Scientists and Nonprofit Organizations Develop Affordable Diagnostics

Such technologies might eventually help lower health care costs in developed countries.

For the developing world, infectious diseases, especially HIV/AIDS, tuberculosis, and malaria, top the list of priorities for which better, more practical, and affordable diagnostics are sorely needed. Bernhard Weigl, leader of the diagnostic development group at the nonprofit Program for Appropriate Technologies in Health (PATH; Seattle, WA, USA) wants to make diagnostics for limited-resource settings instrument-free, even with tests that have traditionally required instruments, such as those based on nucleic acid amplification. He said "The only assays that really have made an impact so far in low-resource settings are devices or assays that don't require instruments." He has visited many labs in developing countries where instruments are in an unusable condition. "The only assays that are being used regularly are things like strip kits, where you just buy the kit and run it," he added.

The team at PATH is working on instrument-free ways of amplifying and detecting pathogenic nucleic acids from patients. Instead of the temperature-cycling instrument normally required to amplify nucleic acids by the polymerase chain reaction (PCR), they use exothermic reactions, with reagents similar to those found in camping hand warmers, to provide the heat needed.

Paul Yager, a bioengineering professor at the University of Washington, (Seattle, WA, USA) thinks that expecting all assays for use in developing countries to be instrument-free is an oversimplification. "You want the assays to work where they're needed," Professor Yager said. "You minimize the power requirements, you minimize the weight, you minimize the complexity, you minimize the cost. But if it needs an instrument, it needs an instrument."

Professor Yager heads a project to develop a diagnostic system, called the DxBox, to be used for infectious-disease monitoring in limited-resource setting. The DxBox reduces the power requirements for PCR by simply shuttling the sample back and forth between heated zones in the instrument, rather than repeatedly heating and cooling a single part of the instrument. Such an approach has the added advantage of speeding up the analysis because you no longer need to wait for the temperature to cycle.

The team set a goal of distinguishing six diseases that are common in the developing world and involve a rapid-onset fever and other undifferentiated symptoms. The pathogens associated with the diseases include three RNA viruses, the malaria parasite Plasmodium falciparum, and two bacteria.
Another initiative is the CD4 Initiative, run by Imperial College London. The initiative was launched in 2005 with an initial award of $8.6 million and a goal of developing a low-cost, instrument-free test for measuring CD4 T cells in HIV/AIDS patients. CD4 T-cell counts are used to determine whether antiretroviral therapy is needed and how well it is working. Three of six original subcontractors supported by the initiative are still participating: Beckman Coulter, (Miami, FL, USA), Zyomyx (Hayward, CA, USA), and the Macfarlane Burnet Institute for Medical Research & Public Health (Melbourne, Australia).

The Burnet Institute's test is based on traditional lateral-flow technology, such as that used in home pregnancy tests, but the other two incorporate novel technology. The Beckman Coulter assay allows visual identification of CD4 cells from whole blood. A blood sample is placed onto a slide loaded with CD4-capture reagents, and lines appear at different spots on the slide depending on the number of CD4 cells in the sample. Zyomyx' assay uses CD4-binding reagents to pull CD4 cells from a blood sample and transfer them to a volumetric region of the device where the volume of the cells can be read from the height of a dark line, similar to how a thermometer is read.

In the future, the focus may shift from detecting infectious diseases to monitoring endocrine diseases, such as diabetes. Professor George Whitesides at Harvard (Cambridge, MA, USA) is developing three-dimensional paper microfluidic devices that could provide a way to do quantitative, low-cost glucose testing. A nonprofit organization called Diagnostics for All (DFA) has been established to develop paper microfluidic devices. The first multiplexed test will be a panel test for liver function.

The new diagnostic methods are described in the March 16, 2009, issue of Chemical & Engineering News, ACS' weekly newsmagazine.

Related Links:
Program for Appropriate Technologies in Health
University of Washington
Beckman Coulter
Zyomyx
Macfarlane Burnet Institute
Harvard
Diagnostics for All