Biotechnologists envision a future in which high-tech gadgets using a single drop of blood can determine a person’s risk for all known genetic diseases. Not only could these technologies be faster and more sensitive than the best diagnostic tools available today, they could be easily portable and low cost. But low cost is a relative term. Scientists developing most medical tests live and work in countries where physicians routinely order tests that can cost hundreds of dollars. In contrast, in the developing world, where healthcare workers battle malaria, AIDS, and other infectious diseases that affect millions of people, a diagnostic test has to cost a dollar or less to make any inroads, says Samuel Sia, a chemist at Harvard University.
To address this financial constraint, he and many other researchers in the field are designing diagnostic tests, based on devices called microfluidic chips, that could be cheap enough for doctors to use wherever they happen to be in the world. “We thought, ‘If you’re in the middle of a village in West Africa, how can you take advantage of microfluidics advances?'” says Sia.
Scaling down
The most widely used method for diagnosing infectious diseases today in industrial countries detects disease-specific antibodies in the blood. The equipment needed to run these enzyme-linked immunosorbent assays, or ELISA tests, takes up a bench top, requires reliable electric power, and costs hundreds of thousands of dollars. Also, notes Sia, “you need a pretty well-set-up lab with trained personnel.”
To make diagnostic tests widely available in the developing world, Sia and a team led by George Whitesides of Harvard invented an automated, miniaturized ELISA test. Their new device relies on a coin-size plastic chip riddled with whisker-size channels.
Each of the microfluidic chips can mix and otherwise manipulate tiny volumes of fluids, essentially mimicking the components of a standard chemistry lab. By altering certain components of the chips, the researchers could apply the strategy to a wide variety of infectious agents.
To prime the device for HIV detection, for example, the Harvard researchers attach to the bottom of each channel a stripe of protein fragments of HIV. When a minuscule blood sample spreads through the channels, any anti-HIV antibodies in the blood will stick to the stripe. Next, a solution containing a second antibody, this one bound to gold nanoparticles, is shunted into the channels, where it attaches to any anti-HIV antibodies stuck to the stripe. In the final step, a solution of silver ions reacts with any gold in the channel to produce a solid silver film that blocks passage of light.
The silver film indicating a positive result is visible to the naked eye. An optical reader in the sensor can instantly quantify the silver buildup and provide a number on a screen, which indicates the concentration of anti-HIV antibodies in a patient’s blood. The whole process takes about 20 minutes, instead of the 5 to 6 hours required by a typical full-scale ELISA test.
To keep costs down, the researchers steered away from conventional scientific supply houses for the parts they needed for the sensor. Instead, they scavenged a laser from a DVD player and a light detector from a photocopy machine. They combined those with a small liquid crystal display and a 9-volt battery, ending up with a palm-size device that costs about $45. The researchers describe their sensor in the Jan. 16 issue of Angewandte Chemie.
The per-test cost would be affordable for mass screening in developing countries, notes Sia, because the detector can be used repeatedly and each chip costs less than a dollar.
“This is certainly encouraging,” says physicist Harold Craighead at Cornell University. “The researchers put these components together in a very nice way and produced some nice results,” he says.
“This could be huge,” adds Johanna Daily, an infectious-disease expert at the Brigham and Women’s Hospital in Boston. She studies malaria and has collaborated with health workers in Malawi and Senegal. Without access to affordable diagnostic tests, rural patients in developing countries can often be misdiagnosed as having malaria, for instance, instead of HIV.
Big prospects
Many of the miniaturized biosensors in development today could serve as low-cost diagnostic tools, says Craighead. His lab has developed a chip device that diffracts light in the presence of certain antibodies.
Chad Mirkin of Northwestern University in Evanston, Ill., has developed a sensor that employs gold nanoparticles on a chip to detect very low concentrations of specific sequences of DNA. The chip could be used to identify bacterial or viral infections.
By deploying such portable biosensors in the field, health care workers might better determine infection rates in different regions, says Daily. With that sort of data, she adds, health ministers can allocate scarce government resources more effectively.
If more researchers were to design their devices with costs in mind, their work could have huge humanitarian payoffs in developing countries and at home, Sia says. For example, tests that generate results in minutes rather than hours could screen thousands of people during a public health crisis.
