Method for screening crystallization conditions in solution crystal growth
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 microchambers 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. For example, crystallization can be effected by a precipitate solution and/or placing an oil barrier over the protein solution. Protein crystal growth in the micro-chambers is then observed.
1. A method of screening protein crystal growth conditions comprising:
dispensing a protein solution into protein solution microchambers of a microarray and separately dispensing precipitate solutions into precipitate solution microchambers of said microarray, said microchambers having a volume from about 0.001 nl to about 500 nl;
allowing liquid-liquid communication between protein solution microchambers and precipitate solution microchambers; and
observing said microchambers for protein crystal growth or protein precipitation.
2. The method of claim 1 wherein said precipitate solution comprises a component selected from the group consisting of buffers, surface active agents, salts, alcohols, polyethylene glycol and mixtures thereof.
3. The method of claim 1 wherein said protein solution is buffered.
4. The method of claim 1 wherein said microarray comprises valves between protein solution microchambers and precipitate solution microchambers.
5. The method of claim 4 wherein said valves control and liquid-liquid communication between microchambers comprising protein solution and a microchambers comprising a precipitate solution.
6. The method of claim 5 wherein controlling protein crystal growth further comprises employing microchambers of varying dimensions.
7. The method of claim 1 wherein said precipitate solution and said protein solution are in fluid communication via micro-channels.
8. The method of claim 4 wherein said precipitate solution and said protein solution are in fluid communication via a channel.
9. The method of claim 5 wherein said allowing liquid-liquid communication of said precipitate solution microchambers and said protein solution microchambers comprises opening said valves.
10. A method of screening protein crystal growth conditions comprising:
transferring samples comprising a volume from about 0.001 nl to about 500 nl of a protein solution into microchambers in a platform;
providing a precipitate solution that is in liquid-liquid communication with the protein solution;
controlling the protein crystal growth conditions of the samples; and observing a protein precipitate or protein crystals in the microchambers.
11. The method of claim 10 wherein controlling the protein crystal growth condition comprises employing a valve disposed in a microchannel between a microchamber comprising protein solution and a microchamber comprising precipitate solution.
12. The method of claim 1 wherein said microarray comprises miniaturized active control elements between protein solution microchambers and precipitate solution microchambers.
13. The method of claim 12 wherein the platform is a microarray.
14. The method of claim 12 wherein the miniaturized active control elements are selected from the group consisting of valves, pumps, and electrodes.