Zapping Individual Cancer Cells

Engineers at the University of Texas at Austin have patented a laser microscalpel that allows a surgeon to operate on tissue one cell at a time, precisely targeting disease while leaving healthy surrounding cells alive.

The device combines two technologies--a femtosecond laser and two-photon fluorescence microscopy--into a single miniaturized, flexible probe. The probe can target single cells in three-dimensional space, penetrating up to 250 micrometers into tissue.

The probe could be a significant advance for endoscopic surgery that requires high precision, such as destroying cancer cells scattered throughout brain tissue or operating on delicate tissue like vocal cords without damaging them, says Adela Ben-Yakar, an assistant professor of mechanical engineering at the University of Texas at Austin. Ben-Yakar developed the microprobe along with Stanford University associate professor Olav Solgaard and with Chris Hoy, a graduate student in Ben-Yakar's lab. The research was published in the June 23 issue of Optics Express.

Small, flexible laser tools are often used in endoscopic surgery to vaporize unwanted tissue. But although they offer greater precision than conventional scalpels, the existing laser tools tend to generate a lot of heat, causing damage in the areas surrounding the targeted tissue. "Current technology is really blasting everything around, causing extensive damage," says Ben-Yakar.

In contrast, femtosecond lasers use less energy than conventional laser-surgical tools, and thus generate less heat in surrounding tissue. Because they are able to destroy targeted cells without causing damage outside the target area, they are beginning to be used for surgery that requires great precision: since 2003, ophthalmologists have used femtosecond laser microscope tools to perform eye surgery. But the tabletop lasers currently in medical use are bulky, so their use is restricted to surface areas of the body, such as the skin or eye.

Likewise, two-photon fluorescence microscopy has also found applications in medicine and biomedical imaging as a way to get three-dimensional images of small structures. But until now, no one has combined it with a femtosecond laser in a device small and flexible enough for endoscopic surgery.

Ben-Yakar and her colleagues were able to combine the two in a handheld probe by using flexible hollow optical fibers to transmit the laser light, potentially allowing surgeons to bring the benefits of femtosecond laser surgery to structures deep inside the body. "You can do surgery on single cells without harming the surrounding healthy cells," she says. "The healing will be much faster, and the removal of tissue will be more precise."

Since the same probe is used to both image cells and destroy them, it is possible to simultaneously identify and treat diseased tissue. The microprobe is controlled by imaging software, allowing surgeons to either target individual cells or use algorithms that can detect diseased cells on the fly and destroy them automatically. Currently, the laser microprobe is still an experimental tool. Its inventors have used it to perform surgery on cancer cells grown in bioengineered tissue in the laboratory, but the device has not yet been used on animals or humans.

A problem that remains to be solved before the device can be used on patients is shrinking the width of the probe from 15 to 5 millimeters--the size of the standard tools used in endoscopic surgery--so that it will be compatible with existing surgical technology. "If you want to be compatible with the existing systems, you have to reduce the size," Ben-Yakar says. "But when you make it smaller, the probe, the optics will be more difficult. It will be hard to keep the current resolution. That's the next step."

Rox Anderson, a professor of dermatology and the director of the Wellman Center for Photomedicine at Massachusetts General Hospital, calls the development of the microprobe "an important step . . . toward the broad opportunity of integrating diagnostic and therapeutic options in biomedicine."

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