X‐Ray Photon Correlation Spectroscopy Towards Measuring Nanoparticle Diameters in Biological Environments Allowing for the In Situ Analysis of their Bio‐Nano Interface

X-ray photon correlation spectroscopy (XPCS), a synchrotron source-based technique to measure sample dynamics, is used to determine hydrodynamic diameters of gold nanoparticles (Au NPs) of different sizes in biological environments. In situ determined hydrodynamic diameters are benchmarked with values obtained by dynamic light scattering. The technique is then applied to analyze the behavior of the Au NPs in a biological environment. First, a concentration-dependent agglomeration in the presence of NaCl is determined. Second, concentration-dependent increase in hydrodynamic diameter of the Au NPs upon the presence of proteins is determined. As X-rays in the used energy range are barely scattered by biological matter, dynamics of the Au NPs can be also detected in situ in complex biological environments, such as blood. These measurements demonstrate the possibility of XPCS for in situ analytics of nanoparticles (NPs) in biological environments where similar detection techniques based on visible light would severely suffer from scattering, absorption, and reflection effects