Speck-sized microscope nears

By Eric Smalley, Technology Research News

The '60s sci-fi movie "Fantastic Voyage" featured a team of scientists who were reduced to microscopic proportions along with their submarine and injected into the bloodstream of a man in a coma.

While the notion of shrinking living beings and complicated machinery remains as fanciful as ever, the idea of getting up close and personal with individual cells inside a living human is firmly within the realm of the technologically possible.

Researchers at the University of California at Berkeley are building a confocal microscope on a chip with the aim of giving physicians and scientists the means to observe the inner workings of cells in their native habitats. Confocal microscopes are tabletop instruments that cost several hundred thousand dollars. They are used to record images of individual cells and cellular components, often from living samples.

The researchers' confocal microscope will be slightly larger than the ball in a ballpoint pen.

"Nanoscopic biophotonic imaging systems can change the... field of quantitative biology," said Luke P. Lee, an assistant professor of bioengineering at the University of with California at Berkeley. The devices could also be used in home diagnostic biochips, and they could eventually serve as vision systems for microrobots, said Lee.

Confocal microscopes focus reflected or fluorescent light from a small spot in a sample through one or more lenses to a pinhole. A sensor on the other side of the pinhole records the light coming through. The pinhole blocks out-of-focus light so the microscope captures focused images of small sections of the sample. Moving the lenses or the sample or bouncing the light off movable mirrors produces a scan, or series of images, of the whole sample.

A key advantage of the researchers' design is that the light source shines directly through the lenses, which allows for a more compact device. The lenses move to produce the scan.

The researchers plan to build an array of three-lens confocal microscopes, each measuring one cubic millimeter, according to Lee. Each microscope will be able to capture three-dimensional images. The Micro Confocal Imaging Array will be "cheap, small [and] mass producible," he said.

The array could be integrated with microfluidic systems to form labs-on-a-chip that channel biological fluids like blood into position under the microscopes, according to Lee. The array could also be built on the tips of endoscopes, which are probes that can be inserted into the body, in order to capture images of cells at work.

So far, the researchers have built scanners consisting of two lenses and the microelectromechanical actuators that move them. The lenses are formed by placing a drop of liquid plastic in a ring about half a millimeter in diameter and hardening the plastic with ultraviolet light. The actuators that move the lenses are microelectromechanical systems (MEMS), which are made using computer chip manufacturing processes.

The lenses work with visible light, and the researchers plan to expand their range to ultraviolet and near infrared, said Lee. The researchers' next step is integrating the lenses and actuators with microlasers and detectors, said Lee. The Micro Confocal Imaging Array could be in use in two to five years, he said.

The researchers' work "is a first step towards a chip-scale confocal microscope," said Ming C. Wu, a professor of electrical engineering at the University of California at Los Angeles. "Miniaturization is important to integrate [microscopes] with lab-on-a-chip type devices," he said.

The Berkeley device compares favorably to other miniature confocal microscopes, said Wu. "Theirs uses scanning lenses, and is a transmission device, which is more compact than reflection devices," he said.

Lee's research colleagues was Sunghoon Kwon. They presented the research at the IEEE International MEMS 2002 Conference in Las Vegas in January. The research was funded by the Defense Advanced Research Projects Agency (DARPA).

Timeline:   2-5 years
Funding:   Government
TRN Categories:   Biotechnology; Data Acquisition; Microelectromechanical Systems (MEMS)
Story Type:   News
Related Elements:  Technical paper, "Stacked Two Dimensional Micro-Lens Scanner for Micro Confocal Imaging Array," IEEE International MEMS 2002 Conference, Las Vegas, January 20-24, 2002


May 29/June 5, 2002

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