Automation for Combinatorial Chemistry and Parallel ... · -Automation-for Combinatorial Chemistry...
Transcript of Automation for Combinatorial Chemistry and Parallel ... · -Automation-for Combinatorial Chemistry...
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-Automation-for Combinatorial Chemistry and Parallel Organic Synthesis
“To people creativity, to machines routine”accelab
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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)
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prepare reaction
automated weighingnot profitable for “normal” smaller laboratories;more industrial applications:e.g. “ContiWeigher” (accelab)weighs up to 7000 samples a day
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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
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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
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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)
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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
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reaction blocks:
“MiniBlock” (Mettler Toledo) “Carousel” Reaction Station (Radleys)
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semiautomated systems:parallelization of reaction conditionsexample: “MiniMapper”
automated transfer of reagents and solventsinert atmosphereparallel heating/coolingparallel reflux conditionsparallel stirring
“MiniMapper” Synthesis Module (Mettler Toledo)
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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.
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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)
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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)
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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)
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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)
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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
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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