CAREER: The fluid dynamics of needle-free intradermal jet injection

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Innovative DNA-based vaccines are currently under development and aim to revolutionize the fight against diseases such as cancer, HIV, Ebola and Zika. However, these vaccines must be delivered into the intradermal region of the skin, which is known to promote an enhanced immune response. Such a precise, consistent delivery of these drugs, which can be quite viscous, has not yet been achieved. One potential method to resolve this issue is needle-free jet injection, whereby liquid is forced out of a narrow orifice at high-speed and punctures the skin. This technique has been routinely applied for deeper (subcutaneous and intramuscular) injections, but now holds promise for intradermal delivery as well. Therefore, the principal aim of this project is to provide a deep understanding of the key factors governing intradermal injection with liquid jets. The project will also encompass significant educational activities, including a multi-year undergraduate research program, industry-based training and an outreach program for the local homeschool community.The goal of this project is to develop a comprehensive picture of needle-free jet injection into intradermal regions of the skin. This complex process involves creation of a high-speed, slender and coherent jet, which impacts and punctures the skin and then disperses in a poro-elastic heterogeneous matrix of tissue. None of these features have been adequately assessed, either experimentally or theoretically. We propose to fill this broad knowledge gap with the combination of a rigorous experimental campaign and theoretical treatment focused in three specific aims: (i) Understanding the role of rheology in jet characteristics, (ii) Defining the criteria for maintaining jet coherency, and (iii) Determining the factors limiting fluid accumulation in the intradermal region. On the experimental side, we will use high-speed video tracking and dynamic force measurements to characterize the jet start-up, steady-stream speed and peak force for a variety of configurations and fluids. We will also perform both ex-vivo and in-vitro injection studies to examine the accumulation of fluid in the intradermal region. On the modeling front, we will focus on stability and coherence of the jet as a function of geometry prior to the orifice and fluid properties. Our approach is expected to yield unprecedented understanding and provide the platform for future innovation in needle-free injection.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.