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  1. Needle-free jet injectors (NFJIs) are one of the alternatives to hypodermic needles for transdermal drug delivery. These devices use a high-velocity jet stream to puncture the skin and deposit drugs in subcutaneous tissue. NFJIs typically exhibit two phases of jet injection – namely – an initial peak-pressure phase (< 5 ms), followed by a constant jet speed injection phase (≳ 5 ms). In NFJIs, jet velocity and jet diameter are tailored to achieve the required penetration depth for a particular target tissue (e.g., intradermal, intramuscular, etc.). Jet diameter and jet velocity, together with the injectant volume, guide the design of the NFJI cartridge and thus the required driving pressure. For device manufacturers, it is important to rapidly and accurately estimate the cartridge pressure and jet velocities to ensure devices can achieve the correct operational conditions and reach the target tissue. And thus, we seek to understand how cartridge design and fluid properties affect the jet velocity and pressure profiles in this process. Starting with experimental plunger displacement data, transient numerical simulations were performed to study the jet velocity profile and stagnation pressure profile. We observe that fluid viscosity and cartridge-plunger friction are the two most important considerations in tailoring the cartridge geometry to achieve a given jet velocity. Using empirical correlations for the pressure loss for a given cartridge geometry, we extend the applicability of an existing mathematical approach to accurately predict the jet hydrodynamics. By studying a range of cartridge geometries such as asymmetric sigmoid contractions, we see that the power of actuation sources and nozzle geometry can be tailored to deliver drugs with different fluid viscosities to the intradermal region. 
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  2. Needle-free jet injections are actuated by a pressure impulse that can be delivered by different mechanisms to generate high-speed jets (Vj ∼ 102 m/s). During filling and transportation of disposable cartridges and ampoules, bubbles can form, which can be problematic especially for viscous fluids. Here, we report on the effect of location and size of entrapped air pockets in cartridges used in spring-powered jet injections. As air bubbles pass through the orifice, they undergo depressurization, which results in intermittent atomization and spray formation, temporarily increasing the jet dispersion. Atomization and dispersion of the jet can lead to product loss during an injection. We find that the effect of bubble location on the jet exit speed, delivery efficiency, and the projected area of the blebs formed after the injection was statistically significant (p < 0.05). The findings of this study have implications for the development of pre-filled cartridges for jet injection applications. 
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  3. The pain felt during injection, typically delivered via a hypodermic needle as a single bolus, is associated with the pressure build-up around the site of injection. It is hypothesized that this counterpressure is a function of the target tissue as well as fluid properties. Given that novel vaccines target different tissues (muscle, adipose, and skin) and can exhibit a wide range of fluid properties, we conducted a study of the effect of volumetric flow rate, needle size, viscosity and rheology of fluid, and hyaluronidase as an adjuvant on counterpressure build-up in porcine skin and muscle tissues. In particular, we found a significant increase in counterpressure for intradermal (ID) injections compared to intramuscular (IM) injections, by an order of magnitude in some cases. We also showed that the addition of adjuvant affected the tissue back pressure only in case of subcutaneous (SC) injections. We observed that the volumetric flow rate plays an important role along with the needle size. This study aims to improve the current understanding and limitations of liquid injectability via hypodermic needles, however, the results also have implications for other technologies, such as intradermal jet injection where a liquid bleb is formed under the skin. 
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  4. We report on an experimental study of high-speed micro-scale liquid jets ejected into low-pressure environments, which has applications for the use of negative pressure modules in jet injector systems. The jets were impulsively started by the action of a stiff spring-piston and ejected through a narrow orifice, D_{0} ~ 100 μm, into partial vacuums ranging from atmospheric pressure down to -80 kPa. We find that due to the high exit velocity, V_{j} ~ 100 m/s, the main jet stream is largely unaffected, but we reveal some fascinating fine features during the startup phase, largely due to the presence of a small liquid volume pulled through the orifice prior to actuating the jet. In particular, as the pressure decreases, the start-up time increases and the initial spray becomes more pronounced. However, the primary outcome of this feasibility study is that use of negative pressures is viable for jet injector applications, and we hypothesize an optimal range of working pressures and configurations. 
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