Claims
- 1. A microscope having an objective lens with a restricted field of view about an optical axis for examination or treatment of a portion of an object lying at the optical axis, including a tiltable focusing member defining a support plane for the object, the focusing member being mounted to rotate about a pre-established hinge axis to position said portion of the object at the focal plane of the microscope, the hinge axis lying in a plane substantially normal to the optical axis at a distance spaced therefrom sufficient that rotation of the portion of the object at the optical axis sufficiently approximates translation along the optical axis to enable focusing, a drive mechanism for rotating the focusing member about the hinge axis effective to bring into focus said portion of the object and a mechanism for rotating the plane about an axis orthogonal to the optical axis and the hinge axis so that the object can be scanned on a line substantially in a direction parallel to the hinge axis.
- 2. The microscope of claim 1 in which the mechanism for rotating the plane about an axis orthogonal to the optical axis and the hinge axis is a device mounted to rotate about a pre-established hinge extending along an axis that is perpendicular to the hinge axis and the optical axis of the instrument.
- 3. The microscope of claim 1 in which the drive mechanism for the tiltable focusing member is a driver located outwardly along the tiltable member, more distant from its hinge than the position in which the optical axis of the microscope intersects the tiltable member, whereby a lever effect is obtained in which a given motion of the driver results in a finer movement of the portion of the object at the optical axis.
- 4. The microscope of claim 3 in which the distance of the driver from the hinge axis is greater than about twice the distance of the optical axis from the hinge axis.
- 5. The microscope of claims 1, 2 or 3 in which the position of the drive mechanism is controlled by an automated control system.
- 6. The microscope of claim 5 in which the control system includes a detector that senses the relationship of the object relative to the microscope.
- 7. The microscope of claim 6 in which the detector is an optical, capacitive or inductive position sensor that senses the height of the object.
- 8. The microscope of claim 7 in which the detector comprises a light source and a sensor arranged to determine the height of the object relative to the microscope on the basis of light reflected at an angle from the object.
- 9. The microscope of claim 6 in which the detector is a through-the-lens image analyzer constructed and arranged to enable determination of best focus position.
- 10. The microscope of claim 1 in which the pre-established hinge is defined by a flexible joint.
- 11. The microscope of claim 10 in which the flexible joint is defined by one or more planar springs or the flexible joint is defined by a thinned section of a support member.
- 12. The microscope of claims 1, 2 or 3 in which a laterally movable carrier is mounted on the tiltable focusing member, the carrier arranged to advance the object, relative to the optical axis.
- 13. The microscope of claim 12 in which the direction of advance includes motion in the direction of the radius of the tiltable focusing member.
- 14. The microscope of claim 12 in which a linear guide rail is mounted on the tiltable focusing member, the moveable carrier member movable along the guide rail, the carrier member having a planar surface for supporting a planar object, the planar surface of the carrier member being parallel to the linear guide.
- 15. The microscope of claim 12 including a driver arranged to position the carrier member under computer control.
- 16. A scanning microscope having an objective lens with a restricted field of view about an optical axis for examination of a portion of an object lying at the optical axis one picture element at a time, including a tiltable focusing member defining a support plane for the object, the focusing member being mounted to rotate about a pre-established hinge axis to position said portion of the object at the focal plane of the microscope, the hinge axis lying in a plane substantially normal to the optical axis at a distance spaced therefrom sufficient that rotation of the portion of the object sufficiently approximates translation along the optical axis to enable focusing, and a drive mechanism for rotating the member about the hinge axis effective to bring into focus said portion of the object, and a mechanism for rotating the plane about an axis orthogonal to the optical axis and the hinge axis, drive mechanism to produce relative oscillating scanning motion between the object and the objective lens in a direction transverse to the radial direction of the tiltable member and a photosensitive detector for detecting the stream of picture elements produced by the objective lens as it is scanned over the object, while the object is scanned substantially in direction parallel to the hinge axis.
- 17. The microscope of claim 16 in which the scanning microscope comprises a moving objective microscope.
- 18. The microscope of claim 17 in which the moving objective is supported upon an oscillating rotary arm that describes an arc generally centered on a radial axis of the tiltable member.
- 19. The microscope of claim 16 in which the objective has resolution of less than about 10 micron and a depth of field less than 200 micron.
- 20. The microscope of claim 1 or 16 in the form of a scanning microscope having a controller constructed to perform dynamic focus by varying the position of the drive mechanism during scanning.
- 21. The microscope of claim 20 in which the controller responds to through-the-objective image data.
- 22. The microscope of claim 21 including a system constructed to determine best focus data for an array of points during a prescan, to store this data, and to employ this data during microscopic examination of the object.
- 23. A scanning microscope having an objective lens with a restricted field of view about an optical axis for examination of an object lying at the optical axis, including a tiltable focusing member defining a support plane for the object, the focusing member being mounted to rotate about a pre-established hinge axis to position said portion of the object at the focal plane of the microscope, the hinge axis lying in a plane substantially normal to the optical axis at a distance spaced therefrom sufficient that rotation of the portion of the object sufficiently approximates translation along the optical axis to enable focusing, and a drive mechanism for rotating the member about the hinge axis, effective to bring into focus said portion of the object, and a mechanism for rotating the plane about an axis orthogonal to the optical axis and the hinge axis to enable the object to be scanned substantially in a line in a direction parallel to the hinge axis, a drive mechanism to produce relative oscillating scanning motion between the object and the objective lens in a direction transverse to the radial direction of the tiltable member, and a photosensitive detector for detecting the stream of single picture elements produced by the objective lens, the microscope constructed and arranged to scan in a direction transverse to the radial direction of the tiltable focusing member, and a laterally movable carrier mounted on the tiltable member, the carrier arranged to advance the object, relative to the optical axis, in motion in the direction of the radius of the tiltable member.
- 24. The microscope of claim 23 in which the scanning microscope comprises a moving objective microscope.
- 25. The microscope of claim 24 in which the microscope includes a flying micro-objective lens.
- 26. The microscope of claim 24 in which the moving objective is supported upon an oscillating rotary arm that describes an arc generally centered on a radial axis of the tiltable member.
- 27. The microscope of claim 1, 16 or 23 in which the depth of field of the microscope is between about 30 and 200 micron, and the drive mechanism is a driver located outwardly along the tiltable member, more distant from the hinge than the position in which the optical axis of the microscope intersects the tiltable member.
- 28. The microscope of claim 27 in which the distance of the driver from the hinge axis is greater than about twice the distance of the optical axis from the hinge axis.
- 29. A method of microscopic examination comprising providing a microscope having an objective lens with a restricted field of view about an optical axis for examination of a portion of an object lying at the optical axis, the microscope including a tiltable focusing member defining a support plane for the object, the focusing member being mounted to rotate about a pre-established hinge axis to position said portion of the object at the focal plane of the microscope, the hinge axis lying in a plane substantially normal to the optical axis at a distance spaced therefrom sufficient that rotation of the portion of the object sufficiently approximates translation along the optical axis to enable focusing, a drive mechanism for rotating the member about the hinge axis effective to bring into focus said portion of the object, and a mechanism for rotating the plane about an axis orthogonal to the optical axis and the hinge axis, enabling the object to be scanned substantially in a direction parallel to the hinge axis, and under control of an automated control system, moving the movable member to bring the portion of the object into the plane of focus of the microscope.
- 30. The method of claim 29 in which the object comprises biological material.
- 31. The method of claim 30 in which the object fluoresces and the microscope is constructed to detect such fluorescence.
- 32. The method of claim 31 in which the object comprises an ordered array of nucleotides that may fluoresce.
- 33. The method of claim 31 in which the object comprises an ordered array of oligonucleotides.
- 34. The method of claim 31 in which the object comprises an ordered array of deposits of nucleic acid fragments.
- 35. The scanning microscope of claim 23 or 25 or the method of claim 29 in which the scanning drive mechanism is a limited rotation oscillating motor operating at a substantial frequency.
- 36. The scanning mechanism of claim 35 in the form of a fluorescence detection microscope.
- 37. The method of claim 29 in which the microscope is a scanning microscope and includes a drive mechanism for rotating the focusing member about the hinge axis, effective to bring into focus said portion of the object, drive mechanism to produce relative oscillating scanning motion between the object and the objective lens in a direction transverse to the radial direction of the tiltable member and a photosensitive detector for detecting the stream of picture elements produced by the objective lens.
- 38. The method of claim 37 in which the microscope is constructed and arranged to repeatedly scan in a direction transverse to the radial direction of the tiltable member, and a laterally movable carrier mounted on the tiltable member, the carrier arranged to advance the object, relative to the optical axis, in motion in the direction of the radius of the tiltable member.
- 39. The method of performing quantified fluorescence microscopy comprising providing a microscope according to any of the claims 1, 16 or 23, calibrating the microscope with a calibrating tool having a surface layer of effective fluorophores, and subsequently scanning a slide or biochip having an array or micro array of specimens.
- 40. A microscope having an objective lens with a restricted field of view about an optical axis for examination or treatment of a portion of an object lying at the optical axis, including a tiltable focusing member defining a support plane for the object, the focusing member being mounted to rotate about a pre-established hinge axis to position said portion of the object at the focal plane of the microscope, the hinge axis lying in a plane substantially normal to the optical axis at a distance spaced therefrom sufficient that rotation of the portion of the object at the optical axis sufficiently approximates translation along the optical axis to enable focusing, a drive mechanism for rotating the focusing member about the hinge axis effective to bring into focus said portion of the object, and a mechanism for rotating the plane about an axis orthogonal to the optical axis and the hinge axis, so that the object can be scanned on a line substantially in a direction parallel to the hinge axis, the lens that rotates about an axis being mounted on an oscillating arm and the hinge axis being located outwardly beyond the lens-carrying end of the arm, further from the axis of rotation of the arm than the location of the lens.
- 41. A microscope having an objective lens with a restricted field of view about an optical axis for examination or treatment of a portion of an object lying at the optical axis, including a tiltable focusing member defining a support plane for the object, the focusing member being mounted to rotate about a pre-established hinge axis to position said portion of the object at the focal plane of the microscope, the hinge axis lying in a plane substantially normal to the optical axis at a distance spaced there from sufficient that rotation of the portion of the object at the optical axis sufficiently approximates translation along the optical axis to enable focusing, a drive mechanism for rotating the focusing member about the hinge axis effective to bring into focus said portion of the object, and a mechanism for rotating the plane about an axis orthogonal to the optical axis and the hinge axis, so that the object can be scanned on a line substantially in a direction parallel to the hinge axis, the support plane being adapted to define at least two positions in sequence along the Y axis to receive objects or modules of differing dimension.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/US99/00730 |
Jan 1999 |
WO |
|
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of co-pending application U.S. Ser. No. 09/500,626, filed Feb. 9, 2000, which is a continuation-in-part of U.S. Ser. No. 09/079,790, filed May 15, 1998, entitled ”Focusing Microscope Systems” now U.S. Pat. No. 6,262,838; continuation-in-part of U.S. Ser. No. 09/079,324, filed May 14, 1998, entitled “Depositing Fluid Specimens On Substrates, Resulting Ordered Arrays, Techniques For Analysis Of Deposited Arrays”; and continuation-in-part of U.S. Ser. No. 09/122,216, filed Jul. 24, 1998, entitled “Depositing Fluid Specimens On Substrates, Resulting Ordered Arrays, Techniques For Deposition Of Arrays” now U.S. Pat. No. 6,269,846; all of which are hereby incorporated by reference. This application also claims priority from PCT Application PCT/US99/00730 (WO99/3670) Entitled “Depositing Fluid Specimens On Substrates, Resulting Ordered Arrays, Techniques For Analysis of Deposited Arrays” incorporated by reference.
[0002] This application is also related to U.S. application Ser. No. 09/045,547, filed Mar. 20, 1998, entitled “Wide Field Of View And High Speed Scanning Microscopy,” now U.S. Pat. No. 6,201,639, U.S. application Ser. No. 09/170,847, filed Oct. 13, 1998, entitled “Wide Field Of View And High Speed Scanning Microscopy” PCT/US99/06097 (WO99/47694), entitled “Wide Field Of View And High Speed Scanning Microscopy all of which are hereby incorporated by reference.
Continuations (1)
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09500626 |
Feb 2000 |
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10172787 |
Jun 2002 |
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Continuation in Parts (2)
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09079790 |
May 1998 |
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09500626 |
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09122216 |
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10172787 |
Jun 2002 |
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