Self-Propelling Microbubblers for Active Cleaning of Biofilm in Confined Spaces

用于主动清洁密闭空间中生物膜的自推进微泡器

• 批准号: 2004719
• 负责人: Hyunjoon Kong
• 金额: $ 49.5万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2004719&HistoricalAwards=false
• 关键词: Self; Propelling; Microbubblers; Active; Cleaning

PART 1: NON-TECHNICAL SUMMARYDense microbial films called “biofilm” often foul medical tools, household items, and infrastructures such as an endoscopes, bathroom tiles, and water supply pipes, and can lead to dangerous infections. These biofilms are slimy aggregates of bacterial cells surrounded by scaffolds adhering to anything they touch. About 80 percent of all medical infections originate from biofilms that invade the inner workings of clinical devices and implants inside patients. Cleaning of biofilms in such a hard-to-reach area is extremely difficult because traditional disinfectants and antibiotics cannot penetrate a biofilm's tough scaffolds. How can we let antibacterial reagents cross over such a barrier of biofilms? This proposed study attempts to develop a small particle that can penetrate and destroy tough scaffolds by generating oxygen bubbles. The particle named “self-propelling microbubbler” would be prepared by loading an oxygen-generating chemical on diatoms – the tiny skeletons of algae. As a consequence, this system would improve the delivery of antibacterial deathblow to the bacterial cells living inside. While tuning the oxygen bubble generation rate and subsequent propulsion speed of the micrububblers, this proposed study will examine extents that the microbubblers can penetrate biofilm clinging to a material with complex topology, damages the scaffold of biofilms, kill bacterial cells protected by the scaffolds, and, ultimately, prevent the return of biofilm formation. In parallel, for broad impacts, the unique microbubblers will be used as education and training tools for a new generation of bioscientists and bioengineers. Overall, this project will serve to improve people’s health, safety, and life quality against infectious diseases and fouling.PART 2: TECHNICAL SUMMARY Biofilms composed of microbial cell colonies and surrounding extracellular polymer substances (EPS) are major causes of medical infection and material deterioration, thus threatening both human health and sustainability. A variety of disinfectants were developed to date, but none of these systems are active in removing biofilms forming in confined spaces. To this end, this proposed study aims to assemble and analyze a “self-propelling microbubbler” that can invade biofilms grown in the hard-to-reach area and, subsequently, clean out both bacterial colonies and EPS. This study hypothesizes that diatom particles doped with zinc oxide (ZnO) or manganese dioxide (MnO2) catalysts decomposing hydrogen peroxide (H2O2) eject oxygen bubbles and, in turn, act as the self-propelling microbubbler in the antiseptic 3% H2O2 solution. After the invasion, the microbubblers would continue to generate oxygen bubbles that fuse to produce a wave of mechanical energy capable of destroying the biofilms. The self-propulsion of microbubblers will be studied by analyzing the activation energy for H2O2 decomposition, the H2O2 decomposition rate, and the kinetic energy. In parallel, the extent that the microbubblers remove biofilm in the micro-grooved substrate will be examined by monitoring invasion of particles into the biofilm and subsequent changes in stiffness, adhesion force, and chemical composition of the biofilms formed by Escherichia coli and Pseudomonas aeruginosa. Finally, the efficacy of microbubblers to killing biofilm bacteria will be evaluated by monitoring the increase of intracellular oxidative stress, the reduction of viable cells, and the recurrence of biofilm. The successful completion of this study will elucidate the unique cleaning mechanism attained by chemical-to-mechanical energy conversion and transform current disinfection strategies that rely on chemicals mostly. In parallel, this project will make broad impacts by incorporating the proposed research modules into several educational programs developed for students at various educational levels and also disseminating the research outcomes to a broad spectrum of communities.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.

第一部分： 非技术概述被称为“生物膜”的致密微生物膜经常污染医疗工具、家用物品和基础设施，如内窥镜、浴室瓷砖和供水管道，并可能导致危险的感染。这些生物膜是细菌细胞的粘糊糊的聚集体，周围是附着在它们所接触的任何东西上的支架。大约80%的医疗感染来源于生物膜，这些生物膜侵入了患者体内的临床设备和植入物的内部工作。在这样一个难以到达的区域清洁生物膜是非常困难的，因为传统的消毒剂和抗生素不能穿透生物膜的坚韧支架。我们如何才能让抗菌剂穿过这样一个生物膜的屏障？这项拟议的研究试图开发一种小颗粒，它可以通过产生氧气泡来穿透和破坏坚韧的支架。这种名为“自推进微气泡”的粒子将通过在硅藻（藻类的微小骨架）上加载一种产生氧气的化学物质来制备。因此，该系统将改善抗菌致命一击的交付生活在里面的细菌细胞。在调整氧气气泡产生速率和随后的微气泡推进速度的同时，这项拟议的研究将检查微气泡可以穿透附着在具有复杂拓扑结构的材料上的生物膜的程度，破坏生物膜的支架，杀死受支架保护的细菌细胞，并最终防止生物膜形成的返回。同时，为了产生广泛的影响，独特的微泡器将被用作新一代生物科学家和生物工程师的教育和培训工具。总的来说，该项目将有助于提高人们的健康，安全和生活质量，防止传染病和污垢。 由微生物细胞菌落和周围的胞外聚合物物质（EPS）组成的生物膜是医疗感染和材料劣化的主要原因，从而威胁人类健康和可持续性。迄今为止开发了各种消毒剂，但这些系统都不能有效地去除在密闭空间中形成的生物膜。为此，这项拟议的研究旨在组装和分析一种“自推进微气泡器”，它可以侵入生长在难以到达区域的生物膜，随后清除细菌菌落和EPS。本研究假设，硅藻颗粒掺杂氧化锌（ZnO）或二氧化锰（MnO 2）催化剂分解过氧化氢（H2 O2）喷射氧气泡，反过来，作为自推进微气泡在防腐剂3%H2 O2溶液。在入侵之后，微泡器将继续产生氧气泡，这些氧气泡融合产生能够破坏生物膜的机械能波。通过分析H2 O2分解的活化能、H2 O2分解速率和动能来研究微泡器的自推进。平行地，微泡器去除微槽基底中的生物膜的程度将通过监测颗粒侵入生物膜以及随后由大肠杆菌和铜绿假单胞菌形成的生物膜的刚度、粘附力和化学组成的变化来检查。最后，将通过监测细胞内氧化应激的增加、活细胞的减少和生物膜的复发来评估微泡器杀死生物膜细菌的功效。这项研究的成功完成将阐明通过化学-机械能转换实现的独特清洁机制，并改变目前主要依赖化学品的消毒策略。与此同时，该项目将通过将拟议的研究模块纳入为不同教育水平的学生开发的多个教育项目中，并将研究成果传播到广泛的社区，从而产生广泛的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。