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Tiny Devices Use Light to Grab Cells

Silicon chips and lasers could pick out and count cells on microfluidic devices.

Tiny optical devices that can grab small particles out of a liquid, using the force of photons, could make it possible to image and identify disease cells on a chip without the need for microscopes. The new types of optical traps, developed by physicists at Harvard University, are designed to be integrated with microfluidic devices, some of which are currently in clinical trials for diagnosing cancer and monitoring patient response to therapies. The Harvard researchers have shown that their optical traps can do on a chip what conventionally requires a large microscope and a powerful laser.

Light force: A silicon chip coated with a gold film (center), when illuminated by laser light shining through a prism, can pull particles out of a liquid solution flowing over the top.

Optical traps, a technology developed in the 1980s, usually cost tens of thousands of dollars and require powerful lasers and microscopes to focus the light onto particles as small as single atoms. Photons have no mass, but they do have momentum, and transferring this momentum to an atom, a molecule, or a cell enables physicists to control the particle’s movement, holding it absolutely still for observation, or pulling on it to monitor its response. Since their invention, optical traps have been used to make many basic science advances. But the Harvard group, led by associate professor of electrical engineering Kenneth Crozier, hopes to use optical traps in diagnostic devices, making them cheap and small enough to be practical in medicine.

The optical traps developed by Crozier with Harvard researchers Ethan Schonbrun and Kai Wang can trap particles just as strongly as more complex systems. Crozier says that the compact traps could be integrated into microfluidics and used to sort and image disease cells in the blood, for example. Microfluidic chips shuttle cells around in a fluid and typically control their movements using physical barriers and variations in pressure and voltage. Crozier’s optical traps could gently pull cells down to the surface of a chip for observation and then be used to sort the cells based on their identity. The group presented their advances at the annual conference of the Optical Society of America this month in San Jose, CA.

Using manufacturing techniques common to the semiconducting industry, the Harvard researchers patterned chips with two different designs. One is a silicon chip patterned with a ring with a radius of five micrometers. When illuminated by a laser, light resonates around the ring, generating an optical force that can pull particles from liquid flowing above the chip. Another is a chip patterned with arrays of 64 bullseye patterns. Each of these can, when illuminated, trap a flowing particle. What’s more, these patterns focus light in a way that’s very similar to a microscope. “Each has the function of a confocal microscope and could be used to get a 3-D picture of a cell,” says Crozier.

Focusing power: This chip, mounted with paperclips on a microscope objective for observation, is patterned with gold films 500 nanometers wide. When light shines on the gold lines through a prism underneath the chip, it forms surface energy waves that can trap particles and push them along.

“If you want to do cell sorting, silicon optics is a good path,” says Tom Perkins, a physicist at the National Institute of Standards and Technology in Boulder, CO. The advantage of silicon systems over conventional optical traps, Perkins says, is compatibility both with microfluidics and with the manufacturing methods already in place for making computer chips.

A third design of Crozier’s is based on gold structures that can generate a form of light energy called plasmons. When a smooth gold film is illuminated, the light couples to the surface in the form of surface waves called plasmons; the forces generated by these waves are very localized and very strong. Crozier has demonstrated that long, tapered gold films patterned on silicon chips can, when illuminated by light shining through a small prism, be used to pull a particle down and then push it along the gold surface. By changing the angle of the light, it’s possible to control a particle’s speed. This type of structure will be particularly useful for cell sorting, Crozier says.

These types of systems might eventually replace clinical-laboratory devices called flow cytometers, says Holger Schmidt, professor of electrical engineering and director of the Keck Center for Nanoscale Optofluidics at the University of California, Santa Cruz. Today’s flow cytometers use bulky optical systems to separate cells in, say, a blood sample based on their size and shape. Chip-scale optics could do the same thing but would cost much less and might be portable, allowing them to be brought to a patient’s bedside. Schmidt, who’s developed compact, sensitive optical systems for trapping cell organelles and detecting single virus particles, says these compact optical traps might be on the market in as few as three to five years.

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