GCR: Collaborative Research: Plasma-Biofilm Interactions at the Intersection of Physics, Chemistry, Biology and Engineering

低温等离子体-电离气体-在大气压下工作，是活性氧和氮物质（RONS）的丰富来源。等离子体产生的RONS具有对抗抗微生物耐药细菌的能力，并作为癌症治疗的新方法。还原-氧化（氧化还原）过程在细胞生命周期中起着重要作用，是有氧生物学的代谢驱动力。细胞中等离子体诱导的氧化还原化学可以潜在地调节这些过程。本计画将探讨电浆控制生物膜的能力--协调细菌的功能群.物理去除生物膜可能非常困难，抗生素和局部去污产品由于多管齐下的生物膜防御而在很大程度上无效。生物膜的控制已经成为一个巨大的社会挑战，因为它们的使用和影响范围非常广泛，从环境工程到生物医学应用。作为一个例子，生物膜引起的腐蚀是一个严重的问题，世界海洋工业。生物膜和抗菌素耐药性也是食品工业和医学中的主要问题。抗菌素耐药性预计将成为2050年的头号健康问题，美国疾病控制和预防中心报告说，每15分钟就有一个人死于抗生素无法有效治疗的感染。虽然生物膜的后果通常被认为是负面的，但生物膜细菌也广泛用于生物反应器中，其有益应用范围从水修复到能量收集。该项目结合了等离子体科学、微生物学和工程学的多项研究进展--每一项都具有重要意义--成为一个融合的、变革性的项目，以研究基本的等离子体诱导的生物膜过程。该项目的目标是发展了解等离子体对活细胞群落影响所需的科学。生物体的等离子体治疗可产生目前尚不清楚的非局部效应和全身反应。在复杂的生物体中，如动物模型，很难量化单个细胞的初始血浆剂量和诊断暴露的后果-动物模型的组成部分相互关联。拟议的研究将通过开发获得生物膜内等离子体相互作用的基本理解所需的科学来解决量化等离子体对生物体影响的迫切需要-一种更简单的生物体通信系统，允许进行诊断和建模。此外，模型生物膜细菌（例如铜绿假单胞菌）在遗传上是易处理的，这有助于在分子水平上对等离子体诱导的效应进行详细研究。通过研究等离子体处理的生物膜相关细菌细胞的生物学反应及其通过细胞外环境的细胞间通讯，将实现对等离子体全身效应的理解。该项目将开发这一新的融合研究前沿，结合等离子体科学，微生物学和最先进的打印方法，使用生物膜作为模型系统。虽然最初专注于全球生物膜对等离子体处理的反应，但该项目将推进等离子体和3D打印前沿，以开发高度受控的空间分辨实验，最终能够处理生物膜中的单个细菌细胞，并跟踪相关的局部和非局部生物影响。这项研究的社会效益将是操纵生物膜的生长和特性的能力-例如，消除不需要的生物膜，或在生物膜是期望产品的情况下提高其增殖。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。

Low temperature plasmas – ionized gases – operating at atmospheric pressure are a copious source of reactive oxygen and nitrogen species (RONS). Plasma-produced RONS have the ability to combat antimicrobial resistant bacteria and serve as a novel approach to cancer treatment. Reduction-oxidation (redox) processes play a major role in the cellular life cycle and are the metabolic driving force for aerobic biology. Plasma-induced redox chemistry in cells can potentially regulate these processes. This project will investigate the capability of plasma for control of biofilms – coordinated functional communities of bacteria. Physically removing biofilms can be extremely difficult, and antibiotics and topical decontamination products are largely ineffective due to multipronged biofilm defenses. The control of biofilms has become a grand societal challenge due to their exceptionally broad range of use and impact, from environmental engineering to biomedical applications. As an example, biofilm induced corrosion is a severe problem for world maritime industries. Biofilms and antimicrobial resistance are also major issues in the food industry and in medicine. Antimicrobial resistance is predicted to become the number one health problem in 2050 and the Centers for Disease Control and Prevention reports that every 15 minutes one person in the US dies because of an infection that antibiotics cannot treat effectively. Although the consequences of biofilms are typically thought of as being negative, biofilm bacteria are also extensively used in bioreactors with beneficial applications ranging from water remediation to energy harvesting. This project combines several research advances in plasma science, microbiology and engineering – each significant in their own right – into a convergent, transformative project to investigate fundamental plasma-induced biofilm processes.The goal of the project is to develop the science required to understand the impact of plasmas on communities of living cells. Plasma treatment of organisms can produce non-local effects and systemic responses which are currently not understood. In complex organisms, such as animal models, it is difficult to quantify both the initiating plasma dose to individual cells and to diagnose consequences of the exposure – components of animal models are simply too inter-related. The proposed research will address the critical need to quantify plasma effects on organisms by developing the science required to obtain a fundamental understanding of plasma interactions within a biofilm – a simpler system of communicating organisms that allows access to diagnostics and modeling. Furthermore, model biofilm bacteria (e.g. Pseudomonas aeruginosa) are genetically tractable, lending themselves to detailed studies of plasma-induced effects at a molecular level. This improvement in understanding of systemic effects of plasma will be accomplished by investigating the biological response of plasma-treated, biofilm-associated, bacterial cells and their intercellular communication through the extra-cellular environment. The project will develop this new and convergent research frontier, combining plasma science, microbiology, and state-of-the-art printing methodologies, using biofilms as a model system. While initially focusing on global biofilm response to the plasma treatment, the project will advance plasma and 3D printing frontiers to develop highly controlled spatially-resolved experiments that could ultimately enable the treatment of a single bacterium cell in a biofilm and track the associated local and non-local biological impacts. The societal benefits of this research will be the ability to manipulate the growth and character of biofilms – for example, to eliminate biofilms where they are not desired, or to enhance their proliferation where biofilms are a desired product.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.