The Bionanoprobe: Synchrotron-Based Hard X-ray Fluorescence Microscopy for 2D/3D Trace Element Mapping

Abstract

Trace elements, particularly metals, play an important role in a large variety of cellular processes in a biological system. In the context of biological organisms and tissues, the term trace element means that over the entire organism an element is present at only trace levels, 100 ppm or lower. Trace element distribution and content can be analyzed using several techniques, for example, visible light optical fluorescence imaging, energy-dispersive X-ray spectroscopy on an electron microscope, synchrotron-based X-ray fluorescence (XRF) imaging, secondary-ion mass spectrometry, and laser ablation inductively coupled with mass spectrometry. Comprehensive reviews on these techniques are given by Lobinski et al. [1] and McRae et al. [2]. Among these techniques, synchrotron-based XRF microscopy, particularly using third-generation X-ray sources and advanced X-ray focusing optics, offers the most suitable capabilities to perform trace element studies of biological samples: the penetrating power and non-destructive nature of X rays allows one to image many-micron-thick biological samples such as whole cells in a way that visible light or electron microscopes cannot; the sensitivity of X-ray-induced XRF is down to parts per million, several orders of magnitude better than standard electron-based techniques due to the absence of bremsstrahlung background in X-ray-induced X-ray emission. The capability of imaging frozen samples in both 2D and 3D with sub-50 nm resolution in various X-ray modes has greatly advanced a broad range of scientific studies. This article describes how this technique can be used to track the incorporation of nanocomposites into cancer cells.