Development of an on-line Raman spectral analytical method for monitoring and endpoint determination of the Cornu Caprae Hircus hydrolysis process

Abstract

Objectives Cornu Caprae Hircus (goat horn, GH), a medicinal animal horn, is frequently used in traditional Chinese medicine, and hydrolysis is one of the most important processes for GH pretreatment in pharmaceutical manufacturing. In this study, on‐line Raman spectroscopy was applied to monitor the GH hydrolysis process by the development of partial least squares (PLS) calibration models for different groups of amino acids. Methods Three steps were considered in model development. In the first step, design of experiments (DOE)‐based preprocessing method selection was conducted. In the second step, the optimal spectral co‐addition number was determined. In the third step, sample selection or reconstruction methods based on hierarchical clustering analysis (HCA) were used to extract or reconstruct representative calibration sets from the pool of hydrolysis process samples and investigated for their ability to improve model performance. Key findings This study has shown the feasibility of using on‐line Raman spectral analysis for monitoring the GH hydrolysis process based on the designed measurement system and appropriate model development steps. Conclusions The proposed Raman‐based calibration models are expected to be used in GH hydrolysis process monitoring, leading to more rapid material information acquisition, deeper process understanding, more accurate endpoint determination and thus better product quality consistency.

Bioprocess in‐line monitoring using Raman spectroscopy and Indirect Hard Modeling (IHM): A simple calibration yields a robust model

“…Raman spectroscopy is highly suitable for the application in aqueous systems since the Raman signal of water is not as dominant as that found with other techniques such as infrared (IR) spectroscopy (Webster et al, 2018; Yan et al, 2020). Unlike fluorescence spectroscopy, Raman spectroscopy is not limited to fluorescent molecules (Bockisch et al, 2019).…”

“…Unlike fluorescence spectroscopy, Raman spectroscopy is not limited to fluorescent molecules (Bockisch et al, 2019). It can be applied in‐situ, non‐destructively, and non‐invasively while showing high specificity because of its “detailed molecular fingerprint” (Yan et al, 2020). Therefore, Raman spectroscopy is an appropriate PAT tool for simultaneous monitoring of several process parameters of a bioprocess (Hirsch et al, 2019).…”

“…For the evaluation of bioprocess Raman spectra, multivariate statistical models such as partial least squares regression (PLSR) are most commonly used (Tulsyan et al, 2020). In literature, this approach has already extensively been applied to monitor cell culture processes of Chinese hamster ovary (CHO) cell lines, Cornu Caprae Hircus hydrolyses, and Saccharomyces cerevisiae ( S. cerevisiae ) fermentations (Ávila et al, 2012; B. Berry et al, 2015; Hirsch et al, 2019; Iversen et al, 2014; Jiang et al, 2020; Kozma et al, 2018; Matthews et al, 2018; Mehdizadeh et al, 2015; Rafferty, Johnson, et al, 2020; Rafferty, O'Mahony, et al, 2020; Rowland‐Jones et al, 2017; Santos et al, 2018; Schalk et al, 2017, 2019; Shope et al, 1987; Tulsyan et al, 2019; Webster et al, 2018; Yan et al, 2020). However, the calibration of statistical models for evaluating bioprocess Raman spectra is effortful, since statistical models are not suitable for quantitative analysis outside the calibration limits, the so‐called design space (Berry et al, 2015; Tulsyan et al, 2019).…”

“…Unlike fluorescence spectroscopy, Raman spectroscopy is not limited to fluorescent molecules (Bockisch et al, 2019). It can be applied in-situ, nondestructively, and non-invasively while showing high specificity because of its "detailed molecular fingerprint" (Yan et al, 2020).…”

Online Quantitative Analysis of Chlorine Contents in Chlorinated Paraffins by Facile Raman Spectroscopy

“…The existing Cl in liquid CP is a typical secondary chloride with both S HH and S HC conformations based on Mizushima’s notation, − representing the C–Cl stretching mode of the CH–Cl units in syndiotactic and isotactic sequences, respectively. The investigation of chlorinated polyethylenes showed that chlorination can affect the structure and conformation of CPs, which, in turn, can be used for the quantitative determination of Cl contents in CPs by the corresponding vibrational frequencies with specific conformations. , In addition to the rapid and nondestructive data acquisition process, Raman spectroscopy has great potential for the online monitoring of chemical productions. − …”