METTLER TOLEDO is pleased to be presenting at AIChE (American Institute of Chemical Engineers) 2012 Annual Meeting.
In situ Real-time Monitoring of Biotransformations – Monday, October 29, 2:36PM, Westmoreland Central (Westin Convention Center Pittsburgh)
Enzymes, as biocatalysts, are a highly suitable, environmentally friendly alternative to heavy metal industrial catalysts. The “Green Chemistry” nature of enzymes as catalysts is based on a number of characteristics. Enzymes are biodegradable and typically produced through fermentation of renewable feedstocks or easily mass produced through recombinant technologies. Enzymes also catalyze chemical reactions under mild temperature (20°C-40˚C) and pH conditions (pH 5-8), and perform well in aqueous environments. The chemical, petroleum, agriculture, polymer, electronics and pharmaceutical industries rely on catalysis to optimize their chemical processes. It is estimated that at least 90% of chemicals produced rely to some extent on catalysis. In recent years researchers have increasingly focused their attention on green chemistry, including catalysis. Examples of enzyme-catalyzed industrial-scale organic reactions include hydrolysis, oxidation, reduction, addition – elimination, halogenation and dehalogenation, and transesterification. This presentation reviews case studies from pharma, academia and the military, showing how in situ mid-IR was used to monitor the enzyme-catalyzed reactions in real time, to enable researchers to understand reaction mechanisms, and determine kinetic parameters and reduce costs.
The Role of Meso-Mixing in Anti-Solvent Crystallization Processes – Tuesday, October 30, 9:20am, Oakmont (Omni William Penn Hotel)
This paper establishes links between the available turbulent mixing capability in a fed-batch reactor and important crystallization characteristics such as the Metastable Zone Width (MSZW) and product nucleation during the anti-solvent crystallization of benzoic acid. As demonstrated an increase in the locally dominant meso-mixing timescale, τD, facilitates the premature and subsequent sporadic nucleation of the solute. An alternative well mixed addition location, defined via Computational Fluid Dynamics (CFD) simulations and turbulent mixing theory, allows this dispersion limiting timescale to be reduced by over 50% across all anti-solvent addition rates assessed. Additionally, a more direct pathway from the feed point to the well mixed region of the impeller is also presented. These more favorable hydrodynamic conditions improve supersaturation dispersion and blending which in turn eliminate the premature and additional nucleation of the solute throughout the batch. Correlations between the population of fine particles and τD are also presented. These relationships demonstrate the sensitivity to the systems crystal size when hydrodynamic properties are improved
Enhanced Development and Control of Continuous Processes Using Real Time in Situ FTIR Analytics – Wednesday, October 31, 1:14pm, Oakmont (Omni William Penn Hotel)
Multiple reactions were studied using ATR-FTIR as a convenient, specific, inline monitoring technique to examine various aspects, challenges, and opportunities posed by flow chemistry: Dispersion in the column, rapid screening of reaction conditions, reactive intermediate identification, hazardous compound detection to protect the experimenter, microliter scales experiments. This initial study showed that the time it usually takes to optimize reaction conditions was shortened. Due to the fast response time and structural information in each of the many reaction mixture spectra obtained, short-lived intermediates were observed in situ, which helped gain a better understanding of reaction mechanism. In a later investigation, formation of a pyrazole derivative, the use of ATR-FTIR enabled precise control of reagent streams addition in a complex multi-step reactions sequence. For the first time, it is therefore possible to control pumps to dispense reagents based upon the real time concentration of reaction intermediates in multi-step processes. As a result of this high level of control via inline monitoring, multi-step sequences were run more efficiently. For instance, in the event of a reaction failure, precious material would be saved since the lowered concentration of intermediate would be accounted for in real-time.
Optimize Solids-Liquid Separation with Inline Particle Size Measurement – Thursday, November 1, 12:55pm, Room 403 David L. Lawrence Convention Center
Water recycle and tailing settling rates are optimized through solids flocculation. Yet as the incoming feed concentration and particle size distribution varies, so does the solids separation efficiency. Tracking changes to the real time particle size distribution and fine particle population enables fast and efficient water recycle. Offline measurement techniques require samples to be extracted and manipulated through dilution or dispersion which alter or destroy flocculated components, and offline measurements cannot be applied to make real-time process control decisions. In situ particle measurement technology, such as FBRM® and PVM®, measure changes to particle size, inline without the need for sampling. This technology is applied across the petroleum and mining industries to optimize tailings dewatering.
In this paper, flocculation performance, dosage costs, and solid-liquid separations were optimized using FBRM® and PVM® technology. These rugged probe based tools were critical to improve water recovery laboratory and on large scale gravity thickener tanks and pipe reactors. The ability to track changes on both the fine and coarse ends of the particle distribution enabled separation performance optimization based on flocculent type, slurry feed distribution, and shear rate.
- Online Particle Size Monitoring During Roller Compaction – Rhye Hamey, Bristol-Myers Squibb
- Design and Characterization of a Continuous Stirred Tank Crystallizer – Guangyang Hou, Mark Barrett and Brian Glennon, School of Chemical & Bioprocess Engineering, University College Dublin(UCD)
- A Multidimensional Population Balance Model for Growth and Dissolution Identified from a Designed Temperature Cycling Experiment – Mo Jiang, MIT – co-authors Dr. Dominique Hebrault and Dr. Des O’Grady
- Effects of an Impurity On the Morphology of an API: Using ATR-FTIR, FBRM® and PVM® to Confirm a Hypothesis – Christopher S. Polster, Eli Lilly
- In Situ Monitoring and Characterization of Liquid-Liquid Phase Separation During Solution Crystallization of Vanillin - Hongxun Hao,School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
- An Integrated Process Analytical Technology (PAT) Approach to Examine the Effect of Temperature On Nucleation Kinetics of a Dynamic Pharmaceutical Co-Precipitation Process – Huiquan Wu, FDA
- Characterizing the Formation of Inverse Solubility Salt Precipitates in Cell Culture Media and Mitigation Strategies During Thermal Treatment for Viral Inactivation – Prince Bhebe, Cell Science and Technology, Amgen
- Application of Process Analytical Technologies (PAT) to Monitor a Continuous Crystallization - Eleftherios Kougoulos, Novan Inc
- Development of an Empirical Framework for Monitoring CSD Using FBRM® in Batch Crystallization – Huayu Li, School of Chemical & Biomolecular Engineering, Georgia Institute of Technology
- Crystallization Kinetics Identification within a Generic Modeling Framework - Kresten Troelstrup Meisler, CAPEC, Department of Chemical and Biochemical Engineering, Technical University of Denmark (DTU)
- Determination of Crystal Growth Rates for Solids Growing From Multiple-Conformers Solutions and Evidence of Growth Inhibition by the Wrong Conformer – Chandrasekar Sivakumar, Chemical Engineering, Carnegie Mellon University – co-authors Bristol-Myers Squibb
- Enabling Predictive Catalyst and Reaction Design in Asymmetric Organocatalysis (Invited) – Prof Donna G. Blackmond, Dept. of Chemistry, The Scripps Research Institute
- Streamlining Process Research Via Reaction Progress Kinetic Analysis - Prof Donna G. Blackmond, Dept. of Chemistry, The Scripps Research Institute
- PAT for Multiphase Reaction Mixtures - Jacob Albrecht,Bristol-Myers Squibb
- Apply PAT-Enabled Platform to Realize the QbD Control Strategy for Crystallization Processes – George Zhou, Merck & Co., Inc.
- Feed-Forward Dynamic Control of an API Crystallization Enabled Through PAT - Shane T. Grosser, Merck & Co., Inc.
- The Role of PAT, Condition Monitoring and Adaptive Control in Delivering QbD - Steve Hammond, Pfizer, Inc.
- In Situ Monitoring and Characterization of Liquid-Liquid Phase Separation During Solution Crystallization of Vanillin - Hongxun Hao, Tianjin University
- Mixture Component Prediction Using Iterative Optimization Technology - Koji Muteki, Pfizer Worldwide Research and Development, Groton, CT
- RAFT Polymerization of Emulsified Microemulsions - Jennifer M. O'Donnell, Iowa State University
- Morphology and Molecular Weight Control of Core-Shell Polymer Nanoparticles - Ibrahim A. El-Hedok, Iowa State University
- Design of a Microreactor for Microwave Organic Synthesis – Wen-Hsuan Lee and Klavs F. Jensen, Massachusetts Institute of Technology (MIT)
Automated Optimization, Kinetic Modeling, and Scale-up of Flow Chemistry Processes - Klavs F. Jensen, Massachusetts Institute of Technology (MIT)
- High Pressure Heterogeneous Catalysis with Continuous Flow Microreactors - Baris Ünal, Massachusetts Institute of Technology (MIT)
- Aerobic Oxidations in Flow: The Functionalization of Olefins - Ulrich Neuenschwander, Massachusetts Institute of Technology (MIT)
Microfluidic Synthesis of Electro-Catalytically Active Nanoparticles - Anand Kumar, Massachusetts Institute of Technology (MIT)
- Continuous Synthesis of Nano Structures - Klavs F. Jensen, Massachusetts Institute of Technology (MIT)
- Microfluidic Cell Deformation As a Robust, Vector-Free Method for Cytosolic Delivery of Macromolecules - Armon Sharei, Massachusetts Institute of Technology (MIT)
- Making PAT an Integral and Sustained Part of Manufacturing Operations - John O'Reilly, Roche
- Application of PAT in a Late-Phase R&D Pilot Plant - Sean Sisk, GlaxoSmithKline (GSK) Cork