FEMTOSECOND LASERS: Full speed – and power – ahead

Speed. Power. Precision. These are the key characteristics of ultrafast lasers.

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Speed. Power. Precision. These are the key characteristics of ultrafast lasers. In the past, the physical sciences had most to gain form the attributes. Now, however, stimulated by new and improved light sources, ultrafast lasing is advancing rapidly into the biomedical arena. From imaging cells and viruses in extraordinary detail to carrying out flow cytometry on the blood vessels of living creatures to the removal of melanomas from human patients, the technology is proving its value in the entire arena of life science and biomedicine.

Laser specialists emphasize that current projects in the biological arena remain largely in the preliminary stages, as research projects intended to explore the technology’s potential. “It’s early days,” says Theodore Norris, director of the University of Michigan’s Center for Ultrafast Optical Science (CUOS). But Norris and others predict that, as a result of the understanding garnered by current research and efforts to reduce costs, ultrafast lasers will find their ways into life science laboratories, hospitals and clinics, and even doctors’ and dentists’ offices.

No collateral damage

Robert Tzou, chairman of the mechanical and aerospace engineering department at the University of Missouri, outlines the reason for life scientists’ interest in ultrafast lasers. “The most important advantage,” he explains, “is the clean cut without collateral damage.” In other words, the power of the ultrafast laser pulse is so concentrated on its target that it does not heat or otherwise damage tissue or other material beyond the target.

That capability of the Missouri’s ultrafast, ultra-intense laser (UUL) presents an obvious opportunity for surgical use. “The high precision and high efficiency of the UUL allow for immediate results. It can remove virtually any kind of materials with minimal collateral damage,” Tzou says. “Look at the removal of melanoma, skin cancer, or breast cancer. If we have a way to use the lasers to kill cancer cells without even touching the surrounding healthy cells, that is a tremendous benefit to the patient. Basically the patient leaves the clinic immediately after treatment with no side effects or damage.”

Tzou’s group is starting out with a somewhat less ambitious project than cancer surgery. “We are working with the Missouri Life Science Research Board on the prevention and treatment of dental caries,” he says. “We can do this because the laser pulses are do short that surrounding healthy tissue doesn’t get heated.” The ultimate goal here is to produce systems affordable enough for dental practices to buy. “The prototypes are already here,” Tzou points out, “But we have to invite the support of local dentists.”

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The University of Missouri’s ultrafast, ultra-intense laser (UUL) is so precise and efficient that it can remove virtually any tissue with minimal collateral damage. (Courtesy University of Missouri).
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CUOS has already developed a commercial success. A few years ago, the center spun off technology devoted to precision optical surgery. The IntraLase system, developed at the center, enhances LASIK eye surgery.

Subcellular surgery

Other advances remain in the development stage at CUOS, which devotes about 30% of its research to biomedicine. “We are looking at subcellular surgery,” Norris says. “You can focus the laser into a very tight submicron size in a cell or on a cellular membrane. So you can focus on a component inside a cell, such as a microtubule, without killing the cell.”

Researchers are also using a CUOS ultrafast laser as an excitation source that enables them to image happenings inside bodily organs. “We’re doing a lot of work on multiphoton excitation, primarily through optical fibers that allow us to avoid scattering problems in tissue,” Norris says. “You can insert the probe into a blood vessel or organ and be minimally invasive.” CUOS scientists have used this approach to measure the uptake of nanoparticles by tumors in mice. They are also exploring the concept of incorporating the fibers into an endoscope, which would permit clinicians to study internal organs precisely, avoiding the need to take random biopsies. And in another promising project, Norris continues, “we have been doing a lot of flow cytometry, exciting a number of fluorophores at the same time in the blood vessel of a living mouse.”

At another level, a CUOS group is examining the use of high-power ultrafast lasers to generate x-rays and to substitute for particle accelerators in generating protons for cancer therapy. In both cases, the group has set out to produce tabletop models that would cost significantly less than current instruments.

Indeed, cost cutting is a consistent theme of efforts to introduce ultrafast lasers into the biomedical market. “If prices come down from $30,000 to $60,000 to $10,000,” Norris says, “you could see this type of flow cytometer in the laboratory.”

Tzou takes a similar view about the commercial prospects of Missouri’s proposed dental system. “Our UUL costs about $700,000,” he says. “We’re making an effort to reduce the price to about $60,000 to $70,000. Then we can convince dentists to use the technology.”

Two new initiatives

The Universities of Michigan and Missouri are not alone in applying the power and precision of ultrafast lasers to the biological universe. Two other institutions have recently started initiatives intended to use ultrafast lasing in research on life science and biomedicine.

In September, the Department of Energy approved the Stanford Linear Accelerator Laboratory’s plans to build new offices and laboratories for its Photon Ultrafast Laser Science and Engineering (PULSE) center. The new facilities, scheduled to be available for limited use in late spring, will include three biology laboratories and one chemistry laboratory. Those labs will serve PULSE’s nanoscale and biomolecular imaging groups, whose goals include using the laser to image cells, viruses, nanoparticles, proteins, and similarly sized entities.

The institution’s linac coherent light source (LCLS) permits researchers to study extremely small entities. “The basic concept is that we can extend the capabilities of current methods in crystallography, especially in solving protein structures,” explains staff scientist Mike Bogan. “We have several beam lines for solving crystal structures and protein-drug interactions.”

Initial experiments using LCLS, planned for September 2009, will focus on simple materials. “We will grow in complexity over time,” Bogan adds. “This will be a transformational tool if the physics holds.”

At Kansas State University, meanwhile, the Macdonald Laboratory is starting projects to tailor biomolecules using its Kansas Light Source. The laboratory’s goals for the source include enabling researchers to tailor molecules that will improve health care. “We’re not trying to be solely a laser technology lab,” explains Laboratory director Itzik Ben-Itzhak. “Rather, we are interested in studying laser-matter interactions on the atomic and molecular scale.”–Peter Gwynne

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