Prospects for Nanobiology with Atom-Probe Tomography
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Nanobiology with Atom-Probe Tomography
Thomas F. Kelly, Osamu Nishikawa, J.A. Panitz, and Ty J. Prosa Abstract 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.
Introduction Materials of all types are being studied and developed at the atomic scale. Materials scientists have a long history of processing materials to obtain new structures and then characterizing these structures as a way to understand both the processing and the properties. Similar approaches are being applied to organic and biological materials (i.e., nanobiology), whether they are synthetically processed or naturally processed. An essential element of any such endeavor is characterization capabilities. Materials science researchers have had microscopies for imaging and analysis at the atomic scale for decades, including transmission electron microscopy (TEM), x-ray diffraction (XRD)/crystallography, secondary ion mass spectroscopy (SIMS), and scanning probe microscopies (SPMs). These techniques do not, however, always offer the same full set of benefits for organic materials. For example, radiation damage and other beam effects in organic 744
materials limit the spatial resolution achieved in TEM to 1 to 2 nm, whereas 0.1 nm is possible in inorganic materials. XRD offers high spatial resolution atomic structure under the special circumstances of a crystallized specimen and large volume (~10−2 mm3) that limit its applicability to a small fraction of biological structures of interest (e.g., less than 15% of technologically important proteins). Thus, the prospect of compositional imaging of biological materials at the atomic scale and in three spatial dimensions would seem to be self-evidently important to achieve. Atom-probe tomography (APT) has the potential to reach this goal, while offering several important advantages for organics analysis. The minimum sample size could be very small (zeptoliters). The time to data and time to knowledge can be short (days). The specimen material could be extracted from a native, likely frozen, environment (see discussion of cryogenic methods later in
this article) without the need for concentration, crystallization, o
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