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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
Michael J. Heller, Ph.D., Chief Technical Officer, 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
Howard H. Weetall, 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
Thomas G. Ebrey*, Ph.D., Professor, University of Washington
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: S. Balashov, University of Illinois
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 š-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
Howard H. Weetall*, Ph.D.
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: K. Helmerson, 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 200ÞC. 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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