Method and apparatus for imaging a sample on a device
First Claim
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1. An apparatus for imaging a sample located on a support, said apparatus comprising:
- a body for immobilizing said support, said support comprising at least a first surface having said sample thereon;
an electromagnetic radiation source for generating excitation radiation having a first wavelength;
excitation optics for transforming the geometry of said excitation radiation to a line and directing said line at said sample for exciting a plurality of regions thereon, said line causing a labeled material on said sample to emit response radiation, said response radiation having a second wavelength, said first wavelength different from said second wavelength;
collection optics for collecting said response radiation from said plurality of regions;
a detector for sensing said response radiation received by said collection optics, said detector generating a signal proportional to the amount of radiation sensed thereon, said signal representing an image associated with said plurality of regions from said sample;
a translator coupled to said body for allowing a subsequent plurality of regions on said sample to be excited;
a processor for processing and storing said signal so as to generate a 2-dimensional image of said sample; and
a focuser for automatically focusing said sample in a focal plane of said excitation radiation.
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Abstract
Labeled targets on a support synthesized with polymer sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, can be detected by exposing selected regions of sample 1500 to radiation from a source 1100 and detecting the emission therefrom, and repeating the steps of exposition and detection until the sample is completely examined.
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Citations
65 Claims
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1. An apparatus for imaging a sample located on a support, said apparatus comprising:
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a body for immobilizing said support, said support comprising at least a first surface having said sample thereon;
an electromagnetic radiation source for generating excitation radiation having a first wavelength;
excitation optics for transforming the geometry of said excitation radiation to a line and directing said line at said sample for exciting a plurality of regions thereon, said line causing a labeled material on said sample to emit response radiation, said response radiation having a second wavelength, said first wavelength different from said second wavelength;
collection optics for collecting said response radiation from said plurality of regions;
a detector for sensing said response radiation received by said collection optics, said detector generating a signal proportional to the amount of radiation sensed thereon, said signal representing an image associated with said plurality of regions from said sample;
a translator coupled to said body for allowing a subsequent plurality of regions on said sample to be excited;
a processor for processing and storing said signal so as to generate a 2-dimensional image of said sample; and
a focuser for automatically focusing said sample in a focal plane of said excitation radiation. - View Dependent Claims (2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 41)
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3. The apparatus as recited in claim 3 wherein said temperature controller comprises a thermoelectric cooler.
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25. A method for imaging a sample located on a support, said method comprising the steps of:
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immobilizing said support on a body;
exciting said sample on said support with an excitation radiation having a first wavelength from an electromagnetic radiation source, said excitation radiation having a linear geometry for exciting a plurality of regions on said sample;
detecting a response radiation having a second wavelength in response to said excitation radiation, said response radiation representing an image of said plurality of regions;
exciting a subsequent plurality of regions on said sample;
processing and storing said response radiation to generate a 2-dimensional image of said sample; and
auto-focusing said sample in a focal plane of said excitation radiation. - View Dependent Claims (26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36)
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37. In a imaging system for imaging a sample on a support having a first surface and a second surface, said second surface being weakly reflective relative to said first surface, a method for focusing on said weakly reflective surface comprising the steps of:
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a) focusing said first surface;
b) focusing said second surface; and
c) finely focusing said second surface. - View Dependent Claims (38, 39, 40)
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42. An apparatus for hybridizing a nucleic acid microarray immobilized on a surface of a solid substrate, the apparatus comprising:
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at least one assembly for securing the solid substrate during hybridization, the assembly comprising a carrier and a cover having a surface facing the carrier, the carrier and the cover dimensioned to receive the solid substrate between the carrier and the surface of the cover so that the surfaces of the cover and the solid substrate define a cavity;
a fluid control module comprising a manifold, at least one liquid reservoir, at least one waste container, and a vacuum source in fluid communication with the waste container, the manifold providing fluid communication between the liquid reservoir and the cavity and between the cavity and the waste container, and the vacuum source providing a pressure difference between the liquid reservoir and the waste container;
at least one thermal management module for controlling temperature of the nucleic acid microarray immobilized on the surface of the solid substrate, the thermal management module thermally contacting the assembly; and
a pulse valve in fluid communication with the cavity, the pulse valve adapted to agitate fluid within the cavity. - View Dependent Claims (43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54)
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55. An apparatus for hybridizing a nucleic acid microarray immobilized on a surface of a solid substrate, the apparatus comprising:
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at least one assembly for securing the solid substrate during hybridization, the assembly comprising a carrier and a cover having a surface facing the carrier, the carrier and the cover dimensioned to receive the solid substrate between the carrier and the surface of the cover so that the surfaces of the cover and the solid substrate define a cavity;
a fluid control module comprising a fluid manifold, at least one liquid reservoir, at least one waste container, a pulse valve in fluid communication with the cavity, and a vacuum source in fluid communication with the waste container, the fluid manifold providing fluid communication between the liquid reservoir and the cavity and between the cavity and the waste container, and the vacuum source providing a pressure difference between the liquid reservoir and the waste container, wherein the pulse valve provides for agitation of fluid within the cavity; and
at least one thermal management module for controlling temperature of the nucleic acid microarray immobilized on the surface of the solid substrate, the thermal management module thermally contacting the assembly. - View Dependent Claims (56, 57, 58, 59)
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60. An apparatus comprising:
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a solid substrate having a nucleic acid microarray immobilized on a surface of the solid substrate;
at least one assembly for securing the solid substrate during hybridization, the assembly comprising a carrier and a cover having a surface facing the carrier, the carrier and the cover dimensioned to receive the solid substrate between the carrier and the surface of the cover so that the surfaces of the cover and the solid substrate define a cavity;
a fluid control module comprising a fluid manifold, at least one liquid reservoir, at least one waste container, a pulse valve in fluid communication with the cavity, and a vacuum source in fluid communication with the waste container, the fluid manifold providing fluid communication between the liquid reservoir and the cavity and between the cavity and the waste container, and the vacuum source providing a pressure difference between the liquid reservoir and the waste container, wherein the pulse valve provides for agitation of fluid within the cavity; and
at least one thermal management module for controlling temperature of the nucleic acid microarray immobilized on the surface of the solid substrate, the thermal management module thermally contacting the assembly. - View Dependent Claims (61, 62, 63, 64, 65)
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Specification