## 5 Detection and Monitoring of Nanoparticles Interaction in Mouse-Serum  
The detection of nanoparticles in complex biological fluids is of relevance to study nanoparticle-protein interactions in a biologically representative environment. We have recently shown that the interaction of gold nanospheres and nanorods can be successfully detected in mouse-serum and have compared their interaction for different aspect ratios of the nanoparticles using the CONTIN algorithm [10]. Figure 4 shows the results based on the analysis using the CORENN algorithm.  
While for nanospheres (aspect ratio 1.0) and for nanorods with an aspect ratio of 2.6 DLS results show only small changes of the hydrodynamic radii of the mouse serum (within the error bars), nanorods with aspect ratios of 3.6 and 5.6 lead to an increase of the hydrodynamic radius related to translational motion. These observations are indicative of interaction between the nanoparticles and the serum. The CORENN analysis confirms the observations based on CONTIN analysis [10].  
In order to investigate whether proteins of the mouse serum interact however with the nanospheres, we monitor citrate stabilized gold nanospheres, nominal diameter of 40 nm, (NanoComposix, San Diego, CA, USA, 0.05 mg/mL dispersed in water) together with a low concentration of the mouse serum over time. For incubation experiments, the mixture of the gold nanoparticle suspension and the mouse serum was prepared from the already diluted mouse serum of 33% concentration, which we used at a concentration of 7% leading to a mouse serum concentration of 2.3% for incubation.  
We monitor the hydrodynamic radii. Figure 5 shows results from cumulants and CORENN analysis of the gold nanospheres together with mouse serum over time. At these low mouse serum concentrations and high nanoparticle concentration, the translational peaks of the nanospheres are  
Figure 4: Hydrodynamic radii of filtered mouse serum upon interaction of mouse serum (33%) with gold nanoparticles analyzed using the CORENN algorithm. The hydrodynamic radii of the pure filtered 33% mouse-serum are shown for the convenience of comparison in the same graph.  
clearly identified. The hydrodynamic radius of the nanospheres initially decreases, which might be due to an increase in viscosity and/or signal contributions from translations of the mouse-serum.  
On a timescale over the first minutes we then observe that the hydrodynamic radius of the nanospheres slightly increases. Cumulants and CORENN results show essentially similar behavior over time, with cumulants values superior to the CORENN values of the hydrodynamic radius (Figure 5). The difference between the hydrodynamic radii obtained from cumulants and CORENN analysis can be attributed to the polydispersity of the sample.  
In summary, at low serum concentrations the motion of nanoparticles can be reliably detected, despite the complexity of the composition of the added biofluid, while at high concentration the characteristics of the mouse-serum, including a distinction of rotation, translation and agglomeration are detected, in the presence of nanoparticles [10]. In both cases, the CORENN analysis of 3D-DLS data shows to be powerful for the DLS data analysis.