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

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.