept. of Computer Science Duke University Computer-Aided Design for DNA Self-Assembly: Process and Applications ICCAD 2005

Motivation log Cost ($/gate) log Length (m) log Switching time (s) [Annotated with CNT technology, original source: George Bourianoff and ITRS, ca. 2003.]

Outline • DNA Basics • Self-assembled Nanostructures • DNA Scaffolds • DNA Guided Self-assembly • CAD Tool Support • Self-assembled Systems • New Constraints • Alternative Architectures • Conclusions

DNA Basics • A DNA strand is: • A linear array of bases (A, T, G, and C) • Directional (one end is distinct from the other) • In nature, the source of genetic information • DNA will form a double helix: • When the bases on each strand (aligned head-to-toe) are complementary: A with T, and G with C • But only under “natural” environmental conditions such as low temperatures (<< 95 C) and in saline.

DNA Basics • DNA hybridization is the process that forms the double helix • Sequence and temperature controls the hybridization event

DNA Basics • A common form of the double helix has some well-known geometric properties: • 3.4 Å per base pitch along the helix • One complete turn between every 10th and 11th base • The bonds along the sugar-phosphodiester backbone of each strand can rotate • single stranded DNA has a 5 – 10 nm persistence length • double stranded DNA has a longer persistence length (50 – 100 nm)

Self-assembled Nanostructures • Self-assembly is ubiquitous in nature • Yet, definitions of self-assembly are elusive... • In this talk, thermodynamics drive the self-assembly process • we can guide the process by the choice of materials and environmental conditions B <100nm feature sizes A·B T A

DNA Scaffolds - Geometry • The geometric properties of double strands can form specific, controlled self-assembled nanostructures: Three strand assembly example figure here

DNA Scaffolds - Hierarchy • Self-assembly can occur in hierarchies: • tiles (from single strands to tiles) • grids (from tiles to grids) • lattice (from grids or tiles to larger lattice)

DNA Scaffolds - Functionalization • Tiles can be functionalized (decorated) with nanoscale components (thus, a scaffold) • Tiles can be functionalized before OR after grid/lattice assembly • Some chemical functionalities include: • biotin / streptavidin • DNA / nanoparticle (rods, spheres, etc.)

DNA Scaffolds - Functionalization • Biotin / streptavidin (protein + active chemicals) • The DNA provides a scaffold for the protein The manufacturing scale is incredible: 1014 – 1015 grids per mL! AFM images of some grids with streptavidin here AFM images of a 1.4 Tb/in2 ROM (barcode)

DNA Scaffolds - Functionalization • Perhaps in the future.... + Crossed carbon nanotube “FET” / SBT DNA Self-assembly

Electrolyte gated carbon nanotubes S. Rosenblatt, Y. Yaish, J. Park, J. Gore, and P. L. McEuen, 2002.

Electrolyte gated carbon nanotubes • CMOS vs. CNT ring oscillators (per inverter) † – Verified against MOSIS reference device T3AZ, Dec. 2003. ‡ – ITRS 2003 prediction. * – Berkeley predictive technology models, Y. Cao et al., 2000-2002.

DNA Scaffolds – Circuit Example

DNA Guided Self-assembly • Nanoparticles (rods, spheres, etc.) can be functionalized with DNA • DNA hybridization stabilizes interactions between particles if the strands are complementary • Sequence design and particle choice yields controlled nanostructure formation

DNA Guided Self-assembly • An active component: • ring-gate FETs (RG-FETs) (or surrounding-gate FETs)

500 nm wide DNA Guided Self-assembly • Active components for circuitry: Au – CdSe – Au (metal, semiconductor, metal or MSM) rods MSM rod assembly figure here (rearranged) + IV data

DNA Guided Self-assembly • Perhaps in the future... • The fabrication of integrated electronic systems • IEEE Trans. on VLSI, • vol. 12, pp. 1214-1220, 2004. • IEEE Trans. on Nano., • 2 (2): pp. 69-74, 2003. • Nanotechnology, • vol. 13, pp. 601-604, 2002.

DNA Guided Self-assembly

Case study: Silicon nanowires to DAMP Interconnect & Integration • IEEE Trans. Nano, • 2 (2): pp. 69-74, 2003.

Self-assembled Nanostructures • Recap: Two Fabrication Methods • Scaffolds • DNA-Guided Assemblies

CAD Tool Support – Circuit Layout • New technology fabric : New tool support • Goal: apply conventional circuit design approaches to these new technologies DNA scaffold layout tool DNA-rod layout tool

CAD Tool Support – Optimized Fabrication • Mismatches between DNA sequences reduce our ability to control the formation of the nanostructure • fewer mismatches mean a higher “yield” of structures example mismatch error

CAD Tool Support – Optimized Fabrication • CAD tool goal: minimize mismatch errors • to enhance yield • Current tool status: • Cluster-based sequence optimization • Layout tools • Carbon-nanotube & MSM device models for a custom SPICE kernel • Assembly orders / “artwork” gen. (for large circuits) • Tool wish list: yield-aware design optimizations, refined (high ) device models, ...

Self-assembled Systems • There are a variety of self-assembled systems • crossbars, micron-scale assemblies, biological systems... • A New Systems Focus: self-assembled computer architectures

New Constraints • Self-assembly imposes: • chaos / randomness at some length scale (>1-10 m) • DNA hybridization imposes: • order at some length scale (< 1-5 m) • The two can work together but some fundamental assumptions must change: • No large-scale interconnect networks / limited local • Large circuit footprints are impractical • Devices can be defective and potentially faulty

Alternative Architectures • Given a device fabric, design a system • The new constraints prevent wholesale adoption of conventional architectures / system designs • Two common system varieties: • reconfigurable • redundant (e.g. TMR, n-MR, etc.)

Alternative Architectures • Four systems: Oracles, DAMP, NANA, and nSIMD: • Oracles: DNA computing with a device twist that enables rapid (electrical) re-use of a DNA computation • DAMP: Decoupled Array Multi-processor, SIMD without an interconnection network- embarrassingly parallel codes – only • NANA: Nanoscale Active Network Architecture, general purpose but imbalanced due to a large communication/execution ratio • nSIMD: (nano) SIMD, similar to NANA but applies a SIMD model onto a reconfigurable network topology

Alternative Architectures Self-assembled Computational nodes Self-assembled Interconnect • Defect model includes: • Rotation, position • Connectivity • Fail-stop nodes (unrealistic)

Alternative Architectures • Reconfigurability is key, however.... • The large number of nodes in a system (as many as we can assemble, ~1014 +) precludes the use of an explicit defect map • A reverse forward-path (RFP) algorithm maps defective nodes during a configuration stage (a single broadcast from the de facto tree root) • The goal: To stitch sufficient computational resources together to execute application code

Shell Arm Core Conclusions Self-assembled device theory

Conclusions Demonstrations of self-assembled devices

Conclusions Self-assembled computer architectures and systems • Oracles: Re-useable DNA computations • DAMP: Decoupled Array Multi-processor • NANA: Nanoscale Active Network Architecture • nSIMD: (nano) SIMD

Acknowledgements Research Sponsors • Graduate students Vijeta Johri Vincent Mao Jaidev Patwardhan Constantin Pistol • Undergraduate students Juan Bermudez Lauren Cohen Josh Johnson Joe Tadduni • AFRL FA8750-05-2-0018 • NSF CCR-0326157, EIA-9972879

Temporal spectrum of Computation Assembly-time • DNA computing • Oracles • ASICs, FPGAs, etc. • Conventional serial & parallel machines • Decoupled array multi-processor (DAMP) Run-time • IEEE Computer, • vol. 38, pp. 56-64, 2005.

R0* R1* R2 R3 R4 ACC* Operation Question0 Questionn-1 Answer0 Answern-1 Status bits B C D R S W Organization & Architecture Oracles Decoupled array multiprocessor (DAMP) log2(n) bits . . . • IEEE Computer, • vol. 38, pp. 56-64, 2005. • IEEE Trans. on VLSI, • vol. 12, pp. 1214-1220, 2004. • Nanotechnology, • vol. 15, 1688-1694, 2004. • Ph.D. dissertation, • Univ. of North Carolina, Chapel Hill, 2003.

Ci A B S Co A B Ci S Co 1 0 0 0 0 0 1 1 0 0 0 0 1 1 0 1 0 0 0 0 1 1 1 0 1 1 0 0 1 1 0 0 1 1 1 0 1 1 1 1 Addition oracle example • Truth table defines binding rules • Each tile is implemented by a self-assembled circuit

Ci A B S Co 1 0 0 1 0 1 1 0 1 0 1 0 0 0 1 1 0 1 1 1 Addition oracle example LSB A = 0 0 1 1 B = 0 1 0 1 Sum = 1 0 0 0 S = 1 0 0 0 “3 + 5 = 8” MSB

Ci A B S Co Addition oracle example • Each tile implemented using logic circuitry Bit from the truth table

R0* R1* R2 R3 R4 ACC* Operation Question0 Questionn-1 Answer0 Answern-1 Status bits B C D R S W Organization & Architecture Oracles Decoupled array multiprocessor (DAMP) log2(n) bits . . . • IEEE Computer, • vol. 38, pp. 56-64, 2005. • IEEE Trans. on VLSI, • vol. 12, pp. 1214-1220, 2004. • Nanotechnology, • vol. 15, 1688-1694, 2004. • Ph.D. dissertation, • Univ. of North Carolina, Chapel Hill, 2003.

Basic system criteria – a framework (i) Linear signal transduction (ii) Non-linear signal modulation by another signal (iii) Signal amplification / restoration (iv) Signal noise immunity (v) Circuit patterning and interconnect (vi) Scale of device integration (vii) Energy consumption (viii) Application runtime performance 10X

Basic system criteria Device-level simulation AND Real-device parameter extraction Interconnect & integration (SPICE, etc.) 10X Organization / architecture & application performance (SimpleScalar, custom, etc.)

N-FET IV Curves P-FET IV Curves Case study: Silicon nanowires to DAMP • Electrical behavior very similar to conventional MOSFETs • E.g., the ring-gated FET

Computer-Aided Design for DNA Self-Assembly: Process and Applications