A small digital microscope that costs just a few dollars can plug into a cell phone and perform basic medical diagnostics that would ordinarily require expensive lab equipment. The microscope, which uses no lenses, saves on cost and weight by using algorithms to get more information from images. The device can generate blood counts and identify disease cells and bacteria from simple images sent through a USB cord to a cell phone that uses software to processes the data. The latest version of the microscope integrates an interference-based contrast method to provide better images in addition to diagnostic information.
The researchers developing the device hope it will bring better medical diagnostics to parts of the world where cell phones are prevalent but access to expensive clinical diagnostic equipment is not. Even basic cell phones now have significant processing power that can be used to analyze images of blood smears and other samples on the spot, enabling a patient to get on the right tuberculosis drug faster and enabling health-care providers to identify drug-resistant strains faster. What sets the new microscope apart from other efforts at integrating optical diagnostics with cell phones is the effort to make it as simple and cheap as possible. That means eliminating expensive lenses, and using software to get medical information from blurry images.
The device was made by researchers led by Aydogan Ozcan, professor of electrical and biomedical engineering at UCLA. It has only two key hardware components: a light-emitting diode to illuminate the sample and an light-sensing chip. These components each cost about 30 to 40 cents. Slides smeared with samples are loaded into the microscope through a small drawer that sits between the LED and the light sensor. A USB port carries power and data between the scope and a cell phone. The tiny microscope measures about six centimeters high and four centimeters on each side; it weighs just 46 grams.
Since the microscope has no lenses, it does not magnify the images. Yet it is able to gain resolution just under two micrometers, and makes images that are about as clear as those made by a conventional 40X microscope. This is made possible by image-processing software. “We compensate for everything in the digital regime,” says Ozcan. As light from the LED passes through a given type of cell, the light bends or diffracts in a characteristic way depending on the cell’s size, shape, and refractive index. Data picked up by the light-sensing chip is carried to a cell phone for analysis. Ozcan has previously demonstrated running software on the phone that consults a library of diffraction signatures characteristic of particular cell types and bacteria to identify and count the cells in the sample.
Eliminating the lens eliminates expense, says Wilbur Lam, a pediatric oncologist at the University of California, San Francisco Children’s Hospital, but doctors used to looking at images under a microscope will demand better images. “Physicians are conservative,” he says. Lam is working with a group of engineers that’s integrating conventional, lens-based microscopy with cell phones.
The UCLA researchers are improving the quality of their images on both the software and hardware fronts. “With more advanced processing, we can do more analysis and extract an image from the shadows with a decent enough resolution to show subcellular features,” says Ozcan.
The UCLA group has also made a new version of the microscope that integrates an optical trick used to enhance image contrast on conventional microscopes. This method, called differential interference contrast, uses a prism to split the light beam into two beams with different polarizations before it illuminates the sample, and a second prism to recombine it after it passes through the sample. Combining the two beams produces an image with enhanced edge contrast. This method makes it possible to see many types of bacteria that are transparent, without the use of a stain. Adding interference contrast to a conventional microscope costs about $1,000 because the prisms must each be painstakingly aligned with lenses. The UCLA method is holographic, in effect generating two images of each cell, each made with light of a different polarization. These images are processed and recombined to get more information on a sample and to produce better contrast.
In the UCLA microscope, the phase-contrast elements can be added and removed through the same small drawer where the sample is loaded because there are no other elements to line up with. The only cost is the $2 materials cost of the prisms, 100-micrometer-thick films of quartz crystal, bringing the total cost of the imager to about $3.
Ozcan is currently working with a startup company called Holoscope, based in Santa Monica, CA, to develop the microscope. He says the company will develop the microscopes along two lines, one for the educational market and one for performing complete blood counts.
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