Method for screening microcrystallizations for crystal formation

Abstract

A method is provided for performing array microcrystallizations to determine suitable crystallization conditions for a molecule, the method comprising: forming an array of microcrystallizations, each microcrystallization comprising a drop comprising a mother liquor solution whose composition varies within the array and a molecule to be crystallized, the drop having a volume of less than 1 microliter; storing the array of microcrystallizations under conditions suitable for molecule crystals to form in the drops in the array; and detecting molecule crystal formation in the drops by taking images of the drops.

1 - 56 . (canceled) 
     
     
         57 . An apparatus for setting up protein crystallization experiments in a protein crystallization plate comprising at least 48 protein crystallization experiment regions, each protein crystallization experiment region comprising a well for housing a mother liquor solution and an adjacent drop region capable of being placed in vapor diffusion communication with the well, the apparatus comprising:
 a mother liquor station moveable relative to the protein crystallization plate and capable of removing mother liquor from at least four different wells of the protein crystallization plate at the same time and delivering aliquots of the removed mother liquor to at least four different drop regions at the same time;   a protein station moveable relative to the protein crystallization plate and capable of delivering an aliquot of solution containing a protein to be crystallized to the drop regions of the protein crystallization plate; and   process control logic for controlling the movements and operations of the mother liquor station and the protein station such that, in either order   the mother liquor station delivers aliquots of mother liquor to at least four different drop regions at the same time,   the protein station delivers aliquots of protein to drop regions,   wherein   the process control logic is capable of forming protein crystallization volumes for wells of the protein crystallization plate in that delivered aliquots of mother liquor and delivered aliquots of protein combine to form protein crystallization volumes and each resulting protein crystallization volume is adjacent to the well of the protein crystallization plate from which the mother liquor contained in the protein crystallization volume was removed.   
     
     
         58 . The apparatus according to  claim 57  wherein the mother liquor station is capable of removing mother liquor from at least eight different wells of the protein crystallization plate at the same time and delivering aliquots of mother liquor to at least eight different drop regions at the same time. 
     
     
         59 . The apparatus according to  claim 57  wherein the protein crystallization plate is a hanging drop protein crystallization plate and each drop region is a cover slip which the apparatus positions over a well of the hanging drop protein crystallization plate. 
     
     
         60 . The apparatus according to  claim 57  wherein the protein crystallization plate is a sitting drop protein crystallization plate and the drop region is a sitting drop region adjacent a well of the sitting drop protein crystallization plate. 
     
     
         61 . The apparatus according to  claim 57  wherein the control logic causes the combined volume of mother liquor and protein solution delivered by the apparatus to at least one of the drop regions to be less than 1 microliter. 
     
     
         62 . The apparatus according to  claim 57  wherein the mother liquor drop station and the protein drop station are each capable of delivering submicroliter volumes within a volume range of less than about 25 nL. 
     
     
         63 . The apparatus according to  claim 57  wherein the mother liquor drop station and the protein drop station are each capable of delivering submicroliter volumes within a volume range of less than about 20 nL. 
     
     
         64 . The apparatus according to  claim 57  wherein the mother liquor drop station and the protein drop station are each capable of delivering submicroliter volumes within a volume range of less than about 15 nL.