Improving healthcare, particularly in the developing world, will require low-cost diagnostic devices that can be used quickly and easily to meet the needs of people living in remote locations that often lack doctors, clean water, and electricity. These diagnostic tools need to be rugged and reliable, inexpensive, and insensitive to changes in temperature and humidity. Ideally, they should run without electricity and fit easily in a backpack that an aid worker could carry on foot or by bicycle.
With its ability to miniaturize sample analysis from milliliters to microliters, all within an area of a few square centimeters, microfluidics has the functional capabilities to fulfill this task. Since the 1990s, the Defense Advanced Research Projects Agency (DARPA) has invested in microfluidics for advancing portable devices on the battlefield. “The difference between what the military needs to do in taking care of soldiers and [what is needed for] global health is actually very, very small,” says Paul Yager, professor of bioengineering at the University of Washington in Seattle.
Although a microfluidic chip drastically reduces both sample and reagent volumes used in laboratories, the devices produced and used in laboratory settings won't work in the developing world. They still require clean water, fluid pumps, and expensive detectors—along with electricity to power these components. Over the last decade, researchers have searched for ways to overcome these technical and manufacturing challenges. Some efforts have scaled down chip analysis into streamlined battery-powered devices with disposable microfluidic cards. But even those devices may prove too costly. Now, a new low-cost solution has emerged from an über-simple concept: devices made from paper and tape.
Shuffling cardsIn the late 1990s, the development of soft lithography methods using polydimethylsiloxane (PDMS) by George Whitesides' group at Harvard University and others brought microfluidics out of the clean room and into the mainstream academic laboratory. Researchers could design and fabricate devices with channels by building layer upon layer of soft plastic. To run, such systems rely on complex networks of pumps and valves with microscopes or fluorescence to detect signals. “Even if [those things] work in a portable setting, they might not be very cheap,” says Samuel Sia of Columbia University.
While a postdoc in the Whitesides group at Harvard, Sia was intrigued by the challenge of rethinking and streamlining microfluidic devices. He and his colleagues looked for ways to put reagents on a disposable plastic card and develop a small portable device that would run it. The big manufacturing challenge was finding a way to produce the microfluidic cards cheaply using molded plastic. He and his colleagues tweaked the parameters used for injection molding, the process used to mass produce plastic objects such as pens. Such processes had generally only been used to make features on the order of millimeters, but Sia and his colleagues found ways to produce micron-sized features. Sia is one of the founders of Claros Diagnostics, which has been developing this handheld system. They have already designed cards for a developed-world application: a quick test for measuring prostate-specific antigen (PSA) as a doctor's office–based screening tool for prostate cancer. They've also done initial tests of the device in Rwanda with a portable ELISA-type assay to screen pregnant women for HIV and other sexually transmitted diseases including syphilis, hepatitis B and C, and herpes.
An important innovation in such systems is the implementation of a simple optical readout that avoids detection schemes requiring fluorescence and additional equipment. The Claros Diagnostics system uses gold nanoparticles bound to IgG which in turn bind to an agent of interest. They then develop those spots using silver to amplify the signal up to a million-fold for inexpensive optical detection.
Another collaboration based at the University of Washington has followed a similar approach. Since 2005, researchers there, along with those from the Seattle-based non-profit PATH and two for-profit companies—Micronics and Nanogen (now part of the ELITech Group)—have been developing a proof-of-concept device through the DxBox project, supported by the Bill and Melinda Gates foundation. Yager and his colleagues were trying to take an idea that they'd developed—pushing liquids around on disposable polylaminate cards under the control of a base station—and make it as accessible and inexpensive as possible. The device has the capability of doing both immunoassays and nucleic acid–based assays to test for a variety of infectious diseases characterized by fever: malaria, typhoid, influenza, rickettsia, measles, and dengue fever.
