For most Americans and residents of the “developed world,” blood draws and urinalysis help physicians confirm health and spot warning signs early.
But in other parts of the world, such seemingly routine analyses are anything but. From Africa to the Middle East, South America to Southeast Asia, people lack access to even the most fundamental healthcare necessities: clean water, electricity, and medical personnel. In such environments, basic medical care can be pretty hard to come by.
Enter Boston-based Diagnostics for All (DFA), an organization developing medical tests requiring none of the infrastructure Western societies take for granted, including electricity. In fact, they require nothing at all, save a few pennies and a stamp-sized slip of paper.
The technology underlying DFA's assays is microfluidics, the science of moving and manipulating tiny volumes of liquid through and in nanoscale channels. Microfluidic instruments, often dubbed “lab-on-a-chip” devices, are traditionally built of plastics, quartz, or a soft rubbery polymer called PDMS. But those structures are generally expensive, and require a macroscale interface (i.e., an expensive machine) to manipulate and interpret the results. DFA chose to move in a different direction.
“What we have are microfluidic devices that don't require any power — not batteries or plug-in electricity — and don't require a machine or a device or a box to make them run,” explains Una Ryan, DFA's president and CEO. “So, they really are ideal for point-of-care in the developing world — and in our world as well. Because who doesn't need cheaper health care?”
Inexpensive point-of-care diagnostics represent just one of many new applications for lab-on-a-chip technology. From DNA sequencing to flow cytometry, and single-cell analysis to the classroom, microfluidics are starting to make a macro-sized impact.
Paper millsGeorge Whitesides, the Flowers University professor at Harvard University, has more than 1,100 publications to his name in everything from robotics to the origin of life. While he is justifiably proud of his accomplishments, for Whitesides, science exists for more than the mere accumulation of citations.
“Somebody pays the bills for this stuff, and I think science has an obligation to help society solve problems.” Toward that goal, one arm of his laboratory is working to develop “zero-cost diagnostics,” microfluidic devices made of paper.
Paper, says Whitesides, is a surprisingly versatile, robust material. People use and discard it without thinking, he says, “but it's actually amazing stuff.” Just take a look at how Whitesides’ lab has used “metalized” paper (paper printed with metal circuitry) to build cheap keyboards and accelerometers.
It was work from Whitesides’ laboratory demonstrating microfluidic devices could be fabricated out of little more than Whatman filter paper that laid the intellectual groundwork for DFA. Dipping paper into liquid causes that liquid to wick; Whitesides’ group (and DFA) figured out that the liquid's movement could be directed by printing walls of hydrophobic material onto the paper. In one application, paper glucometry strips for diabetes monitoring were developed, mimicking the fluidic design of standard strips at a fraction of the cost.
The design of those strips is modular: Simply changing the test reagents dried on the paper, test strips for such biomarkers as cholesterol and urea can be designed. Such designs, Whitesides says, enables physicians to collect additional patient data at very little extra cost. Paper chips can even be extended into the third dimension by stacking and binding different sheets such that fluids flow not just laterally but between sheets as well enabling designs that include, for instance, a filtration step, useful in separating blood cells from plasma.
Starting from Whitesides’ original designs and the organization's own in-house technologies, DFA has developed fully engineered, working prototypes, focusing both on novel chip architectures as well as the engineering, quality control, and manufacturing issues required to bring a diagnostic to market. Several chips are in development for maternal care and agricultural applications, and one colorimetric assay for enzymes released by antiviral medication-induced liver damage is currently in a 750-patient clinical trial in Vietnam, according to Ryan.
