Method for screening crystallization conditions in solution crystal growth

• US 7,247,490 B2
• Filed: 05/30/2002
• Issued: 07/24/2007
• Est. Priority Date: 04/06/1999
• Status: Expired due to Fees

• Current Assignee: UAB Research Foundation (University of Alabama System)
• Original Assignee: UAB Research Foundation (University of Alabama System)
• Inventors: DeLucas, Lawrence James
• Primary Examiner(s): Cole; Monique T.
• Application Number:
  US10/161,141
• Publication Number:
  US 20030022384A1
• Time in Patent Office: 1,881 Days
• Field of Search: 436/86
• US Class Current: 436/86
• CPC Class Codes: B01D 9/0063 Control or regulation control per se G05
• CPC Class Codes: B01D 9/0072 Crystallisation in microfluidic devices
• CPC Class Codes: B01D 9/0077 Screening for crystallisation conditions or for crystal forms
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00756 Compositions, e.g. coatings, crystals, formulations
• CPC Class Codes: B01L 2300/041 Connecting closures to device or container
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 3/06 Crystallising dishes
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: C30B 29/58 Macromolecular compounds
• CPC Class Codes: C30B 7/00 Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 50/08 : Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 33/00 : Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
• CPC Class Codes: G01N 33/68 : involving proteins, peptides or amino acids involving lipoproteins G01N33/92

Abstract

A method of screening protein crystal growth conditions with picogram to microgram amounts of protein in picoliter or nanoliter volumes is provided. A preferred method comprises a microarray with a plurality of micro-chambers in the microarray. A protein solution is placed into the micro-chambers by an automated dispensing mechanism. The protein crystal growth conditions of each of the micro-chambers is adjusted so that the protein crystal growth conditions in at least two of the micro-chambers differs. Crystallization of the protein solution in the micro-chambers is effected. Protein crystal growth in the micro-chambers is then observed.

Claims

1. A method for determining crystallization conditions for a protein, the method comprising:

delivering material to micro-chambers connected by micro-channels within a micro-array to form a plurality of different crystallization samples, the plurality of different crystallization samples comprising a protein to be crystallized and crystallization conditions which vary among the plurality of different crystallization samples;

allowing crystals of the protein to form in the plurality of crystallization samples within the microfluidic device; and

,

identifying which of the plurality of crystallization samples within the microfluidic device comprise a precipitate or a crystal of the protein.

2. A method for determining crystallization conditions for a protein, the method comprising:

within a microfluidic device, delivering material to an enclosed microchamber via means for transmitting a fluid to the microchamber from an external source to form a plurality of different crystallization samples,

the plurality of different crystallization samples comprising a protein to be crystallized and crystallization conditions which vary among the plurality of different crystallization samples;

allowing crystals of the protein to form in the plurality of crystallization samples within the microfluidic device; and

,

identifying which of the plurality of crystallization samples within the microfluidic device comprise a precipitate or a crystal of the protein.