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Shining light on cold atmospheric plasmas and their interaction with liquids

照亮冷大气等离子体及其与液体的相互作用

基本信息

批准号：
EP/P026621/1
负责人：
Grant Ritchie
金额：
$ 57.3万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FP026621%2F1
关键词：
Shining light cold atmospheric plasmas

项目摘要

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.

冷大气等离子体(CAPS)在空气中运行，是活性氧和氮物种RON的丰富来源。这些核糖体中的许多也是在细胞中自然产生的，可以调节细胞和生理过程，因此与医学相关。CAPS在医学上的应用越来越多；当应用于活组织时，它们可以有效地净化覆盖着细菌生物膜的伤口，并摧毁或至少显著缩小癌症肿瘤的大小。目前的假设是，等离子体影响生物活性的潜在机制是由等离子体产生的RON与生物液体、细胞和组织的成分相互作用的方式定义的。然而，目前尚不清楚等离子体产生的Ron如何刺激生物膜或肿瘤深处的细胞死亡，这些生物膜或肿瘤的厚度可能是微米到毫米。在癌症治疗的背景下，有人提出，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的通信被更深地传递到组织中，其方式类似于在其他形式的细胞应激中看到的方式。尽管这些假设似乎可信，因为许多由等离子体直接产生的Ron是高度活性的，寿命很短，并且只能在真实组织中短距离扩散，但实际上几乎没有定量证据支持这一点--这项建议试图通过应用最先进的光谱方法来解决这种情况。这项工作将量化重要的等离子体产生的Ron在气相中的绝对浓度，当它们撞击到纯水和生物界面时，识别和确定二次Ron在液体中形成和损失的动力学，并确定终点化学。这些研究将以几微米或更小的空间分辨率实时进行，并为我们对等离子体科学的这一应用提供一个阶段性的改变。特别是，它将首次确定剧毒的过氧亚硝酸根的扩散长度，为帮助确定等离子体诱导破坏生物膜和肿瘤内的微生物和癌细胞的机制提供关键证据。这项工作将确定等离子体产生的RON对生物相关靶的穿透深度，例如琼脂糖，一种作为真实组织替代品的多糖聚合物材料，并将探索RONS穿透深度与CAP喷射暴露时间和等离子体源-靶距离以及替代组织的成分和厚度的关系。这些数据将对等离子医疗设备的未来发展和避免不必要的组织损伤具有重要意义。实时监测RON在生物膜和液相中的传输将有助于阐明这样一个假设，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输送到深入受影响组织中的细胞中。通过开发最先进的反应扩散模型，将提供对RON在气相和液相内和之间产生、传输和丢失的机制的详细理论理解，该模型将通过参考新的实验数据进行优化。