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Posted: Apr 24, 2012
Northwestern University and Argonne National Lab Using Breakthrough Xradia Microscopy Solution to Advance Life Science Research
(Nanowerk News) Researchers at Northwestern University's Department of Radiation Oncology and the U.S. Department of Energy's (DOE's) Argonne National Laboratory recently deployed a new non-destructive X-ray microscopy solution from Xradia to image cryogenically preserved cells and advance studies of intra-cellular biology. Northwestern's joint development of trace element imaging methodologies with the DOE Office of Science's Advanced Photon Source (APS), Argonne's synchrotron radiation facility, informs the study and potential treatment of cancer, neurological disorders and other diseases and conditions involving the accumulation of metals within cells.
A recent addition to Xradia's UltraSPX™ family of non-invasive 3D X-ray microscopes, the Bionanoprobe represents the only imaging solution able to deliver high-resolution X-ray trace element mapping and tomography of cryogenically preserved samples down to 30 nanometers. Dr. Gayle Woloschak, Professor of Radiation Oncology at the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, believes these combined capabilities will uniquely advance researchers' understanding of what occurs inside cells.
"We'll be asking questions such as, What role do trace metals such as Zinc or Iron play in natural cellular processes like cell division and aging? Can we get nanoparticles into the nucleus and produce the reaction we want? What part of a cell does Mercury or Plutonium end up in when exposure occurs?" says Dr. Woloschak, principal investigator of the Bionanoprobe project. "We will now be able to detect patterns and basic biological processes with much greater sensitivity than we could in the past."
The need for an X-ray imaging instrument that could achieve the resolution and sensitivity obtained by the Bionanoprobe was identified by Dr. Woloschak and a group of colleagues more than a decade ago, and its development by Xradia was made possible by recent U.S. government stimulus programs. "Over the years, the community of X-ray fluorescence microscopy researchers has identified a number of requirements that need to be met to take this area of science to the next level," says Dr. Stefan Vogt, Microscopy Group Leader at the APS, who contributed to the design of the Bionanoprobe. "We really needed a new class of instruments that can image whole, unsectioned cells in 3D, in their natural, hydrated state, and at a resolution significantly below 100 nm."
Deployed last fall at the APS beam line operated by the Life Sciences Collaborative Access Team (LS-CAT), the Bionanoprobe is already enabling new, more cohesive imaging procedures. "We expect this unique capability to produce new insights into the behavior of nanoparticles within cells, in pharmacology and toxicology, environmental studies and other vital areas," says Dr. Keith Brister, LS-CAT Operations Manager.
Unveiled in 2011, Xradia's Bionanoprobe enables imaging in four different modes: high resolution X-ray Fluorescence (XRF), transmission, spectroscopy, and tomography. The combination of these techniques provides information on elemental content, structure and chemical state, in 3D, over a wide range of length scales. Previously, to examine cells and other samples at progressively higher resolutions, researchers typically switched between multiple techniques such as magnetic resonance imaging (MRI), computed tomography (CT), visible light microscopy and electron microscopy, often using different samples and different preparation techniques for each one.
"Using one technique makes it possible to compare elements more precisely," says Dr. Woloschak. "Traditionally, looking at tissue under a regular microscope then moving to an electron microscope requires that we use different sections and preparation techniques, which can introduce artifacts and make it hard to compare and co-localize features. The best we could do is match as closely as possible; we couldn't look at the exact item under varying conditions."
The Bionanoprobe is also the first imaging solution to combine ultra-high resolution trace element mapping with cryogenic sample preservation and tomographic capabilities. Cryo preservation is essential to study cells and tissue in a state closely resembling that of being alive, while minimizing the effects of radiation damage that can distort the results. Tomography, or 3D imaging, is needed to exactly localize the features of interest inside the cell.
"The Bionanoprobe's cryogenic sample-handling system allows researchers to move the same cryogenically preserved sample from the X-ray nanoprobe to a transmission X-ray microscope, or potentially other cryo instruments," says Dr. Wenbing Yun, founder and CTO of Xradia, Inc. "Scientists look at tissue down to subcellular locations with one technique, which is virtually impossible otherwise."
About the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine
The Lurie Cancer Center is one of only 40 NCI-designated "Comprehensive" cancer centers in the nation and is a founding member of the National Comprehensive Cancer Network (NCCN), an alliance of 21 of the world's leading cancer centers dedicated to improving the quality and effectiveness of care.
The Life Sciences Collaborative Access Team (LS-CAT) is a consortium of eight institutions led by Northwestern University to provide state of the art synchrotron radiation instrumentation for biological experiments. LS-CAT researchers, along with several other biological facilities at the Advanced Photon Source at Argonne National Labs, lead the world in the area of macromolecular crystallography with substantial contributions to biology, genomics, and drug discovery. The collaboration between the APS, Xradia, and LS-CAT leverages the LS-CAT staff's expertise to provide new capabilities both to the LS-CAT members and to the general scientific community.
The eight institutional members of LS-CAT are Michigan State University, University of Michigan, Wayne State University, Van Andel Research Institution, University of Wisconsin at Madison, Vanderbilt University, University of Illinois, and Northwestern University. Additionally, researchers from other universities and companies regularly use the LS-CAT facilities.
About APS at Argonne National Laboratory
The Advanced Photon Source (APS) at the U.S. Department of Energy's Argonne National Laboratory provides the United States' brightest storage ring-generated X-ray beams for research in almost all scientific disciplines. These x-rays allow scientists to pursue new knowledge about the structure and function of materials in the center of the Earth and in outer space, and all points in between. The knowledge gained from this research can impact the evolution of combustion engines and microcircuits, aid in the development of new pharmaceuticals, and pioneer nanotechnologies whose scale is measured in billionths of a meter. These studies promise to have far-reaching impact on our technology, economy, health, and our fundamental knowledge of the materials that make up our world.
Xradia designs and manufactures microscopes for industrial and academic research applications. Xradia's solutions offer unparalleled high contrast and high resolution imaging capabilities for a large range of sample sizes and shapes. The company's heritage began in the synchrotron and extends to the laboratory. Xradia's two laboratory product families, the UltraXRM-L and VersaXRM™, together offer a multi-length scale solution delivering full volume 3D imaging with resolution down to 50 nm. Energy-tunable, ultra-high resolution 3D X-ray microscopes for synchrotron facilities include the UltraSPX™ and the UltraXRM-S. Additional information can be found at www.xradia.com.