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magazine home > archives > fall 2004 > features

Researchers at the U of M's Integrated Microscopy Center focus on seemingly invisible landscapes in an effort to improve the community around them.

The Scope of Things to Come
by Jamie Peters

The Integrated Microscopy Center transforms mundane insides of carrots into sci-fi landscapes and illuminates the hidden intricacies of the human body.

  Sharon Frase and Lewis Coons, two electron microscope photos

1. Sharon Frase, IMC coordinator, and Dr. Lewis Coons, the center's director, use the confocal laser scanning microscope to hone in on a specimen sample
2. Self-assembled vesicles, which are used as templates to fabricate nanocapsules for a broad range of applications such as drug delivery devices
3. These slender rod shapes, nanorods, hold promise as miniturized light detection sensors and light-emitting diodes, which are electronic devices

In assisting endeavors such as medical diagnoses and artificial joint improvements, the microscopes of the facility also uncover the aesthetic grandeur in familiar objects. It's nature's artistry discovered by way of magnification. IMC excavates worlds within worlds in its crucial role of providing tools that aid doctors, scientists and other researchers in addressing syndromes, solving problems and improving products.

This wide range of efforts occurs under just one roof at the IMC at the University of Memphis. But like the act of placing a specimen under the lens of one of IMC's high-powered microscopes, a closer look at the center and its eclectic projects reveals hidden depths and seemingly limitless opportunities.

The IMC, which is affiliated with the FedEx Institute of Technology, has grown substantially since its inception in 1976, expanding its line of equipment and sharpening the resolution of its microscopes. The center, which specializes in equipment with tech-intensive-sounding microscopes with names such as electron scanning and atomic force as well as various approaches for specimen preparation, currently serves 50 to 60 off-campus clients and 30 to 40 on-campus users a year, estimates Dr. Lewis Coons, IMC director and a U of M professor of biology.

The center also is making a push to reach out to the orthopedic and musculoskeletal communities. It already has conducted projects for Medtronic, Wright Medical Technology Inc. and the University of Tennessee. "There's not a bone histology lab in the city, and we're trying to develop one here, so that they have some place in town to get the work done," says Sharon Frase, IMC coordinator. "We've been working toward that goal for a couple years. And we're about there."

Other IMC clients include Cargill, the largest private company in the United States; St. Jude Children's Research Hospital; and professors at Rhodes College and Christian Brothers University.

The IMC's relationship with the FedEx Institute of Technology on campus has helped jumpstart relationships that will open the doors to new opportunities. "It's been very valuable for us in networking," Coons says.

After all, the center, which operates on a fee-for-service basis, isn't restricted to a specific department. Rather, it's a resource for the U of M, the community and beyond. "It's here for everybody who has a qualified need for it," says Coons.

Carrot Top (and carrot insides)

There's no doubt that Cargill, an international provider of food, agricultural and risk management services, has a qualified need for IMC - the center has aided hundreds of Cargill projects since 1999, says Dr. John McDonald (PhD '86), a research fellow based in the company's Minneapolis headquarters.

 
Carrot through an electron microscope
 
Cargill, the largest private company in the United States, has used the Integrated
Microscopy Center’s microscopes for numerous projects, including analyzing the effects of a new preservative on the cellular structure of a carrot.

What started out as engaging IMC's capabilities to make "pretty pictures" of certain Cargill projects soon evolved into more in-depth undertakings, says McDonald. While Cargill conducts research on most of its commercial projects with its own imaging technology, it continues to cultivate a number of ideas at the IMC that shape its ventures. "Any time we have things that are more fundamental and have some knowledge to gain, the University environment is more suitable to do that than in house," McDonald says.

Michael Blackburn, director of research for Cargill's scientific resources center, says the technicians at IMC bring a fresh point of view that can benefit the company's projects. "They look at things differently and may see things that we didn't see," Blackburn says.

In addition to using the IMC equipment to examine the size and arrangement of the holes in marshmallows, which determine their textures, Cargill also tested a preservative it had developed. In that experiment the center analyzed the carrot's cellular structure with numerous techniques, including laser scanning confocal microscopy, which can optically slice through thick samples and still provide high resolution. The preserved carrot tissue exhibited intact nuclei. In contrast, in the unpreserved carrot, the network of cell walls had "melted" into an undefined mass.

What purpose did this all serve? As a result of these findings, Cargill decided to sell the preservative in the United States.

Memphis under a lens

The Memphis community is using the IMC in a diverse array of applications that underscore the versatility of the center. The full-time staff of research specialists Lou G. Boykins, Jackie Craft and Jennifer Tzefakes plays a vital role in facilitating these varied undertakings.

Duckworth Pathology Group, which provides services to the Methodist Hospital system in Memphis, has used IMC to help make certain diagnoses and rule out others. In several instances, the use of the electron microscopes has enabled doctors to identify abnormalities in cilia, which sweep dust and debris through the respiratory tract, in a rare condition that can afflict children who have recurring respiratory infections, says Dr. Thomas O'Brien, a pathologist with Duckworth. "We use electron microscopy because it can magnify the structure of the cilia so greatly we can actually use that to look for specific defects in the substructure and make diagnoses based on that," O'Brien says.

Dr. Karen Hasty, a professor in the Department of Orthopaedic Surgery/Campbell Clinic at the University of Tennessee Health Science Center, has used the IMC's equipment to aid research related to arthritis therapies and to develop tissue-engineering methodology to replace cartilage that has been destroyed.

"In degenerative arthritis you just wear down your cartilage surface," says Hasty. "We take animals [pigs], with cartilage defects, and we put healthy cells back onto the eroded surface of the cartilage, and then we let them walk around. At some time after the replacement surgery, we have to go back in to see if the transplanted tissue is surviving after normal physical activity."

That's where IMC comes in.

In order "to really make some sort of statement about what's going on there, you have to be able to see it at a really high magnification," Hasty says.

Dr. Ann M. Viano, assistant professor of physics at Rhodes College, is researching ways to extend the life of artificial-joint biomaterials. Viano uses the transmission electron microscope to examine a polymer in the artificial joint "that's supposed to do what human cartilage does, which is provide a slippery surface," she says. The primary question Viano's research revolves around is "why can't we make this last forever?"

The problem resides in the limited lifespan of the material, and the potential detrimental effects this can produce. "In your body this actually wears, and little pieces come off," Viano says. "You're body says, "Hey, that looks like something foreign. I'm going to attack it.' And you get an infection, and the joint fails. So our goal is to figure out what's going on" in regards to the wear of the material.

Barbara Blum, senior materials engineer at Wright Medical Technology, says her company has used electron microscopy at the center to examine the infrastructure of materials used to contain bone graft materials in bone defects, which could have resulted from trauma or cancerous lesions. Wright Medical also has used the IMC's instruments to look at materials that augment rotator cuff repair.

Dr. Malinda Fitzgerald (B.S. '76, M.S. '79), associate professor of biology at Christian Brothers University, not only uses the IMC to conduct her research, but she also has sent five of her students there during summers to conduct required research for their majors. "It helps the center and it helps the student," Fitzgerald says. "It's a very, very good working relationship."

Magnifying opportunities

The IMC also has enabled U of M professors and students to pursue other opportunities that might not have materialized without the center's presence.

Rat osteoclasts
Dr. Richard Smith in the Orthopaedic Surgery Department at the University of Tennessee Health Science Center used the IMC equipment and staining to examine the osteoclasts - cells that exist in bone - in a sample from a rat.

The IMC played a key role in the establishment of the INDIUM Institute for Nanomaterials Development and Innovation at the U of M this past spring, says Dr. Eugene Pinkhassik, assistant professor of chemistry and director of the institute.

The inclusion of IMC as an integral resource during the grant-writing process helped the institute secure funding from the National Science Foundation. "It's hard to speculate, but if we didn't have anything like that on campus I don't know whether this grant would be awarded simply because people would question the possibility to do all the work," Pinkhassik says.

Potential applications of the nanomaterials include the development of a drug delivery capsule that would be able to hone in on a specific organ and thus eliminate common side effects that can occur when a typical drug is disseminated through the body.

U of M student Dwight Bordelon, a PhD candidate in biomedical engineering, has used the atomic force and laser scanning confocal microscopes to gauge the thickness of the membrane coating on biosensors. The thickness of the material is crucial to the effectiveness of the sensors, which can be used by the medical community to measure certain elements in blood samples such as potassium and sodium, according to Bordelon, a student of Dr. Erno Lindner, professor of analytical chemistry and biomedical engineering.

Meanwhile, other efforts at the IMC are rounding the curve from distant prospects to imminent reality. And then there are those infinitesimal landscapes that remain beyond not only the human eye, but also the realm of human imagination at the moment. As technology continues to evolve in its sophistication, expect IMC to bring those unexplored topographies into sharp focus.

 

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