Conference Agenda

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Welcome and Opening Remarks

Toward Productive Nanosystems: Launching the Technology Roadmap

The Technology Roadmap for Productive Nanosystems aims to provide guidance regarding the challenges and opportunities for productive nanosystems, describing strategic objectives for current research and their relationship to long-term goals for advanced nanotechnology. Its scope includes:

• Current capabilities in design, modeling, fabrication, and testing
• Overall readiness for developing next-generation productive nanosystems
• Strategies for developing more advanced systems
• Potential products of systems at successive levels of development

Both biological examples and analyses based on molecular physics indicate that productive molecular machine systems can enable economical, large-scale fabrication of products built with atomic precision. However, a daunting implementation gap separates the nanostructures of today from the complex productive nanosystems of the future. How can this gap be narrowed and eventually closed? The development of adequate tools to build these systems will require several intermediate stages, each building on the results of the previous stage, and each having its own commercial applications.

The Building Blocks of Molecular Nanotechnology

My laboratory has developed a new technology for constructing large molecules with designed three-dimensional shapes and designed function. We do this by synthesizing rigid molecular building blocks that we couple through pairs of bonds to create well defined three-dimensional structures. We have developed computer software package called CANDO that builds models of macromolecules and tests them for their ability to carry out designed functions. In this presentation, I will describe our molecular building block methodology, the automated synthesis of macromolecules, our computer aided design methodology and some applications that we are developing. I will also sketch an outline of how our molecular building block technology could lead to the development of sophisticated molecular nanotechnology.

Atomic Precision Patterned Atomic Layer Epitaxy: A Path to Atomically-Precise Manufacturing and Productive Nanosystems
John Randall, Vice President, Zyvex Labs

A precursor to productive nanosystems is an atomically precise manufacturing (APM) process. While multiple paths to APM exist, the one that appeals the most to an engineer (or at least the author), is one where top-down brute-force control of the process is maximized. One such path would integrate atomically precise depassivation lithography using a scanning tunneling microscope (STM) and atomic layer epitaxy (ALE) in a well known crystalline material system. Hydrogen depassivation lithography has been demonstrated on Si (001) 2x1 surfaces by Lyding and others. Atomically precise patterning in rudimentary forms has already been demonstrated. ALE has been demonstrated with disilane and other precursors with excellent monolayer or sub-monolayer control. Selective deposition of Si in depassivated areas has been demonstrated though not yet with atomic precision. This paper will describe efforts to develop atomic precision patterned ALE of Si, early commercial applications of that technology, approaches to dramatically improve the throughput of the process and plans to extend atomic precision patterned ALE to include other semiconductors, insulators, and metals.

Break

Biological Molecular Motors for Bionanotechnology

Biological molecular motors can provide useful devices for nanotechnology. They readily self-assemble, many are able to transport material along specific tracks, or can spin objects providing forward motion. In this presentation I will briefly describe a few well known molecular motors, illustrate their potential uses within nanodevices and detail our own work with an unusual molecular motor that provides a link between the biological world and the silicon world, acting as a molecular dynamo, but with huge potential in areas as diverse as biosensing, drug delivery, responsive materials and single molecule drug screening.

Atomistic Modeling of NanoScale Systems

Next generation massively parallel computers offer unprecedented opportunities to design stable atomic structures. Typical approaches include classical molecular dynamics using force fields, quantum mechanical calculations based on density functional theory, and traditional quantum chemistry. Almost all of the codes now being used were developed for a single processor, or a relatively small computer cluster (100 nodes). Current machines, such as IBM's Blue Gene/L or the CRAY XT4, utilize tens to hundreds of thousands of processors. Such machines will require new codes and in some cases new algorithms with optimal scaling properties. The rewards however can be great. For example, molecular dynamics simulations of protein structures, composed typically of 100,000 atoms, for several microseconds of simulated time can be performed in matters of weeks on such machines. This is important because it corresponds to actual folding times observed in the laboratory. Similarly, inorganic clusters such as those used in supported metal catalysts, which typically contain thousands of atoms, have been inaccessible to quantum mechanical calculation. The new machines will enable prediction of the geometrical arrangement of the atoms or the optical absorption probability. I will describe recent results in both areas obtained using large scale parallelism and discuss limitations which still exist in our ability to predict atomic scale properties.

Keynote: Mapping Roads to Advanced Nanotechnologies
K. Eric Drexler, Chief Technical Advisor, Nanorex

The Roadmap project has surveyed capabilities and prospects for the design and fabrication of atomically precise functional nanosystems. In particular, structural DNA nanotechnology now can implement frameworks containing millions of atoms, with the prospect of using these frameworks to organize nanosystems containing thousands of diverse, functional components. This approach leverages productive nanosystems that occur in nature, and its products can enable both direct applications (sensing, medicine, information processing), and next-generation, artificial productive nanosystems that can be used to build a broader class of structures. Progress in this direction can be quantified in terms of performance metrics for materials, devices, and systems. Pathways can be charted in terms of successive generations of enabling technologies. Progress along these pathways will require an increasing focus on system-level design and development. Experience in the semiconductor industry demonstrates the benefits of an ongoing road mapping process for coordinating system development work spread across multiple disciplines and organizations.

Feynman Prize Luncheon

Engineering Atomically-Precise Devices to Transform Molecular Structures

Combined theoretical and experimental approaches for protein design can be used in the engineering of atomically precise devices capable of precise manipulation of other molecular structures.

The Hellinga laboratory has developed and experimentally validated computational design methods for the design of proteins with novel ligand-binding sites and enzyme activities. This approach starts with a protein of known structure, and uses design algorithms to predict the set of mutations necessary to alter or introduce ligand binding or enzyme activity in that structure.

These designs are then produced by oligo-nucleotide-directed mutagenesis (typically 10-20 mutations) and heterologous protein expression. Using this approach we have engineered various members of the periplasmic binding protein (PBP) super family to alter radically their ligand-binding specificity. These engineered receptors can be further engineered to function as reagentless fluorescent or electrochemical sensors by constructing appropriate conjugates with reporter groups.

In this way we have constructed biosensors for a wide variety of ligands including TNT, nerve agent surrogates, and metabolites. Furthermore, the designed receptors can be re-introduced into E. coli where they drive two-component signal transduction pathways. In this way we have constructed synthetic circuits that control gene expression in response to xenobiotics (such as TNT).

New Synthetic Strategies to Build Protein Based Nanomaterials

DNA Nanotube-Enabled Alignment of Membrane Proteins for NMR Structure Determination

The pace of investment in enabling technologies toward atomic-precision molecular manufacturing will depend on the successful realization of near-term demand-meeting applications. I will describe the construction of atomically-precise, micron-length nanostructures that enable structure determination of membrane proteins, which represent the majority of drug targets, yet have proven exceedingly difficult to characterize. Residual dipolar couplings (RDCs), commonly measured for biological macromolecules weakly aligned by liquid-crystalline media, are important global orientation restraints for NMR structure determination. However, none of the existing liquid-crystalline media used to align water-soluble proteins are compatible with the detergents required to solubilize membrane proteins. We generated detergent-resistant liquid crystals of 0.8-µm-long DNA nanotubes that enable weak alignment of detergent-reconstituted ζ-ζ transmembrane domain of the T-cell receptor. Measurements of backbone NH and C_αH_α RDCs validate the high-resolution structure of the transmembrane homodimer. This DNA-nanotube liquid crystal will extend the advantages of weak alignment to NMR structure determination of membrane proteins. I also will discuss the employment of DNA nanotube struts to self-assemble icosahedral cages that are 100 nanometers in diameter. These cages may have future applications as encapsulation devices and drug delivery vehicles.

Break

Multifunctional Carbon Nanotube-Based Systems: Linking Synthesis and Function

Single-wall carbon nanotubes (SWNTs) exhibit unique properties reflecting their atomic perfection and quantized dimensions. Their extreme tensile strength, high electrical and thermal conductivities, and fascinating optical properties are critically dependent on the precision of their construction, and promise new generations of multifunctional supermaterials. However, translating the properties observed for individual nanostructures to macroscale composites has proven difficult. This talk addresses the roadmap from nanoscale synthesis to macroscale functionality, starting with fundamental understanding of nanotube and nanohorn synthesis gained through in situ time-resolved characterization of their growth. Then, effects of processing and assembly on the path toward functional macroscale systems is illustrated with several examples.

Panel Discussion: Pathways

Multiple technologies are competing-and cooperating-in the drive to achieve atomically-precise manufacturing. This panel will debate how these R&D pathways interact and converge and how each pathway will be accelerated by unique achievements and payoffs in fields ranging from medicine to new materials to computation.

Panelists:

	Christian E. Schafmeister, Department of Chemistry, Temple University
	John Randall, Vice President, Zyvex Labs
	K. Eric Drexler, Chief Technical Advisor, Nanorex
	Keith Firman, School of Biological Sciences, University of Portsmouth