California NanoSystems Institute
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December 02, 2003

Steve Quake
Biological Large Scale Integration

The current industrial approach to addressing biological integration has come in the form of enormous robotic fluidic workstations that take up entire laboratories and require considerable expense, space and labor, reminiscent of the macroscopic approach to circuits consisting of massive vacuum-tube based arrays in the early twentieth century. This automation has been highly productive and led to whole genome sequencing and analysis - a new revolution in biology. At Caltech, my group has developed microfluidic technologies that may now allow the automation of biology to proceed to a scale comparable to modern integrated circuits. Microfluidics, which is essentially miniaturized plumbing, offers the possibility of solving outstanding system integration issues for biology and chemistry. We recently developed the first microfluidic large scale integration, in which we have shown how to fabricate chips with thousands of mechanical valves. These chips have proven their value for high throughput measurements of single cell biochemistry, protein crystallization screening, and highly parallel genetic analysis. Besides the expected economies of scale that accompany the miniaturization and parallelization inherent in these devices, there have also been unexpected discoveries about how the unique physics of fluids in small dimensions can be used to achieve performance that is impossible with benchtop laboratory devices.

November 25, 2003

Leonard Rome
Vaults: Biologically Based Nanocapsules

With a molecular mass of 13 Mda, the vault is the largest known ribonucleoprotein particle and yet it has a relatively simple molecular composition with multiple copies of just three different proteins (MVP, VPARP and TEP1) and one to three different untranslated RNA molecules (vRNAs). The vault nanocapsule has been honed by millions of years of evolution to assemble from multiple copies of a few subunits into a stable structure. The particle adheres to and is transported along cytoskeletal elements in the cell, and is likely to open and close in response to cellular signals. We have used an insect cell system to produce bioengineered vaults containing chemically active peptides and proteins inside the particle.

Biographical Sketch

Leonard H. Rome is a cell biologist and biochemist who has served on the UCLA School of Medicine faculty since he joined the Department of Biological Chemistry in 1979. He became a full professor in 1988 and has been Senior Associate Dean for Research in the School of Medicine since 1997 and Associate Vice Chancellor for Research for the Life and Health Sciences since 2001. Dr. Rome earned his B.S. in Chemistry and M.S. and Ph.D. in Biological Chemistry at the University of Michigan, Ann Arbor. He was a postdoctoral fellow at the National Institutes of Health, where he worked on lysosome biogenesis. Dr. Rome has chaired the School of Medicine Faculty Executive Committee and is actively involved in graduate and medical education. He co-chairs the Human Biochemistry and Nutrition Laboratory, and is a recipient of the School of Medicine Award for Excellence in Education. Since becoming Senior Associate Dean for Research, he has organized a strategic plan for research in the School and spearheaded campus-wide efforts in genomics, proteomics, and computational biology. His laboratory research centers on a novel cellular organelle called a "vault" which was discovered in his laboratory. The vault is a naturally occurring nano-capsule thought to carry out a basic cellular function. Dr. Rome is presently organizing a Nanoscience Interdisciplinnary Research Team, a collaboration of disciplines including cell biologists, engineers, chemists, and structural biologists who will engineer vaults for use in drug delivery and as components of nano-electrical machines. Dr. Rome has received a number of honors for his research including a March of Dimes, Basil O'Connor Grant, an American Cancer Society Faculty Research Award, and the California State University, Northridge, Chemistry Club's 1998 Distinguished Lecturer of the Year.


Stephen, A.G., Raval-Fernandes, S., Huynh, T., Torres, M., Kickhoefer, V.A. and Rome, L.H.: Assembly of vault-like particles in insect cells expressing only the major vault protein J. Biol. Chem. 276: 23217-23220 (2001).

Kong, L.B., Siva, A.C., Kickhoefer, V.A., Rome, L.H., and Stewart, P.L.: RNA location and modeling of a WD40 repeat domain within the vault. RNA 6: 1-11 (2000).

Recent Review:

Suprenant, K. A.: Vault ribonucleoprotein particles; sarcophagi, gondolas or safety deposit boxes? Biochemistry 41: 14447-14454 (2002).

November 18, 2003

Stephen Chou
Princeton University
Nanostructure Engineering -- A Path to Discovery and Innovation

Our ability in patterning nanostructures offers a unique path to discovery and innovation in science and technology. When nanostructures are smaller than a fundamental physical length scale, conventional theory may no longer apply and new phenomena emerge, leading to discovery and innovation. The talk will present some intriguing phenomena manifested in nanostructures and their applications in the areas of electronics, optics, magnetic, biotech and materials. Furthermore, the talk will address one of the grand challenges that are essential to the success of nanotechnology and its commercialization: high-throughput and low-cost nanopatternings (i.e., nanomanufacturing). Two different approaches will be presented. One is nanoimprint lithography (NIL) and alike. The other is guided self-assembly (GSA), in particular, those that can give aligned self-assembly over entire wafers, such as lithographically-induced self-assembly (LISA) and shear-force guided self-assembly.

November 04, 2003

Kang Wang
Nanoelectronics - Today and Beyond

In nanoelectronics, the feature size of transistors will be scaled down to a few tens of nanometers in the next decade. The major challenges as anticipated by ITRS (The International Technology Roadmap for Semiconductors) are the fundamental limit of CMOS scaling, and power dissipation, maintaining continued increase of functional throughput and the reducing cost of manufacture. In this talk, we will discuss nano device issues as scaled to atomic and molecular levels, in particular the salient features of ultimate CMOS and other new potential nano-devices, which may be based on Si, organic, and biomaterials. From the material point of view, the self-assembly at the atomic and molecular levels may become a viable fabrication process for nanoelectronics systems. We will present a discussion on the need of a paradigm change of architecture along with a plausible roadmap to future integrated nanosystems. The approach may include the use of self-assembly to form eventually hybrid nanosystems integrating semiconductor with molecular and bio nanosystems.


1. K.L. Wang, "Issues of Nanoelectronics: A Possible Roadmap", Journal of Nanoscience & Nanotechnolog, 2(3-4), 235-266, June- August 2002.
2. Victor V. Zhirnov and Daniel J.C. Herr, "New Frontiers: Self-Assembly and Nanoelectronics", IEEE Computer, p.34-43, (2001).
3. Yu V. Gulayev, S. P. Gubin, G. B. Khomutov, V. V. Kislov, E. S. Soldatov, K. S. Sulaimankulov, A. S. Trifonov, "Molecular nanocluster electronics: device and technology", 7th International Conference on Nanometer-Scale Science and Technology and 21st Europe Conference on Surface Science, 2002, pp.2, Sweden.

October 29, 2003

Thomas Bjornholm
University of Copenhagen, Denmark
Organic Molecules in Electronic Devices

Organic molecules are becoming increasingly important as the active component in electronic devices both in the form of low-tech high market volume applications (e.g. organic light emitting diodes) or as components in nanoscale devices based on a few single molecules. In both cases the ability to structurally organize and inter-connect the molecular constituents is a central issue which requires a successful combination of molecular self-organization and lithography.

The talk will highlight our recent results on single molecule single electron transistors (1), self-assembly of gold nanoparticles into molecular electronic circuitry (2-3), structural nanoscale studies of self-assembled biological relevant systems (4-5), self-organized electronic thin films (6), and organic synthesis of thiol end-capped ?-systems (7).

Our most recent collaborative results on electrical transport at 4 Kelvin through a single oligo-p-phenylenevinylene molecule (OPV, Fig.1) placed in a gap of about 2 nm between source and drain electrode of a single electron transistor device (SET) will be given special emphasis (1). The molecules visits nine distinct redox states which are strongly influenced by image charges in the electrodes.

The OPV molecule has been synthesized by a new method developed in our laboratories (7) which allows thiol end-capping in a synthetically versatile way. Progress in fabrication of integrated nanoscale circuits by self-assembling gold nanoparticles and thiol end capped OPV's will also be presented (2-3).


[1] S. Kubatkin, T. Bjornholm et al. Nature, accepted for publication (2003).
[2] T. Hassenkan, M. Brust, T. Bjornholm et al. Adv. Mat. 14, 1126-1130 (2002).
[3] K. Norgaard, M. Brust, T. Bjornholm et al. Faraday Discussions 125, accepted (2003).
[4] T. R. Jensen, K. Kjaer, T. Bjornholm et al. Phys. Rev. Lett. 90, 086101 (2003); P. Ball, News & Views, Nature 423, 25-26 (2003).
[5] L. K. Nielsen, T. Bjornholm, O.G. Mouritsen, Nature 404, 352 (2000).
[6] N. Reitzel, R. D. McCullough, T. Bjornholm, et al. J. Am. Chem. Soc. 122, 5788-5800 (2000).
[7] N. Stuhr-Hansen, T. Bjornholm et al. J. Org. Chem. 68, 1275 (2003).

October 28, 2003

Ben Cravatt
The Scripps Research Institute
Chemical Strategies for Activity-Based Proteomics

The field of proteomics aims to characterize dynamics in protein function on a global scale. However, several classes of enzymes are regulated by posttranslational mechanisms, limiting the utility of conventional proteomics techniques for the characterization of these proteins. Our research group has initiated a program aimed at generating chemical probes that interrogate the state of enzyme active sites in whole proteomes, thereby facilitating the simultaneous activity-based profiling of many enzymes in samples of high complexity. Progress towards the generation and utilization of active site-directed chemical probes for the proteomic characterization of several enzyme classes will be described. These enzyme classes fall into two general categories: 1) enzymes for which active site-directed affinity agents have been well-defined, and 2) enzymes for which active site-directed affinity agents have been lacking. The application of activity-based protein profiling to the functional characterization of enzyme activities that vary in human cancer specimens will be highlighted, as will be the use of this strategy as a screen to discover potent and selective reversible enzyme inhibitors.

Adam, G.C., Sorensen, E.J., Cravatt, B.F. "Proteomic Profiling of Mechanistically Distinct Enzyme Classes Using a Common Chemotype." Nat. Biotechnol. 2002, 20, 805-809.

Jessani, N., Liu, Y., Humphrey, M., Cravatt, B.F. "Enzyme Activity Profiles of the Secreted and Membrane Proteome that Depict Cancer Invasiveness." Proc. Natl. Acad. Sci. U.S.A. (Track II) 2002, 99, 10335-10340.

October 21, 2003

Tim Baker
Purdue University
Cryo-Electron Microscopy of Viral Nano-Machines

Viruses are cellular parasites. A deeper understanding of many aspects of viral life cycles has emerged from coordinated molecular and structural studies carried out with a wide range of viral pathogens. Structural studies of viruses by means of cryo-electron microscopy (cryo-EM), 3D image reconstruction, and pseudo-atomic modeling methods have grown explosively in the last decade. These methods have been successfully employed in the investigation of a wide range of icosahedral viruses, ranging in size from as small as 30nm to as large as 200nm. Particular emphasis will be devoted to recent results with small enveloped viruses, where transmembrane helices can be discerned at 0.95 nm resolution.


Kuhn, R. J., W. Zhang, M. G. Rossmann, S. V. Pletnev, J. Corver, E. Lenches, C. T. Jones, S. Mukhopadhyay, P. R. Chipman, E. G. Strauss, T. S. Baker, and J. H. Strauss (2002) Structure of dengue virus: Implications for flavivirus organization, maturation, and fusion. Cell 108:717-725.

Baker, T. S., N. H. Olson, and S. D. Fuller (1999) Adding the third dimension to virus life cycles: Three-Dimensional reconstruction of icosahedral viruses from cryo-electron micrographs. Microbiol. Molec. Biol. Reviews 63:862-922.

October 14, 2003

Philip Wong
IBM T.J. Watson Research Center
Nanoscale Science and Technology - A Device and Engineering Perspective

Novel alternative materials and devices such as strained silicon and double-gate FET are being actively explored to extend silicon technology. We begin this talk by briefly reviewing recent developments in nanoscale silicon FETs [1]. On the other hand, the new opportunities offered by nanotechnologies such as new materials, new fabrication/assembly methods, and new devices are exciting. While some of these new devices have achieved experimental results that may rival some of the best silicon FETs [2], most of these devices have yet to show electrical characteristics beyond the basic, functional level. This talk presents an analysis of the potential performance of carbon nanotube FET and nanodiode arrays [3]. We also benchmark the performance of these devices against Si CMOS. The potential benefits of nanoscale fabrication techniques will be discussed. We conclude with an outlook for nanotechnology for the next 20 years.


[1] H.-S. P. Wong, "Beyond the Conventional Transistor", IBM J. Research & Development, p.133, 2002.
[2] H.-S. P. Wong, J. Appenzeller, V. Derycke, R. Martel, S. Wind, Ph. Avouris, "Carbon Nanotube Field Effect Transistors Fabrication, Device Physics, and Circuit Implications", International Solid State Circuits Conference (ISSCC), San Francisco, February, p. 370, 2003.
[3] H.-S. P. Wong, G.S. Ditlow, P.M. Solomon, X. Wang, "Performance estimation and benchmarking for carbon nanotube FETs and nanodiode arrays", invited paper, Conferences on Solid State Devices and Materials (SSDM), Japan, September 16 - 18, 2003.
October 07, 2003

Shimon Weiss
Single Molecule Nanoscale Rulers
Abstract: Single molecule methods have come of age and are now able to decipher individual molecular events in the test tube and in living cells. Single-pair FRET (spFRET) is used to follow structural changes, translocation and dynamic transitions of the enzyme RNA polymerase during initiation of transcription and promotor escape. Peptide-coated inorganic semiconductor nanocrystals (quantum dots - qdots) are used as fluorescent probes in cellular imaging. The peptides provide both solubilization and functionalization of the nanocrystals. Such qdots are targeted to cell-surface receptors of ex-vivo cultured cancerous HeLa cells with an exquisite specificity. Qdot targeting allows to follow the trafficking of individual proteins in live cells. References: X. Michalet, A.N. Kapanidis, T. Laurence, F. Pinaud, S. Doose, M. Pflughoefft, S. Weiss, "The Power and Prospects of Fluorescence Microscopies and Spectroscopies", Ann. Rev. Biophys. Biomol. Struct. 2003, 32:161-82 X. Michalet, F. Pinaud, T.D. Lacoste, M. Dahan, M. Bruchez, A.P. Alivisatos and S. Weiss, "Properties of fluorescent semiconductor nanocrystals and their application to biological labeling", Single Molecules, 2, 261-276 (2001)