A bench-top K X-ray fluorescence system for quantitative measurement of gold nanoparticles for biological sample diagnostics

Abstract

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 xray source, capable of quantitative measurement of gold nanoparticle concentration of thicker samples. The developed system achieved a measured detection limit of between 0.2-0.6 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 quantification. 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.

Technical Note: A benchtop cone‐beam x‐ray fluorescence computed tomography (XFCT) system with a high‐power x‐ray source and transmission CT imaging capability

“…On the other hand, benchtop XFCT also suffers other obstacles due to the polychromatic nature of the x-ray source (e.g., low photon flux for excitation of XRF photons) as well as other technical difficulties (e.g., relatively low energy resolution of room-temperature detectors). Nevertheless, there have been ongoing research efforts by many research groups to develop various benchtop XFCT systems, 2,3,[9][10][11][12][13][14][15][16] since the current research group originally demonstrated the feasibility of benchtop XFCT by imaging of small-animal-sized objects containing low (~1 wt. %) concentrations of GNPs.…”

Monte Carlo modeling of gold nanoparticles detection limits of benchtop three‐dimensional L‐ and K‐shell X‐ray fluorescence mapping systems

“…On the other hand, focusing on the detection limit of GNP concentrations from a biological sample (which is not for an imaging system) using a benchtop X‐ray source was experimentally investigated and estimated to be 0.0005 wt% for L‐XRF system and 0.02–0.06 wt% for K‐XRF system in 0.8‐cm‐diam. plastic tubes 24,25 . In those two studies, the radiation doses delivered to the GNP‐loaded samples were not been considered.…”

Simulation Research of Potential Contrast Agents for X-Ray Fluorescence CT with Photon Counting Detectors

“…X-ray fluorescence computed tomography (XFCT) is a novel method to detect early-stage cancer, combining X-ray computed tomography (X-CT) with X-ray fluorescence technology (XRF) [1][2][3]. For conventional X-CT imaging, the reconstructed image is the absorption coefficient of incident X-ray, which is difficult to distinguish the diseased and normal tissue for the slight difference of absorption.…”