Exacting world of laser surgery can change in a femtosecond

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CAMBRIDGE, Mass., Nov. 13, 2003 – Eric Mazur never planned to be a welder or a surgeon.

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As a physicist at Harvard University, all he really wanted to do was study the behavior of lasers in very short bursts: femtosecond (that’s one-quadrillionth of a second) blasts of light delivered at nanosecond intervals. In fact, he got his start 10 years ago when the Japanese government tapped him to explore uses of lasers in micromachining.

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Today, however, Mazur and his research group have cracked open a very different field: nanoscale laser surgery.

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Scalpel and needle will always remain ideal instruments for most medical work, and biological compounds will still be crucial to prod cells to certain actions. What has been missing so far, however, is something to manipulate cellular structures at the micrometer and nanometer scale.

Enter Mazur’s laser. “Now I think we have the tool to close that gap,” he said.

They’ve discovered that by cutting a strand of mitochondria in one place, it will disintegrate into several pieces. Harvard Medical School professor Don Ingber says the technology might be scaled up to do surgery without scarring or perhaps to deliver drugs through the skin.

In his lab now, Mazur can target a specific organelle inside a single cell (a mitochondrion, for example, or a strand on the cytoskeleton) and zap it out of existence without disrupting the rest of the cell. One of his graduate students is using the laser pulses on a flatworm, severing various structures in nerve cells to see what happens. By cutting a single strand in a single cell, the student disabled the worm’s sense of smell.

The breakthrough? By delivering femtosecond pulses of laser light, Mazur discovered that he could alter the structure of transparent matter — previously considered impossible, because light is supposed to pass through transparent material. Yet Mazur found that with the ferociously intense energy created by such short bursts, he could create micro-explosions several hundred nanometers long within the glass itself.

“It’s like being able to put a torch inside solid material and still move it around,” he said.

Then came the medical angle. In 2000, Mazur heard Ingber give a talk about his attempts to manipulate cellular structures. His chief complaint: Mechanical devices such as microneedles were too large for the cellular scale, while biological and chemical tools could only act on the cell as a whole rather than on any one specific mitochondrion or other structure.

Not for the first time, Mazur saw the light. “It occurred to me that we had the perfect tool,” he said.

Mazur and Ingber teamed up to fire laser pulses at cells. The lasers neatly zapped specific structures without harming the cell or hitting other mitochondria only a few hundred nanometers away. Mazur’s team has been able to carve channels slightly less than 1 micron wide, well within a cell’s diameter of 10 to 20 microns.

While other techniques can also disable cellular structures, Ingber says the real value here is that the lasers can vaporize an entire target. That opens the door to researching how cytoskeletons give a cell its shape, or how organelles function independently from each other rather than a whole system.

“One key question now relates to the role of compartmentalization and spatial position of structural and signaling molecules within cells, how they impact cell behavior,” Ingber says. “This method may provide ways to address these questions with nanometer resolution.”

The physics behind the laser pulses is relatively simple. By firing a pulse for only 10 to 15 femtoseconds in beams only one micron wide, the amount of photons crammed into each burst becomes incredibly intense: 100 quadrillion watts per square meter, 14 orders of magnitude greater than outdoor sunlight. That searing intensity creates an electric field strong enough to disrupt electrons on the target and create a micro-explosion.

But because the pulse is so brief, the actual energy delivered into the cell is only a few nanojoules. (About the same needed for a mosquito to land on your skin.) To achieve that same intensity with nanosecond or millisecond pulses would require so much more energy the cell would be destroyed.


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