Automated sample analysis system and method

• US 7,596,251 B2
• Filed: 01/30/2004
• Issued: 09/29/2009
• Est. Priority Date: 01/31/2003
• Status: Active Grant

• Current Assignee: NEXUS Biosystems, Inc. (Azenta, Inc.)
• Original Assignee: NEXUS Biosystems, Inc. (Azenta, Inc.)
• Inventors: Neeper, Robert K., Levin, Robert K., Bodnar, Mike, Affleck, Rhett L., Lillig, John E.
• Primary Examiner(s): Strege; John B
• Application Number:
  US10/769,462
• Publication Number:
  US 20040256963A1
• Time in Patent Office: 2,069 Days
• Field of Search: 382/128, 382/153, 312/209, 312/236, 312/294, 312/319.5
• US Class Current: 382/128
• CPC Class Codes: B01L 9/523 for multisample carriers, e.g. used for 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: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 2001/4027 evaporation leaving a concentrated sample
• CPC Class Codes: G01N 2015/1493 Particle size
• CPC Class Codes: G01N 2035/00356 Holding samples at elevated temperature (incubation)
• CPC Class Codes: G01N 2035/00455 Controlling humidity in analyser
• CPC Class Codes: G01N 2035/00881 network configurations
• CPC Class Codes: G01N 2035/042 moved independently, e.g. by fork manipulator
• CPC Class Codes: G01N 2035/0425 Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 2035/0463 in incubators
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G02B 21/0016 Technical microscopes, e.g. for inspection or measuring in industrial production processes

Abstract

An automated biological sample analysis system and method for use in incubating and analyzing multiple samples for protein crystallization. A temperature controlled cabinet houses sample storage, sample transport, and sample imaging systems. The operation of the system is automated and can be controlled by software, which can be reconfigured remotely. An array of storage shelves includes multiple shelf columns arranged around a core. Multiple banks of removable shelves arranged as magazines are accessed through a door on the cabinet. Each shelf stores a multi-well plate and different sizes can be stored in different shelves. The core houses a sample transport system that includes a multi-axis robot that rotates about a vertical axis to access the shelves in the shelf array. The transport system retrieves and replaces the multi-well plates in the shelves and can move plates from the shelves to an imaging system where each sample can be automatically imaged.

Claims

1. An automated multi-well plate imaging system comprising:

a cabinet configured to selectively provide a stabilized temperature within an interior of the cabinet;

a plurality of stationary shelves within the interior of the cabinet, each shelf configured to store a multi-well plate, wherein the plurality of stationary shelves is arranged in a plurality of shelf columns to define an at least partially enclosed center, the plurality of shelf columns comprising full shelf columns and at least one partial shelf column, wherein the at least one partial shelf column is configured to accept a removable magazine comprising a plurality of shelves;

a transport assembly disposed within the at least partially enclosed center so that the plurality of shelf columns at least partially surrounds the transport assembly, the transport assembly having an elevator assembly and a plate handler configured to retrieve the multi-well plate from one of the plurality of shelves, remove the multi-well plate from the shelf, and transport the multi-well plate from the shelf to a destination outside of the core; and

an optical assembly disposed within the cabinet, outside of the at least partially enclosed center, the optical assembly having a sample mount which is the destination that receives the multi-well plate from the transport assembly, and an imaging device which images at least a portion of the multi-well plate when the multi-well plate is positioned on the sample mount.

2. The system of claim 1, further comprising a filter plate that is moved by the transport assembly to a location between the multi-well plate and an imaging device at the optical assembly.

3. The system of claim 2, wherein the filter plate comprises a polarization filter.

4. The system of claim 1, further comprising a plate adapter that is moveable by the transport assembly to the sample mount at the optical assembly, the plate adapter being configured to hold a small multi-well plate having smaller dimensions than the multi-well plate.

5. The system of claim 1, further comprising a plate tray configured to house one or more multi-well plates.

6. The system of claim 1, further comprising:

a door attached to a front of the cabinet and configured to provide access to the interior of the cabinet; and

a plate access door attached to the front of the cabinet and configured to provide access to a selected multi-well plate.

7. The system of claim 6, wherein the transport assembly retrieves the selected multi-well plate from one of the plurality of shelves and transports the selected multi-well plate to the plate access door.

8. The system of claim 1, further comprising a plurality of removable shelves configured to be selectively attached to the interior of the cabinet and configured to store the multi-well plate, and wherein the transport assembly is further configured to retrieve the multi-well plate from the plurality of removable shelves.

9. The system of claim 1, further comprising:

a thermal regulation unit configured to maintain the stabilized temperature within the interior of the cabinet; and

an isolation assembly connected to the thermal regulation unit and the cabinet and configured to substantially mechanically isolate the thermal regulation unit from the cabinet during an operating period and mechanically locate the thermal regulation unit to the cabinet during a cabinet transport period.

10. The system of claim 1, wherein the plurality of stationary shelves is arranged in an arc.

11. The system of claim 1, further comprising a second plate handler connected to the elevator assembly and configured to retrieve a second multi-well plate, wherein the elevator assembly is configured to move the first and second plate handlers at least up and down in order to retrieve multi-well plates.

12. The system of claim 1, wherein the optical assembly further comprises:

a lens attached to a movable mount, wherein the movable mount is configured to selectively move the lens in a first direction and in a second direction perpendicular to the first direction;

wherein the imaging device is coupled to the lens and configured to automatically capture an image of at least a portion of the multi-well plate using the lens, wherein selective movement of the lens in the first direction and the second direction allows movement of the lens so that the imaging device may capture images of substantially any portion of the multi-well plate.

13. The system of claim 12, wherein the optical assembly further comprises:

an optical axis extending from the lens of the imaging device to an area of interest on the multi-well plate;

a first light source positioned away from the optical axis by a first distance so that light emitted from the first light source that is incident on the area of interest on the multi-well plate is off-axis from the optical axis;

a second light source positioned away from the optical axis by a second distance, the second light source positioned substantially opposite the optical axis from the first light source.

14. The system of claim 13, wherein the area of interest on the multi-well plate includes at least a portion of a well.

15. The system of claim 1, wherein each shelf of the plurality of shelves comprises:

a support surface having a recess to provide access to at least a portion of a bottom of a multi-well plate positioned on the shelf;

a first pair of rails secured on the support surface which directly engage and support a first multi-well plate having a first outline.

16. The system of claim 15, wherein the first pair of rails comprise outer walls on opposite sides of the support surface.

17. The system of claim 15, further comprising a second pair of rails on the support surface which directly engage and support a second multi-well plate having a second outline, the second pair of rails having a different height above the support surface from the first pair of rails.

18. The system of claim 15, further comprising first and second side surfaces having mounting guides configured to align a first shelf with a second shelf along a vertical axis.

19. The system of claim 15, further comprising:

a side surface; and

a tab extending from the side surface and configured to cooperate with a sensor to provide information relating to a position relative to the support surface.

20. The system of claim 1, further comprising:

a compressor assembly associated with the cabinet and movable from a first position in which the compressor assembly is mounted to the cabinet and a second position in which the compressor assembly is seated on a floor or other support surface and is separate from and not mounted to the cabinet, whereby vibration isolation is provided between the cabinet and the compressor assembly in the second position of the compressor assembly.

21. The system of claim 1, wherein

the transport assembly includes a first receptacle and a second receptacle, each receptacle adapted to receive a multi-well plate, and further comprising:

a controller linked to the transport assembly, including a computer readable medium having stored thereon one or more sequences of instructions which control the operation of the transport assembly such that while a first multi-well plate is in the sample mount, the transport assembly retrieves a second multi-well plate into the second receptacle, and then moves the first multi-well plate from the sample mount into the first receptacle and moves the second multi-well plate into the sample mount prior to returning the first multi-well plate into the storage area and retrieving a third multi-well plate.

22. The system of claim 15, wherein the first pair of rails support the first multi-well plate at a location spaced above the support surface and have upper, plate engaging sliding surfaces which slidably engage the first multi-well plate and allow sliding movement of the first multi-well plate onto and off the shelf.

23. The system of claim 1, wherein the plurality of shelf columns comprises full shelf columns and at least one partial shelf column, and wherein the at least one partial shelf column is configured to provide a passage between the at least partially enclosed area and the optical assembly disposed outside of the at least partially enclosed area.

24. The system of claim 1, further comprising a door attached to a front of the cabinet and configured to provide access to the interior of the cabinet for removal or insertion of the removable magazine.

25. An automated multi-well plate imaging system comprising:

a cabinet configured to selectively provide a stabilized temperature within an interior of the cabinet;

a plurality of stationary shelves within the interior of the cabinet, each shelf configured to store a multi-well plate, wherein the plurality of stationary shelves is arranged in a plurality of shelf columns to define an at least partially enclosed center, the plurality of shelf columns comprising full shelf columns and one or more partial shelf columns, wherein at least one partial shelf column is configured to provide a passage between the at least partially enclosed area and the optical assembly disposed outside of the at least partially enclosed area;

a transport assembly disposed within the at least partially enclosed center so that the plurality of shelf columns at least partially surrounds the transport assembly, the transport assembly having an elevator assembly and a plate handler configured to retrieve the multi-well plate from one of the plurality of shelves, remove the multi-well plate from the shelf, and transport the multi-well plate from the shelf to a destination outside of the core; and

an optical assembly disposed within the cabinet, outside of the at least partially enclosed center, the optical assembly having a sample mount which is the destination that receives the multi-well plate from the transport assembly, and an imaging device which images at least a portion of the multi-well plate when the multi-well plate is positioned on the sample mount.

26. The system of claim 25, wherein the one or more partial shelf column comprises at least one second partial shelf column configured to accept a removable magazine comprising a plurality of shelves.

27. The system of claim 26, further comprising a door attached to a front of the cabinet and configured to provide access to the interior of the cabinet for removal or insertion of the removable magazine.

28. The system of claim 25, further comprising a plate adapter that is moveable by the transport assembly to the sample mount at the optical assembly, the plate adapter being configured to hold a small multi-well plate having smaller dimensions than the multi-well plate.

29. The system of claim 25, further comprising a plate tray configured to house one or more multi-well plates.

30. The system of claim 25, further comprising:

a door attached to a front of the cabinet and configured to provide access to the interior of the cabinet; and

a plate access door attached to the front of the cabinet and configured to provide access to a selected multi-well plate.

31. The system of claim 30, wherein the transport assembly retrieves the selected multi-well plate from one of the plurality of shelves and transports the selected multi-well plate to the plate access door.

32. The system of claim 25, further comprising a plurality of removable shelves configured to be selectively attached to the interior of the cabinet and configured to store the multi-well plate, and wherein the transport assembly is further configured to retrieve the multi-well plate from the plurality of removable shelves.

33. The system of claim 25, further comprising:

a thermal regulation unit configured to maintain the stabilized temperature within the interior of the cabinet; and

an isolation assembly connected to the thermal regulation unit and the cabinet and configured to substantially mechanically isolate the thermal regulation unit from the cabinet during an operating period and mechanically locate the thermal regulation unit to the cabinet during a cabinet transport period.

34. The system of claim 25, wherein the plurality of stationary shelves is arranged in an arc.

35. The system of claim 25, wherein the optical assembly further comprises:

a lens attached to a movable mount, wherein the movable mount is configured to selectively move the lens in a first direction and in a second direction perpendicular to the first direction;

wherein the imaging device is coupled to the lens and configured to automatically capture an image of at least a portion of the multi-well plate using the lens, wherein selective movement of the lens in the first direction and the second direction allows movement of the lens so that the imaging device may capture images of substantially any portion of the multi-well plate.

36. The system of claim 35, wherein the optical assembly further comprises:

an optical axis extending from the lens of the imaging device to an area of interest on the multi-well plate;

a first light source positioned away from the optical axis by a first distance so that light emitted from the first light source that is incident on the area of interest on the multi-well plate is off-axis from the optical axis;

a second light source positioned away from the optical axis by a second distance, the second light source positioned substantially opposite the optical axis from the first light source.

37. The system of claim 25, wherein each shelf of the plurality of shelves comprises:

a support surface having a recess to provide access to at least a portion of a bottom of a multi-well plate positioned on the shelf;

a first pair of rails secured on the support surface which directly engage and support a first multi-well plate having a first outline.

38. The system of claim 37, wherein the first pair of rails comprise outer walls on opposite sides of the support surface.

39. The system of claim 37, further comprising a second pair of rails on the support surface which directly engage and support a second multi-well plate having a second outline, the second pair of rails having a different height above the support surface from the first pair of rails.

40. The system of claim 37, further comprising first and second side surfaces having mounting guides configured to align a first shelf with a second shelf along a vertical axis.

41. The system of claim 37, further comprising:

a side surface; and

a tab extending from the side surface and configured to cooperate with a sensor to provide information relating to a position relative to the support surface.

42. The system of claim 25, further comprising:

a compressor assembly associated with the cabinet and movable from a first position in which the compressor assembly is mounted to the cabinet and a second position in which the compressor assembly is seated on a floor or other support surface and is separate from and not mounted to the cabinet, whereby vibration isolation is provided between the cabinet and the compressor assembly in the second position of the compressor assembly.

43. The system of claim 25, wherein

the transport assembly includes a first receptacle and a second receptacle, each receptacle adapted to receive a multi-well plate, and further comprising:

a controller linked to the transport assembly, including a computer readable medium having stored thereon one or more sequences of instructions which control the operation of the transport assembly such that while a first multi-well plate is in the sample mount, the transport assembly retrieves a second multi-well plate into the second receptacle, and then moves the first multi-well plate from the sample mount into the first receptacle and moves the second multi-well plate into the sample mount prior to returning the first multi-well plate into the storage area and retrieving a third multi-well plate.