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William Costerton

Lights! Camera! Bacteria!

Tiny probe scopes out infections

Imagine a microscope so tiny it could fit between your teeth and gums. Or so small, it could pierce your daughter's ear drum and send back pictures of the inflamed cells in her middle ear.

That's what Bill Costerton and David Dickensheets did.

The Montana State University-Bozeman researchers imagined an ultra-miniature confocal microscope that would let them and others look at cells inside the body without taking the cells out of the body. That vision is now materializing with the help of a $515,000 grant from the National Science Foundation.

"These two teams - the ear team and periodontal teams - are just sitting around chomping at the bit and saying, 'How is the probe coming?'" said Costerton, director of MSU's Center for Biofilm Engineering. "They really want to do this big time."

It's almost universally accepted, he explained, that biofilms are involved in infections of the gums and middle ear. Biofilms are slimy communities of bacteria that can form inside the body and are generally resistant to antibiotics. Collaborators in Pittsburgh are working with Costerton to see if they can find a better way to treat ear infections. Colleagues in Seattle are doing the same with gum disease.

The ultra-miniature confocal microscope that uses lasers, fiber optics and a tiltable mirror will let researchers from both camps see something as small as 0.6 microns, Costerton said. Bacterial cells are one micron across. Instead of having to remove tissue samples or extract fluid, the scientists will be able to rotate the side-looking microscope 360 degrees and observe cells where they are. They won't need to grow cultures in a petri dish and discover - once more - that cells grow differently in the laboratory than in their natural environment.

"This kind of laser microscope is wonderful," Costerton commented.

Dickensheets, assistant professor in MSU's Microptics and Imaging Lab, had already developed a micromachined confocal optical microscope before coming to MSU from Stanford University. Looking more like a pencil than a microscope, the microscope fit inside a hypodermic tube that had an outside diameter of 3.4 millimeters.

David Dickensheets
The grant that Dickensheets and Costerton received will improve the resolution of that instrument and reduce the tip size by almost half.

"The mouth could handle something a little bit bigger, but when you talk about getting between the teeth and gums, you might not want something larger," Dickensheets said.

Garth Ehrlich, executive director of the Center for Genomic Sciences at the Allegheny Singer Research Institute in Pittsburgh, said the ultra-miniature microscope will be "very significant" for his work on ear infections.

"Now we can only look at the infecting bacteria after we sacrifice chinchillas and dissect out the tympanic bullae, which is less than ideal," Ehrlich said.

A chinchilla's bullae encloses a fairly large space that can hold fluid. Since chinchilla ears are almost as large as human ears, chinchillas provide a good way to better understand the human ear, Ehrlich added. The new microscope will allow him to look inside the middle ear of chinchillas and possibly humans who have bacterial infections.

Costerton said the microscope will be used first on animals then, it's hoped, on people.

"This probe is heaven-sent for us really," he commented.

The midget microscope that can fit into an endoscope and send pictures back to a television screen is just one tool that Dickensheets is designing in his laboratory. Another probe will demonstrate what can be done on Mars with a remotely-operated microscope and spectrometer. The project was funded by the National Aeronautics and Space Administration (NASA) and was done in collaboration with TRI of Wyoming and the late David Wynn-Williams of Britain. A related project will look at the lichens that grow in soil and rock of Antarctica.

"There's a lot of overlap between the projects," Dickensheets commented.

The ultra-miniature confocal microscope is a four-year project that began in the fall of 2000. Its first application will be looking at biofilms, Dickensheets said. It could eventually be used as a less invasive tool to help doctors diagnose cancer and other diseases.

Evelyn Boswell
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