Continuous-flow liquid-phase dehydrogenation of 1,4-cyclohexanedione in a structured multichannel reactor

A highly selective, scalable and continuous-flow process is developed for the liquid-phase dehydrogenation of 1,4-cyclohexanedione to hydroquinone in a millimetre-scale structured multichannel reactor. The square shaped channels (3 mm × 3 mm) were filled with 10 wt% Pd/C catalyst particles and utilized for the dehydrogenation reaction in single-pass and recycle modes. For the purpose to enhance process understanding and to maximize conversion and selectivity by process optimization, Design of Experiment (DoE) methodology was utilized by studying the effect of operating parameters on the catalytic performance in kinetic regime. The results demostrated the strong influence of temperature and liquid feed flow on the conversion and selectivity, with liquid feed and N₂ flows influencing pressure drop significantly. A multi-objective optimization methodology was used to identify the optimum process window with the aid of sweet spot plots, with design space plots developed to establish acceptable boundaries for process parameters. In single-pass mode, complete conversion per pass per channel was not achievable whereas conversion increased from 59.8% in one-channel to 78.3% for two-channel-in-series while maintaining selectivity (> 99%) with intermediate hydrogen removal. However, for without intermediate H₂ removal step, selectivity was declined from > 99% in one-channel to 82.3% at the outlet of second-channel. In recycle mode, dehydrogenation reaction was resulted in almost complete conversion (> 99%) with very high selectivity (> 99%) and yield (> 98%). This combination of mm-scale multichannel reactor and DoE methodology opens the way to developing highly selective and scalable dehydrogenation proocesses in the fine chemical and pharmaceutical industries

Predicting Mab product yields from cultivation media components, using near-infrared and 2D-fluorescence spectroscopies

The yield of monoclonal antibody (Mab) production processes depends on media formulation, inocula quality, and process conditions. As in industrial processes tight cultivation conditions are used, and inocula quality and viable cell densities are controlled to reasonable levels, media formulation and raw materials lot-to-lot variability in quality will have, in those circumstances, the highest impact on process performance. In the particular Mab process studied, two different raw materials were used: a complex carbon and nitrogen source made of specific peptones and defined chemical media containing multiple components. Using different spectroscopy techniques for each of the raw material types, it was concluded that for the complex peptone-based ingredient, near-infrared (NIR) spectroscopy was more capable of capturing lot-to-lot variability. For the chemically defined media containing fluorophores, two-dimensional (2D)-fluorescence spectroscopy was more capable of capturing lot-to-lot variability. Because in Mab cultivation processes both types of raw materials are used, combining the NIR and 2D-fluorescence spectra for each of the media components enabled predictive models for yield to be developed that out-performed any other model involving either one raw material alone, or only one type of spectroscopic tool for both raw materials. For each particular raw material, the capability of each spectroscopy to detect lot-to-lot differences was demonstrated after spectra preprocessing and specific wavelength regions selection. The work described and the findings reported here open up several possibilities that could be used to feed-forward control the process. These include, for example, enabling specific actions to be taken regarding media formulation with particular lots, and all types of predictive control actions aimed at increasing batch-to-batch yield and product quality consistency at harvest. (C) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 27: 1339-1346, 201