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

目前正在开发创新的基于dna的疫苗，旨在彻底改变对抗癌症、艾滋病、埃博拉和寨卡等疾病的斗争。然而，这些疫苗必须进入皮肤的皮内区域，已知这可以促进增强的免疫反应。如此精确、一致地给药，这些药物可能相当粘稠，目前还没有实现。解决这一问题的一种潜在方法是无针喷射注射，即液体以高速从狭窄的孔中挤出并刺穿皮肤。该技术已常规应用于深层（皮下和肌肉内）注射，但现在也有望用于皮内注射。因此，本项目的主要目的是深入了解控制液体喷射皮内注射的关键因素。该项目还将包括重要的教育活动，包括一个多年的本科研究项目、基于行业的培训和一个面向当地家庭学校社区的推广项目。这个项目的目标是开发一个全面的图像无针喷射注射到皮肤的皮内区域。这个复杂的过程包括产生高速、细长和连贯的射流，它撞击并刺穿皮肤，然后分散在多孔弹性的异质组织基质中。无论是实验还是理论上，这些特征都没有得到充分的评估。我们建议通过严格的实验活动和理论治疗相结合来填补这一广泛的知识空白，重点关注三个具体目标：(i)了解流变学在射流特性中的作用，（ii）定义保持射流一致性的标准，以及（iii）确定限制皮内区域流体积聚的因素。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，以检查皮内区域液体的积聚。在建模方面，我们将重点关注射流的稳定性和相干性，将其作为几何函数，而不是孔口和流体特性。我们的方法有望产生前所未有的理解，并为未来的无针注射创新提供平台。该奖项反映了美国国家科学基金会的法定使命，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.