Atom Probe Tomography Investigations of Biologically Relevant Nanoparticles

Licentiate thesis, 2022

The study of materials at the nanoscale is essential in many scientific disciplines. For example, in materials science the size of the building blocks of a material is directly linked to its properties. New materials are constantly being developed having features at the nanoscale, for example nanoparticles that are used in fields such as catalysis, electronics, and medicine. In biology, many features exist which have nanosized structures including proteins. The 3D secondary structure of proteins is directly linked to their functions; hence structure determination of proteins is of high interest to gain information of biological processes that serves the development of future medicines.

Due to the importance of nanostructures, many methods for their investigation have been developed such as X-ray diffraction, electron microscopy, and atom probe tomography. These methods rely on different probes and are thus often considered complementary as they provide different information. For the same reason, they put different constraints or limitations on the materials studied.

In this work, two novel methods for studying nanoparticles of biological relevance, gold nanoparticles and hydroxyapatite nanoparticles, have been developed for analysis using atom probe tomography.

Gold nanoparticles are popularly used as markers for biomolecules and to immobilize biomolecules on surfaces with retained function and activity. Several methods have been developed in the last decade to study nanoparticles using atom probe tomography, generally involving forming a metal matrix embedding the particles in a material from which a specimen can be made. In this thesis, an alternative approach utilizing a silica matrix made by a sol-gel method used to embed a gold nanoparticle covered surface is presented. This silica-based method provides an environment for the particles that is similar to an aqueous environment.

Nanoparticles of hydroxyapatite, a mineral that is found in bone and teeth, are commonly used as biomaterials, for example as coatings to improve the performance of surgical implants. In this thesis, hydroxyapatite nanoparticles immobilized onto titanium are examined. The analysed surfaces were sputter coated with chromium, forming a matrix that allows for correlative transmission electron microscopy and atom probe tomography analysis. It is shown that calcium and phosphorous integrated into the surface oxide of the titanium, revealing detailed insights on immobilization of the nanoparticles on the surface. This integration resembles the osseointegration of bone when compared to similar titanium implants being introduced to the human body.