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Objective Needle free jet injection is a drug delivery technique that uses the momentum of the fluid drug to break through the skin. This technique has recently also been applied to blood release, aiming to collect samples from capillaries in the skin without needing a lancet prick. This work provides new information about the wound geometry and tissue disruption caused by shallow jet injection with circular shaped and slot shaped jets. Methods We use histological analysis to compare the disruption of tissue, including blood vessels, caused by lancet-pricking and jet injection with a circular shaped jet and a lancet-inspired slot shaped jet. Results Intradermal injection into porcine skin using a slot shaped jet disrupted more vascular endothelium in the tissue than a circular shaped jet and did so at a smaller penetration depth with smaller wound volume. Our results suggest that shallow jet injections may have the potential to release more capillary blood than a lancet prick. Conclusion These findings demonstrate that a reversible jet injector might be used in diabetes management as a device to release and collect blood samples, in addition to being used to deliver insulin. Significance Tissue disruption is crucial to consider when using jet injection to deliver drug and release capillary blood.

Objective: Fear of dental procedures is a common barrier to effective dental care. A promising technique to overcome dental anxiety is needle-free jet injection, which involves delivering local anaesthetic as a high-speed jet capable of penetrating the oral mucosa without a needle. Previous efforts have used loud, uncontrolled injectors designed for transdermal delivery that have failed to achieve significant uptake in dental practice. Methods: In this work, we present and validate a controllable jet injection device driven by a silent electric motor for the delivery of dental local anaesthetic. The injector includes a novel tubular attachment at its distal end, which allows the delivery to be performed comfortably throughout the mouth. The expected pressure loss resulting from the use of this attachment is analysed. This analysis predicted that a 75 mm long tubular attachment of 0.53 mm radius would result in negligible pressure loss. To validate delivery in human tissue, the injection system was used to perform 18 injections into the mouths of two Thiel-embalmed human cadavers. These injections were visualised using cone-beam computed tomography (CBCT). Results: Benchtop testing of the prototype injector verified the expected pressure loss along the attachment. The CBCT scans demonstrated that the fluid was successfully delivered to the desired locations, adjacent to the root apex of the teeth, at every injection site. Conclusion: These outcomes validate the performance of this novel needle-free injector, demonstrating its potential as a tool to reduce dental anxiety. Clinical and Translational Impact Statement— Our controllable jet injection device overcomes key limitations associated with previous attempts to deliver dental local anaesthetic needle-free. This could greatly reduce barriers to effective dental care.

We present a new mechanism for achieving needle free jet injection that significantly reduces the power required to perform a given injection. Our ‘compound ampoule’ produces two phases of jet speed under a constant force input by changing the effective piston area part-way through the injection. In this paper we define the benefits associated with a compound ampoule, relative to those of the conventional single piston design, by developing expressions for the power and energy required to perform an injection. We demonstrate that a compound ampoule can reduce the maximum input power required to perform a jet injection to less than one fifth of that previously required, enabling motors of less than half the mass to perform the same injection. We then detail the development of a prototype compound ampoule injector. Results from testing of this prototype demonstrate the function of a compound ampoule and verify the expected reduction in the required power and energy. Injections into post mortem porcine tissue confirm that our compound ampoule prototype can achieve the delivery of 1 mL of liquid into post-mortem tissue at least as effectively as a conventional ampoule. This approach will advance progress toward light-weight and power-efficient needle-free jet injectors for transdermal drug delivery.

We present a new lancet-free method of capillary blood collection for the measurement of blood glucose concentration using a needle-free jet injector. This technique is tested on living animals and directly compared to the current best practice, lancet prick. Shallow jet injection into porcine outer-ear was performed using a portable needle-free jet injector with a slot-shaped nozzle. The jet injections presented used about 25 µL of injectate to penetrate porcine skin to about 1.4 mm, which is within the WHO standards for capillary blood sampling. The blood and fluid released by the jet injections and lancet pricks was collected. The volume and colour of these samples were analysed. The results demonstrate that jet injection is a feasible technique for the collection of capillary blood, despite the small volume of blood samples retrieved from all four pigs. Jet injection may be used in the future to retrieve capillary blood samples from human fingertips.

In this paper, we present a dual laser system to estimate blood dilution in a sample of capillary blood collected by a needle-free jet injector. Our needle-free blood collection technique requires injection of a small quantity of fluid containing Indocyanin green as a marker, which subsequently dilutes any extracted blood. We conducted experiments to measure the fluorescent intensity of this fluorophore in blood samples with different hematocrit levels. In order to compensate for the impact of hematocrit on fluorescent intensity, this system used a transmission measurement to first estimate the hematocrit. In this work we characterize the dependence of our fluorescent and transmission measurements on hematocrit and ICG concentration using samples of bovine blood. We then use this information to predict the dilution of a series of representative samples. The results demonstrate that this system is able to estimate blood dilution in dilutions of more than 50% with a high level of accuracy.

Most transdermal drug delivery systems are designed to inject drugs through the skin in a direction normal to the skin surface. However, in some applications, such as local anaesthesia, it is desirable to disperse the drug in a direction parallel to the surface of the skin. In this paper we present nozzles for needle-assisted jet injection that are designed to laterally disperse the fluid drug at a chosen depth in tissue. These nozzles were manufactured by laser machining holes in the walls of 0.57 mm (24 G) hypodermic needles, and sealing the ends of the needles. An existing controllable jet injection system was used to test the nozzles. High-speed video recordings were taken to examine the shape of the high-speed jets emitted from the orifices, and jet injections into post mortem porcine tissue were performed to evaluate the resulting dispersion pattern. These injections demonstrated the ability of these nozzles to achieve a widely spread dispersion at a depth of 3 mm to 4 mm in tissue. We observed that the widest dispersion occurred at the same depth as the orifices, and dispersion was greater in the direction of the jets. Further investigation, including an in vivo study, is now required to evaluate whether this technique can reduce the time, cost or pain associated with transdermal local anaesthetic delivery.

Jet injection presents a promising alternative to needle and syringe injection for transdermal drug delivery. The controllability of recently-developed jet injection devices now allows jet speed to be modulated during delivery, and has enabled efficient and accurate delivery of volumes up to 0.3 mL. However, recent attempts to inject larger volumes of up to 1 mL using the same methods have highlighted the different requirements for successful delivery at these larger volumes. This study aims to establish the jet speed requirements for delivery of 1 mL of liquid using a controllable, voice coil driven injection device. Additionally, the effectiveness of a two-phase jet speed profile is explored (where jet speed is deliberately decreased toward the end of the injection) and compared to the constant jet speed case. A controllable jet injection device was developed to deliver volumes of 1 mL of liquid at jet speeds140 m/s. This device was used to deliver a series of injections into post-mortem porcine tissue in single and two-phase jet speed profiles. Single-phase injections were performed over the range 80 m/s to 140 m/s. Consistent delivery success (80% of the liquid delivered) was observed at a jet speed of 130 m/s or greater. Consistent penetration into the muscle layer coincided with delivery success. Two-phase injections of 1 mL were performed with a first phase volume of 0.15 mL, delivered at 140 m/s, while the injection of the remainder of fluid was delivered at a second phase speed that was varied over the range 60 m/s to 120 m/s. Ten two-phase injections were performed with a second phase speed of 100 m/s producing a mean delivery volume of 0.8 mL ± 0.2 mL, while the single-phase injections at 100 m/s achieved a mean delivery volume of 0.4 mL ± 0.3 mL. These results demonstrate that a reduced jet speed can be used in the later stages of a 1 mL injection to achieve delivery success at a reduced energy cost. We found that a jet speed approaching 100 m/s was required following initial penetration to successfully deliver 1 mL, whereas speeds as low as 50 m/s have been used for volumes of0.3 mL. These findings provide valuable insight into the effect of injection volume and speed on delivery success; this information is particularly useful for devices that have the ability to vary jet speed during drug delivery.

Subcutaneous delivery of nicotine was performed using a novel electrically-operated needle-free jet injector, and compared to hypodermic needle delivery in a porcine model. Nicotine was delivered as a single, one-milligram dose into the abdominal skin, formulated as a 50 microliter aqueous solution. Plasma levels of nicotine and cotinine, its main metabolite, were then monitored over 2 h, following which the injection site was excised for histological examination. No irritation or tissue damage were found at the injection sites, and the jet-injected nicotine exhibited comparable absorption into the systemic circulation to that injected using a conventional needle and syringe. The needle-free jet injection of nicotine is a promising and well tolerated method. The data presented from this porcine model will support a first in human trial towards a new promising nicotine replacement therapy.

The effect of varying velocity during jet injection on the dispersion of fluid into tissue is investigated using a custom-built X-ray imaging system. Injections are performed into ex-vivo porcine abdominal tissue using a voice coil actuated injection device. Single velocity and two-phase velocity injections reveal the complex nature of the dispersion of the fluid jet in layered tissue and highlight the effects of changing the jet velocity following the initial penetration of the liquid into the tissue.

We present a needle-free jet injection device controllably actuated by a voice coil and capable of injecting up to 1.3 mL. This device is used to perform jet injections of ∼900 μL into porcine tissue. This is the first time that delivery of such a large volume has been reported using an electronically controllable device. The controllability of this device is demonstrated with a series of ejections where the desired volume is ejected to within 1 % during an injection at a predetermined jet velocity.

We present a new design for a needle-free injector ampoule, using two concentric pistons to pressurize the fluid during the injection. The smaller, inner piston is used to provide an initial high-velocity piercing jet; it then engages the outer piston to deliver the remaining drug via a low-velocity jet. The goal of this design is to enable needle-free delivery of relatively large volumes to controlled depths in tissue, a task impractical with conventional ampoules and actuators. We demonstrate this concept by constructing a 1.2mL ampoule, measuring the jet velocity it produces in free air, and performing a set of injections into post-mortem porcine tissue. The ampoule smoothly produces the two desired phases of an injection, with a smooth transition of jet velocity as the two pistons engage. The injection is able to penetrate porcine skin to a controlled depth and deliver fluid to the subcutaneous and/or intramuscular layers, though further investigation is required to ensure that all of the fluid delivered can be retained at the desired depth.