Diffraction system for biological crystal screening

• US 6,836,532 B2
• Filed: 04/09/2002
• Issued: 12/28/2004
• Est. Priority Date: 06/29/2001
• Status: Active Grant

• Current Assignee: Bruker AXS Incorporated (Bruker Corporation)
• Original Assignee: Bruker AXS Incorporated (Bruker Corporation)
• Inventors: Durst, Roger D., He, Bob Baoping
• Primary Examiner(s): Glick, Edward J.
• Assistant Examiner(s): Ho, Allen C.
• Application Number:
  US10/118,981
• Publication Number:
  US 20030147496A1
• Time in Patent Office: 994 Days
• Field of Search: 378/71, 378/73, 378/76, 378/79, 378/80, 378/208, 117/14, 117/68, 117/69, 117/84, 117/85, 117/201, 117/206, 117/901
• US Class Current: 378/73
• 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: G01N 23/207 Diffractometry using detectors, e.g. using a probe in a central position and one or more displaceable detectors in circumferential positions
• CPC Class Codes: Y10T 117/1004 with means for measuring, testing, or sensing
• CPC Class Codes: Y10T 117/1024 for crystallization from liquid or supercritical state

Abstract

A biological crystal formation screening apparatus uses an x-ray diffraction technique to analyze the sample containers of a sample tray for the presence of crystal formation. An x-ray source is directed toward a sample under investigation, and a two-dimensional x-ray detector is located to receive any diffracted x-ray energy. A positioning apparatus allows the different sample containers of a tray to be sequentially aligned with the source and detector, allowing each to be examined. The sample container is arranged such that a sample is located relative to the well solution so that the x-ray beam is directed to the sample without being incident on the well solution.

Claims

1. A sample container for containing a sample during monitoring of crystal formation in a crystal growth medium by transmission of x-ray energy from an x-ray source on a first side of the container to he sample, presence of crystalline material resulting in diffraction of the x-ray energy toward a detector located on a second side of the container opposite the first side, the sample container comprising:

a reservoir region within the container in which a well solution may be located for inducing evaporation of a liquid portion of the sample by vapor diffusion; and

a platform within the container upon which the sample resides during monitoring under the force of gravity, wherein the reservoir region and the platform are arranged such that a beam of said x-ray energy travels from the x-ray source through the platform to the sample location without being incident on the well solution, the platform being physically separated from the first side of the container such that the x-ray beam passes through a region of the container having no solid material prior to encountering the platform.

2. A sample container according to claim 1 herein a dimension of the platform perpendicular to a primary direction of travel of the x-ray energy is smaller within a portion of the platform through which a maximum amount of x-ray energy passes than in surrounding portions of the platform.

3. A sample container according to claim 1 wherein a surface of the platform upon which the sample resides is concave.

4. A sample container according to claim 1 wherein the platform comprises primarily amorphous material.

5. A sample container for containing a sample during monitoring of crystal formation in a crystal growth medium by transmission of x-ray energy from an x-ray source on a first side of the container to the sample, presence of crystalline material resulting in diffraction of the x-ray energy toward a detector located on a second side of the container opposite the first side, the sample container comprising:

a reservoir region within the container in which a well solution may be located for inducing evaporation of a liquid portion of the sample by vapor diffusion; and

a sample location within the container in which the sample is retained during monitoring, wherein the reservoir region and the sample location are arranged such that a beam of said x-ray energy travels from the x-ray source to the sample location without being incident on the well solution wherein the sample resides on a platform within the container under the force of gravity and a surface of the platform opposite the surface upon which the sample resides is concave.

6. A sample container for containing a sample during monitoring of crystal formation in a crystal growth medium by transmission of x-ray energy from an x-ray source on a first side of the container to the sample, presence of crystalline material resulting in diffraction of the x-ray energy toward a detector located on a second side of the container opposite the first side, the sample container comprising:

a reservoir region within the container in which a well solution may be located for inducing evaporation of a liquid portion of the sample by vapor diffusion; and

a sample location at which the sample resides on the underside of a surface within the sample container under the force of surface tension, the sample location being aligned with a hollow baffle surrounding an x-ray portion of the container through which the x-ray energy passes, the baffle segregating the well solution from the x-ray portion such that said x-ray energy travels from the x-ray source through the hollow baffle to the sample location without being incident on the well solution.

7. A screening apparatus for use in monitoring crystal formation in a liquid sample, the apparatus comprising:

an x-ray source that outputs x-ray energy that is incident on the sample and that undergoes diffraction in the presence of a crystal structure;

a sample container within which the sample may be located, the sample container including a reservoir region in which a well solution may be located for inducing evaporation of a liquid portion of the sample by vapor duffusion and a sample location within the container including a platform upon which the sample is retained during monitoring under the force of gravity, wherein the reservoir region and the sample location are arranged such that a beam of said x-ray energy travels from the x-ray source through the platform to the sample location without being incident on the well solution, the x-ray source directing x-ray energy toward a first side of the sample container and the platform being physically separated from said first side of the container such that the x-ray beam passes through a region of the container having no solid material prior to encountering the platform; and

an x-ray detector that receives x-ray energy diffracted from said crystal structure and provides a signal indicative of the presence of the crystal structure in the sample container.

8. A screening apparatus according to claim 7 further comprising a positioning apparatus for positioning the sample container relative to the x-ray source and the x-ray detector.

9. A screening apparatus according to claim 8 wherein the positioning apparatus comprises a support that is remotely movable in at least two dimensions.

10. A screening apparatus according to claim 8 wherein the sample container is a first sample container and wherein the apparatus is arranged to operate on a plurality of sample containers each representing a separate crystal growing medium.

11. A screening apparatus according to claim 10 wherein the sample containers are all part of a contiguous sample array and wherein the positioning apparatus is capable of moving the sample array so as to sequentially position the sample containers relative to the x-ray source and x-ray detector to allow sequential examination of the sample containers.

12. A method of monitoring of crystal formation in a crystal growth medium by transmission of x-ray energy from an x-ray source to a sample under test, presence of crystalline material in the sample resulting in diffraction of the x-ray energy toward a detector located on a second side of the container opposite the first side, the method comprising:

providing a sample container having a reservoir region in which a well solution may be located that is capable of inducing evaporation of a liquid portion of the sample by vapor diffusion; and

locating a sample on a platform within the container such that the platform and reservoir are arranged so that a beam of said x-ray energy travels from the x-ray source through the platform to the sample without being incident on the well solution, the platform being physically separated from the first side of the container such that the x-ray beam passes through a region of the container having no solid material prior to encountering the platform.

13. A method according to claim 12 wherein dimension of the platform perpendicular to a primary direction of travel of the x-ray energy is smaller within a portion of the platform through which a maximum amount of x-ray energy passes than in surrounding portions of the platform.

14. A method according to claim 12 wherein surface of the platform upon which the sample resides is concave.

15. A method according to claim 12 wherein the platform comprises primarily amorphous material.

16. A method of monitoring of crystal formation in a crystal growth medium by transmission of x-ray energy from an x-ray source to a sample under test, presence of crystalline material in the sample resulting in diffraction of the x-ray energy toward a detector located on a second side of the container opposite the first side, the method comprising:

providing a sample container having a reservoir region in which a well solution may be located that is capable of inducing evaporation of a liquid portion of the sample by vapor diffusion; and

locating a sample at a sample location within the container such that the sample location and reservoir are arranged so that a beam of said x-ray energy travels from the x-ray source to the sample location without being incident on the well solution wherein the sample resides on a platform within the container under the force of gravity and a surface of the platform opposite the surface upon which the sample resides is concave.

17. A method of monitoring crystal formation in a crystal growth medium by transmission of x-ray energy from an x-ray source to a sample under test, presence of crystalline material in the sample resulting in diffraction of the x-ray energy toward a detector located on a second side of the container opposite the first side, the method comprising:

providing a sample container having a reservoir region in which a well solution may be located that is capable of inducing evaporation of a liquid portion of the sample by vapor diffusion; and

locating the sample at a sample location on the underside of a surface within the sample container under the force of surface tension, the sample location being aligned with a hollow baffle surrounding an x-ray portion of the container through which the x-ray energy passes, the baffle segregating the well solution from the x-ray portion such that said x-ray energy travels from the x-ray source through the hollow baffle to the sample location without being incident on the well solution.

18. A screening apparatus for use in monitoring crystal formation in a liquid sample, the apparatus comprising:

an x-ray source that outputs x-ray energy that is incident of the sample and that undergoes diffraction in the presence of a crystal structure;

a sample container within which the sample may be located,the sample container including a reservoir region in which a well solution may be located for inducing evaporation of a liquid portion of the sample by vapor diffusion and a sample location within the container on the underside of a surface at which the sample is retained under the force of surface tension, the sample location being aligned with a hollow baffle surrounding an x-ray portion of the container through which the x-ray energy passes, the baffle segregating the well solution from the x-ray portion such that said x-ray energy travels from the x-ray source through the hollow baffle to the sample location without being incident on the well solution; and

an x-ray detector that receives x-ray energy diffracted from said crystal structure and provides a signal indicative of the presence of the crystal structure in the sample container.

19. A screening apparatus according to claim 18 further comprising a positioning apparatus for positioning the sample container relative to the x-ray source and the x-ray detector.

20. A screening apparatus according to claim 19 wherein the positioning apparatus comprises a support that is remotely movable in at least two dimensions.

21. A screening apparatus according to claim 19 wherein the sample container is a first sample container and wherein the apparatus is arranged to operate on a plurality of sample containers each representing a separate crystal growing medium.

22. A screening apparatus according to claim 21 wherein the sample containers are all part of a contiguous sample array and wherein the positioning apparatus is capable of moving the sample array so as to sequentially position the sample containers relative to the x-ray source and x-ray detector to allow sequential examination of the sample containers.