This blog will expose readers to many facets of scientific investigation and discovery. Recent news in science will be shown and expanded on to teach far more. Biographies of scientists will give a deeper insight than what you may have read in textbooks. I hope that the posts will help improve scientific literacy, expand your interest in many fields of science, and inform you about some important scientists.
Many people don't like needles, the type for injecting vaccines at hospitals and clinics. Yes, they hurt and sometimes cause bodily harm if used improperly. How else could vaccines be administered in a more painless and safer way without needles? The Star Trek world figured it out decades ago (and it was actually developed earlier in the real world). One of its names is jet injector, and that's what this article is all about. And they have been around for a long time!
In 1963, Gene Roddenberry conceived of the science fiction TV program Star Trek. It went on air in 1966. His medical characters used a syringe that did not employ needles because the network's standards and practices banned their use on TV back then. Roddenberry then developed a device called a "hypospray" which injected medicine by a type of pressure. Clips from the original series show a hypospray that was capable of being loaded with a liquid cup at one end, and pressurizing it into the body with a hissing special effect sound, whether through direct contact with the skin, a shirt, or even several layers of a spacesuit. It could be used on multiple patients without risk of cross-contamination because it never came into contact with the person's blood. And the injection site didn't have to be sterilized beforehand.
Star Trek original series hypospray in use
Later iterations of the show changed the design of the hypospray and where it injected, but they were all based on this needleless format. Each design had some means to adjust dosage, so different sizes were not needed. According to the fictional Star Fleet Medical Reference Manual, written a decade later to appease fans' curiosity, it uses a high-speed air jet to deliver a colloidal suspension of the medicine.
Excerpt from the Star Trek manual
What is a colloidal suspension? It's a mixture of particles floating evenly in a liquid. Examples are milk, ink, shaving cream, and mayonnaise. The particles aren't dissolved; they are suspended. In the fictional hypospray, those particles are the medicines, and Star Trek didn't go any further in describing the details.
The concept of injecting without needles came about in 1935 by accident. A mechanical engineer saw a worker get injured by a high-speed jet stream. John Roberts at Columbia University College of Physicians and Surgeons took that incident and wrote a doctoral dissertation on its potential applicability for medicine. A year later, Marshall Lockhart (another engineer) filed for a patent on a spring-loaded hypodermic injector. Lockhart's design showed various patterns of how liquid could be dispersed on injection, depending on how far the injector was held from the skin.
In 1947, a clinical study with this device was conducted at the Maryland Medical School, using water suspensions and colloidal suspensions on living patient volunteers and cadavers.
Lockhart theorized what sort of pattern the injected fluid would have. He sketched them out in his patent but made no actual tests. The clinical study showed x-ray images from top and side of a newborn infant's arm and thigh after injection moment after the infant had died, so you can see the spray pattern near the surface and how deep it went.
Lockhart's patent did not provide any dimensions for his device, but the University of Maryland study did for theirs and measured the spray patterns. Penetration of 0.25 cc (about 5 drops) of a dye on arm, thigh, and buttocks reached 0.3-2.5 cm (0.1-1.0 inches), with spread areas from 1.0 x 1.0 cm to 6 x 6 cm. With doctor volunteers, they used 3,500 psi (pounds per square inch) pressure, and with the dead infants they used 2,300 psi. Adults compared the pain to that of a standard needle in various locations:
60 claimed no pain
51 claimed mild pain but less than a needle
5 claimed mild pain with skin cuts
2 claimed more pain than a needle
Various modifications of the jet injector design were made on the pore size and the method to pressurize the liquid (spring, solenoid, compressed air, or an explosive charge). The U.S. Army Medical Services Graduate School recognized the value in jet injectors, and in 1951 they created and tested one that did not have to be refilled after each injection, thus saving time in mass vaccinations.
1959 U.S. Army jet injector for typhus vaccine (Wikipedia)
These were used around the world for a variety of diseases including typhus, polio, and smallpox. Kids programs on TV demonstrated with familiar friendly characters just how painless it was, like this one-minute clip with Bozo the clown.
From Babies and BreadwinnersYouTube video (starting at 12:27 in original)
By the 2000s, there was some concern about tiny drops of blood oozing out of injection sites. Also, some splashing back from the skin sometimes occurred and hit the injector. People thought this might mean the nozzle of the jet injector would become contaminated and spread disease (like hepatitis B) to the next patients. So several designs arose that were single-use disposable injectors.
The 1980s saw the use of injecting powders or particles instead of liquids or colloids. Protein powders or DNA-coated gold particles were shot into the skin to carry materials that stimulated the immune response. This was discontinued for various technical reasons, like poor stability of the DNA, insufficient dosage that actually made it into the body, and storage problems of the medicine.
Two researchers at the University of Texas - Dallas may have overcome some of these problems. Dr. Jeremiah Gassensmith and his graduate student Yalini Wijesundara put two twists into the existing technology. Gassensmith was bored during the early years of the COVID-19 pandemic and had used jet injector parts to shoot table salt at people at home. He then handed it over to Wijesundara to work on more seriously.
The first difference compared to earlier technology was the powder itself, the carrier for vaccine material. They chose a unique carrier called MOF. This metal-organic framework is a hybrid substance that is very porous, and whose porosity can be adjusted to hold various sized molecules (like drugs) inside, not outside. Wijesundara demonstrated how MOFs could be used to shoot genes into onion cells and protein into mice.
MOF (blue particles) injection under mouse skin and into onion cells (Chemical Science, 2022)
The metal in her MOF was zeolite (a compound made of aluminum, silicon, and oxygen), which is much cheaper than gold. What's more, since it is dry, it does not have to be stored in refrigerated conditions.
The second innovation was choosing which type of gas used to pressurize the MOF-drug into the body. Many types had been used in the past, but Wijesundara found that carbon dioxide was very useful. When it mixes with water, including the water inside cells, carbon dioxide normally changes to a weak acid (carbonic acid). It is made by the body when cells digest food, and the acid helps keep the body pH in check. In the case of a MOF-drug bullet, carbonic acid breaks apart the MOF carrier, so the drug is released into the cells and tissues around it.
Injecting OVA protein with a ZIF (zinc) type of MOF carrier (SciTech Daily)
If a delivery of a drug needs to be fast, carbon dioxide gas can be used, but if the drug delivery should be slower, Wijesundara found using plain air (which contains only 0.04% carbon dioxide) to pressurize the MOF-drug works just fine. How did Gassensmith and Wijesundara measure this to produce the graphs below and the drawing above?
Comparison of carbon dioxide vs air as a gas for MOF-drug (SciTech Daily)
They attached a fluorescent red dye to the protein in the MOF particle. It was released and then faded away as carbon dioxide dissolved the MOF and allowed it to disperse in the body. It stayed at the injection site longer when air was used.
MOF with red dye stayed longer with air (left) than carbon dioxide (right) (Chemical Science, 2022)
In their experiments, the U of Texas researchers found that they needed only 500 psi to successfully transfer the MOF particles, thus producing a softer pressure on the skin than earlier experiments using 2,500-3,000 psi. Gassensmith described the MOFs and injection process as follows:
“These things are thinner than the width of a human hair, essentially. They go so fast [that] they slip through the cells on the skin, [which] are all dead,” says Gassensmith. “It doesn’t tear any tissue. You do make holes, they’re just so small you can’t see them. They’re so small, blood can’t come out [because] red blood cells are way bigger than these particles.”
So, this recent news from Dallas researchers may be used down the road for vaccines. Gassensmith and Wijesundara are investigating MOF delivery of chemotherapeutic chemicals for melanoma treatment right now, but who knows about the future?
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