A Renaissance in Atom-Probe Tomography

The merits of atom-probe tomography (APT) of inorganic materials are well established, as described in this volume. However, one of the long-held aspirations of atom-probe scientists, structural and chemical characterization of organic and biological materials at near-atomic resolution, has yet to be fully realized. A few proof-of-concept type investigations have shown that APT of organic materials is feasible, but a number of challenges still exist with regard to specimen preparation and conversion of raw time-of-flight mass spectrometry data into a three-dimensional map of ions containing structural and chemical information at an acceptable resolution. Recent research aided by hardware improvements and specimen preparation advances has made some progress toward this goal. This article reviews the historical developments in this field, presents some recent results, and considers what life science researchers might expect from this technology. Prospects for Nanobiology with Atom-Probe Tomography Thomas F. Kelly, Osamu Nishikawa, J.A. Panitz, and Ty J. Prosa this article) without the need for concentration, crystallization, or staining. Threedimensional (3D) compositional mapping may be obtained from complex structures with high specificity on location. The spatial resolution of the data could be better than 0.5 nm. As a mass spectrometrybased technique, APT has high sensitivity (≈10 atomic parts per million) and high detector efficiency (≈50%) for all elements in the periodic table and molecular components. This is a powerful list of performance specifications that would surely have an important impact on imaging and analysis of organic and biological materials. But can it really be achieved? This article explores this question, presents some historical background for the work, and concludes that useful results from APT of organics is likely, although exactly how good remains to be demonstrated. Molecular Imaging in High Electric Fields The field-electron-emission microscope (FEEM) and the field-ion microscope (FIM) provide a simple and elegant way to observe a metal surface in near atomic resolution. In these devices, electrons or ions are projected almost radially from a sharply curved surface of radius, R, to an imaging detector a distance, D, from the surface. The projection magnification, M ≈ D/R, for a given radius can be changed by varying D. Magnification is achieved without the aberrations of a lens system, and these microscopes are immune to vibration because of the typically high projection magnification. For many years, attempts were made to use the FEEM to image organic molecules by Müller1–3 and Melmed and Müller. 4 These attempts were inspired by the simplicity of the technique and the potential for achieving high image contrast, magnification, and resolution. By 1950, the FEEM had demonstrated a usable magnification of 106 and an image resolution better than 2 nm. As a result, there was growing optimism that individual molecules might eventually be imaged. Although striking images displaying the correct symmetry of individual flaventrene and copper-phthalocyanine molecules were observed, it soon became apparent that identical FEEM patterns were produced by many different molecules.5–7 It is not known why these molecules were chosen for this work, but it may be because these molecules are planar, so they do not perturb the local field much, and they can be sublimed in vacuum. Several theories were advanced to explain the field-emission patterns.8–1