Good on Paper
As we develop new point-of-care diagnostics for resource-limited settings, the humble sheet of paper has a lot to offer...
Andres Martinez |
Diagnostic assays can play a critical role in remote, resource-limited settings where doctors or other trained medical personnel are not available (1). In these environments, most existing technologies are either too expensive or not compatible with the extreme conditions encountered (2). The answer? Low cost, point-of-care tests (POCTs) – if developed appropriately – have the potential to overcome both of these challenges.
A POCT is the combination of assay chemistry and a platform (i.e. a device) to support that chemistry. To be useful in resource-limited environments, the device must be cheap, small and portable; the reagents must be stable at room temperature; the results of the assay chemistry need to be accurate and easy to interpret; the assay should have minimal power requirements (ideally the assay should not require electrical power, but battery-powered assays are an option); and the assay should be relatively simple to perform – ideally, the user need only apply the sample to the device and then read the results. The WHO released the “ASSURED” criteria to describe the ideal assay: affordable, sensitive, specific, user-friendly, rapid, equipment-free and deliverable to end-users. Paper-based platforms were developed specifically to meet the demands of resource-limited settings.
Paper has many inherent characteristics that make it well suited as a platform for POCTs – it is cheap and widely available, it wicks fluids by capillary action, it has a large surface-to-volume ratio, and it provides a white background that makes color changes easy to see. The first examples of paper-based devices were simple dipstick assays (like litmus paper) that monitored the concentrations of certain analytes using color changes. Then came lateral-flow immunoassays, such as the rapid diagnostic test for malaria and the home pregnancy test, which vastly expanded the range of analytes that could be detected on paper by relying on antibodies for detection. A global community of researchers is now working on the next generation of paper-based devices known as microfluidic paper-based analytical devices, or microPADs.
MicroPADs are devices made from paper, or other porous membranes, patterned with hydrophobic inks to create hydrophilic channels. Like conventional microfluidic devices made from glass or plastic, microPADs comprise a network of channels that can be used to process small volumes of sample and perform multiplexed assays. Unlike conventional microfluidic devices, microPADs wick fluids by capillary action, so they don’t rely on pumps or other supporting equipment. The combination of microPADs with new assay chemistries is leading to more sensitive and quantitative assays that should expand the applications and utility of paper-based tests (2).
Though POCTs for use in resource-limited settings must be cheap, rapid and simple, the process of developing these devices is challenging, expensive and time consuming. However, the potential benefits of new diagnostic technologies easily justify the investment in time and resources required to develop them. And who knows – the device originally developed to use in rural villages could one day end up serving the populations of major cities too.
- D Mabey et al., “Diagnostics for the developing world”, Nat Rev Microbiol, 2, 231–240 (2004). PMID: 15083158.
- AK Yetisen et al., “Paper-based microfluidic point-of-care diagnostic devices”, Lab Chip, 13, 2210–2251 (2013). PMID: 23652632.