is big < 100 ms is immediate > 1 min is slow factor 100: 100 ms to 1 ms: not impressive 17 h to 10 min: makes a difference 10 min to 6 s: very impressive
• composed of – synthesis of new compound – isolation, characterisation – bioassay • a significant effort in pharmaceutical industry, involving new technologies
volume of the vessel Easy up-scale / down scale Up-scale / down-scale difficult [scaling laws!] Fluid handling inherently there Robotics, valve switching or manual Interfacing of components easy: volume flow rate is the only parameter Interfacing of components may need wait times / dummy loops Different reaction times needed can be achieved by difference in length / cross-section The slowest step in the sequence defines the rhythm of switching, if multiple samples have to be processed
without changing the channel hardware Good flexibility in change of timing Not all analysis / synthesis methods are available All analysis / synthesis methods available Band broadening is critical, if different samples should travel through the system in sequence Different samples = separate batches Problem: to create a sequence of samples is a batch process!!!
green x x x x x x x x x x x x x double stranded DNA SYBR green x x x x x x x x x x x x x x x x x x x x x x x x SYBR green complex [fluorescing] x x x x 1) 2) 3)
A meets a molecule B and reacts to give AB • many reactions are diffusion controlled • reaction time of hours in conventional lab • reaction time of 30 min in micro well plate
and DuPont, Wilmington], chemical performance and high temperature characterization of micromachined chemical reactors, Transducers 97, Vol.1,p163-166 (1997) Figure 1: Schematic diagram of the microreactor [9] with Pt heaters and temperature sensors represented as electrical resistors.
phosphonium brom ide p-nitrobenza ldehyde colourless NaOMe NO2 Me OH colourless P(Ph)3 + + Wittig reaction N + O O Cl Cl Cl Cl O O Cl Cl Cl N Enamine Chloranil blue 2,3,5-trichlor-6-(2-piperidin -1-yl)-[1,4]- benzoquinone Synthesis of a substituted aminovinyl-p-quinone SYNTHESIS
Real-time optimisation Solution-phase synthesis Well-defined On-line purification... Serial or parallel Solid-Phase Off-line analysis Workup process Off-line identification Off-line optimisation Solid-supported synthesis Physical Handling Ease of purification Parallel (split/pool) Batch Microfluidic Influence of support on chemistry Additional steps required No support No additional steps
UK European Commission, B Schlumberger, UK Casect, UK Agilent, D Forensic Lab, UK Asahi Kasei, Japan Lab of the Government Chemist, UK CSEM, Switzerland Amersham Pharmacia, UK Kodak, UK Glaxo Wellcome, UK Glaxo-Wellcome Heidelberg Instruments Hybaid MICROFABRICATION Alberta Microelectronics Centre, Canada Caliper Technologies, California MESA, University of Twente, The Netherlands CSEM, Switzerland