In-line Monitoring of Monomer and Polymer Content During Microgel Synthesis Using Precipitation Polymerization via Raman Spectroscopy and Indirect Hard Modeling

Abstract

This contribution presents in-line monitoring of microgel synthesis by precipitation polymerization based on Raman spectroscopy. The spectra are evaluated via multivariate Indirect Hard Modeling (IHM) regression. Therefore, mechanistic models of the pure component spectra for solvent, monomer, and microgel are created by a sum of adaptable parameterized peak functions (Gaussian-Lorentzian). Instead of individual calibrations for each analyte, one comprehensive model is calibrated to predict both the monomer and microgel fraction while ensuring a consistent mass balance. As a novelty, this leads to an in-line microgel quantification based on an interactive spectral model. The results show cross-validation errors (RMSECV) of monomer and microgel fractions as low as 0.028 wt % and 0.084 wt %, respectively. The ability of IHM to account for non-linear spectral changes was found to reduce the microgel RMSECV by a factor of two compared to linear CLS regression. The calibration model allows simultaneous observation of the decrease in monomer content and the formation of microgels. Long as well as short focus immersion optics reveal characteristic vibrations of the turbid microgel suspension, although long focus optics are influenced by scattering particles to a greater extent. Precise examination of the model proves that the prediction is robust against changes in microgel particle size or temperature, which opens up the application of Raman spectroscopy as a comprehensive process analytical technology in microgel synthesis.

Monitoring Microgel Synthesis by Copolymerization of N‐isopropylacrylamide and N‐vinylcaprolactam via In‐Line Raman Spectroscopy and Indirect Hard Modeling

“…While component fractions have been monitored in‐line during microgel homopolymerization based on VCL, component fractions during copolymerization based on VCL and N‐isopropylacrylamide (NIPAM) have previously been studied only by sampling and subsequent off‐line analysis . This contribution extends our previous work to in‐line monitoring to microgel syntheses based on homopolymerization of NIPAM and to syntheses based on copolymerization of VCL and NIPAM to investigate the interaction between both monomers. Microgel syntheses based on VCL and NIPAM were simultaneously monitored using in‐line turbidity and in‐line Raman measurements.…”

“…To predict component fractions from mixture spectra of the water, VCL, PVCL, NIPAM, and PNIPAM system, pure component models are created for each component for the spectral range 800–3000 cm −1 . For water, monomer VCL, and polymer PVCL, the pure components from our previous model are reutilized . For monomer NIPAM and polymer PNIPAM, they are created using complemental hard modeling (CHM) .…”

“…The utilization of water as a rather Raman‐inactive solvent enables detection of weak peaks as well. The homopolymerization of microgels based on N‐vinylcaprolactam (VCL) was thus monitored using in‐line Raman spectroscopy and multivariate indirect hard modeling (IHM) regression . From spectra taken during microgel homopolymerization, IHM enabled to determine the individual fraction of monomer and the spectrally weaker contributions of the polymer.…”

Polymer particle sizing from Raman spectra by regression of hard model parameters

“…For model creation, the spectra are cropped to the 1,020–2,000 cm −1 spectral region, which contains characteristic water and polymer peaks. For the polystyrene–water system, using the entire spectrum for component modeling was found to result in lower accuracy of predicted component weight fractions, because nonlinear variation in Raman baseline intensity cannot be handled by IHM's linear baseline . No further pretreatment such as baseline subtraction, standardization, or smoothing is carried out, because these methods might deteriorate the particle influences which are to be detected.…”

Functional Microgels: Recent Advances in Their Biomedical Applications

“…Recently, Meyer‐Kirschner et al employed indirect hard modeling and Raman spectroscopy for the preparation of PVCL microgels by precipitation polymerization in order to monitor the monomer conversion along with reaction starting and ending times . It was observed here that when the synthesis of PVCL microgels is performed at 60 °C, then maximum monomer is consumed in the initial 15–20 min and afterward, the residual monomer concentration remains constant.…”