By combining a standard BBQ lighter with superfine microneedles that are common in medical and cosmetic procedures, researchers have developed a $1 device that uses electricity to inject certain vaccines more efficiently—and less painfully. Its developers say it could expand global access to vaccines containing genetic material, including the ones that fight COVID-19.
“Everybody across the planet has a basic right to modern nucleic acid tools,” says Saad Bhamla, a chemical engineer at the Georgia Institute of Technology and co-developer of the pen-sized device, called the ePatch. The “tools” he refers to are DNA and mRNA vaccines, which use a portion of a pathogen’s own genetic code to evoke an immune response (in contrast, traditional vaccines use actual pieces of a pathogen, or its weakened or inactive form). DNA and mRNA vaccines are less expensive to manufacture than traditional ones, and they are easier to modify—a major selling point for dealing with newly emerging variants of a virus. But some genetic-material vaccines also have expensive and difficult-to-stabilize components, which require special handling; this makes them less accessible in many parts of the world, especially more remote or less-developed areas. Bhamla and his colleagues’ mission with the ePatch is to make vaccines like these available to everyone. Their work was published November 9 in Proceedings of the National Academy of Sciences.
For any vaccine to work, it has to get inside a person’s cells—and the genetic material in mRNA and DNA vaccines needs a little extra help in crossing cell membranes. In the case of mRNA vaccines (including the ones currently being used against COVID-19), the mRNA is coated in a wee glob of fat called a lipid nanoparticle. These particles help the genetic material slip into cells, while also stabilizing the easily degraded molecules. But they also need to be kept frozen prior to injection, which means the whole vaccine requires storage at extremely low temperatures. DNA vaccines can go without freezing because they do not require lipid nanoparticles: They are more stable than mRNA even without the added fat, and to break into cells, they instead use a “vector virus,” a modified virus different from the one being targeted. But these vaccines have their own drawbacks: ongoing safety concerns about this mode of delivery, and the fact that DNA vaccines tend to generate less of an immune response.
One way to improve prospects for genetic-material vaccines might be through electroporation: injecting the vaccine while delivering a very mild electrical shock, which prompts cells to temporarily open holes in their membranes and let in the vaccine. In theory, applying electroporation alongside genetic-material vaccines could improve both effectiveness and accessibility. For mRNA vaccines, genetic material might be able to enter cells without lipid nanoparticles; this means the vaccines could possibly be stored at room temperature. For DNA vaccines, which are already stable at higher temperatures, researchers have higher hopes. They think electroporation would help generate a stronger immune response—and perhaps make DNA vaccines more widely adopted.
Thus far, this technology has only been tried with DNA vaccines in clinical trials—and even this use is still in its early stages. It has not yet led to a licensed vaccine, explains Shan Lu, who works as an immunologist at the University of Massachusetts Medical School and was not involved in the new study. “Electroporation has been demonstrated to markedly increase DNA vaccine delivery and potency, but currently has several limitations including cost, the requirement for a device, ease of use, and tolerability issues,” says Jeffrey Ulmer, industry consultant and former head of preclinical research and development at health care company GlaxoSmithKline (Ulmer also was not involved in the new study). In other words, traditional electroporators are bulky machines that cost thousands of dollars and require a power source. The cheap and simple ePatch, made with easily available parts, circumvents all of these problems.
The ePatch design was partly based on Bhamla’s previous work in developing an affordable electroporator for laboratory experiments. This penlike device used a BBQ lighter’s piezoelectric crystal, which generates a pulse of electricity when pressure is applied to it. To adapt it for vaccine delivery, Bhamla’s lab attached an array of microneedles to the device’s tip. These act as both a method of pushing vaccine into the body and as electrodes, funneling the vaccine and the electric pulse down into the cells just below the skin’s surface.
When the team used the ePatch to deliver a DNA vaccine in mice, they found that it produced an immune response about 10 times greater than that from a typical injection. And their results were comparable to those from similar studies with traditional electroporators. “That gave us some encouragement that what has been seen with electroporation with big machines, we should be able to accomplish with these inexpensive, potentially disposable electroporators,” says Mark Prausnitz, a chemical engineer at the Georgia Institute of Technology and study co-author.
Ulmer says the system could potentially make electroporation more accessible, “but it’s in its early stage and requires validation in humans," he adds. Lu agrees. “Over the last few decades there have been vaccine studies using microneedle injections that worked well in mice but did not translate in humans,” he notes.
Human trials are still a long way off. Instead, the Georgia Tech team’s next step is to optimize the device and test DNA vaccine delivery with the ePatch in larger animals. The researchers also hope to test the device with mRNA. Bhamla is not certain it will work, because mRNA is unstable, but he says he feels compelled to try, because if it does eventually work it could remove the current lipid nanoparticle requirement.
Beyond increasing access to genetic vaccines, Bhamla sees low-cost, accessible devices like the ones he develops as part of a “frugal science” ethos that can make experiments cheaper and more accessible. He says he hopes his latest project will prompt people to view technology a little differently: “I want them to think, ‘If this guy can look at a BBQ lighter and think of a DNA vaccine delivery device, then what can I do?’”