Combining characterization tools for screening of critical parameters leading to reproducible synthesis of silver nanoparticles

Surface enhanced Raman scattering (SERS) attracts the interest of many researchers around the world thanks to its high sensitivity and specificity including short analysis times. Nowadays, major studies are centered on the development of new kind of SERS substrates aiming to give more perspectives to SERS in routine analysis knowing that the size, the shape and the metal used can influence the response intensity. However, these substrates remain very expensive and require sophisticated techniques. In this context, the objective of the present study is focused on the optimization of a silver nanoparticles (AgNps) synthesis using an innovative approach based on Quality by Design strategy in order to obtain homogeneous and repeatable syntheses. The Lee and Meisel protocol, widely used by the SERS community, was chosen as starting point. It is based on a chemical reduction of silver nitrate by sodium citrate but it leads to inhomogeneous AgNps in terms of size and shape. A screening design was first performed in order to evaluate the synthesis critical parameters with the highest influence. Among these ones, trisodium citrate solution concentration and pH, time and temperature of reaction and synthesis volume were selected thanks to the literature and the laboratory experice. The critical quality attributes selected were the highest SERS intensity and the lowest RSD% as well as the polydispersity index (PDI). First results revealed AgNps sizes from 25 to 99 nm with PDI values from 0.119 to 0.476. Regarding to the SERS experiments, intensities up to 34 000 and RSD% below 3 % (n=9 per synthesis) were obtained using a model molecule. These results showed that citrate concentration could have a significant impact on the stability, the yield of reaction and the SERS response. Moreover, reaction time could also have an impact on the synthesis homogeneity. In parallel, inductively coupled plasma mass spectrometry (ICP-MS) was used to evaluate the synthesis yields by determining consumed silver. These varied from 38.9 % to 99.6 %. In perspective, a statistical analysis will be performed on the screening data before computing the design of experiments dedicated to the optimization step.