Near Atomic Scale Analysis of Biomaterials and Proteins

Doctoral thesis, 2024

Modern analytical techniques have greatly advanced our understanding of the smallest building blocks of materials and biological systems. In materials science, the structure and composition at the nanoscale directly influence a material's properties, while in biology, the three-dimensional structure of proteins is intimately tied to their function. Biomaterials, designed to interact with biological systems, have significantly contributed to healthcare and improved quality of life by aiding in the treatment of diseases and alleviating injuries. The 3D structure of proteins is key to their function, and to determine this structure is essential for developing therapeutics that address current healthcare challenges.

The structure of biomaterials, as well as proteins at the atomic scale, is crucial to their functionality, necessitating analysis at this size level. This thesis explores the use of Atom Probe Tomography (APT) for various biomaterials used in medical devices as well as protein structures. APT is a powerful characterization technique employed in various domains of materials science, providing near-atomic-resolution analysis of the chemical composition of materials in 3D with high sensitivity.

Biomaterials are often used in medical devices for therapeutic purposes. Despite their success, challenges remain, including difficulties in integrating with the body, hard-to-treat bacterial infections, and mechanical failures. Different design strategies for implantable biomaterials were studied to improve integration with bone, antibacterial properties, and mechanical performance. These materials are analysed using correlative electron microscopy and APT to investigate their microstructures and how these affect the desired material properties.

To study proteins using APT, they must be embedded in a matrix that can withstand the conditions required for analysis while retaining the molecules in their native state. Silica synthesized via a sol-gel process is one such material and is studied in this work. Proteins embedded in silica, either directly in solution or after adsorption to a nanostructured surface, allow for specimen preparation for nanoscale analysis from the obtained material. By utilizing new atom probe instrumentation, where atoms are field evaporated by a deep-UV laser, isotope-labelled proteins are unambiguously detected and studied in quantities previously unattained by APT.