scholarly journals Digital Twins for Continuous mRNA Production

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1967
Author(s):  
Heribert Helgers ◽  
Alina Hengelbrock ◽  
Axel Schmidt ◽  
Jochen Strube

The global coronavirus pandemic continues to restrict public life worldwide. An effective means of limiting the pandemic is vaccination. Messenger ribonucleic acid (mRNA) vaccines currently available on the market have proven to be a well-tolerated and effective class of vaccine against coronavirus type 2 (CoV2). Accordingly, demand is presently outstripping mRNA vaccine production. One way to increase productivity is to switch from the currently performed batch to continuous in vitro transcription, which has proven to be a crucial material-consuming step. In this article, a physico-chemical model of in vitro mRNA transcription in a tubular reactor is presented and compared to classical batch and continuous in vitro transcription in a stirred tank. The three models are validated based on a distinct and quantitative validation workflow. Statistically significant parameters are identified as part of the parameter determination concept. Monte Carlo simulations showed that the model is precise, with a deviation of less than 1%. The advantages of continuous production are pointed out compared to batchwise in vitro transcription by optimization of the space–time yield. Improvements of a factor of 56 (0.011 µM/min) in the case of the continuously stirred tank reactor (CSTR) and 68 (0.013 µM/min) in the case of the plug flow reactor (PFR) were found.

Processes ◽  
2019 ◽  
Vol 7 (9) ◽  
pp. 615 ◽  
Author(s):  
Peter Toson ◽  
Pankaj Doshi ◽  
Dalibor Jajcevic

The tanks-in-series model (TIS) is a popular model to describe the residence time distribution (RTD) of non-ideal continuously stirred tank reactors (CSTRs) with limited back-mixing. In this work, the TIS model was generalised to a cascade of n CSTRs with non-integer non-negative n. The resulting model describes non-ideal back-mixing with n > 1. However, the most interesting feature of the n-CSTR model is the ability to describe short recirculation times (bypassing) with n < 1 without the need of complex reactor networks. The n-CSTR model is the only model that connects the three fundamental RTDs occurring in reactor modelling by variation of a single shape parameter n: The unit impulse at n→0, the exponential RTD of an ideal CSTR at n = 1, and the delayed impulse of an ideal plug flow reactor at n→∞. The n-CSTR model can be used as a stand-alone model or as part of a reactor network. The bypassing material fraction for the regime n < 1 was analysed. Finally, a Fourier analysis of the n-CSTR was performed to predict the ability of a unit operation to filter out upstream fluctuations and to model the response to upstream set point changes.


2018 ◽  
Vol 7 (4) ◽  
pp. 1995 ◽  
Author(s):  
Mostafa Ghobashy ◽  
Mamdouh Gadallah ◽  
Tamer T.El-Idreesy ◽  
M. A.Sadek ◽  
Hany A.Elazab

We report here, the hydrolysis of ethyl acetate by using caustic soda which is followed by means of conductance measurements which is widely used in chemical industry. The main aim of this research is to study the parameters of production of ethyl acetate by chemical reaction kinetics using an anion ion-exchange acting as a catalyst and acid-base titrations. The reaction of ethyl acetate and sodium hydroxide (caustic-soda) is done in a plug-flow reactor (steady-state tubular reactor) under the effect of different parameters including temperature, concentration and flow-rate, which allows the determination of activation energy and rate constants, due to large number of experiments. Factorial design method is used for the calculations of the experiment. It was determined that the order of the reaction is a second-order reaction.  


Catalysts ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 262 ◽  
Author(s):  
Rowan Lindeque ◽  
John Woodley

Enzyme catalyzed reactions are rapidly becoming an invaluable tool for the synthesis of many active pharmaceutical ingredients. These reactions are commonly performed in batch, but continuous biocatalysis is gaining interest in industry because it would allow seamless integration of chemical and enzymatic reaction steps. However, because this is an emerging field, little attention has been paid towards the suitability of different reactor types for continuous biocatalytic reactions. Two types of continuous flow reactor are possible: continuous stirred tank and continuous plug-flow. These reactor types differ in a number of ways, but in this contribution, we focus on residence time distribution and how enzyme kinetics are affected by the unique mass balance of each reactor. For the first time, we present a tool to facilitate reactor selection for continuous biocatalytic production of pharmaceuticals. From this analysis, it was found that plug-flow reactors should generally be the system of choice. However, there are particular cases where they may need to be coupled with a continuous stirred tank reactor or replaced entirely by a series of continuous stirred tank reactors, which can approximate plug-flow behavior. This systematic approach should accelerate the implementation of biocatalysis for continuous pharmaceutical production.


Author(s):  
Nattaporn Chutichairattanaphum ◽  
Phavanee Narataruksa ◽  
Karn Pana-Suppamassadu ◽  
Sabaithip Tungkamani ◽  
Chaiwat Prapainainar ◽  
...  

This paper aims to study the effect of raschig ring packing patterns using Computational Fluid Dynamics (CFD). CFD module of particle tracing was established to measure particles diffusing through the packed bed. The support raschigs catalyst was modeled in three patterns within a tubular reactor &ndash; namely, vertical staggered, chessboard staggered and reciprocal staggered pattern. A case study of Dry Methane Reforming (DMR) was investigated at 600&deg;C, 1 atm. The study of Mean Resident Time (MRT) and E(t) function were investigated to identify the packing pattern performance. The results showed that the minimum value of the E(t), which means the flow behavior, was close to ideal plug flow behavior. MRT can be used to systematically identify the deviation from the ideal plug flow reactor of the three different packing patterns.


Author(s):  
Ricardo Aguilar-López ◽  
Ricardo Acevedo-Gómez ◽  
Marí­a Isabel Neria González ◽  
Alma Rosa Domí­nguez-Bocanegra

The goal of this work is to describe the design of a feedback controller to regulate the Hexavalent chromium (Cr (VI)) concentration in industrial plating wastewater in a tubular reactor. Cr(VI) is a major pollutant present in industrial wastewaters common to the metal and mineral processing as well as to plating industries. For control purposes, a dynamic model of a plug flow reactor with dispersion is developed in the form of partial differential equations (PDE) via applying classical conservation principles; this model is experimentally corroborated using laboratory data. The proposed controller is based on uncertainty observer to infer unknown terms as diffusive transport and Cr(VI) kinetic rate; also Generic Model Controller (GMC) is coupled with this estimation methodology to provide robustness against model uncertainties. The controller leads to nonlinear PID plus double integral action, where the tuning rules are given in terms of the observer and GMC gains. A theoretical frame is given in order to show the stability properties of the closed-loop system under the proposed controller. Numerical simulation illustrates performance of the methodology proposed; a comparison with observer based I/O linearizing controller and a well tuned PID controller is done, which allows concluding that the observer based Generic Model Controller exhibits better performance.


2016 ◽  
Vol 4 ◽  
pp. 3
Author(s):  
Hudson Jean Bianquini Couto ◽  
Raphael Andrade Eloy Oliveira ◽  
Paulo Fernando Almeida Braga

Foi realizado um trabalho para avaliação da fluidodinâmica de uma coluna piloto de flotação, por meio da aplicação da técnica de distribuição de tempos de residência - DTR, em função das variáveis mais importantes do processo de flotação como velocidade superficial de alimentação, ar e água de lavagem, e da concentração de espumante. Foi ainda realizado um estudo comparativo entre as diferentes metodologias utilizadas para determinação dos parâmetros hidrodinâmicos de DTR, como ajuste dos modelos CSTR (Continuous Stirred-Tank Reactor) em série e PFR (Plug-Flow Reactor) de dispersão axial, aos dados experimentais.


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