NEW YORK – Researchers from Tufts University have developed a paper-based blood collection card that can be used for HIV viral load testing to improve accuracy compared to standard-of-care devices.
The device, which the researchers dubbed a patterned dried plasma spot card, is described in a paper published in PNAS earlier this month. In the study, they showed that in a clinical pilot study their device is more accurate than the industry gold standard for dried plasm collection, the Roche plasma separation card. Among 75 South African HIV patients who were tested, the Tufts device showed nearly 91 percent accuracy, while Roche's plasma separation card showed about 83 percent accuracy, the researchers wrote. Sensitivity was nearly 88 percent for the Tufts' device, while sensitivity for the Roche card was 77 percent.
The project began eight years ago after a request for proposals from the Bill and Melinda Gates Foundation for devices that could simplify blood collection in the field for clinical laboratory testing, said Charlie Mace, an associate professor in the department of chemistry at Tufts University whose team developed the card.
The researchers started working with whole-blood samples and tried to "design the device in a way that really helped to control where the blood flowed, so that way it prepared a better sample for labs to test," he said. They didn't want to impact how a clinical laboratory or user handled the card, but by focusing on "being more thoughtful about what the blood was doing once it was applied" to the card, Mace added, "we found that we were able to do more with it."
The researchers were particularly interested in piloting the device in real-world settings and getting feedback from clinicians about how it could work in those settings. They spoke with laboratory technicians who process plasma cards, including scientists from South Africa's National Institute for Communicable Diseases (NICD), to understand their needs and preferences and learned that technicians weren't satisfied with how existing dried plasma cards for HIV viral load testing were performing in terms of usability and accuracy, Mace said. Scientists from NICD also helped conduct the clinical validation study.
The PNAS paper noted that the patterned dried plasma spot card itself consists of three layers of materials — a top layer of a polyester membrane that removes white blood cells from the blood to increase the efficiency of plasma production; a second layer of an asymmetric polysulfone plasma separation membrane that removes red blood cells and platelets and allows the cell-free plasma to pass to the collection medium; and a third layer of patterned cellulose cardstock that is designed to receive, direct, and store the plasma.
According to Mace, other blood collection cards, like the Whatman 903 card, use superficial circles that don't allow for control over where the blood sample flows, which can lead to bad samples.
"With cards like these, if you're not controlling volume, it's almost like rolling the dice," he said. "You don't know with the amount of accuracy that you want what you're working with."
In the Tufts device, the cellulose layer includes four circles where blood is applied that physically remove plasma from the rest of the blood cells, allowing for "higher-quality plasma" that is not affected by those cells. Using laser cutting, the researchers made patterns to help control where the sample goes and to help a laboratorian pluck out the dried plasma with tweezers, improving the usability of the card.
The Tufts researchers also used hydrophobic wax on the device so blood can only saturate the paper where the wax isn't located, limiting its ability to flow everywhere.
"By defining those features chemically with that wax or mechanically with some cutting, we could control where the blood was going, how fast it took to get there, [and] how much volume it took to saturate that area of paper that we defined geometrically, and that led to really reproducible performance across the board," Mace noted.
Once blood is applied to the card, plasma is separated in about five minutes and ready to be dried. After a few hours of drying, the card is ready to be sent to the clinical laboratory, where the sample is punched out and added to a buffer solution for rehydration and testing.
The device is meant to be a universal collection system for any type of test, not just HIV viral load testing, but the researchers "wanted to go after a very high-value, very important, and also kind of finicky test," he said. Accuracy is essential when testing for HIV viral load because a slight change in the measurement can indicate a problem for a patient. However, the dried plasma device can be used for "anything that you would want to develop a wet chemistry for in a laboratory setting," Mace said, such as lipid panels or biomarkers for general wellness.
It could also be used for home collection of blood samples that are then sent to a central laboratory for testing, he added.
Although the team is pleased with the device's performance so far, Mace said that the researchers want to align it even further with how clinical laboratories handle these devices and samples and continue to improve it.
Mace and his team intend to commercialize the device because there is "only so much we can do as an academic lab." They plan to work with partners to ensure the card can be manufactured and scaled up to "get this into the hands of the greater public," he said.