CAMD Receives NSF Grant for New Wiggler
The National Science Foundation, or NSF, has awarded LSU $1.26 million to purchase and install a new superconducting multi-pole wiggler, or MPW, at the Center for Advanced Microstructures and Devices, or CAMD, synchrotron ring. The award is believed to be the largest peer-reviewed equipment grant ever received by LSU.
 
Figures 1 & 2. Calculated photon flux from proposed 11-pole, 7.5 T wiggler versus current wavelength shifter and bending magnets at CAMD. Important for protein crystallography is the 12-fold increase at 12.66 keV (Se K edge). Similarly, tomography will enjoy 12- and 15-fold increases at 13.47 and 33.17 keV (Br and I K edges).
The MPW will increase the production of high-energy X-rays by 8 – 10 fold. Such X-rays are used for determining the structure of proteins, for the development of improved cancer treatments and for determining the nature of toxic metal atoms in pollutants among other uses. Studies will continue using the existing x-ray source until the MPW becomes fully operational in about two years.
The funding was secured through the NSF’s Major Research Instrumentation Program, a highly competitive nationwide program to fund large items of scientific equipment. The principal investigator on the grant is Professor Marcia Newcomer who is a protein crystallographer and chair of the LSU Department of Biological Sciences.
“Grant reviews emphasized the importance of CAMD as a regional resource for Gulf Coast scientists,” said Newcomer. “They also praised the facility for providing access to cutting-edge science to minorities and underrepresented groups.”
The LSU synchrotron at CAMD is an electron storage ring that produces intense beams of x-rays and ultraviolet light by passing the electrons through magnetic fields. The new MPW will have 11 superconducting magnets with a field strength of 7.5 Tesla – about 75,000 times stronger than the earth's magnetic field.
The new wiggler will serve four existing experimental stations called “beamlines,” which will be upgraded to withstand the greatly increased X-ray flux. The beamlines are dedicated to tomography and medical radiology, protein crystallography, X-ray absorption spectroscopy and deep-etch X-ray lithography.
Tomography uses x-rays to non-destructively visualize the internal structures of solids, similar to medical CAT scans but with approximately 1000 times better resolution. The same beamline is used by a medial radiology group to develop anti-cancer agents that can allow radiation to be more efficiently targeted to tumors.
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Tomography
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Figure 3. 3D reconstruction of absorption tomography data showing basic tissues in an adult cat claw.(32)
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The complex architecture of about 40 cat claws has been studied (see Figure 3). The cat claw serves as an example of a cornified organ (like human finger nails, bird beaks, and horse hooves) and of a complex structure that can be studied intact because the entire claw fits into the beam size at CAMD and APS and also because it is more complex that the claws of rats or mice. Although traditional histological and cytological techniques have been applied, only X-ray tomography was able to provide data instrumental in revealing the mechanism of claw shedding in cats. Due to this discovery, it was recently discovered that certain dogs also shed their claws! In addition, a fascinating variety of structural differences have been discovered for cats of different ages and for front versus rear paws. Diseased or damaged cornified organs (e.g., horse and cattle hooves, beaks of companion birds) cost multimillions of dollars in veterinary medicine and in losses to the owners of such animals. The study of the cat claw provides baseline data that can be applied towards a better understanding of the biology and pathology of all cornified organs.
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While CAMD is not a clinical imaging site, the proposed MPW will also facilitate projects relevant to research on breast cancer diagnostic imaging and therapeutic techniques which could be implemented on future clinical monochromatic X-ray devices. For breast radiology, several cancer types have been reported to alter the radiation contrast of breast tissue, providing a diagnostic means to identify breast cancer. CAMD can provide the monochromatic Xray beams to investigate these subtle changes. The higher flux and improved energy range from the MPW also facilitate phase-contrast imaging wherein X-ray refraction at tissue boundaries provides information on tissue morphology and composition that is unavailable with conventional X-rays. Thus, the proposed MPW will facilitate a larger user base of cancer researchers to utilize monochromatic x-ray imaging as a research tool. The Mary Bird Perkins Cancer Center will be receiving funding through DoD for exploration of new radiation treatment methods, which will be investigated in conjunction with LSU at CAMD. The DoD funding will upgrade the CAMD tomography beamline with a bigger experimental hutch as well as a second in-series monochromator with a 60 keV energy range and larger beam area. The objective is radiology experiments on biological samples, with an anticipated time allocation of 70% tomography and 30% biomedical.
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Radiation Therapy (K-edge Capture Therapy) |
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 Figure 4. Cell survival experiments
showing decreased survival with increasing replacement of thymidine by IUdR.
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A major focus of current research is K-edge capture therapy in which the radiation dose is localized by means of a drug (e.g. iododeoxyuridine, IUdR) that targets the DNA within cancer cells. Dose delivery is achieved by irradiating with monochromatic X-rays at energies just above the K-edge of a high atomic mass atom (e.g. iodine) attached to the drug, producing short-range Auger electrons. The proposed MPW is important to future research of K-edge capture therapy due to its approximately 13-fold higher flux at the iodine K edge (33.1 keV). Dr. Kenneth Hogstrom, who directs this program and is affiliated with the Mary Bird Cancer Center, has provided funding for a postdoctoral fellow, parttime radiation biologist, and graduate students. This group’s research is aimed at (1) developing clinically useful methods for beam dosimetry, (2) validating methods of dose calculations to be used for patient treatment planning, and (3) improving our understanding of the radiation biology associated with K-edge capture therapy. Experiments by his group (Figure 4) demonstrate the enhanced cell killing achieved by K-edge capture therapy with IUdR replacing ~17% of thymidine in DNA (orange diamonds), beyond the well-known radiosensitizing effect of IUdR to MeV radiation (red triangles).
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Protein crystallography is another experiment that is used to determine the three-dimensional shape of protein molecules, particularly enzymes. It has become an essential tool for the development of new drugs.
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Protein Crystallography
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The higher brightness from the proposed wiggler will provide opportunities for students and researchers to exploit this facility for studies involving smaller crystals and/or higher resolution data sets, both requiring intensity levels currently unavailable. The image on the left illustrates the Crystal structure of fosfomycin resistance kinase FomA from Streptomyces wedmorensis, from the Protein Data Bank. Of the 6311 X-ray structures deposited into the Protein Data Bank (PDB) in 2008, 4976 (79%) were from synchrotron data.
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Figure 5. An image from the Protein Data Bank showing the Crystal structure of fosfomycin resistance kinase FomA from Streptomyces wedmorensis complexed with diphosphate.
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X-ray absorption spectroscopy can determine the chemical state and type of chemical bonds of metal atoms. It has been used to investigate environmental samples resulting from flooding resulting from Hurricane Katrina, and to evaluate candidate catalysts for the production of synthetic fuels. The deep-etch X-ray lithography beamline is unique in the United States and can produce microstructures with very deep but also very narrow features, enabling LSU researchers to build “lab on a chip” devices for medical applications.
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X-ray Spectroscopy |
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 Figure 6. Transmission electron micrographs (TEM) of soot particles containing Cu-containing nanoclusters generated by combustion.
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Professors Dellinger and Poliakoff are involved in studies of nanoparticles that are generated in the combustion process. Depending on the source materials these soots can contain nanoparticles of transition metals and these can prove toxic in the environment. In their study of combustion-generated nanoparticles shown here, the clusters are clearly visible as the black dots on the fly-ash.
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 Figure 7. X-ray Absorption Near Edge Spectra (XANES) showing that the nanoclusters all contain Cu(II) species.
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The XANES spectra taken at CAMD clearly demonstrate that the Cu particles are C(II) species like that exhibited by CuO. Professor Dellinger is the lead PI on a new Superfund Center to study the “Health impacts of toxic Combustion by-products” funded by the National Institute for Environmental Health and Safety (NIEHS). |
“We are very excited about the new research that this instrumentation will enable in studies of energy, the environment, medicine and drug discovery.” says Professor Richard Kurtz, interim Director of CAMD. “This device will allow new cutting edge research programs and keep our faculty competitive, serving new centers like our new DOE Energy Frontier Research Center and the Superfund Center recently established through funding from the National Institute of Environmental Health and Safety.”
The new wiggler will serve four existing beamlines which will be upgraded to withstand the greatly increased x-ray flux. The beamlines are dedicated to Tomography and Medical Radiology, Protein Crystallography, X-Ray Absorption Spectroscopy and Deep-Etch X-Ray Lithography. We expect the MPW to become fully operational in about two years. The beamlines will continue to operate with the present single-pole system in the interim.
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