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 nm. 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 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 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 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.