System, Method, and Product for Imaging Probe Arrays with Small Feature Sizes
First Claim
Patent Images
1. A method for resolving features on a probe array, comprising:
- acquiring a plurality of micro-shifted images of a region of a probe array using an image acquisition device comprising an objective lens and a sensing element having pixels;
shifting the images by less than one half a size of the pixel of a sensing element while maintaining a fixed spatial relationship between the probe array and an objective lens of the image acquisition device;
reconstructing an image of the probe array using the micro-shifted images; and
deriving intensity values for one or more probe features disposed on the probe array from the reconstructed image.
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Abstract
An embodiment of a method for resolving features on a probe array is described that, comprises acquiring a plurality of micro-shifted images of a region of a probe array; reconstructing an image of the probe array using the micro-shifted images; and deriving intensity values for one or more probe features disposed on the probe array from the reconstructed image.
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Citations
15 Claims
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1. A method for resolving features on a probe array, comprising:
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acquiring a plurality of micro-shifted images of a region of a probe array using an image acquisition device comprising an objective lens and a sensing element having pixels; shifting the images by less than one half a size of the pixel of a sensing element while maintaining a fixed spatial relationship between the probe array and an objective lens of the image acquisition device; reconstructing an image of the probe array using the micro-shifted images; and deriving intensity values for one or more probe features disposed on the probe array from the reconstructed image. - View Dependent Claims (2, 3, 4)
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5. A method for obtaining subpixel resolution, comprising:
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creating a set of uniformly micro-shifted images using an image acquisition device comprising an objective lens and a sensing element having pixels; shifting the images by less than one half the size of the pixel of a sensing element while maintaining a fixed spatial relationship between the probe array and an objective lens of the image acquisition device; applying a set of linear equations to the images, the equations describing the relationship between subpixel intensities and the pixel intensities in the micro-shifted images caused by the subpixel intensities; and applying techniques of linear algebra to solve for those subpixel intensities. - View Dependent Claims (6, 7, 8)
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9. A method for obtaining an image, comprising;
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providing a probe array in an image acquisition device comprising an objective lens, a shift element and a sensing element having pixels; acquiring an image of the probe array; moving the shift element by less than one half the size of a pixel of the sensing element while maintaining a fixed spatial relationship between the probe array and the objective lens of the image acquisition device; acquiring a second image of the substrate; repeating as necessary, in both X and Y dimensions; and processing the images using a set of linear equations. - View Dependent Claims (10, 11, 12, 13, 14)
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15. A method for obtaining an image, comprising;
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acquiring an image of a nucleic acid probe array using an image acquisition device comprising a CCD camera, an objective lens, and a tube lens; translating the tube lens relative to the CCD by less than one half a pixel size of the CCD; acquiring a second image of the probe array; repeating as necessary; creating a single image from a set of shifted images using one pixel from a common location within each of the shifted images and tiling the pixels in the single image according to the spatial orientation corresponding to the shift direction and magnitude used during image acquisition; creating an Unboxed image from the single image, wherein it is recognized that the individual pixels of the single image are made up of subpixels, the pixels in proximity to each other within an single image share common subpixels; creating a deconvolved image by using the single image as the starting image, the Unboxed image as the initial guess, and physical properties such as the point spread function of the optical system, the deconvolved image is created using the Richardson-Lucy with Total Variation Regularization algorithm which has been modified to use, on a per iteration basis, parameters alpha, which includes overrelaxation or acceleration, and beta, which includes momentum; and deriving intensity values for one or more probe features disposed on the probe array from the reconstructed image.
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Specification