Plasma injection system: Reaching beyond the surface in plasma medicine applications

等离子体是物质的第四种状态，它提供了一种独特的方法，可以在低气体温度下创造反应环境，这对许多科学和技术应用都很有用。例如，制造现代芯片所需的步骤中有一半以上需要等离子体。其他成熟的数百万应用包括照明和平板显示器行业。虽然大多数已建立的技术利用低压等离子体，但近年来，人们对开发可以在大气压下操作但仍保持在低温下的等离子体的兴趣越来越大。特别是，低温大气压等离子体使得对温度敏感且不能置于真空环境中的生物材料的处理成为可能，从而诞生了一门快速发展的科学学科，称为等离子体医学。等离子体医学研究气体等离子体和活细胞的相互作用，并且正在考虑用于广泛的生物医学应用，包括医疗设备的灭菌，伤口消毒，伤口愈合，癌症治疗，口腔/牙科护理和食品安全。与任何新兴技术一样，最初的努力集中在证明等离子体杀死、修饰或刺激活细胞的潜力上。这主要是在体外研究中进行的，其中靶细胞的单层通常由血浆处理。已经证明了等离子体修饰生物分子的能力以及与活细胞相互作用的潜在治疗价值，现在是该领域解决其他基本问题的时候了。可以说，在等离子体被生物医学界广泛接受之前，等离子体医学需要解决的两个主要问题是：（1）选择性，换句话说，等离子体可以破坏恶性细胞而不伤害健康细胞;（2）渗透性，等离子体可以到达表面之下以推断其治疗价值。在本可行性研究中，我们重点关注后一个问题：渗透。鉴于等离子体中产生的化学的非平衡特性，它们的作用通常限于表面。虽然这对于我们希望保持本体材料特性的表面改性应用是理想的，但大多数设想的生物医学应用需要等离子体处理以达到细胞的第一单层之外。虽然等离子体处理渗透在过去没有被详细研究，文献中有间接的证据表明，等离子体处理削弱了几十微米。例如，如果细胞嵌入生物膜中，甚至只是简单地堆叠在另一个上，等离子体的杀菌特性就会迅速衰减。为了解决这一潜在的技术杀手，拟议的工作承担了等离子体注射系统的开发，其中等离子体射流和无针液体注射器的组合协同操作，以使等离子体物质渗透到生物靶内。以启发式的方法，旨在证明等离子体注射系统的可行性，我们将研究的杀菌性能的He/O2/水等离子体注射系统对细菌的保护凝胶作为生物屏障。该项目将包括对该系统的初步定性，但设想在后续研究中进行详细分析，以揭示基本的物理化学过程。

Plasma, the fourth state of matter, provides a unique means for creating reactive environments at low gas temperature useful for many scientific and technological applications. For example more than half the steps required to fabricate a modern chip require plasma. Other well established multi-million applications include the lighting and the flat panel display industries. While most established technologies utilize low pressure plasmas, in recent years there has been a growing interest on developing plasmas that can be operated at atmospheric pressure and yet remain at low temperature. In particular, low temperature atmospheric pressure plasmas have made possible the treatment of biological materials that are temperature sensitive and cannot be put in vacuum environments, given birth to a fast growing scientific discipline referred to as Plasma medicine . Plasma medicine studies the interaction of gas plasmas and living cells and is being considered for a wide range of biomedical applications including sterilization of medical equipment, wound disinfection, wound healing, cancer treatment, oral/dental care, and food safety. As in any emerging technology, initial efforts have been focused in demonstrating the potential of plasmas to either kill, modify or stimulate living cells. This has been largely done in in-vitro studies where often monolayers of targeted cells are treated by plasma. Having been demonstrated the capability of plasma to modify biomolecules and the interact with potential therapeutic value with living cells, it is now time for the field to address other fundamental questions. Arguably the main two issues that plasma medicine needs to address before plasmas become widely accepted by the biomedical community are (1) selectivity, in other words, can plasma damage malignant cells while sparing healthy ones; and (2) penetration, can plasma reach underneath the surface to infer its therapeutic value. In this feasibility study we focus on the latter issue: penetration. Given the non-equilibrium character of the chemistry developed in plasmas, their action is typically limited to the surface. While this is ideal for surface modification applications where we want to preserve the properties of the bulk material, most envisaged biomedical applications require plasma treatments to reach beyond the first monolayer of cells. Although plasma treatment penetration has not been studied in detail in the past, the literature has indirect evidence that suggest that plasma treatments weaken in tens of microns. For example, the bactericidal properties of plasmas rapidly decay if cells are embedded in a biofilm or even simply stacked one on another. Addressing this potential technology killer, the proposed work undertakes the development of a plasma injection system where a combination of a plasma jet and a needle-free liquid injector are operated synergistically to enable the penetration of plasmas species inside a biological target. Taking a heuristic approach aimed at demonstrating the feasibility of the plasma injection system, we will examine the bactericidal properties of a He/O2/water plasma injection system against bacteria protected by gels acting as biological barriers. The project will include an initial characterization of the system although detailed analysis aimed at unravelling the underlying physico-chemical processes are envisaged in follow-up studies.