A Novel Safer Formulation Concept for Flame Generated Engineered Nanomaterials

去年，全球纳米技术产业达到了1.5万亿美元，已经成为21世纪的主要经济力量，为我们的社会带来了巨大的利益。工程纳米材料是迄今为止纳米技术市场中最大的部分，占所有收入的80%，在许多消费产品中普遍存在。因此，在过去十年中，研究工程纳米材料（ENMs）毒性的纳米- ehs研究变得越来越重要。然而，毒性的潜在机制目前尚不清楚，大多数努力都集中在体外筛选试验的发展上。令人惊讶的是，在开发更安全的ENM配方概念方面所做的研究非常有限，这些概念可以被纳米技术工业用于ENM的合成，以尽量减少纳米- ehs的影响。我们相信，这是一个非常重要的研究领域，对纳米技术行业及其追求合成“绿色”ENM和可持续性。在这里，我们提出了一个系统的、综合的、多学科的方法来研究一个新的更安全的配方概念，以生产规模最大的ENM家族之一，火焰生成纳米金属。火焰合成ENM是可扩展ENM合成的首选途径，因为它不会产生液体副产物，比液体更容易从气体中收集颗粒，并产生高纯度的材料。我们计划研究和优化在火焰合成过程中，在飞行中一步添加纳米薄层无定形SiO2和密封涂层火焰生成的enm的概念。无定形SiO2被认为是一种生物和环境惰性材料，是保护潜在毒性芯材与环境和生物介质相互作用的理想材料。因此，我们建议研究和理解所提出的飞行涂层工艺的材料依赖基础，并将其应用于广泛使用的enm，如Ag， ZnO,CeO2， Fe2O3和TiO2。此外，enm -生物和环境的相互作用将被彻底调查，以评估所提出的更安全的配方概念的有效性。这包括在细胞和有机体水平上使用各种生理学相关的生物测定对纳米生物相互作用的比较评估。物理化学和形态学ENM性能和表面涂层效率也将使用最先进的分析方法进行验证。智力优势：提议的研究将材料科学和粒子技术与纳米毒理学和纳米生物学相结合。通过为最大的ENMS系列产品开发和验证更安全的配方概念，我们将进一步加深对表面涂层和火焰合成材料基本原理的理解。更重要的是，我们将更好地了解与常用enm相关的纳米生物和环境相互作用以及表面功能化的一般影响。此外，通过比较细胞和体内生物测定的数据，我们将能够评估生物测定系统的性质如何影响生物学结果。研究结果将能够促进“绿色”纳米材料的开发和生物学评价，同时推进评估纳米材料健康和安全所需的方法和策略。更广泛的影响：如果成功验证，提出的更安全的配方概念可以扩大规模，并被行业用于合成火焰生成的enm，用于广泛的应用。该项目还包括研究和教育活动的综合计划。它将为哈佛大学各个学科的博士后和研究生提供独立研究的机会。它还将启动HSPH纳米技术和纳米毒理学中心、政府机构（NIOSH）、工业界和欧洲研究机构之间的合作伙伴关系。结果将通过同行评审出版物、会议发言和其他外联活动传播给相关利益攸关方。

1235806DemokritouThe global nanotechnology industry reached over 1.5 trillion USD last year and has become a major economic force in the 21st century with enormous benefits to our society. Engineered nanomaterials are by far the largest segment of the nanotechnology market,accounting for 80% of all revenues and prevalent in numerous consumer products. Consequently, nano-EHS research investigating the toxicity of engineered nanomaterials (ENMs) has gained much importance over the last decade. However, the underlying mechanisms for toxicity are currently not well understood, with most efforts focusing on the development of in-vitro screening assays. Surprisingly, very limited research has been done in terms of developing safer ENM formulation concepts that can be adopted and used by the nanotechnology industry in the synthesis of ENMs in order to minimize nano-EHS implications. We believe that this is a research area of great importance for the nanotechnology industry and its quest towards synthesis of "green" ENM's and sustainability. Here, we propose a systematic, integrated, multidisciplinary approach to study a novel safer formulation concept for one of the largest ENM families by production volume, the flame generated nanometals. Flame-synthesis of ENMs is the preferred route for scalable ENM synthesis, as it does not create liquid by-products, offers easier particle collection from gases than liquids, and results in high purity materials. We plan to study and optimize the concept of adding in-flight, in one step approach, a nano-thin layer of amorphous SiO2 and hermetically coat flame generated ENMs during their flame synthesis. Amorphous SiO2 is considered a biologically and environmentally inert material, and ideal to shield otherwise potentially toxic core-materials from any interactions with environment and biological media. We therefore propose to study and understand the material-dependent fundamentals of the proposed in-flight coating process and apply it to a wide range of widely-used ENMs such as Ag, ZnO,CeO2, Fe2O3 and TiO2. Furthermore, the ENM-biological and environmental interactions will be thoroughly investigated in order to assess the validity of the proposed safer formulation concept. This includes the comparative assessment of the nano-bio interactions at the cellular and organismal level using a variety of physiologically relevant bioassays. The physico-chemical and morphological ENM properties and surface coating efficiency will also be validated using state of the art analytical methods.Intellectual Merit: The proposed research combines excellence in material science and particle technology with nanotoxicology and nano-biology. By developing and validating a safer formulation concept for the largest by production volume family of ENMS, we will further enhance our understanding on the fundamentals related to surface coatings and flame synthesis of materials in general. More importantly, we will better understand the nano-bio and environment interactions related to commonly used ENMs and the impact of surface functionalization in general. Furthermore, by comparing data from cellular and in-vivo bioassays,we will be able to assess how biological outcomes are influenced by the nature of the bioassay system. The results will be able to enhance the development and biologic evaluation of "green" ENMs and at the same time advance the methods and strategies needed to evaluate the health and safety of nanomaterials.Broader impacts: The proposed safer formulation concept, if validated successfully, can be scaled up and utilized by the industry in the synthesis of flame-generated ENMs for a wide range of applications. The project also involves an integrated plan of research and educational activities. It will generate opportunities for independent research for post-doctoral fellows and graduate-level students from various disciplines within Harvard University. It will also initiate collaborative partnerships between the HSPH Center for Nanotechnology and Nanotoxicology, government agencies (NIOSH), the industry and European research institutions. Results will be disseminated to relevant stakeholders through peer review publications and conference presentations and other outreach activities.