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

目前正在开发基于DNA的创新疫苗，旨在彻底改变对癌症，艾滋病毒，埃博拉和寨卡等疾病的斗争。然而，这些疫苗必须被递送到皮肤的皮内区域，这是已知的促进增强的免疫应答。尚未实现这些药物的这种精确、一致的递送，其可以是相当粘稠的。解决这个问题的一种潜在方法是无针喷射注射，其中液体以高速被迫从狭窄的孔口流出并刺穿皮肤。该技术已常规应用于更深（皮下和肌内）注射，但现在也有望用于皮内给药。因此，本项目的主要目的是提供一个深层次的理解的关键因素皮内注射液射流。该项目还将包括重要的教育活动，包括多年的本科研究计划，基于行业的培训和当地家庭学校社区的推广计划。该项目的目标是全面了解无针喷射注射到皮肤皮内区域的情况。这一复杂的过程涉及产生高速、细长且连贯的射流，该射流冲击并刺穿皮肤，然后分散在多孔弹性异质组织基质中。这些特征都没有得到充分的评估，无论是实验还是理论。我们建议填补这一广泛的知识空白，结合严格的实验活动和理论治疗集中在三个特定的目标：（i）了解射流特性的流变学的作用，（ii）定义的标准，以保持射流的一致性，（iii）确定的因素限制在皮内区域的流体积聚。在实验方面，我们将使用高速视频跟踪和动态力测量来表征各种配置和流体的射流启动，稳定流速度和峰值力。我们还将进行离体和体外注射研究，以检查皮内区域的液体蓄积。在建模方面，我们将重点放在稳定性和连贯性的射流作为一个功能的几何之前的孔和流体属性。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.