Microscope 'could fit into cellphones'

Researchers at the California Institute of Technology have built a microscope for taking images of cells by creating an array of tiny pinhole cameras on top of a digital camera's image sensor.

The microscope operates without lenses but has the magnifying power of a standard optical microscope. The current design takes images equivalent to those acquired from optical microscopes with a x20 objective. The Caltech sensor was developed to look at mutations in long, worm-like bacteria but its creators believe it could be used in the field to analyse blood samples for malaria or check water supplies for giardia and other pathogens, and can be mass-produced for around $10.

“The whole thing is truly compact - it could be put in a cell phone - and it can use just sunlight for illumination, which makes it very appealing for Third-World applications,” claimed Changhuei Yang, assistant professor of electrical engineering and bioengineering at Caltech, who developed the device, dubbed an optofluidic microscope, together with colleagues.

“Our research is motivated by the fact that microscopes have been around since the 16th century, and yet their basic design has undergone very little change and has proven prohibitively expensive to miniaturise. Our new design operates on a different principle and allows us to do away with lenses and bulky optical elements,” said Yang.

The fabrication of the microscopic chip is disarmingly simple. A layer of metal is coated onto a grid of the same kind of charge-coupled device (CCD) sensor that is used in some digital cameras. Then, a line of tiny holes, less than one-millionth of a metre in diameter, is punched into the metal, spaced 5µm apart. Each hole corresponds to one pixel on the sensor array. A microfluidic channel, through which the liquid containing the sample to be analysed will flow, is added on top of the metal and sensor array. The entire chip is illuminated from above: sunlight is sufficient, the researchers claimed.

When the sample is added, it flows horizontally across the line of holes in the metal. As cells or small organisms cross over the holes, one hole after another, the objects block the passage of light from above onto the sensor below. This produces a series of images, consisting of light and shadow, akin to the output of a pinhole camera.

Because the holes are slightly skewed, so that they create a diagonal line with respect to the direction of flow, the images overlap slightly. All of the images are then pieced together to create a two-dimensional picture of the object.

Yang is now in discussion with biotech companies to mass-produce the chip.

“We could build hundreds or thousands of optofluidic microscopes onto a single chip, which would allow many organisms to be imaged and analysed at once,” said Xiquan Cui, the lead graduate student on the project.

The researchers reckon that versions of the sensor could be implanted: “An implantable microscope analysis system can autonomously screen for and isolate rogue cancer cells in blood circulation, thus, providing important diagnostic information and helping arrest the spread of cancer,” said Yang.

The research has been published in an advance edition of the Proceedings of the National Academy of Sciences.

Further information:
www.pnas.org/content/early/2008/07/25/0804612105.full.pdf+html

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