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US 8,175,452 B1Granted
Method and system for imaging high density biochemical arrays with sub-pixel alignment
AssigneeComplete Genomics, Inc.
InventorsBryan P. Staker, Craig E. Uhrich
Life of this patent
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Abstract
A system and associated method for imaging high density biochemical arrays comprises one or more imaging channels that share a common objective lens and a corresponding one or more time delay integration-type imaging cameras with optical alignment mechanisms that permit independent inter-channel and intra-channel adjustment of each of four degrees: X, Y, rotation and scale. The imaging channels are configured to independently examine different spectra of the image of the biochemical arrays.
Claims13
A microscope comprising:
- a time delay integration camera for producing an integrated image from scanning of a sample along a scanning axis normal to an axis of rotational symmetry;
- an objective lens for directing an image of the sample to the time delay integration camera along the axis of rotational symmetry;
- a rotational stage, the rotational stage supporting the time delay integration camera, the rotational stage independently rotatable around the axis of rotational symmetry at the time delay integration camera;
- a sample positioning stage, the sample positioning stage being independently rotatable in a plane normal to the axis of rotational symmetry and independently translatable in X and Y in the plane normal to the axis of rotational symmetry;
- a zoom lens system of constrained magnification capability, the zoom lens system for independently changing scale of the image directed to the time delay imaging camera along the axis of rotational symmetry;
- and
- a lateral offset system along the axis of rotational symmetry, the lateral offset system for independently shifting the position of the image in the camera in a plane normal to the scanning axis.
4 more elements
A microscope comprising:
- a first imaging channel;
- a second imaging channel;
- a beam splitter for directing an image of a first selected spectrum to the first imaging channel and of a second selected spectrum to the second imaging channel;
- an objective lens having an axis of rotational symmetry;
- and
- a sample positioning stage, the sample positioning stage being independently rotatable in a plane normal to the axis of rotational symmetry and independently translatable in X and Y in the plane normal to the axis of rotational symmetry;
- wherein the first imaging channel comprises:
- a first time delay integration camera for producing an integrated image from scanning of a sample along a scanning axis normal to an axis of rotational symmetry;
- a first rotational stage, the rotational stage supporting the time delay integration camera, the rotational stage independently rotatable around the axis of rotational symmetry at the time delay integration camera;
- a first tube lens and a helper lens forming a zoom lens system of constrained magnification capability, the zoom lens system for independently changing scale of the image directed to the time delay imaging camera along the axis of rotational symmetry;
- and
- a first lateral offset system along the axis of rotational symmetry, the first lateral offset system for independently shifting the position of the image in the camera in a plane normal to the scanning axis, and
- a second time delay integration camera for producing an integrated image from scanning of a sample along a scanning axis normal to an axis of rotational symmetry;
- a second rotational stage, the rotational stage supporting the time delay integration camera, the rotational stage independently rotatable around the axis of rotational symmetry at the time delay integration camera;
- a second tube lens and a helper lens foaming a zoom lens system of constrained magnification capability, the zoom lens system for independently changing scale of the image directed to the time delay imaging camera along the axis of rotational symmetry;
- and
- a second lateral offset system along the axis of rotational symmetry, the lateral offset system for independently shifting the position of the image in the camera in a plane normal to the scanning axis.
14 more elements
A method for aligning a microscope comprising:
- (a) providing a fluorescence microscope comprising:
- an x-y positioning stage for manipulating a planar array of biochemical experiments in a sample structure;
- and,
- a time delay integrating camera having a CCD imaging array having a rotational orientation;
- (b) obtaining an image on the CCD imaging array of the array of the biochemical experiments in the sample structure along a rotational axis of symmetry;
- (c) calculating a first angle between the camera imaging array and the biochemical array around the rotational axis of symmetry;
- (d) calculating a second angle between the biochemical array and the x-y positioning stage around the axis of rotational symmetry;
- (e) rotating the array by the second angle to align the biochemical array with positioning stage;
- and
- (f) rotating the camera by the sum of the angles found in steps (c) and (d) to align the camera CCD imaging array with the x-y positioning stage.
7 more elements
Dependencies are inferred from the claim text.