Analysis of Biologics Molecular Descriptors towards Predictive Modelling for Protein Drug Development Using Time-Gated Raman Spectroscopy

Abstract

Pharmaceutical proteins, compared to small molecular weight drugs, are relatively fragile molecules, thus necessitating monitoring protein unfolding and aggregation during production and post-marketing. Currently, many analytical techniques take offline measurements, which cannot directly assess protein folding during production and unfolding during processing and storage. In addition, several orthogonal techniques are needed during production and market surveillance. In this study, we introduce the use of time-gated Raman spectroscopy to identify molecular descriptors of protein unfolding. Raman spectroscopy can measure the unfolding of proteins in-line and in real-time without labels. Using K-means clustering and PCA analysis, we could correlate local unfolding events with traditional analytical methods. This is the first step toward predictive modeling of unfolding events of proteins during production and storage.

Operando time-gated Raman spectroscopy of solid catalysts

“…Kerr-gated Raman spectroscopy (KG-RS) has been applied for the study of carbonaceous species on solid catalysts, including the formation of coke species during the MTO reaction 22 and carbon deposits on other strongly fluorescent zeolite-based catalyst materials, 23,24 as well as in battery research. 25,26 CMOS-SPAD-based time-gated Raman spectroscopy was used for numerous different type of samples, including biological samples and pharmaceuticals, [27][28][29][30][31] rareearth-element containing rock samples, 32 high-temperature melts, 33 and pickle liquor. 34 Precisely assessing the beneficial effect of time gating on spectral quality remains challenging.…”