In what is being seen as a major step forward in taking clinical microscopy out of specialized labs and into the field, UC Berkeley researchers have developed what they are calling the CellScope, a cell phone turned into a fluorescent microscope. The prototype, which hopes to bring low-cost lab tools into field settings for disease screening and diagnoses, takes color images not only of malaria parasites but of tuberculosis bacteria labeled with fluorescent markers. Shown is the portable CellScope prototype set up for fluorescent imaging. (Images: David Breslauer)“The same regions of the world that lack access to adequate health facilities are, paradoxically, well-served by mobile phone networks,” said Dan Fletcher, UC Berkeley associate professor of bioengineering and head of the research team developing the CellScope. “We can take advantage of these mobile networks to bring low-cost, easy-to-use lab equipment out to more remote settings.” The engineers attached compact microscope lenses to a holder fitted to a cell phone. Using samples of infected blood and sputum, the researchers were able to use the camera phone to capture bright-field images of Plasmodium falciparum, the parasite that causes malaria in humans, and of sickle-shaped red blood cells. They were also able to take fluorescent images of Mycobacterium tuberculosis, the bacterial culprit that causes TB in humans. Moreover, the researchers showed that the TB bacteria could be automatically counted using image analysis software. “The images can either be analyzed on-site or wirelessly transmitted to clinical centers for remote diagnosis,” said David Breslauer, co-lead author of the study and a graduate student in the UC San Francisco/UC Berkeley Bioengineering Graduate Group. “The system could be used to help provide early warning of outbreaks by shortening the time needed to screen, diagnose and treat infectious diseases.” A camera-equipped cell phone took this bright-field microscope image of malaria-infected blood. The parasites appear as dark blue dots inside the larger, lighter blue cells.The engineers had previously shown that a portable microscope mounted on a mobile phone could be used for bright-field microscopy, which uses simple white light –such as from a bulb or sunlight – to illuminate samples. The latest development adds to the repertoire of fluorescent microscopy, in which a special dye emits a specific fluorescent wavelength to tag a target – such as a parasite, bacteria or cell – in the sample. “Fluorescence microscopy requires more equipment – such as filters and special lighting – than a standard light microscope, which makes them more expensive,” said Fletcher. “In this paper we’ve shown that the whole fluorescence system can be constructed on a cell phone using the existing camera and relatively inexpensive components.” The researchers used filters to block out background light and to restrict the light source, a simple light-emitting diode (LED), to the 460-nm wavelength necessary to excite the green fluorescent dye in the TB-infected blood. Using an off-the-shelf phone with a 3.2-megapixel camera, they were able to achieve a spatial resolution of 1.2 umicrometers. In comparison, a human red blood cell is about 7 micrometers in diameter. “LEDs are dramatically more powerful now than they were just a few years ago, and they are only getting better and cheaper,” said Fletcher. “We had to disabuse ourselves of the notion that we needed to spend many thousands on a mercury arc lamp and high-sensitivity camera to get a meaningful image. We found that a high-powered LED – which retails for just a few dollars – coupled with a typical camera phone could produce a clinical quality image sufficient for our goal of detecting in a field setting some of the most common diseases in the developing world.” Shown is the layout schematic for the cell phone microscope, or CellScope, for fluorescence imaging. For bright field imaging, the two filters and LED are removed. The researchers pointed out that while fluorescent microscopes include additional parts, less training is needed to interpret fluorescent images. Instead of sorting out pathogens from normal cells in the images from standard light microscopes, health workers simply need to look for something the right size and shape to light up on the screen. "Viewing fluorescent images is a bit like looking at stars at night," said Breslauer. "The bright green fluorescent light stands out clearly from the dark background. It's this contrast in fluorescent imaging that allowed us to use standard computer algorithms to analyze the sample containing TB bacteria." Breslauer added that these software programs can be easily installed onto a typical cell phone, turning the mobile phone into a self-contained field lab and a "good platform for epidemiological monitoring." While the CellScope is particularly valuable in resource-poor countries, Fletcher noted that it may have a place in this country's health care system, famously plagued with cost overruns. "A CellScope device with fluorescence could potentially be used by patients undergoing chemotherapy who need to get regular blood counts," said Fletcher. "The patient could transmit from home the image or analyzed data to a health care professional, reducing the number of clinic visits necessary." The CellScope developers have even been approached by experts in agriculture interested in using it to help diagnose diseases in crops. Instead of sending in a leaf sample to a lab for diagnosis, farmers could upload an image of the diseased leaf for analysis. The researchers are currently developing more robust prototypes of the CellScope in preparation for further field testing. Other researchers on the team include Robi Maamari, a UC Berkeley research associate in bioengineering and co-lead author of the study; Neil Switz, a graduate student in UC Berkeley's Biophysics Graduate Group; and Wilbur Lam, a UC Berkeley post-doctoral fellow in bioengineering and a UCSF pediatric hematologist. Funding for the CellScope project comes from the Center for Information Technology Research in the Interest of Society (CITRIS) and the Blum Center for Developing Economies, both at UC Berkeley, and from Microsoft Research, Intel and the Vodafone Americas Foundation. The CellScope prototype is described in the July 22 issue of the online journal PLoS ONE. For more information, visit: www.berkeley.edu