Molecular BioElectronics & Hybrid Electronic Systems - Recent Advances in Engineering and Application of Molecular Electronic Devices

Overview

Featuring Extensive Coverage of Bacteriorhodopsin

Recent advances in this heated field have shown very promising commercial opportunities:

Protein-based 3-dimensional optical memory and associative processors prototypes created are terabytes of memory around the corner?
FringeMaker first commercial holographic camera using protein as optical recording media
Biological and organic sensors and molecular microcircuits

An impressive pool of speakers have been invited from a variety of market sectors and academia in order to provide a well rounded and extensive dialogue covering:

Highlights of research, technology development, and commercial applications of bacteriorhodopsin as an excellent model for integrating biological materials into technical systems
Design approaches in nanoelectronics, nanobiotechnology, molecular engineering, and self-assembling on a sub-micron level
Photo-inspired molecular electronic systems and light-induced biological proton pumps
Optical data storage and image processing hybrid electronic devices
Nanotechnology and advanced imaging holographic systems

Please take a few moments to review the comprehensive program agenda and then reserve your place today!

Agenda

Thursday, October 19, 2000

8:00 Registration and Exhibit/Poster Set-Up, Coffee and Danish

Molecular BioElectronic Applications

9:00 Chairperson's Opening Remarks
Norbert A. Hampp, Ph.D., Professor, Institute of Physical Chemistry, University of Marburg, Germany

9:15 PROTEIN-BASED THREE-DIMENSIONAL MEMORIES AND ASSOCIATIVE PROCESSORS
Robert R. Birge, Ph.D., Professor, Departments of Chemistry, Molecular & Cell Biology, University of Connecticut
Molecular electronics offers a powerful and cost-effective path towards computer miniaturization and the generation of neural and three-dimensional architectures. Bioelectronics explores the use of native and genetically modified biomolecules and offers advantages because nature has generated unique materials with optimized properties through evolution and natural selection. This presentation will explore the use of the protein, bacteriorhodopsin, in optical three-dimensional memories and parallel associative processors. Three-dimensional memories store information in a memory volume element, and provide as much as a thousand-fold improvement in memory storage capacity over current technology. The comparative advantages and disadvantages of holographic, two-photon and sequential one-photon volumetric architectures will be discussed. The associative memory operates in a fashion somewhat analogous to the human brain and responds to input data by finding (in a few nanoseconds) the closest match within the database and feeding this information, and any associated information, to the output. Such a memory is critical to the development of artificial intelligence. The use of site-directed mutagenesis to improve the properties of the protein for specific applications will also be discussed. Although a number of working prototypes have been developed, a number of cost/performance and architectural issues must be resolved prior to commercialization.

9:45 SELF-ASSEMBLED SUB-MICRON LIPID TUBULES AND THEIR APPLICATIONS IN ELECTRONICS
Joel M. Schnur*, Ph.D., Director, Center for Bio/Molecular Science and Engineering, Naval Research Laboratory
Recent fundamental research has revealed the possibility to rationally form supramolecular aggregates from bio-molecules such as lipids, polypeptides or proteins. These self-assembled structures range in size from several nanometers (containing a few molecules) to hundreds of microns containing billions of molecules in well-defined molecular architectures. The ability to control both the morphology and size of these aggregates through modifications of both molecular structure, dispersion medium, and solution conditions suggests the possibility that they might be exploited to solve important problems in the development of advanced material applications in such diverse areas as controlled release or electro active composites. Tubules formed from phospholipids constitute a unique self-assembled microstructure and show promise in a number of technological applications. This talk will discuss advances that have led to the understanding of chiral behavior and the subsequent ability to control the structure of lipid-derived tubules and the resulting impact of this on materials applications.
*In collaboration with: A. Singh, R. Price, M. Spector, P. Schoen, and J. Selinger, Center for Bio/Molecular Science and Engineering, Naval Research Laboratory

10:15 PHOTOSYNTHESIS-INSPIRED MOLECULAR ELECTRONIC DEVICES
Elias Greenbaum*, Ph.D., Corporate Fellow and Research Group Leader, Oak Ridge National Laboratory
The nanobiotechnology research group at Oak Ridge National Laboratory has performed the first measurements of photovoltages from a single photosynthetic reaction center. The photosynthetic reaction center, Nature's photobattery, is approximately 5 nanometers in size. It is the specialized molecular structure in green plants that captures solar energy and converts it into electrical energy. We previously discovered that the photosynthetic reaction center is a nanometer size diode. These results, combined with our latest progress in the fabrication of dissimilar metal electrodes with nanometer interelectrode distances suggest a rational approach to the construction of biologically-inspired molecular electronic logic devices and ultra-light weight photovoltaic power sources.
*In collaboration with: I. Lee, J. W. Lee, M. A. Guillorn, and M. L. Simpson, Oak Ridge National Laboratory

10:45 Refreshment Break and Exhibit/Poster Viewing

11:15 USE OF ACTIVE MICROELECTRONIC DNA ARRAYS FOR FLUORESCENT PERTURBATION AND OTHER BIOPHOTONIC-BASED ANALYSES
Carl Edman, Ph.D., Senior Staff Scientist, Nanogen Inc.
Microelectronic chip-based systems are being developed for single nucleotide polymorphism (SNP) analysis, pharmacogenomic research, DNA diagnostics, and drug screening applications. A 100-test site active microelectronic chip and cartridge device have been fabricated for the DNA hybridization-based applications. A programmable chip addressing component is designed to provide the end-user with make your own chip capabilities. A fluorescent reader and controller component is designed to carry out rapid and reliable multiplex DNA hybridization for single nucleotide polymorphism (SNP), point mutation and short tandem repeat polymorphism (STR) analysis for genetic disease diagnostics and for forensic applications. A unique fluorescent perturbation technique has been developed which allows single base mismatches to be rapidly detected using a single fluorescent probe. The technique involves using a pulsing electric field to perturb the fluorescent emission from the reporter probe. Match and mismatched DNA targets produce a different oscillating fluorescent signal that allows the targets to be easily differentiated.

11:45 MICROELECTRONIC INTERFACES FOR ONE AND TWO WAY COMMUNICATIONS WITH ORGANISMS
Alan S. Rudolph, Ph.D., MBA, Program Manager, Defense Sciences Office, DARPA
Significant advances in the design and fabrication of small integrated electronic interfaces have enabled new research and development directed at tapping into the sensory processing in organisms from single cells to complex animal systems.The ability of such interfaces to measure signals in freely moving, behaving organisms as they interact with their environment has enabled a number of applications such as cell-based sensors and diagnostics, automated behavioral monitoring systems based on olfaction or other sensor modalities, and new biomimetic pattern recognition algorithms inspired from such efforts.

12:15 Special Key Note Lecture
THE ADVANCED TECHNOLOGY PROGRAM AT NIST TO FUND HIGH RISK INNOVATIVE R&D TOWARDS COMMERCIALIZATION
Gradimir Georgevich, Ph.D., Program Manager, National Institute of Standards and Technology
The Advanced Technology Program (ATP) at the National Institute of Standards and Technology is a program that funds innovative research projects that bridge the gap between the research lab and the marketplace stimulating prosperity through innovation. ATP helps companies develop their technologies and get new ideas and innovations to the marketplace more quickly. ATP provides cost-sharing funding in the critical early stages of R&D. We can fund up to $2,000,000 in direct costs over a period not to exceed 3 years for single companies and up to half the total of a project for joint ventures for a period up to 5 years. ATP encourages R&D partnerships and consortia, and can provide guidance in putting together a joint research venture. Our rigorous peer-review system provides an independent, objective, and confidential evaluation of the strength of your R&D and business plans. Companies control and retain the intellectual property rights to the results of their research.

12:45 Lunch, Sponsored by The Knowledge Foundation

Bacteriorhodopsin: Research and Technology Development

1:55 Chairperson's Remarks
Deepak Srivastava, Ph.D., Senior Scientist and Task Leader, NASA Ames Research Center

2:00 PHOTOCHROMIC APPLICATIONS OF MODIFIED BACTERIORHODOPSINS
Norbert A. Hampp, Ph.D.
Bacteriorhodopsin (bR) served during the last decade as a model system to explore the strategies to include functional biological materials into conventional systems. There are several reasons which make bR a first choice candidate for this approach. The first one is the thermodynamic stability of bR which is due to its occurence as a two-dimensional crystalline array. Second is that the molecular function of bR is known with nearly atomic resolution. Third is that the genetic tools have been developed to modify the natural occuring bR at will. And last but not least, each of the physical functions of bR, i.e. its photoelectric,
photochromic and proton pumping properties, is a candidate
for a technical application. In this presentation the different photochromic applications are reviewed and their future technical potential is analyzed.

2:30 MOLECULAR CONTROL OF LIGHT-INDUCED PROTON MOVEMENT IN BACTERIORHODOPSIN
Sergei Balashov*, Ph.D., Senior Scientist and Research Professor, Center for Biophysics, Departments of Cell and Structural Biology & Biochemistry, University of Illinois at Urbana-Champaign
Light absorption by bacteriorhodopsin leads to deprotonation of the Schiff base which attaches the retinal chromophore to the apoprotein. Almost coincident with this event at neutral pH, a proton is released from the extracellular surface of the pigment. The timing and pH dependence for the released proton can be altered in mutant pigments. Ways to manipulate this process are discussed.
*In collaboration with: T.G. Ebrey, University of Washington

3:00 Refreshment Break and Exhibit/Poster Viewing

3:30 CRYSTALLOGRAPHIC STUDY OF THE STRUCTURE AND PHOTOCHEMICAL CYCLE OF BACTERIORHODOPSIN
Janos K. Lanyi, Ph.D., Professor and Chair, Department of Physiology and Biophysics, University of California, Irvine
The atomic structure of the light-driven ion pump bacteriorhodopsin was determined to 1.55 Å resolution by X-ray diffraction of protein crystals. In the extracellular region an extensive 3-dimensional hydrogen-bonded network of protein residues and seven water molecules leads from the buried retinal Schiff base and the proton acceptor asp-85 to the membrane surface. Near lys-216 where the retinal binds, transmembrane helix G contains a -bulge that causes a non-proline kink. The bulge is stabilized by hydrogen-bonding of the main-chain carbonyl groups of ala-215 and lys-216 with two buried water molecules located between the Schiff base and the proton donor asp-96 in the cytoplasmic region. The changes in this structure during the photochemical cycle were determined for the M intermediates of the D96N and E204Q mutants, to 1.8 and 2.0 Å resolutions, respectively. These photoproducts arise after proton transfer from the retinal Schiff base to asp-85, with and without release of a proton to the extracellular membrane surface, but before reprotonation of the Schiff base. Their density maps describe displacements of main-chain and side-chain atoms and water molecules near the retinal induced by its photoisomerization to 13-cis,15-anti. They account for the changed pKs of the Schiff base, asp-85, and asp-96. The structural changes detected suggest the means for conserving energy at the active site, and for ensuring the directionality of the proton translocation.

4:00 NMR PROBES OF SUB-ÅNGSTROM CHANGES IN THE ACTIVE SITE OF BACTERIORHODOPSIN: Evidence for an Electrostatic Steering Mechanism of Energy Transduction
Judith Herzfeld, Ph.D., Professor, Department of Chemistry, Brandeis University
Diffraction studies suggest that very subtle rearrangements of the active site are responsible for vectorial action in bacteriorhodopsin. Solid state NMR allows highly sensitive measurements of interactions, internuclear distances and dihedral angles in the photocycle intermediates. The results are consistent with electrostatic control of a decisive switch in connectivity between the two sides of the membrane during proton transport.

4:30 Selected Oral Poster Presentations and Discussion

5:15 Close of Day One

Friday, October 20, 2000

8:15 Coffee, Danish and Exhibit/Poster Viewing
Molecular Electronic Engineering and Design Approaches

8:45 Chairperson's Remarks
Joel M. Schnur, Ph.D.

9:00 MOLECULAR ENGINEERING USING THIN ORGANIC FILMS
Michael C. Petty, Ph.D., Professor, Co-Director, Durham Centre for Molecular Electronics, University of Durham, United Kingdom
Molecular Electronics is concerned with the exploitation of organic compounds in electronic and optoelectronic devices. The subject can be divided into two main themes (although there is substantial overlap). The first concerns the development of devices exploiting the unique macroscopic properties of organic compounds. Examples here are organic electroluminescent displays, pyroelectric imaging devices and chemical sensors. The second strand to molecular electronics recognizes the dramatic size reduction in the individual processing elements in integrated circuits. Molecular-scale electronics therefore deals with the manipulation of organic materials at the nanometer level. There are relatively few techniques currently available to manipulate organic materials on this scale. Examples are Langmuir-Blodgett deposition, self-assembly and layer-by-layer electrostatic adsorption. This presentation will provide an overview of such methods and discuss applications of these organic superlattices to the field of molecular electronics.

9:30 DESIGN APPROACHES TO NANOELECTRONICS AND BIOELECTRONICS
Jorge M. Seminario, Ph.D., Associate Professor
and Director of Physical Chemistry Laboratories, University of South Carolina
A top-priority objective in nanoelectronics and bioelectronics is the design of logical and control circuits using molecules so that the feature size of present computers can be dramatically reduced by several orders of magnitude. I will show plans and techniques developed in our group for the design of nanoelectronic and bioelectronic devices. Biomolecules present redundancy characteristics in order to perform time-dependent and nonlinear operations, which are nature's brilliant solutions to our existence, and our goal is to use them in the development of nanoelectronics.

10:00 MOLECULAR BIO- AND HYBRID-ELECTRONICS FROM AN APPLICATION PERSPECTIVE
Deepak Srivastava, Ph.D.
Molecular bio- and hybrid-electronics is reviewed from an applications perspective. Contributions coming from diverse disciplines such as bio-molecular systems, conjugated organic molecular systems, and nanoscale materials molecular systems give rise to numerous applications possibilities. Prominent among these are devices and switches based on individual molecules, molecular wires and tubules as interconnects, functional molecules as sensors, detectors and diagnostic tools, and molecular implementation of simple logic functions. This talk will review, compare and contrast the above applications for biomolecules such as DNA and bacteriorhodopsin, conjugated organic molecules, and nanomaterials molecular systems such as carbon and protein nanotubes.

10:30 Refreshment Break and Exhibit/Poster Viewing

11:00 OPTICAL TWEEZERS-BASED IMMUNOASSAY DETECTS ATTOMOLAR CONCENTRATIONS OF ANTIGENS AND NUCLEIC ACID TARGETS
Kristian Helmerson*, Ph.D., Physicist, Atomic Physics Division, National Institute of Standards and Technology
Tightly focused beams of laser light can be used to trap and remotely manipulate polarizable objects. Such devices are capable of trapping latex and glass spheres in the micron size range. The basic principle behind the optical trapping is the gradient force of light that manifests itself when a transparent material with a refractive index greater than the surrounding medium is placed in a light intensity gradient. As light passes through the polarizable object, it induces fluctuating dipoles in the material. These dipoles interact with the electromagnetic field gradient, resulting in a force directed towards the brighter region of the light. Hence the object is pulled into the focus of the laser beam that is the local maximum of the light field. Latex beads have been coated with antigen and used to determine the minimum laser power required to pull the sphere into the trap and break the bonds between the antigen (Ag) and the glass coverslip coated with either non-specific protein or specific antibodies (Ab). Greater laser power (force) is required to break the specific Ab/Ag bond versus the non-specific binding cases. We have observed that difference even at the level of a single Ag/Ab bond. Using a competitive binding approach, we have been able to detect less then 100 molecules in a 100 µL sample. Similarly this same process can be followed for the interaction of complementary DNA or RNA probes on a latex particle and a glass coverslip at the same sensitivity level, thus eliminating the need for amplification technologies. This technology also should be applicable to the detection of endotoxins, receptor binding molecules, and any other system involving binding pairs. This approach has not yet been optimized for time or sensitivity.
*In collaboration with: H.H. Weetall, R. Kishore and W.D. Phillips, National Institute of Standards and Technology

11:30 THE DESIGN AND CONSTRUCTION OF A GENETIC TOGGLE SWITCH IN ESCHERICHIA COLI
James J. Collins*, Ph.D., Professor, Department of Biomedical Engineering, Boston University
Advances in biology and medicine are making gene therapy an increasingly practical approach to the treatment of human diseases. However, the range of regulatory behaviors permitted by current gene-expression systems is limited to the up- or down-regulation of genes in response to a sustained small-molecule signal. Here, we present the construction of a genetic toggle switch a bistable gene expression network in Esherichia coli. The toggle, which exhibits two stable expression states and a nearly ideal switching threshold, is flipped between states using transient chemical or thermal induction. The generality of the toggle switch design suggests that it will be applicable in higher organisms. As a practical device, the genetic toggle switch has significant implications for gene therapy and biotechnology. In addition, the toggle switch is a flexible and addressable cellular memory unit. Thus, it forms the basis for programmable, synthetic gene regulatory networks.
*in collaboration with T.S. Gardner, and C.R. Cantor, Boston University

12:00 BIOIMAGING USING VOLUME HOLOGRAPHIC OPTICAL ELEMENTS
George Barbastathis, Ph.D., Assistant Professor, Massachusetts Institute of Technology
Volume holograms are the most powerful optical elements, since they allow maximum degrees of freedom in transforming optical fields. We present several imaging architectures based on volume holography; in particular, a) a pinhole-free confocal microscope where the volume hologram acts as a depth-selective matched filter, b) a four-dimensional imaging system where several multiplexed volume holograms redistribute the three spatial and one spectral degress of freedom of a semi-transparent polychromatic object onto a detector surface where the object is imaged in real time, c) super-resolved imaging where some of the degrees of freedom of the volume hologram are used to overcome the usual resolution limit imposed by the optical aperture. Such powerful imaging systems promise significant advances in the dynamic study of biological systems ranging from single molecules to neurons and to entire organs.

12:30 Lunch on your own

Protein-Based Hybrid Electronic Systems

1:55 Chairperson's Remarks
Robert R. Birge, Ph.D.

2:00 FRINGEMAKER THE FIRST COMMERCIAL SYSTEM BASED ON BACTERIORHODOPSIN
Norbert A. Hampp, Ph.D.
The FringeMaker system is a holographic camera which uses bacteriorhodopsin (bR) films as photowritable/photoerasable optical recording media. This system is designed for applications in non-destructive testing, vibration analysis and size measurement. To our knowledge this is the first commercialized optical system were bR-films are employed. The FringeMaker System is able to resolve deformations down to 5 nm (l/100) and operates in 20 frames/second. The camera head is dust proof sealed and internally damped for applications in an industrial environment. All control and display devices are mounted in a 19 rack which comes with the FringeMaker system. The system can be applied without any specific knowledge on bR.

2:30 IMPROVED SENSITIVITY IN BLUE-MEMBRANE BACTERIORHODOPSIN FILMS
Richard Needleman, Ph.D., Professor, School of Medicine, Wayne State University
The mutant D85N/V49A has significantly improved optical properties compared with wild type bacteriorhodopsin. Absorption studies of the mutant in solution show that it forms P(490) at light levels comparable to wild-type films. Theoretical calculations based on Kramers-Kronig transformation of light induced absorption data predict that refractive index is three times larger than that of mutant D85N. Holographic measurements performed on gelatin-based films confirm that sensitivity is improved by a factor of 50 over D85N.

3:00 HYBRID BACTERIORHODOPSIN-BASED SEMICONDUCTOR DEVICES
Jeffrey A. Stuart*, Ph.D., Assistant Professor, W.M. Keck Center for Molecular Electronics, Syracuse University
Molecular electronic applications for bacteriorhodopsin (bR) have been primarily photonic in nature, from holographic and three-dimensional optical memories to spatial light modulators and associative processors. Newer applications employ the protein's photoelectric properties, consisting of the sub-picosecond photovoltaic effect and a millisecond photocurrent. These properties have been harnessed to produce prototype photovoltaic cells and fast photodetectors, as well as artificial retinas. More recently, efforts have been made to incorporate bR into microscale and nanoscale semiconductor devices, with the goal of utilizing its light-induced electrical signal to modulate the properties of the device. For example, a thin polymer film containing bacteriorhodopsin could be used as the gate in a field effect transistor. The artificial retina and the bR-gated FET represent a new hybrid technology, integrating bacteriorhodopsin with semiconductor-based devices. Ongoing research at the W. M. Keck Center for Molecular Electronics at Syracuse University is aimed at development of bR-based hybrid technologies. Recent advances in the development of this technology will be discussed, with specific emphasis on the artificial retina and obstacles that must be overcome in order to make robust hybrid bR-semiconductor devices possible.
*In collaboration with: D.L. Marcy, Syracuse University, R.R. Birge, University of Connecticut

3:30 Refreshment Break and Exhibit/Poster Viewing

4:00 RHODOPSIN-BASED ELECTRONIC DEVICES AND MATERIALS
Claudio Nicolini, Ph.D., Professor and Chairman, Department of Biophysical Sciences and Technologies, University of Genova, Italy
Thin LB layers of light sensitive proteins, such as photosynthetic reaction centers and rhodopsins, either alone and/or their hybrids with organic and inorganic materials, are reviewed, form the basis of molecular bioelectronics and its numerous applications resulting from the above supramolecular architectures. Properly oriented Langmuir-Blodgett films of purple membranes and of rhodopsins from various organisms confirmed their potential in providing unique properties in molecular recognition, transudation, information processing and energy conversion, because of their unique structural and functional stability to long storage, experimental manipulation bottom-up and temperatures up to 200_C. Similarly their integration with conducting polymers and other new material such as fullerenes provide unique candidates for competitive electronic devices, namely transducers, photovoltaic cells, memories, displays and sensors. Some properties of the formed structures are quite superior to traditional electronic technology approaches. A few key examples of rhodopsin-based molecular bioelectronic devices are summarized in the presentation.

4:30 OPTICAL DATA STORAGE, IMAGE PROCESSING AND BIOSENSING WITH BACTERIORHODOPSIN
Vladimir B. Markov*, Ph.D., Head of Applied Optics Group, MetroLaser Inc.
Bacteriorhodopsin (bR) has been proven to be an effective media for a variety of engineering applications, such as optically addressable spatial light modulators, volumetric memories, optical image processing systems, optical sensors, optical correlators and biosensors. However, practical realization of such systems with a bR depends upon the specific characteristics of this material. In this report we present experimental results of the time evolution and intensity dependent characteristics of a bR in the gelatin film and liquid form. In particular we studied the spectral dependence of the optical density/refraction index modulation. The two-channel time evolution technique was used for biosensor applications, in which the response of the modified and non-modified bR is compared to retrieve the information. A holographic technique was used to investigate the exposure characteristics of photorefraction and recording versus storage time. Also the connection between the diffraction efficiency of the recorded grating and light induced scattering (noise) the parameters that are of primary importance for such applications as high-density memory systems and optical correlators was investigated.
*In collaboration with: A. Khizhnyak, A.K. Lal, J.E. Millerd, J. Trolinger, MetroLaser Inc., and R. Needleman, Wayne State University

5:00 General Discussion

5:30 Chairperson's Remarks

5:35 Close of Conference

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Call for Posters

Call for Posters
Industry and academic scientists are encouraged to submit poster titles for this event. One-page Abstracts (8 1/2. x 11. with 1-inch margins) must be submitted no later than August 10, 2000 for inclusion in conference documentation. Additional poster submissions will be accepted until August 31, 2000 but may not be included in conference documentation. Note: The poster board reservation fee is $35. If you are submitting a poster, you MUST be registered and paid in advance to ensure that a posterboard is reserved for you.

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