Upload
others
View
15
Download
0
Embed Size (px)
Citation preview
-Automation-for Combinatorial Chemistry and Parallel Organic Synthesis
“To people creativity, to machines routine”accelab
typical workflow in combinatorial synthesistypical workflow in combinatorial synthesis::
1) prepare reaction 1) prepare reaction (building blocks and reagents; appropriate (building blocks and reagents; appropriate reaction vessels)reaction vessels)
2) set up and run reaction2) set up and run reaction
3) work up reaction3) work up reaction(isolation and purification of products)(isolation and purification of products)
prepare reaction
automated weighingnot profitable for “normal” smaller laboratories;more industrial applications:e.g. “ContiWeigher” (accelab)weighs up to 7000 samples a day
reaction vesselsmicrotiter plates, filterplates and vials available in different materials (e.g. borosilicate glass, PP, PS, Teflon etc.), formats and volumes
384 well mtp vials in mtp format
filterplate with frits at the bottom: simultaneous emptying of the wells or collection of products in conjunction with appropriate collection plates can be achieved
parallel filling of vials with a multichannel pipette
pipetting robot
4 variable spacing probes deliver, aspirate, mix etc. different volumes of liquidscan fill reactors with solids (e.g. resins, powders, salts etc.)
simultaneous liquid and powder dispensing
“LIPOS” (Zinsser Analytic)
reaction blocks:solid blocks made of chemically resistant materials containing single separable reaction vessels heating/cooling, stirring, reflux, filtration, inert atmosphere and other can be parallelized
reaction blocks:
“MiniBlock” (Mettler Toledo) “Carousel” Reaction Station (Radleys)
semiautomated systems:parallelization of reaction conditionsexample: “MiniMapper”
automated transfer of reagents and solventsinert atmosphereparallel heating/coolingparallel reflux conditionsparallel stirring
“MiniMapper” Synthesis Module (Mettler Toledo)
some possibilities of semiautomated or partially automated systems:
automation/parallelization of:
pipetting, dispensing of solidsstirring, mixing(ultrasonic-) dissolvinginert atmospheretemperature, pressurerefluxing
cleavagefiltration and washingextractionevaporation, lyophilizationprecipitationdrying
and combinations.
solid-phase extractionspecial SPE-columns, cartriges or plates (pre-)filled with different sorbents automated conditioning, loading, washing and elution is possible
“VacMaster-96” (Biotage) “Carousel Work-Up Station” (Radleys)
liquid-liquid extraction
automated addition of solventsefficient mixing and dissolvingautomatic sensor-controlled boundary detectionseparation of two phasesdistribution of phases into vessels of choice
“ALLEXis” Automated Work Up and Extraction Station (Mettler Toledo, Autochem)
evaporation
vacuum centrifuges with regular heating blocks (“acrosyn98”): no problem to remove poor volatile solvents like DMF or DMSO shakers with IR-lamps (“CombiDancer”)removal of water via freeze-drying (lyophilization)
“acrosyn98” (accelab)
“CombiDancer” (Hettlab, Zinsser)
fully automated system:handles any kind of reaction vessel, e.g. 25mL glass tubes or up to nine 96-well mtps simultaneouslytransport by a robotic arm to heating/cooling/washing or parking stations (all vortex)able to run different synthesis in each reaction blockreflux under inert conditionstop filtration
“SOPHAS” Automated Synthesizer (Zinsser Analytic)
4 independent three-channel pipetting probes deliver or aspirate reagents, solvents, gas or vacuum simultaneouslyrobotic arm can pick up tools and sensors (temperature, pH etc.)easy-to-use software
literature and links:
Handbook of Combinatorial Chemistry; Nicolau, Hanko, Hartwig; Wiley-VCHCombinatorial Chemistry. A Practical Approach; Bannwarth, Felder; Wiley-VCHwww.zinsser-analytic.comwww.biotage.com
www.chemspeed.comwww.combichemlab.comwww.hp-lab.comwww.mtautochem.comwww.eppendorf.dewww.aapptec.comwww.radleys.comwww.accelab.de