Raman Spectroscopy of Carbon Nanostructures

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					Biophysics Group Overview of Capabilities

The focus is on measurement science and technology in support of:
   Structural Biophysics
        Novel spectroscopies and microscopies to elucidate structure
        Theory and modeling to help interpret and guide measurements
   Functional and Dynamical Biophysics
        Imaging to delineate molecular mechanisms
        Spectroscopy for molecular dynamics
        Theory and modeling to elucidate underlying physics
   Systems Biology
        Complementary measurements to address complex problems
        Integrated measurements for diagnostics and screening
        Nanobiological probes for more sensitive and selective detection
        First principles modeling to predict outcomes

Overview of the toolset:
   Spectroscopy and Microscopy:
      to enable biochemical imaging to determine molecular composition
      to measure structures and dynamics
      to elucidate biochemical kinetics
      to understand interactions at the single molecule level
      to visualize nanoscopic interactions in a larger context
   Nanobiological Probes:
      to elucidate signaling pathways
      to enhance detection sensitivity and selectivity
      to facilitate imaging
   Theory and Modeling to Delineate the Underlying Physics:
      to understand mechanisms
      to interpret and inform experiment
      to validate predictive models using first principles
Overviews of selected projects:

Laser Studies of Polypeptide structure and dynamics
David Plusquellic

THz radiation interrogates the lowest frequency collective motions of biomolecular
systems. These collective modes characterize the incipient motions for the large scale
conformational changes along the torsional coordinates responsible for the flexibility of
protein, polynucleotide and polysaccharide backbones during folding and activation. The
unique properties of this spectral region are evidenced by the sensitivity to the ii)
collective motions that extend across large portions of the biomolecular framework with
length scales that extend over tens of angstroms, ii) protein/water interaction dynamics
that occur on sub-ps timescales and iii) an energy domain similar to the thermal energies
required for biological activity. Furthermore, the THz region provides a sensitive probe
of crystalline order, temperature, conformational form, peptide sequence, solvent
interactions, H-bonding force constants and anharmonic character of the force fields. In
our lab, high-resolution continuous-wave terahertz (THz) sources are used to measure the
spectra of bulk (pellet) samples and aqueous samples over a wide range of temperatures
as low as 1.6 K, We have also developed methods to enhance absorption sensitivity for
orientated thin-film (<1 um) samples deposited on waveguide interfaces. Numerous co-
solvated peptide crystals have been investigated including a series of hydrophilic and
hydrophobic nanotube structures. Of biological significance is the water permeability
through hydrophobic pore regions as exemplified in the disparate behavior across these
nanotube structures. For example, alanyl-isoleucine dipeptide is known from x-ray
studies and confirmed in our THz studies to act reversibly to the exchange of water while
its retroanalog, isoleucyl-alanine, does not accept water into its pore region. Quantum
chemical (DFT/PW91) calculations performed on periodic solids in combination with
gas-phase microwave data on numerous peptide mimetics have aided in characterizing
the nuclear motions probed in the THz region and have elucidated some of the principal
deficiencies in classical force field models like CHARMm. These calculations also serve
to better understand the subtle balance that determines guest water absorption and
conduction through the hydrophobic channels. For example, examination of the
vibrational character of the THz modes with and without water suggests water mode
coupling/decoupling with collective modes of the nanotubes may play an important role
in the permeability dynamics.

Nanobiophotonics for Quantitative Biophysics and Next Generation Medical
Jeeseong Hwang
                                        We have been developing and applying advanced
                                        molecular imaging techniques to enhance the speed
                                        and accuracy in the measurement of multiple
                                        biomarkers in cells and biomimetic samples at the
                                        molecular level. We are also developing novel
                                        image-based combinatorial molecular pathology
                                         methods such as multiplexed enzyme-linked
 Brightfield (L) and fluorescent (R)     immunosorbent assay (ELISA) using a protein
 images of a human erythrocyte infected  microarray platform. Current imaging techniques
 with a malaria parasite. Parasite-      include non-linear multiphoton microscopy and
 produced      target     proteins were  fluorescence    lifetime    imaging;    engineered
 genetically modified to express GFP     nanocrystals (quantum dot and metal nanoshell)
 and tetracysteine domains so the        biosensors capable of targeting, analyzing, and
 protein trafficking can be studied at   photo-thermally eradicating tumor cells and
 different stages of infection.          pathogens; and multimodal 5D (x, y, z, t, )
                                         imaging capabilities for the study of fundamental
                                        cellular mechanisms involving specific biomarkers.
Terahertz Tools for Investigating Protein Interactions
David Plusquellic

                         The THz region provides an unprecedented measure of biophysical
                                       properties that are necessary to improve
                                       predictability in drug discovery and design but not
                                       readily obtainable using other methods. We develop
                                       measurement tools and techniques to enhance
                                       detection sensitivity and selectivity of the
                                       fundamental elements of protein structure in bulk
                                       and within waveguide structures. These studies, for
                                       example, have provided benchmark data of peptide
                                      nanotubes for the validation of classical and
 THz waveguide geometry for peptide   quantum chemical models, and have demonstrated
 studies. Inset is a peptide nanotube the exquisite sensitivity of this region to crystalline
 chemical structure.                  order, temperature, conformational form, peptide
                                      sequence and local solute environment.

Pharmaceutical Terahertz Spectroscopy and Infrared Chemical Imaging
Edwin Heilweil

                                          Novel process analytical technologies (PATs) are
                                          being sought by the FDA to improve quality control
                                          during online tablet production.           Terahertz
                                          spectroscopy applied to biomolecular systems
                                          shows promise because of its specificity to drug
                                          structure, hydration levels and tablet pressing
                                          conditions. Infrared hyperspectral imaging, being
                                          developed to determine composition, chemical, and
                                          drug location in tissues relevant to medical imaging
                                          technologies will also be presented.

 THz image of an Excedrin tablet. Such
 online hyperspectral imaging methods
 are being developed to identify tablet
 constituents during processing.
Quantitative Optical Imaging for Clinical Use
Maritoni Litorja

                                          We apply our technical expertise in calibration and
                                          validation of optical instrumentation used for
                                          remote sensing to applications in optical imaging
                                          for clinical use. Current projects include the
                                          development of an electronic phantom as a
                                          calibration tool for hyperspectral imagers, the
                                          development of a lighting source with enhanced
                                          color contrast for intraoperative use based on vision
                                          science models, and the development and assembly
                                          of a research-grade, fast hyperspectral imager as a
                                          visualization tool for a surgeon.

Near-infrared hyperspectral image data
are used to extract the location of the
bile duct during a cholecystectomy.

Raman Spectroscopy of Carbon Nanostructures
  A Hight Walker

The multibody effects in the optical spectra of single-walled carbon nanotubes (SWCNT)
and other carbon nanostructures are investigated using resonant Raman spectroscopy.
Resonance enhancement of the Raman scattering intensity of the radial breathing mode in
SWCNTs is used as a probe of tube chirality and of one-dimensional electronic structure.
The confocal magneto-Raman microscope at NIST permits continuously tunable laser
excitation from the near-infrared to the ultraviolet. This novel Raman facility consists of
a microscope capable of working over a wide range of temperatures (T = 4.2-300 K) and
magnetic fields (H = 0-8 T) coupled to a triple grating spectrometer with ultimate Raleigh
rejection capabilities, thereby permitting low-frequency or Terahertz Raman
spectroscopy. As a member of a multidisciplinary NIST team focused on nanometrology
for carbon nanostructures, we obtain measures of sample characteristics of value to
academic,                 industrial                 and              nano-environmental,
-health, and -safety (Nano EHS) communities such as sample quality, purity, alignment,
and physical features (e.g. diameter and length). Unprecedented nanotube samples are
available permitting the study of fundamental physical properties. Characterization of
bulk, single, DNA-wrapped, suspended, and nanoparticle-functionalized SWCNT
samples are all of interest to the program. Furthermore, the unique optical properties of
complementary materials such as graphene are critical components. A large, NIST-wide
program in graphene measurement science is underway to explore the underlying physics
of this novel material. It includes the combination of Raman, STM, QHE, with device
fabrication and substrates of, but not limited to, SiC and SiO2.
Nanoparticle Engineering, Production, Assembly, and Characterization
  A Hight Walker

Photonic and magnetic nanoparticles have shown great potential in a wide range of
applications such as catalysis, information storage, energy, and medicine. Our research
program focuses on engineering these nanoparticles with desired physical and chemical
properties and specified functionality via wet-chemistry synthesis. We are particularly
interested in engineering photonic nanoparticles such as gold, silver, and copper with
novel optical properties and magnetic nanoparticles such as iron and cobalt and exploring
their biological applications through optical spectroscopy and magnetic measurements.
Their physico-chemical properties are being studied specifically for their relevance to
Nano-EHS and toxicology. Synthesis, assembly, characterization, and application of
nano-engineered materials are all critical components of the program. A wide variety of
tools are available for this effort, including HR-TEM, SEM, UV-VIS, SQUID, and

Enhanced Raman Spectroscopy of Biological Molecules
  A Hight Walker

Research efforts are underway to probe biological molecules with Raman spectroscopy in
three states—crystal, semi-solid, and solution—to illuminate the structural
transformations that occur across phases. The optical characterization of biological
molecules using vibrational spectroscopy supplies critical, detailed structural information
unavailable through fluorescent measurements and unhampered by water absorption. To
observe Raman-active vibrational modes, physiological concentrations, enhancement of
the Raman scattering cross-section is often necessary. Enhancement factors of orders of
magnitude are achievable through resonance Raman (i.e., matched laser excitation with
electronic transition, or surface enhanced Raman), where anisotropic, metallic
nanoparticles of silver or gold are placed in close proximity to the molecule, either in
solution or on a surface. Two Raman spectrometers are available for this effort, including
a microscope and multiple laser lines. Also exciting is a combination of Raman
microscopy and microfluidic technology to monitor the vibrational spectra of
biomolecules while rapidly changing the buffer environment to induce conformational
changes. Raman spectroscopy can be used to query the structure of membrane proteins
immobilized in supported, synthetic lipid bilayers both on a surface and in suspended
liposomes. Furthermore, Raman microscopy can be used to view protein concentration
gradients throughout a cell.
    Another angle of our research effort focuses on the low-frequency torsional modes
(<200 cm-1) of proteins and polynucleotides. This region of the spectrum is rich with
dynamical and structural information. A triple-grating monochromator provides the
rejection capabilities necessary for observing these low-frequency vibrations. A
companion molecular modeling effort is absolutely critical due to the complexity and
nascency of this spectroscopic region, and is implemented with the aid of a 6-node UNIX
cluster and computational software. The combination of this effort, with both its
experimental and theoretical sections, with the complementary CW Terahertz
Spectroscopy effort described elsewhere, greatly increases our ability to assign torsional
vibrational modes to the flexibility of the biological molecule and provide the force field
information needed to delineate the driving forces responsible for protein structure,
folding, and function.

Computational Methods to Investigate the Dynamics and Interactions of Biological
  Anne Chaka

In order for DNA to function, it must stretch, bend, zip and unzip in response to external
forces and interactions with other biological molecules. Understanding the mechanisms
and dynamics of DNA behavior is important for understanding gene replication,
regulation, and aspects of cancer and chemotherapy. In addition, the last 15 years have
seen the development of single molecule experiments that can measure the response of
isolated DNA molecules to applied forces that is laying the groundwork for a wide array
of applications of DNA in biotechnology such as nano- and pico-scale sensors and
mechanical devices. Our work focuses on the current challenge to relate structural and
dynamic changes in DNA to observed biological and mechanical properties through the
use of molecular dynamics simulations and quantum mechanical methods and close
collaboration with experimentalists.

Quantifying the Underlying Physics of Molecular Interactions
  Anne Chaka

Weak nonbonded interactions between molecules are extremely important in determining
the structure and properties of a wide range of phenomena – including biological systems,
industrial fluids, polymers and composites, molecular crystals, self-assembled
monolayers, and molecular aggregates. Constructing predictive models that describe
these systems is challenging because these weak forces depend on subtle quantum effects
that are difficult to capture with the phenomenological models currently in use. We work
to delineate the fundamental chemistry and physics that drives molecular interactions,
including the balance of enthalpy and entropy as well as van der Waals forces,
electrostatics, and hydrogen bonding. We are currently focusing on using quantum
mechanics and molecular dynamics simulations to quantify the interactions and calculate
the thermodynamics of biological molecules, molecular crystals, and fluids.

Surface Properties by Design: Theory of Metal Oxide Surfaces in a Complex
Environment for Industrial and Environmental Applications
   Anne Chaka

Metal oxide surfaces of both nanoparticles and bulk materials are extremely important in
a wide variety of technological applications such as catalysis, sensors, microelectronics,
and wear and corrosion protection in mechanical and structural components. In addition
the reactivity of metal oxides surfaces play a dominant role in determining whether toxic
pollutants such as lead, chromium, and arsenic are bioavailable in ground water or are
sequestered on nanoscale mineral particles. Most experimental and theoretical work is
done under high vacuum conditions on clean, regular, well-characterized surfaces, which
can be very different from ―real‖ surfaces exposed to industrial or geological conditions.
We use first-principles density functional theory integrated with thermodynamics to
determine phase diagrams and reactivity of surfaces in a complex environment to predict
what happens under realistic conditions where it is difficult to probe experimentally.
Current research focuses on mixed metal oxide systems for (1) catalysis, chemical
sensors, and design of coatings to passivate metal alloys, (2) design of nanoparticles
surface properties, (3) adsorption and reactivity of environmental pollutants on
nanoparticles surfaces. Collaboration is encouraged with experimental groups within
NIST, in academia, and in industry.

General Computational Chemistry and Physics Capabilities
   Anne Chaka

Delineating reaction mechanisms; determining activation barriers in reaction pathways;
calculating spectra such as IR, Raman, NMR chemical shifts, UV/Vis, electronic
excitations, core level shifts; determining structure-property relationships.