SBIR Phase I: Novel platform for the preparation of nanomaterial samples for cryo-TEM imaging: capturing nanostructures at unparalleled time scales without artifacts

该小型企业创新研究第一阶段项目旨在开发一个用于低温透射电子显微镜（cryo-TEM）样品制备的上级平台。Cryo-TEM提供了纳米分辨率的液体样品的形态和结构图像，这为制药、化学和消费品等行业的材料开发提供了至关重要的见解。Cryo-TEM样品制备需要样品减薄步骤，这导致约10-100 nm厚的膜，其适用于样品玻璃化和成像。商业平台提供具有印迹过程的薄样品，这具有许多缺点。由于在样品结构上诱导的剪切，印迹导致各种显著的样品伪影。此外，印迹所需的时间限制了动态过程研究的时间分辨率。专有的无印迹样品稀释策略减少了样品上诱导的剪切，并提高了样品制备的时间分辨率，数量级。将具有这些优势的创新工艺集成到商业平台中将占据很大一部分低温TEM样品制备市场，甚至由于对许多行业至关重要的改进和扩展的表征能力而扩大低温TEM市场。该项目的智力价值包括开发一种创新的无印迹样品制备工艺，该工艺克服了现有技术的商业状态的上述缺点，同时提供了用于成像的薄样品膜的广泛区域。实验和模拟将建立一个严格的理解这些过程中的关键属性，即流体流动的过程中引起的，和相应的剪切样品中，所需的时间，用于去除多余的样品体积和样品膜面积成像的最终产量。这项研究将提供一个上级样品减薄过程，将被集成到一个破坏性的低温TEM样品制备平台的控制。该平台将提供对材料和工艺的无与伦比的洞察力，这将降低风险并加快许多使用纳米材料的行业的开发时间表。

This Small Business Innovation Research Phase I project is aimed at developing a superior platform for the preparation of samples for cryogenic Transmission Electron Microscopy (cryo-TEM). Cryo-TEM provides images of morphologies and structures of liquid-based samples with nanometer resolution, which provides crucial insight for the development of materials in the pharmaceutical, chemicals and consumer goods industries, amongst others. Cryo-TEM sample preparation requires a sample thinning step, which results in a ~10-100 nm thick film that is appropriate for both sample vitrification and imaging. Commercial platforms provide thin samples with a blotting process, which has many drawbacks. Blotting leads to a variety of significant sample artifacts due to shear induced on sample structures. Furthermore, time required for blotting limits temporal resolution for studies of dynamic processes. A proprietary blotless sample thinning strategy reduces shear induced on the sample, and improves temporal resolution of sample preparation, by orders of magnitude. The integration of an innovative process with these advantages into a commercial platform would capture a large portion of the cryo-TEM sample preparation market, and even expand the cryo-TEM market due to improved and expanded characterization capabilities crucial to many industries. The intellectual merit of this project involves the development of an innovative blotless sample preparation process that overcomes the aforesaid drawbacks of the commercial state of the art, while providing extensive areas of thin sample film for imaging. Experiments and simulations will build a rigorous understanding of the critical properties of these processes, namely fluid flow induced by the process, and corresponding shear in the sample, the time required for removal of excess sample volume and the resulting yield of sample film area for imaging. This research will provide control of a superior sample thinning process that will be integrated into a disruptive cryo-TEM sample preparation platform. This platform will provide unparalleled insight into materials and processes that will reduce risk and accelerate development timelines for many industries utilizing nanomaterials.