Shining light on cold atmospheric plasmas and their interaction with liquids

冷大气等离子体（CAPs）在空气中运行，是活性氧和活性氮（RONS）的丰富来源。这些ron中的许多也在细胞中自然产生，可以调节细胞和生理过程，因此与医学科学相关。cap正在发现越来越多的医疗应用；当应用于活体组织时，它们可以有效地净化被细菌生物膜覆盖的伤口，并摧毁或至少显着缩小癌变肿瘤的大小。目前的假设是等离子体影响生物活性的潜在机制是通过等离子体产生的RONS与生物液体、细胞和组织成分相互作用的方式来定义的。然而，目前尚不清楚等离子体产生的RONS是如何刺激生物膜或肿瘤深处的细胞死亡的，这些生物膜或肿瘤的厚度可能在微米到毫米之间。在癌症治疗的背景下，有人提出，由肿瘤表面的等离子体产生的ron刺激触发细胞死亡的细胞信号机制，并且这些信号通过细胞间通信以类似于在其他形式的细胞应激中所见的方式传递到组织的更深层次。虽然这些假设似乎可信，因为许多直接由等离子体产生的ron具有高度的反应性，寿命短，只能在真实组织中扩散很短的距离，但实际上很少或根本没有定量证据支持这一观点——本提案试图通过应用最先进的光谱方法来解决这一问题。这项工作将量化气相中重要的等离子体产生的罗恩的绝对浓度，因为它们撞击纯水和生物界面，识别和确定液相中二次罗恩的形成和损失动力学，并确定终点化学。这些研究将实时进行，空间分辨率为几微米或更小，并为我们对等离子体科学应用的理解提供了一个台阶。特别是，它将使高毒性过氧亚硝酸盐自由基的扩散长度首次被确定，为帮助确定等离子体诱导的生物膜和肿瘤内微生物和癌细胞的破坏机制提供关键证据。这项工作将确定等离子体产生的RONS对生物相关靶标（如琼脂糖，一种替代真实组织的多糖聚合物材料）的渗透深度，并将探索ron渗透深度与CAP射流暴露时间、等离子体源靶距离以及替代组织的组成和厚度的依赖关系。这些数据对于等离子医疗设备的未来发展和避免不必要的组织损伤将是重要的。实时监测通过生物膜和液相的ron的运输将阐明这样一种假设，即等离子体不仅可能刺激组织表面的生物膜和肿瘤的失活，而且可能将ron输送到受影响组织深处的细胞中。在气相和液相内部和之间，对ron产生、传输和丢失机制的详细理论理解，将通过开发最先进的反应扩散模型来提供，该模型将通过参考新的实验数据进行优化。

Cold atmospheric plasmas, CAPs, operate in air and are a rich source of reactive oxygen and nitrogen species, RONS. Many of these RONS are also produced naturally in cells and can regulate cellular and physiological processes, and as such are relevant to medical science. CAPs are finding an increasing number of medical applications; when applied to living tissue, they can effectively decontaminate wounds covered with bacterial biofilms and destroy, or at least significantly reduce the size of, cancerous tumours. It is currently assumed that the underlying mechanisms by which plasma influences biological activity are defined by the way in which plasma-generated RONS interact with the components of biological liquid, cells and tissue. However, it is unclear how plasma-generated RONS stimulate cell death deep within a biofilm or tumour, which could be micrometres to millimetres in thickness. In the context of cancer treatment, it has been suggested that RONS, generated by plasma at the surface of the tumour, stimulate cellular signalling mechanisms that trigger cell death and that these signals are transmitted deeper into the tissue through cell-to-cell communication, in a manner similar to that seen in other forms of cell stress. While these hypotheses seem credible given that many of the RONS generated directly by plasma are highly reactive, have short lifetimes and can only diffuse over a short distance in real tissues, there is in fact little or no quantitative evidence to back this up - this proposal seeks to address this situation by applying state-of-the-art spectroscopic methods to this problem. The work will quantify the absolute concentrations of important plasma-generated RONS in the gas phase as they impinge upon pure water and biological interfaces, identifying and determining the kinetics of formation and loss of secondary RONS within the liquid phase, and determining the end point chemistry. These studies will be conducted in real time and with a spatial resolution of a few microns or less, and offer a step-change in our understanding of this application of plasma science. In particular, it will allow the diffusion length of the highly toxic peroxynitrite radical to be determined for the first time, providing crucial evidence to help determine the mechanism of plasma-induced destruction of micro-organisms and cancer cells within biofilms and tumours. The work will determine the penetration depth of plasma-generated RONS into a biologically relevant target, such as agarose, a polysaccharide polymer material which is a surrogate for real tissue, and will explore the dependence of the RONS penetration depth upon the CAP jet exposure time and plasma source-target distance, as well as the composition and thickness of the surrogate tissue. The data will be important for the future development of plasma medical devices and for avoiding unwanted tissue damage. Monitoring the transport of RONS in real time through a biofilm and within the liquid phase will shed light on the hypothesis that plasma may not only stimulate the deactivation of biofilms and tumours at a tissue's surface, but potentially deliver RONS into cells embedded deep within affected tissue.A detailed theoretical understanding of the mechanisms by which RONS are generated, transported and lost, both within and between the gas and liquid phases, will be provided by development of a state-of-the-art reaction diffusion model which will be optimised by reference to the new experimental data.