Probing the Near-Atomic Scale Structure of Hard Biological Materials with Atom Probe Tomography: A Review

Atom probe tomography (APT) is a powerful analytical technique that generates atom-by-atom reconstructions of matter, providing quantitative three-dimensional elemental and isotopic analyses at near atomic-scale resolution across the entire periodic table. It has advantages in chemical sensitivity, spatial resolution, and 3D compositional reconstruction capability. Atom probe tomography was originally applied in the discipline of metallurgy, and has recently expanded to multiple new disciplines, including semiconductors, geology and biology, due to the ability to study less conductive materials that is afforded by laser-induced evaporation within the atom probe. Breakthrough research findings on the near atomic-scale structure of biological materials, such as bone and teeth, have been reported in the last decade, and we now have the opportunity to develop atom probe to utilise the technique for further breakthroughs in medical science and beyond. Here we review studies of the near atomic-scale structure of hard biological materials with atom probe tomography. We cover challenges associated with the analysis of biomaterials and possible solutions, including specimen preparation of non-conductive biological composite materials, bespoke optimisation of atom probe experimental running parameters, interpretation of complex mass spectra, and understanding the reproducibility and accuracy of the 3D atomistic reconstructions.