Freeze-frame microscope could demystify cancer

California university says laboratory tool `surprises' mutant cells


IRVINE, Calif. -- The first microscope that can penetrate the mysteries of living human cells has been built by University of California-Irvine researchers, with the possibility it will eventually change the way diseases like cancer are diagnosed and treated.

The technology uses shock waves produced by laser beams to capture, freeze and chemically analyze the contents of a cell.

This ability to surprise a cell before it has time to change its internal chemistry in defense is a key factor to learning how diseased cells behave, and what types of drugs might treat them best.

"We've had so much interest in what we're doing that we're going to try to accelerate the program," said Dr. Michael Berns, director of the Beckman Laser Institute at UCI, which received $2.2 million from the National Institutes of Health last month.

The grant will be used to develop a miniaturized commercial prototype of the microscope over the next few years. Researchers hope that eventually hospitals and medical labs will use the technology to study the chemistry inside the living cells of sick people in the same way that blood tests are given today.

"(Berns) is proposing a major breakthrough in our capacity to understand what happens in diseased cells," said Dr. Michael Morron, director of biomedical technology for the National Center for Research Resources. "The hope is to try to distinguish what makes cancer cells go bad."

The idea started two years ago with Dr. Nancy Allbritton, a UCI medical researcher studying how cancer cells behave.

Like many scientists, Allbritton was frustrated with her inability to study the internal processes of cells, which are the building blocks of the human body.

Cancer begins when normal cells start reproducing wildly. No one knows why they do this, but researchers like Allbritton hope that learning what triggers this erratic behavior in a cell can teach them how to turn it off.

Today, the most common way of analyzing cellular chemistry is to take millions of cells, put them in a blender, and then study the chemicals that are left.

But this doesn't tell scientists how living cells actually perform.

The difficulty is that cells are so small: a billionth of a millimeter in size. Each is surrounded by a plasma membrane; inside are tens of thousands of molecules, each with their own chemistry.

Scientists have figured out how to get inside that plasma membrane -- using detergent to dissolve it, for example -- but not without dramatically altering the cell's composition.

"It's pretty difficult to analyze a very tiny speck that you can barely see under the microscope and figure out how all these tens of thousands of molecules are interacting with each other," said Bruce Tromberg, director of Beckman's biotechnology resource center. "But those cells are determining how long you are going to live and how you are going to fight disease."

At a lunch in 1997, Allbritton confided her frustration to Tromberg.

He responded that laser technology at the Beckman institute could probably help. Within months, the pair had come up with a system that uses focused bursts of light to explode a cell within 30 milliseconds -- so fast that it doesn't have time to react defensively.

Then, the chemical contents of the cell are transferred into a micropipette -- a glass tube -- where its molecules are electrically sorted and measured by computer.

"The cell is alive until the moment we do this," Allbritton said. "We do it so fast, we freeze all the reactions."

After the success of the technology, UCI applied for a patent and for a federal grant to expand its capabilities. Now, the college wants to share.

If Berns and his team of scientists working jointly from several UCI departments succeed in their goal of building a miniature computer microchip with the laser information embedded in it, it could be developed by a manufacturing company and marketed worldwide.

Most immediately, Allbritton, her husband, Chris Sims, who is also a member of the team, and four others are studying how tumor cells react while working on a version of the microscope that can be placed on a device only a few inches square.

"The idea is to develop systems to fit on a small glass or plastic device that is easily transportable," Sims said. "Then, everybody could have it in their lab to analyze cells."

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