In a twist on traditional smart-phone accessories, researchers have demonstrated fluorescent microscopy using a physical attachment to an ordinary cell phone. The researchers behind the device say that it could identify and track diseases like tuberculosis (TB) and malaria in developing countries with limited access to health care, or in rural areas of the U.S.
Snap diagnosis: The Cellscope uses a blue-light LED and filters for fluorescence imaging. The sample is inserted next to the metal focusing knob.
The “Cellscope,” which came out of an optics-class project at the University of California, Berkeley, could capture and perform simple analysis of magnified images of blood and sputum samples, or transmit the images over the cell-phone network for analysis elsewhere.
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The contraption–a tube-like extension hooked onto the cell phone with a modified belt clip–works just like a traditional microscope, using a series of lenses that magnify blood or spit samples on a microscope slide. To detect TB, for example, a spit sample is infused with an inexpensive dye called auramine. An “excitation” wavelength is emitted by the light source–a blue light-emitting diode (LED) on the opposite end of the device from the cell phone–and absorbed by the auramine dye in the spit sample, which fluoresces green to illuminate TB bacteria. Then automated software can count the green bacteria for a diagnosis in real time, or the image can be transmitted via cell network to a separate facility where doctors can analyze it and respond.
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“The cell phone approach is very valuable for all parts of the world where [medical] resources are scarce,” says Aydogan Ozcan, an assistant professor of electrical engineering at UCLA, who is working to develop a lens-free method for mobile cell imaging. “It’s a great step forward in this important area.”
The researchers involved with the project, led by Berkeley bioengineering professor Daniel Fletcher, describe their work in a paper published in the journal PLoS One. They previously demonstrated a prototype device that used white light, or bright-field imaging, to capture magnified images of blood cells stained to detect malaria parasites, an approach that could also identify the oddly shaped red blood cells indicating sickle cell disease. Fluorescence adds a new capability that could be particularly useful if made cheaper and portable.
“Fluorescence microscopy in resource-poor countries is hard,” says Wilbur Lam, a bioengineer and physician in the UCSF School of Medicine who worked on the project as a clinical expert. “Lab-grade [fluorescence] technology is expensive and hard to operate,” he says. “You need a dark room, a mercury lamp, and a lot of training.” These facilities aren’t available in many areas of developing nations, which, Lam notes, are the places that most need the technology to detect common diseases like TB. The Cellscope device could be distributed to health workers in remote areas, extending the reach of fluorescence-based medical imaging.
According to Fletcher, fluorescence is increasingly preferred by the World Health Organization as a TB detection tool, because it’s easier for the untrained eye to spot something green than to pick out a colored stain against a bright-field background. However, with traditional fluorescence equipment, health workers still have to count spots on a microscope slide by eye, which can be unreliable. The Berkeley group developed software that counts the green spots automatically; when installed on the smart phone, it could make the process easier and faster.
The cell-phone microscope could also be useful for TB therapy, Lam says. TB patients must be directly observed taking their medication over several weeks, to prevent drug resistance buildup. The phone can store images for comparison, and it provides immediate feedback, so patients could go to their local health worker and see their progress each week, rather than waiting a month for samples to come back from a centralized processing location, or seeing complications of the disease show up three or four months later.
That ability to transmit microscope images makes the Cellscope a new tool for telemedicine, says Lam. And because the images can have GPS tags associated with them, they could provide early warning for disease outbreaks.
Digitizing medical records is another problem for health workers in the field. Fletcher’s group ran into the issue while demonstrating their technology in Bangladesh and the Democratic Republic of Congo. Pen-and-paper records are easily lost–a problem that the cell-phone microscope could solve by attaching patient-identification information to each digital image. Records could then be called up for easy reference when a patient returns to the health clinic.
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The researchers’ key innovation, Lam says, was not inventing a new medical test, but rather taking a standard test and presenting it in a new way. Their technology “just happens to be smaller, cheaper, and attached to a cell phone,” he says.
In a world with four billion cell phones, many in developing countries, Ozcan says, the cell-phone microscope could take advantage of existing infrastructure to fight disease on a new, more mobile front.
