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 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.

Source:  Xradia