An easy-to-use, portable T-cell counter
By Andreas von Bubnoff
Earlier this year, the World Health Organization announced new treatment guidelines recommending that antiretroviral therapy (ART) be initiated in HIV-infected adults when the CD4+ T-cell count reaches 500—up from the previous threshold of 350. The guidelines pose a considerable challenge because of the limited availability and cost of ART, especially in developing countries.
Another problem is that most HIV-infected people in developing countries don’t have easy access to facilities that can measure their CD4+ T-cell counts. Currently, such measurements are typically taken with flow cytometers. These large, refrigerator-sized devices weigh around 90 pounds, cost up to US$100,000, and require trained people to draw blood and do the analysis. One analysis can take several hours.
One reason such devices are so costly is that they use laser light to detect fluorescent antibodies that bind to CD4+ T cells. But Rashid Bashir at the University of Illinois at Urbana Champaign and his colleagues have built a device that lacks optical components and can count all white blood cells, as well as CD4+ and CD8+ T cells, using plain old electrical current. Better yet, the device can be used by any untrained person—even the patients themselves—to count these cells in less than 15 minutes (Sci. Transl. Med. 5, 214ra170, 2013). All that’s needed is a drop of blood from a finger prick.
While the current version is just a prototype, the researchers plan to commercially develop a smaller, $500-$1000 toaster-oven sized version of their new device in the next 2-3 years. “This approach has the potential to be realized as a handheld, battery-powered instrument that would deliver simple HIV diagnostics to patients anywhere in the world, regardless of geography or socioeconomic status,” they write.
To be sure, a portable CD4+ T-cell counter is already commercially available. It’s a table top device called Pima that uses optical components and is made by a company called Alere. And Bashir himself has cofounded a company called Daktari Diagnostics to commercially develop an electronics-based portable device that will be tested in Africa.
But the new device, once commercially developed, could be the first electronics-based handheld portable device that can also count all white blood cells and CD8+ T cells, in addition to CD4+ T cells. That’s important, Bashir says, because doctors can use the total white blood cell count and the CD4/CD8 ratio to determine the status of a patient’s immune system and to better monitor whether their treatment is working.
The way the new device counts cells is quite simple: It measures how an electrical current changes as cells pass through a group of tiny electrodes. Antibodies are then used to capture CD4+ or CD8+ T cells, and the cells are counted again. The difference between the two counts equals the number of captured CD4+ or CD8+ T cells. What makes the device so affordable, says Bashir, is the lack of optical components and the fact that all measurements and biochemical reactions take place on a chip that is similar in size and composition to a computer microchip.
Because the device can be used by any untrained person, it should make CD4/CD8 counts much more accessible to people in the developing world. “[People] just can’t make it to the labs,” Bashir says. “This technology can take the lab to the patients rather than the patients to the lab, so a case worker can go to very remote settings and do the test right there in the field.”
But not everyone thinks that CD4+ T-cell counts will remain as important in the future as they are now. Some researchers say that offering treatment at any CD4+ T-cell level (an approach called Test and Treat) is the right way to go because there is evidence that the earlier HIV-infected people start treatment, the better. Julio Montaner, who runs a Test and Treat program in British Columbia, says the study is very good news. “However,” he adds, “as we move towards a full Test and Treat strategy (hopefully in the very near future), the need for CD4 cell count monitoring decreases sharply.”
But Bashir is already thinking of other applications. Because the technology can in principle be developed to count any type of cell that’s recognized by a specific antibody, he plans to develop a version that can replace flow cytometers in performing a very common test that’s done pretty much every time someone gets a physical: the complete blood count, which measures most of the types of cells found in the blood.