12 December 2008

Three Cents’ Worth of Paper and Tape Help Diagnose Diseases

New microfluidic device could improve health services in developing world

In a microPAD prototype, red, yellow, green and blue fluids cross each other multiple times without mixing.

By Daniel Gorelick
Staff Writer

Washington — Using paper and adhesive tape, scientists have developed an inexpensive device to analyze bodily fluids for signs of disease. The low-tech diagnostic tool could bring tremendous benefits to public health in poor nations.

The three-dimensional microfluidic paper analytical devices (3D microPAD) are small, easy to transport and require no pumps or electricity to use. This makes them appropriate for use in developing countries as diagnostic devices, wrote Harvard University researchers Andres Martinez, Scott Phillips and George Whitesides in the December 16 edition of the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Whitesides, a chemistry professor who led the research, founded a nonprofit company, Diagnostics-For-All, to make sure the technology gets to developing nations.

“Developing a low-cost and broadly applicable test system designed to be deployed in regions with no or little access to complex laboratory diagnostic equipment, we hope to make a real impact on public health,” Whitesides wrote.

In October, the Whitesides laboratory developed a centrifuge using a $2 eggbeater, plastic tubing and tape. The device can be used to separate plasma from blood, a prerequisite for performing many types of medical tests. (See “$2 Egg Beater May Help Diagnose Disease in Developing Countries.”)

MICROFLUIDIC DEVICES

In microfluidic devices, fluids are manipulated in small spaces, often less than one millimeter (one-thousandth of a meter) — imagine water flowing through a microscopic pipe. Such microchannels can be etched on silicon, glass, plastic or, in this case, paper.

The 3D microPAD pilot device is a card, several centimeters square, that can detect levels of sugar and protein in urine — markers of diabetes and kidney failure.

When a sample of fluid is touched to one corner of the microPAD, the fluid travels through microchannels to a detection zone. Chemicals that measure levels of sugar or protein have been pre-spotted onto the detection zones. Once the fluid reaches the detection zone, a chemical reaction begins and the spot changes color, reflecting the amount of sugar or protein present.

The tests take about 30 minutes to complete. The color can be read and interpreted by people with minimal training.

Multiple microchannels can lead a single sample to multiple detection zones, enabling health care providers to test the same sample for sugar levels multiple times, a process required for a precise measurement.

Different colors reflect different concentrations of proteins or sugar as a microPAD is used to test artificial urine.

A second advantage of the microPAD is that multiple samples can be tested on the same card — the microchannels overlap but, like closely spaced pipes, do not connect or leak.

Unlike microfluidic devices made from plastic or glass, microPAD requires no pump to propel the fluid through microchannels.

MEDICAL TESTS FOR THE DEVELOPING WORLD

In fabricating paper-based microfluidic devices, the scientists’ goal was to produce inexpensive diagnostic tests using “technologies especially suited for developing countries,” graduate student Andres Martinez, who helped develop the microPAD and is an author of the study, told America.gov.

Paper has a number of advantages in microfluidic devices, according to Martinez.

Paper is light and thin, making it easy to transport large numbers of test kits to remote regions. Paper is also flammable, so burning used kits is a simple disposal option to prevent contamination from bodily fluids. Widespread availability of paper means that paper-based analytical devices one day could be produced locally.

In the future, technology to manufacture paper products, such as that used in printing newspapers and magazines, could be harnessed to produce paper-based diagnostic devices in bulk, Martinez said.

Martinez is adapting the microPAD to test blood, a more complex fluid than urine, with the goal of developing a test for liver failure by adapting the microPAD to detect elevated levels of enzymes in the blood, which are a hallmark of liver failure.

Whole blood, however, cannot be tested. First, the red blood cells must be removed, leaving behind blood plasma. Building on the previous work of the laboratory, Martinez envisions using the $2 eggbeater centrifuge to separate plasma from whole blood, then spotting the plasma onto a microPAD to test for liver enzymes.

Many medications have harmful side effects on the liver, but currently there is no rapid, low-cost way of reliably monitoring a patient’s liver function in the field, Martinez said. He hopes to be able to use microPAD to identify microbial and viral infections in blood.

DIAGNOSTICS-FOR-ALL

To commercially produce and distribute the microPAD, Whitesides and colleagues formed Diagnostics-For-All. Spearheaded by Hayat Sindi, a visiting scientist from Saudi Arabia, Diagnostics-For-All is a nonprofit company whose mission is to deliver affordable diagnostic solutions to the global medical community.

Sindi, one of the company’s co-founders, helped write the company’s business plan, which won several awards, including the prestigious Massachusetts Institute of Technology (MIT) $100K Entrepreneurship Competition and the Harvard Business School Business Plan Contest.

Diagnostics-For-All beat more than 230 other teams, including both for-profit and nonprofit entities, to win the MIT competition and the $100,000 prize in May, marking the first time a nonprofit company has won the competition.