The Berkeley Science Review: Articles

Needle-less Injections
Taking the sting out of vaccinations (view PDF)
by Jessica H. Harvey

Medicine may be one step closer to earning the approval of Star Trek’s Dr. McCoy with a recent development: needle-free injections. The Fletcher lab at UC Berkeley, in collaboration with Samir Mitragotri at UC Santa Barbara and Ravi Srinivasan at Stratagent, reported the development of a new kind of needle-free jet injector in the March 13 issue of the Proceedings of the National Academy of Sciences. The injector works by harnessing the power of shape-changing crystals. Instead of piercing the skin with a sharp piece of metal, tiny jets of liquid are pumped out at speeds sufficient to penetrate it.

The obvious benefit of this research is to eliminate pain from injections. Needles are painful due to their thickness, which is mostly required for structural reasons. “You’re making a large hole that is catching a lot of nerves just because you need rigid walls for the needle,” says bioengineering professor Dan Fletcher. But eliminating the needle as an injection device does not necessarily eliminate the pain. Needle-free injectors have actually been around for quite some time, but developed a reputation for causing pain and bruising due to the volume of liquid that they delivered. The first jet injectors were developed in the 1940s for mass administration of vaccines to US soldiers. “They were effective at delivering vaccines,” says Jeanne Stachowiak, an engineering graduate student in the Fletcher lab, because “as long as you inject enough [vaccine], you will have an immune response.” These first injectors used compressed gas to propel milliliters of liquid into the skin, even into muscle. “I think they were very intimidating,” Stachowiak remarks.

Today, there are commercially available jet injectors that derive from these military prototypes, like the Biojector from Bioject Inc., but they suffer from the same drawbacks as their predecessors. Perhaps the most formidable drawback is the size of the penetrating jet. At around the diameter of a human hair, the stream size may seem neglible in comparison to a metallic needle, but it’s still large enough to hurt. “Consumers aren’t going to opt for a drug-delivery system that’s painful,” says Fletcher.

There are also compelling reasons for avoiding needles that are unrelated to pain. Needles are expensive, so in the developing world they’re often re-used, but “needle re-use is very dangerous,” says Stachowiak. “Cleaning to appropriate standards is difficult.” Yet no viable alternative is currently available. Multi-use jet injectors were, according to Stachowiak, “actually shown to be responsible for the spread of disease, and their use was discouraged by the World Health Organization.”

The reason older injectors spread disease was due to wide injection streams that caused a significant amount of splashback onto the injector, contaminating it. “Large volume injections will likely always have splashback issues,” says Stachowiak. With pulsed microjet injectors, the Fletcher lab and collaborators hope to have solved this problem.

At the heart of their design is the piezoelectric actuator, a device that uses shape changing crystals to deliver hundreds of small injections, each containing a miniscule volume of liquid. When a voltage pulse is applied, the crystals move, but only a few micrometers, a distance invisible to the naked eye. The movement pushes a plunger and a stream of liquid is forced out of a small hole barely a tenth of a millimeter wide, at speeds of around 100 meters per second, slower than a conventional jet injector, but fast enough to penetrate the skin given the reduced diameter of the jet. A spring then returns the plunger to its original position. When this happens, pressurized liquid stored in the reservoir flows into the nozzle, refilling it. Velocity, penetration depth and dosage can all be shaped by altering characteristics of the voltage pulses so that operationally, the design is similar to that of a commercial inkjet printer, which also uses a piezoelectric actuator to pump out liquid. As Fletcher puts it, “what we tried to add was something the printer industry has done very well—precise control.”

Thanks to the narrowness of the ejected fluid stream, splashback is reduced to miniscule levels. Were a conventional jet injector to use such a narrow stream, a long injection length would be required, causing pain. The microjet injector avoids this by repeating the injection procedure many times over. By appropriately limiting the length and velocity of the stream, penetration depth is reduced to 100-150 micrometers. This region of the skin contains few nerves and blood vessels (meaning negligible pain and bruising), but is still deep enough for many drugs to be effective.

Fletcher describes his long-term goal as “the development of a platform for controlled delivery” for any liquid, but one of the main therapeutic targets is insulin. Apart from requiring accurate dosage, insulin delivery is trickier than vaccine injections as it only works if it gets into the blood. While Fletcher and collaborators have shown their device can change the blood glucose levels of rats, “the next big step”, as Fletcher refers to it, is to start Phase I clinical trials in humans. In anticipation of successful trials, one company has already sprung up with the goal of bringing this technology to market. Stratagent Corporation, which Fletcher helped found, plans to incorporate microjet injectors into wearable devices that periodically sample blood to determine whether or not injections are needed, and if so, provide them.
Dr. McCoy would be proud.

Jessica H. Harvey is a graduate student in chemistry.

Want to know more?
Check out fletchlab.berkeley.edu

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