Elaboration d'un plan de screening pour l'optimisation de nanoparticules d'argent synthétisées par réduction chimique à partir d'une approche de "Quality by design"

peer reviewedSurface-enhanced Raman scattering (SERS) has shown great scientific interest all over the world, notably in the pharmaceutical and biomedical fields. Indeed, this vibrational technique presents several advantages like a high specificity and sensibility. This technique requires metallic nanoparticles (Nps) to enhance the Raman scattering signal, by a factor of 109 on average by the fact that the interested molecule will be near the surface of Nps. These Nps, also called SERS substrates can be synthesized by different methods. This study was focused on the Lee-Meisel chemical reduction protocol to synthesize silver nanoparticles (AgNps). This process has many advantages like the rapidity, simplicity of manufacturing but also for the low cost. However, Nps obtained based on this chemical reaction are not repeatable in terms of shape and size into a suspension but also from a synthesis to another one. That causes an issue, particularly for quantitative analyses because nature, size and shape of Nps influence the SERS response leading to unrepeatable signal. In this framework, an innovative approach based on an Analytical Quality by Design (AQbD) strategy was introduced by using design of experiments in order to optimize this synthesis protocol and thus to overcome this limitation. For this first step, a “D-Optimal design” was selected to test several interactions with a limited number of experiments. Moreover, this design was separated into blocks taking into account that three syntheses can be made on the same day. Five parameters were selected, one as categorical variable, the reaction volume and the others as continuous variable, the reaction time and temperature, the pH and the concentration of the trisodium citrate solution. The responses in terms of critical quality attributes (CQAs) were the SERS intensity (to maximize), the relative standard deviation on SERS intensities (RSD% - to minimize) and the polydispersity index (PDI – to minimize). These preliminary results were promising with PDI situated from 0.119 to 0.476. SERS analyses were made using a model molecule, the violet crystal. Interesting results were obtained with intensities up to 34 000 counts and RSD% of 3 % (n=9 per synthesis). Finally, the interpretation of this screening design showed parameters which are important to optimize to synthesize repeatable and homogeneous AgNps. Concentration and pH of citrate solution seemed to have an important impact on their formation while temperature and reaction time had a lower one