Microscope allows research to go where it never has

Although prostate cancer is the No. 1 cancer found in men, it remains difficult to detect. The problem is that despite the fact that researchers know what to look for, they lack the capability of seeing the microscopic elements inside human tissue that serve as “red flags” for the disease.

“We’re trying to find thesvery small cells called fibroblasts which we can’t find at home because they’re so small,” says Paul Bassan, a Ph.D. student at the University of Manchester in England.

It was this elusiveness that brought Bassan and his colleagues from England to southern Wisconsin this past fall as part of a workshop to learn about a major development in the world of microscopy at the Synchrotron Radiation Center (SRC). They were at UW–Madison to learn about a new world-class microscope called IRENI, or Infrared Environmental Imaging, a microscope that uses synchrotron-based infrared light to produce previously unobtainable images.

IRENI, funded with a $1 million award from the National Science Foundation, produces infrared images with previously impossible to see detail and whose reach will be far ranging. When it comes to seeing things that were previously unseen or rather blurry, IRENI’s director, Carol Hirschmugl, sees an untapped world of biological research and beyond.

“It’s like going from X-rays to MRIs,” says Hirschmugl, professor of physics at UW–Milwaukee who partnered with UW–Madison on the project. “With MRI there’s so much more and so much different information than you just get from X-rays.”

IRENI images reveal vivid detailed information in comparison to conventional methods (known as tabletop instruments). This unmatched clarity challenges researchers’ imaginations in and outside of the biological field.

“IRENI opens up the possibility of applying this to things that people would never have thought of applying it to before, because they can see visually what they’re not used to seeing,” says Hirschmugl.

Since its commissioning in late 2009, research using IRENI includes alternative energy and how algae might be put to use to reduce pollution in dirty smokestacks. Others areas include understanding formations of volcanic rock, analyzing ancient art, and even understanding how teeth form. And in addition to Bassan’s prostate cancer work, medical applications include Alzheimer’s, other cancers, malaria and stem cells.

IRENI’s powers come from an unusual facility. SRC is a national research facility, home to a particle accelerator nicknamed Aladdin, which produces a steady stream of light ranging from X-ray to infrared. The use of light for research includes disease research, environmental science, astronomy, geology, future energy sources, nanotechnology, materials science and more. Beginning in the 1970s, SRC pioneered this use of light for research and remains a leader in light-source technology today. UW–Madison is leading an effort to build a next-generation light source, called a free electron laser. As part of the WiFEL (Wisconsin Free Electron Laser) program, UW–Madison last fall received a $4.5 million award from the U.S. Department of Energy to begin planning and construction of an electron source for such a facility — a light source that will take science to now-unattainable places in much the same way IRENI has revolutionized research using infrared.

For now, when it comes to IRENI, the Aladdin accelerator acts as a bright source of infrared light which is used to unveil the inner workings inside of matter. The key feature is that this infrared light illuminates a different sort of image in comparison to regular white light. In turn, IRENI is producing never before seen images for researchers, because even though infrared microscopy exists, it pales in comparison to synchrotron-based infrared imaging.

“Images with other tools don’t reveal chemical information like infrared does,” says Kathy Gough, University of Manitoba researcher. Gough, a longtime user of infrared light at SRC, explains that there are major differences when it comes to using light for biological research. “X-rays would burn [the samples], and visible light will show you the shape but not the chemistry.”

The “chemistry” Gough refers to is at the heart of infrared research. Infrared microscopes show the chemical makeup of biological samples and can depict, for example, the presence of key biological substances such as proteins, fats, sugars and other chemicals. In comparison, a researcher examining a sample such as a cell under a conventional visible-light microscope sees only a zoomed in view of the cell’s color and shapes; not a chemical makeup. The conventional use of low-intensity infrared in other tabletop instruments lends itself to long-sessions of light gathering and waiting on the scientist’s part. The key milestone with IRENI is the fact that it produces images much more rapidly and also with inimitable detail.

“You can get data in, say, a minute or two depending on the sample with unprecedented spatial resolution,” says SRC physicist Michael Nasse.

Spatial resolution is paramount to biological research and ensures high definition chemical information at the microscale; the key variable with infrared microscopy is the intensity of the light beam. A tabletop instrument is like a flashlight shined from afar whereas IRENI is like a laser-pointer. This high-intensity beam decreases the time it takes to get images with tabletop instruments from several hours to just a few minutes with IRENI, which is precisely what has attracted the attention of researchers from around the world hoping to find answers to the questions that have eluded them.

And so now Hirschmugl’s already-packed job description includes marketing IRENI’s revealing capabilities. SRC welcomes researchers from around the world and locally to work at this facility and learn firsthand what this new technology can provide for their research topic of interest. Those interested should contact Hirschmugl directly.

“Other people in biology and medicine can make great use of this but they might not ever hear about it,” says Bassan. “They might not be aware that this sort of facility exists.”

Hirschmugl will present IRENI to the campus community during two upcoming talks. “Synchrotron Based Infrared Imaging — Emerging Biospectroscopy with Potential Applications in Stem Cell Differentiation” will be presented from noon-1 p.m. on Tuesday, Feb. 1, at the Wisconsin Institute for Discovery (WID). “High Spatial Resolution Chemical Imaging: Biomedical Applications for Pathology and In vivo Imaging” will be presented at noon on Monday, Feb. 7, in the Tong Auditorium, Room 1003, Engineering Centers Building. Learn more about bioscience research at the SRC.