A new sample substrate for imaging and correlating organic and trace metal composition in biological cells and tissues (original) (raw)
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Metals and metalloids play fundamental roles in many physiological processes in biological systems, but imbalance of these elements in the body may cause many diseases, such as Parkinson's disease, Alzheimer's disease, and even cancers. Thus, to better understand the metallome in health and disease, quantitative determination of their localization, concentration, speciation, and related metabolism at cellular or subcellular levels is of great importance. X-ray fluorescence (XRF) imaging, as a new generation of analytical technique, has been reported as an ideal tool to quantitatively map multiple metals and metalloids in tissues with reasonable sensitivity, specificity, and resolution. In the current review, we have introduced the general concept of XRF imaging technique, reviewed the recent advances using XRF imaging to investigate toxicology of metals and metalloids in life science, and discussed the roles of metals and metalloids in various diseases, including cancers and...
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Very little is known about the sub-cellular distribution of metal ions in cells. Some metals such as zinc, copper and iron are essential and play an important role in the cell metabolism. Dysfunctions in this delicate housekeeping may be at the origin of major diseases. There is also a prevalent use of metals in a wide range of diagnostic agents and drugs for the diagnosis or treatment of a variety of disorders. This is becoming more and more of a concern in the field of nanomedicine with the increasing development and use of nanoparticles, which are suspected of causing adverse effects on cells and organ tissues. Synchrotron-based X-ray and Fourier-transformed infrared microspectroscopies are developing into wellsuited sub-micrometer analytical tools for addressing new problems when studying the role of metals in biology. As a complementary tool to optical and electron microscopes, developments and studies have demonstrated the unique capabilities of multi-keV microscopy: namely, an ultra-low detection limit, large penetration depth, chemical sensitivity and three-dimensional imaging capabilities. More recently, the capabilities have been extended towards sub-100 nm lateral resolutions, thus enabling sub-cellular chemical imaging. Possibilities offered by these techniques in the biomedical field are described through examples of applications performed at the ESRF synchrotron-based microspectroscopy platform (ID21 and ID22 beamlines).
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X-ray Spectrometry, 1993
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Gold nanoparticles can be targeted to biomarkers to give functional information on a range of tumour characteristics. X-ray fluorescence (XRF) techniques offer potential quantitative measurement of the distribution of such heavy metal nanoparticles. Biologists are developing 3D tissue engineered cellular models on the centimetre scale to optimise targeting techniques of nanoparticles to a range of tumour characteristics. Here we present a high energy bench-top K-X-ray fluorescence system designed for sensitivity to bulk measurement of gold nanoparticle concentration for intended use in such thick biological samples. Previous work has demonstrated use of a L-XRF system in measuring gold concentrations but being a low energy technique it is restricted to thin samples or superficial tumours. The presented system comprised a high purity germanium detector and filtered tungsten X-ray source, capable of quantitative measurement of gold nanoparticle concentration of thicker samples. The developed system achieved a measured detection limit of between 0.2 and 0.6 mgAu/ml, meeting specifications of biologists and being approximately one order of magnitude better than the detection limit of alternative K-XRF nanoparticle detection techniques. The scatter-corrected K-XRF signal of gold was linear with GNP concentrations down to the detection limit, thus demonstrating potential in GNP concentration quan-tification. The K-XRF system demonstrated between 5 and 9 times less sensitivity than a previous L-XRF bench-top system, due to a fundamental limitation of lower photoelectric interaction probabilities at higher K-edge energies. Importantly, the K-XRF technique is however less affected by overlying thickness, and so offers future potential in interrogating thick biological samples.
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Characteristic X-ray fluorescence is a technique that can be used to establish elemental concentrations for a large number of different chemical elements simultaneously in different locations in cell and tissue samples. Exposing the samples to an X-ray beam is the basis of X-ray fluorescence microscopy (XFM). This technique provides the excellent trace element sensitivity; and, due to the large penetration depth of hard X-rays, an opportunity to image whole cells and quantify elements on a per cell basis. Moreover, because specimens prepared for XFM do not require sectioning, they can be investigated close to their natural, hydrated state with cryogenic approaches. Until several years ago, XFM was not widely available to bio-medical communities, and rarely offered resolution better then several microns. This has changed drastically with the development of third-generation synchrotrons. Recent examples of elemental imaging of cells and tissues show the maturation of XFM imaging technique into an elegant and informative way to gain insight into cellular processes. Future developments of XFM-building of new XFM facilities with higher resolution, higher sensitivity or higher throughput will further advance studies of native elemental makeup of cells and provide the biological community including the budding area of bionanotechnology with a tool perfectly suited to monitor the distribution of metals including nanovectors and measure the results of interactions between the nanovectors and living cells and tissues.