Lasers grasp cell-size water balloons

By Ted Smalley Bowen, Technology Research News

Researchers commonly use liposomes to mimic the membranes of living cells. These artificial sacs are made up of phospholipids, which are groups of fatty acids that readily form membranes in water. Phospholipids are also a key part of living cells.

Liposomes smaller than a micron across -- which is about the diameter of a bacterium -- have several practical uses.

They are regularly used as Lilliputian test tubes to separate or transport minute samples in ultra small-scale labs, and to deliver drugs or other chemicals like enzymes and DNA to specific areas within the human body. The sacs can be injected or swallowed and allow the drug to reach its destination without being broken down.

Liposomes as large as cells, with diameters up to 10 microns, are more difficult to work with, however. They can be likened to large balloons bulging with liquid, and are prone to fusing and deforming when they are manipulated. Because they are similar in size and chemical composition to human cells, they are potentially useful models of their biological cousins.

To date, these giant liposomes have been handled using tapered micropipettes, which can cause damage where they touch.

A pair of Japanese researchers have found a more suitable way to manipulate large liposomes. Moving them using an infrared laser is both less damaging and more precise than using micropipettes, according to Masatoshi Ichikawa, a researcher at Kyoto University.

Although laser beams are regularly used as tweezers to manipulate small objects, it's difficult to create a giant liposome that will withstand the process, according to Ichikawa. Laser tweezers move and trap objects by bombarding them with photons.

The process hasn't worked well for giant liposomes in the past because they're susceptible to warping or splitting, and are likely to slip out of the laser's grasp, according to Ichikawa. The researchers found that things get better, however, depending on what the liposomes contain.

The researchers created a variety of single-layer giant liposomes measuring from 0.1 to 10 microns across with a membrane about 0.005 microns thick. A micron is a thousandth of a millimeter.

They found that they could successfully move liposomes with lasers if they filled them with liquid that had a greater refractivity than the surrounding medium, according to Ichikawa.

Light travels at different speeds through different media. It travels through water, for instance, at about three-quarters the speed it travels through air. Because of this, different types of materials refract, or bend light to different degrees. When a light beam hits the boundary between materials that have different refractivity rates, it bends, which is why an object that is partly in air and partly in water looks distorted.

The researchers tested two kinds of liposomes -- one type that contained and was surrounded by purified water and another type filled with glucose and surrounded by saltwater. Glucose is more refractive than saltwater.

To manipulate the liposomes, the researchers bounced an infrared laser beam off a dichroic mirror, then through a microscope toward the liposome they wanted to transport. Dichroic mirrors are coated with thin layers of different metals that transmit and reflect only certain wavelengths.

The change in refractivity at the boundary of the liposome caused the laser light to act on the contents of liposome, rather than just its thin membrane, increasing the tractability of the glucose-filled liposomes in saltwater by about an order of magnitude, according to Ichikawa.

The water-filled liposomes were also more prone to damage because there was more pressure at the point where the photons bombarded them. Changing the refractive index made for less local pressure. "We [produced] attractive and repulsive forces by controlling inner and outer conditions," Ichikawa said.

While other types of lasers can grasp liposomes and other small containers, infrared lasers are best, said Ichikawa. This is because infrared light penetrates deeply into living matter without immediately damaging it or disturbing biochemical reactions, he said.

The work is a sound demonstration of techniques for working with cell-sized liposomes, said Daniel Chiu, an assistant professor of chemistry at the University of Washington. "The method that traps higher refractive index into the vesicle is new. Most large liposomes would have the same refractive index inside and outside," he said.

There has not been a lot of work done in manipulating very large liposomes, Chiu said. Although a few groups have previously used optical tweezers to manipulate these large liposomes, adding the refractive index difference improves the method, he said.

Laser-manipulated liposome test tubes could be put to use in a variety of small-scale experiments, Ichikawa said. "We are considering widespread applications, especially for biotechnology. For example, enzymatic reactions inside giant liposomes," he said.

The method can also be used to manipulate other types of microscopic containers, said Ichikawa. "Our idea [applies] not only [to] liposomes but also many kinds of vesicles and capsules," he said.

Ichikawa's research colleague was Kenichi Yoshikawa of Kyoto University. They described the work in the December 31, 2001 issue of Applied Physics Letters. The work was funded by Kyoto University and the Japan Science and Technology Corporation.

Timeline:  Now
Funding:   University, Government
TRN Categories:   Nanotechnology
Story Type:   News
Related Elements:  Technical paper, "Optical transport of a single cell-sized liposome", Applied Physics Letters, December 31, 2001.


March 13, 2002

Page One

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Lasers grasp cell-size water balloons

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