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CHIP SCALE MICROSCOPY: By Ravi Athale and Pranava Raparla SUMMARY: Chip-scale microscopes are low-cost, portable imaging systems that can be readily integrated into small electronic devices, including cell phones. They possess the potential to provide the imaging capabilities of light microscopes for the general user or in resource-limited environments such as developing countries or in military operations. Old Fashioned Optics In antiquity, people knew that you could magnify objects by looking at them through a glass globe filled with water. However, it was not until the 17th century that Robert Hooke and Anton van Leeuwenhoek invented the modern microscope and, by using it to study microorganisms and other microstructures, the field of microscopy. In spite of the remarkable advances in optics technology, the basic design of microscopes hasn't fundamentally changed in the past 350 years. The modern light microscope still requires expensive lenses, a large frame, and a skilled operator to capture and interpret its images. Designs for cheaper and more portable microscopes could make an essential medical diagnostic tool accessible in remote areas, developing countries, and military operations.
Diffraction Subtraction Replacing costly microscope lenses will be the greatest challenge in these new designs. Despite the revolution in integrated microelectronic technologies that has seen silicon-based photodetector chips and computer processors replace photographic film and developers, lenses are still an integral part of any imaging system, whether found in microscopes, telescopes, or point-and-shoot cameras. A fundamental property of light is that it spreads (diffracts) as it carries the image of an object to the observer. The farther it travels, the more it diffracts. The diffraction scrambles the details of the image. Microscopic details practically vanish by the time light travels only a few millimeters. Lenses counter this spreading by bending light through refraction and re-creating the details. Lens cost, complexity, and size grow explosively as the level of fine details to be recovered grows. However, unlike other imaging systems that need to capture light from objects far away, microscopes can be brought very close to the object, thereby minimizing diffraction. This feature provides minimal benefit with a human observer at the microscope because the human eye cannot focus closer than 4–8 inches. But replace a human observer with a silicon photodetector array and the technique of capturing microscopic images from extremely close in can start paying off.
Breaking the Limits Researchers at Stanford University first demonstrated microscopy using a silicon photodetector array, or "chip-scale microscopy," in 2005. As with every imaging system, a chip-scale microscope system has two factors limiting resolution: the detector pixel size and the diffraction effects. The detector limit dictates that an imaging system can resolve features no smaller than itself; a detector with 1-micrometer pixel sizes can resolve features no smaller than 1 micrometer. The diffraction limit indicates how blurry the image is when it reaches the detector. Chip-scale developers can counter the detector limit by resolving the smallest object features through computational imaging. They can counter the diffraction effects by bringing the detector closer to the object. The Stanford researchers placed objects to be viewed directly on a silicon photodetector array, a technique called "direct-imaging" or "shadow-casting." Caltech scientists in 2006 attempted to overcome the detector limit. They designed a shadow-casting microscope whose photodetector array was covered by an opaque mask with submicron size openings, thus simulating a much smaller detector pixel. The design also exploited the newly emerging field of microfluidics, using channels of fluid to scan the sample past a stationary detector array, thereby encoding the fine details in the object as a time signal. Computational processing then recovered the finer details in the object, generating a much higher resolution image than normally possible given the size of the detector array pixels. Researchers at Xerox Palo Alto Research Center invented another variation on using microfluidics for sample transport. They flowed cell samples past a mask patterned with special codes placed in front of a single large detector to create a time signal that encodes spatial information about the sample. Their goal was to develop a chip-scale version of a lab instrument used in studying and analyzing cells for biomedical research. MITRE has been collaborating with the Palo Alto researchers in adapting their design to instruments for sensing pathogens in the environment. In 2008, scientists at UCLA attempted to overcome the diffraction limit with a chip-scale microscope that employed digital holography. Instead of conventional illumination, the researchers used light emitting diodes with a narrow wavelength spread. The photodetector array records both diffracted light and non-diffracted light from the diodes, allowing the recording of a high-resolution image of an object after processing the interference pattern between the diffracted and non-diffracted light. Micro Apps Researchers can design chip-scale microscopes for specific applications. They can also be integrated with other "lab-on-a-chip" technology for improved medical diagnostics or object analysis. Chip-scale microscopes that employ computer processing for resolution improvement can take advantage of object detection algorithms to classify images and provide additional analysis that may be useful in diagnosing diseases. Advances in chip-scale technology will lead to microscopes that are smaller, cheaper, and more powerful. These advances may ultimately lead to microscopes that will allow everyday consumers to analyze blood, water, and other fluids. Chip-scale microscopes might even become as common a cell phone feature as GPS units. After all, most modern cell phones have cameras, which are essentially image detectors, the primary component of a chip-scale microscope. As cell phones with powerful computers and high-quality cameras proliferate, the microcosm first discovered by Robert Hooke and Anton van Leeuwenhoek may become available for everyone to explore. Related Information Articles and News
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For more information, please contact Ravi Athale and Pranava Raparla using the employee directory. Page last updated: February 22, 2012 | Top of page |
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