Laboratory Liquid-Jet X-ray Microscopy and X-ray Fluorescence Imaging for Biomedical Applications

Abstract

Diffraction-limited resolution and low penetration depth are fundamental constraints in optical microscopy and in vivo imaging. Recently, liquid-jet X-ray technology has enabled the generation of X-rays with high-power intensities in laboratory settings. By allowing the observation of cellular processes in their natural state, liquid-jet soft X-ray microscopy (SXM) can provide morphological information on living cells without staining. Furthermore, X-ray fluorescence imaging (XFI) permits the tracking of contrast agents in vivo with high elemental specificity, going beyond attenuation contrast. In this study, we established a methodology to investigate nanoparticle (NP) interactions in vitro and in vivo, solely based on X-ray imaging. We employed soft (0.5 keV) and hard (24 keV) X-rays for cellular studies and preclinical evaluations, respectively. Our results demonstrated the possibility of localizing NPs in the intracellular environment via SXM and evaluating their biodistribution with in vivo multiplexed XFI. We envisage that laboratory liquid-jet X-ray technology will significantly contribute to advancing our understanding of biological systems in the field of nanomedical research.

High-Spatial-Resolution Benchtop X-ray Fluorescence Imaging through Bragg-Diffraction-Based Focusing with Bent Mosaic Graphite Crystals: A Simulation Study

“…This may also include other promising candidates such as molybdenum (Mo), ruthenium (Ru), rhodium (Rh), silver (Ag), iodine (I), etc. [9,10,15,21]. Utilization of X-ray optics may offer promising progress towards using XFI with conventional X-ray tubes for various potential applications involving interesting NP formulations, e.g., within pre-clinical oncology, drug development, and more.…”

“…In contrast to PET/SPECT, XFI allows external control over radiation exposure, variable size scales (from variable resolution and beam positioning), and nondecaying substances, such as those based on nanoparticles (NPs). This enables serial, longitudinal, multiplexed, and targeted imaging at lower radiation doses [9,10,15,[18][19][20][21]. Furthermore, XFI exhibits superior spatial resolution and depth of tissue penetration compared to current optical imaging methods while achieving resolution on par with computed tomography (CT) and MRI [9,13,15,[17][18][19].…”

“…Benchtop XFI systems, while more accessible, still face trade-offs between these performance factors [9,[22][23][24][25]. However, recent studies using focusing optics with a liquid-metal-jet X-ray source have demonstrated promising results for achieving high in vivo spatial resolution, potentially bridging the gap between synchrotron and benchtop performance [18,19,21,26,27]. These studies combine the high brightness from a Galinstan (Ga/In/Sn alloy) target with focusing from a double-bounce multilayer Montel mirror that has been optimized for exploiting indium (In) K α characteristic X-rays (∼24 keV).…”