Analysis of nanoparticles by AF4 in combination with multiple detectors such as MALLS, DLS and RI can be quite challenging compared to the analysis of molecules in solution. Due to the large size of the particles (i.e., 20-1000 nm), the scattering intensity is much higher compared to an average lignin molecule of around 3-6 nm in solution. This high scattering intensity can cause that even very low sample concentrations (0.01 % w/v) exceed the upper detector range of the MALLS detector (i.e., signal clipping). One way to overcome this problem would be to reduce the sample concentration until the scattering signal remains within the detector limits. However, the minimum concentration is dictated by the less sensitive RI detection which is needed for the calculation of particle size distributions and is negatively affected by low signal intensities. During method development, we struggled to find an optimum sample concentration with adequate MALLS and RI signal intensities, however, the more straightforward solution to this fundamental problem was to adjust the laser power of the MALLS detector. The optimal laser power for our experiments was determined by measuring the PS particle standards (rh = 50 nm) at 100, 80, 60, 40 and 20 % laser power, respectively (Figure and Figure ). Reducing the laser power to 20 % significantly improved the MALLS signal quality and prevented clipping without compromising the signal intensity of the RI measurement (Figure and Figure ). Therefore, a laser power of 20 % was used for all of our LNP measurements.