ESR 3 - Cascading chemo-enzymatic reaction steps with in-line process monitoring on a microfluidic scale

Host: UCL; Supervisors: Nicolas Szita, Frank Baganz

Objectives
  • Fabricate microfluidic plug and play assembly for enzymatic and chemical reactions
  • Develop a modular interface for chemo-enzymatic reaction and define integration issues between the chemical and enzymatic conversions for a 2-step process.
  • Establish integrated optimal chemo-enzymatic integration strategies which may require multi-phase microfluidics, novel catalyst immobilisation strategies, and perform microfluidic cycloadditions (e.g. Diels-Alder) + TK reaction with selected analogues.
  • Develop microfluidic reactors with advanced sensor technology for process monitoring
  • Define design criteria for the developed modular chemo-enzymatic microfluidic assemblies
  • Perform compound characterisations and integrate with / develop analytical systems to monitor reaction progress
  • Investigate extension of plug and play assembly to downstream/separation methods
Tasks and methodology
  • Investigate different modular microfluidic assemblies, related micro fabrication methods, and develop a platform technology for reactor fabrication
  • Together with TUG, investigate integration of novel optical sensors, both for in-depth understanding of reaction progress in closed channels, and for process output control
  • Together with UL investigate suitability of multi-phase systems
  • Establish microfluidic baseline data for chemical and enzymatic reactions with a model D-A and TK systems; reaction parameters for use in the individual microreactors (temperature, residence time, solvent usage) will be established to achieve maximum conversion and purity; benchmark against batch/bench-scale reactions (in collaboration with CerCell)
  • Integrate established optical sensor technology to determine process parameters and UV-based  substrate/product detection
  • Analyse design parameters and variations
  • Integrate all components on single modular platform
Results
  • Microfluidic platform for chemical and enzymatic reactions, amenable for different immobilization methods
  • Microbioreactors with integrated optical sensors and IR probes for the application in biocatalytic screening toolbox (WP6)  and biocatalysis (WP7)
  • Evaluation of immobilization methods suitable for a wide range of biocatalysts and for multi-enzyme and chemo-enzymatic process conditions completed.