Claims
- 1. A method of crystallizing a biomolecule, comprising the steps of:
flowing a biomolecule solution containing a biomolecule to be crystallized through a biomolecule channel; and dialyzing the biomolecule solution through a membrane in the biomolecule channel to form a crystal of the biomolecule.
- 2. The method of claim 1, wherein the step of dialyzing the biomolecule solution sets effectors in the protein solution to promote crystallization of the biomolecule.
- 3. The method of claim 2, wherein the effectors comprise ions exchanged through the membrane.
- 4. The method of claim 2, wherein the effectors comprise the pH of the protein solution.
- 5. The method of claim 2, wherein the effectors comprise the temperature of the protein solution.
- 6. The method of claim 2, wherein the effectors comprise detergents that are exchanged with the protein solution through the membrane.
- 7. The method of claim 1, further comprising the step of observing the crystal formation.
- 8. The method of claim 1, further comprising the step of harvesting the crystal formed during observation.
- 9. The method of claim 1, further comprising the step of freezing the crystal for x-ray diffraction.
- 10. A method of crystallizing biomolecules, comprising the steps of:
flowing a biomolecule solution containing a biomolecule to be crystallized through a biomolecule channel; and concentrating the biomolecule by removing solvent from the biomolecule solution at a concentration station formed along the biomolecule channel.
- 11. The method of claim 10, wherein the step of concentrating comprises evaporating the solvent from the biomolecule solution through an aperture formed in a sidewall of the biomolecule channel.
- 12. The method of claim 10, wherein the step of concentrating comprises filtering the biomolecule solution through a biomolecule impermeable membrane to remove the solvent from the biomolecule solution.
- 13. The method of claim 10, further comprising the step of observing the crystal formation.
- 14. The method of claim 10, further comprising the step of harvesting the crystal formed during observation.
- 15. The method of claim 10, further comprising the step of freezing the crystal for x-ray diffraction.
- 16. A method of crystallizing a biomolecule, comprising the steps of:
flowing a biomolecule solution containing a biomolecule to be crystallized through the biomolecule channel; dialyzing the biomolecule solution through a membrane to set effectors in the biomolecule solution; and concentrating the biomolecule by removing solvent from the biomolecule solution at an concentration station formed along the biomolecule channel, whereby a crystal of the biomolecule is formed in the biomolecule channel.
- 17. The method of claim 16, further comprising the step of observing the crystal formation.
- 18. The method of claim 16, further comprising the step of harvesting the crystal formed during observation.
- 19. The method of claim 16, further comprising the step of freezing the crystal for x-ray diffraction.
- 20. A system for crystallizing a biomolecule, comprising:
a substrate; a microchannel formed in the substrate for conveying a biomolecule solution containing a biomolecule to be crystallized; and a concentration substation formed in the substrate along the first microchannel for concentrating the biomolecule solution to promote crystallization of the biomolecule.
- 21. A system for crystallizing a biomolecule, comprising:
a membrane for exchanging solutes between a first chamber on a first side of the membrane and a second chamber on a second side of the membrane; a first microchannel for transmitting a biomolecule solution containing a biomolecule to be crystallized to the first chamber; a second microchannel for delivering a buffer solution to the second chamber, wherein the biomolecule solution exchanges solvents with the buffer solution to promote crystallization, and a first flow source in communication with the first microchannel for inducing a flow in the biomolecule solution.
- 22. A system for crystallizing a biomolecule, comprising:
a substrate; a first microchannel in the substrate for conveying a biomolecule solution containing a molecule to be crystallized; a second microchannel intersecting the first microchannel for conveying a buffer solution for promoting crystallization of the molecule; a recess formed in the substrate in communication with the second microchannel; a membrane for exchanging solutes between the first microchannel and the second microchannel; and a cap disposed above the membrane to define a crystallization chamber.
- 23. A microfluidic chip for crystallizing a biomolecule, comprising:
a substrate; an effector setting substation formed in the substrate for setting effectors in a biomolecule solution containing the biomolecule to be crystallized to promote crystallization of the biomolecule; a concentration substation formed in the substrate for concentrating the biomolecule solution; a detection substation formed in the substrate for detecting a crystal formed in the biomolecule solution; and a harvesting substation for removing the crystal from the microfluidic chip.
- 24. A system for crystallizing a biomolecule comprising:
a main channel through which the biomolecule solution flows; an effector setting station formed along the main channel for selective exchange of solutes of particular size between a buffer solution and the biomolecule solution to promote crystallization of the biomolecule; a concentration station formed along the main channel for controlled removal of solvent from the biomolecule solution; an observation station for observing a crystal formed in the main channel; and a crystal harvesting station for removing a formed crystal from the main channel.
- 25. A crystallization system for crystallizing a biomolecule, comprising:
a substrate, a biomolecule channel for conveying a biomolecule solution containing a biomolecule to be crystallized; and a plurality of crystallization regions formed in series along the biomolecule channel for crystallizing the biomolecule.
- 26. The system of claim 25, further comprising:
one or more condition re-setting substations between each crystallization region for re-setting conditions in the biomolecule channel after the biomolecule solution passes through each crystallization region.
- 27. The system of claim 25, further comprising:
an observation station formed along the biomolecule channel for observing crystallization of the biomolecule.
- 28. The system of claim 25, further comprising:
a harvesting station formed along the biomolecule channel for extracting a formed crystal from the channel.
- 29. A system for crystallizing a biomolecule, comprising:
a channel for conveying a crystal formed of the biomolecule; and an observation station formed along said channel for observing the crystal.
- 30. The system of claim 29, further comprising:
a harvesting station for removing the crystal from the channel.
- 31. The system of claim 30, wherein the harvesting station comprises:
an aperture formed in a sidewall of the channel; and a harvesting pin configured to be inserted into said aperture for acquiring the crystal on the pin.
- 32. The system of claim 31, wherein the harvesting pin comprises a first tip and a second tip spaced from the first tip to form a crystal acquisition region for holding the crystal.
- 33. A method of handling a crystal, comprising:
forming a crystal in a channel; removing the crystal from the channel using a harvesting device; and freezing the crystal on the harvesting device.
- 34. The method of claim 33, wherein the harvesting device comprises a first pin having a first tip and a second pin having a second tip spaced from the first tip to form a crystal acquisition region for holding the crystal.
- 35. A microfluidic system for crystallizing biomolecules, comprising:
a biomolecule channel formed in a substrate for conveying a biomolecule solution; a first crystallization region formed along the biomolecule channel for promoting crystallization of a biomolecule in the biomolecule solution; and a second crystallization region formed along the biomolecuie channel and in series with the first crystallization region for promoting crystallization of a biomolecule in the biomolecule solution.
- 36. The system of claim 35, further comprising:
a dialysis station formed between the first crystallization region and the second crystallization region for dialyzing the biomolecule solution.
- 37. A method of manufacturing a biomolecule crystallization system, comprising:
providing a substrate; forming a channel in the substrate; and providing a substation along the channel for processing a biomolecule solution in the channel.
- 38. A collective rational drug design method, comprising:
utilizing parameters derived from a family of protein crystal structures such that a drug is designed.
- 39. In a rational drug design method wherein the improvement comprises, the use of a family of protein structures.
- 40. A crystallized polypeptide having a integration ratio of less than 1:2500.
- 41. A crystallized polypeptide formed under dynamic conditions.
- 42. The crystallized polypeptide of claim 41, wherein said polypeptide is useful in structural determination.
- 43. A crystallized polypeptide formed using the method of claim 1.
- 44. The crystallized polypeptide of claim 43, wherein said crystallized polypeptide is useful in structural determination.
- 45. The crystallized polypeptide of claim 43, wherein said crystallized polypeptide is formed under static conditions.
- 46. The crystallized polypeptide of claim 43, wherein said crystallized polypeptide is formed under dynamic conditions.
RELATED APPLICATIONS
[0001] The present application claims priority to U.S. Provisional Patent Application Serial No. 60/427,620, filed Nov. 19, 2002, entitled “Microfluidic Chip for Protein Crystallization”, U.S. Provisional Patent Application Serial No. 60/409,489 filed Sep. 9, 2002, and U.S. Provisional Patent Application Serial No. 60/410,685, filed Sep. 13, 2002. The present application is related to U.S. patent application Ser. Nos. 10/028,852, 10/027,484, 10/027,516 and 10/027,171. The present application is further related to an application (Attorney Docket Number TGZ-028) entitled “Microfabricated Two-Pin System for Biomolecule Crystallization,” filed on even date herewith. The contents of each of the foregoing applications are expressly incorporated herein by reference.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60427620 |
Nov 2002 |
US |
|
60410685 |
Sep 2002 |
US |
|
60409489 |
Sep 2002 |
US |