US 9,284,659 B2Granted

Device and method for monitoring crystallization

AssigneeXtal Concepts GmbH

InventorsChristian Betzel, Rolf Hilgenfeld, Dierk Hilterhaus, Thomas Klupsch, Peter Muehlig, Karsten Dierks, Arne Meyer

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Abstract

A method for crystallizing a substance dissolved in a solvent, including the following steps: introducing a solvent volume containing the substance into a chamber having a preset temperature, humidity, and gas composition, adding a predetermined volume of a precipitant to the solvent volume containing the substance, allowing the solvent to evaporate while simultaneously observing structural changes in the solvent volume containing the substance and the precipitant by means of dynamic light scattering, detecting weight changes and determining the molarities, making an association with the location in the phase diagram on the basis of the DLS measurement and the results of the molarity determination, allowing a predetermined number of crystal nuclei to form by adding solvent or adding precipitant, putting the solvent volume containing the substance and the precipitant into a metastable state by adding solvent and/or protein solution or by allowing the concentration of the dissolved substance to decrease by allowing nucleation cores to form, maintaining the metastable state by adding a predetermined amount of the substance to the solvent volume containing the substance and the precipitant or allowing the solvent to evaporate until at least one crystal of a predetermined size is formed.

Claims7

Dependent claims

A method for crystallization of a substance dissolved in a solvent, comprising the steps:

introducing a substance-containing solvent volume into a chamber with a constant temperature, humidity and gas composition,
adding a predetermined volume of a precipitant to the substance-containing solvent volume,
allowing the solvent to evaporate and at the same time observing structural changes in the substance- and precipitant-containing solvent volume by means of dynamic light scattering using an optical device with sub-microscopic resolution to determine the molecular size distribution of the substance being crystallized, detecting changes in weight and determining the molarities,
mapping to the location in a phase diagram on the basis of the dynamic light scattering measurements and the results of determination of molarities,
forming a number of crystallization nuclei by adding solvent or by adding precipitant,
transitioning of substance- and precipitant-containing solvent volume to a metastable condition by addition of solvent and/or protein solution or by allowing reduction of concentration of the dissolved substance by formation of nucleation seeds, and
maintaining the metastable condition by addition of an amount of the substance to the substance- and precipitant-containing solvent volume or allowing evaporation of the solvent until at least one crystal of a predetermined size is formed.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/806,149Filed 30 Jun 2011
Priority: DE 10 2010 025 8421 Jul 2010
Published: US 2013/0139749 A16 Jun 2013
Granted: 15 Mar 2016
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C30B 7/02
Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions: by evaporation of the solvent
C30B 7/00
Single-crystal growth from solutions using solvents which are liquid at normal temperature
C30B 7/08
Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions: by cooling of the solution
C30B 29/54
Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape: organic compounds