Method and apparatus for imaging a sample on a device
OwnerMark Trulson, David Stern +3inventors
InventorsMark Trulson, David Stern, Richard P. Rava, Stephen P. A. Fodor, Peter Fiekowsky
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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.
Claims83
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.
The apparatus as recited in claim 3 wherein said temperature controller comprises a thermoelectric cooler.
The apparatus as recited in claim 19 wherein the tilt stage is controlled by said processor.
A method for imaging a sample located on a support, said method comprising the steps of:
- 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.
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:
- a) focusing said first surface;
- b) focusing said second surface;
- and
- c) finely focusing said second surface.
A method, comprising the acts of:
- providing a substrate having a surface including biological polymers and at least one fluorescent label associated with at least one of the biological polymers;
- providing a stage constructed to receive said substrate and being coupled to an autofocusing module;
- generating an excitation laser beam;
- scanning said laser beam relative to said surface;
- collecting fluorescent radiation using optics, said fluorescent radiation being emitted from said at least one fluorescent label in response to said excitation beam;
- detecting said collected fluorescent radiation;
- and
- tilting said stage to focus said surface including the biological polymer with respect to said optics.
A method of detecting hybridization between biological polymers, comprising the acts of:
- providing a flow cell including a light transparent substrate, said substrate having a surface located inside said flow cell, said surface including biological polymers and at least one fluorescent label associated with at least one of the biological polymers;
- generating an excitation laser beam;
- scanning said laser beam relative to said surface and delivering said laser beam to said biological polymer and said fluorescent label;
- collecting fluorescent radiation emitted from said fluorescent label located inside said flow cell using optics;
- and
- detecting said collected fluorescent radiation.
A system for detecting hybridization between biological polymers, comprising:
- a laser source constructed to generate an excitation beam having a first wavelength;
- a stage constructed to support a hybridization cell comprising a first surface including at least one biological polymer and at least one fluorescent label;
- optics constructed to deliver said excitation beam to a region of said first surface to cause emission of fluorescent radiation from said fluorescent label;
- a detector constructed and arranged to detect said fluorescent radiation and to generate a signal representing said detected fluorescent radiation;
- a processor constructed and arranged to process said signal and generate an image corresponding to said fluorescent radiation detected over said first surface;
- and
- an autofocuser, coupled to said stage, constructed and arranged to position said region of said first surface in focus with respect to said optics.
A system for detecting a hybridized sample, comprising:
- a laser source constructed and arranged to generate an excitation beam;
- a stage constructed and arranged to support a cell having a first surface including a biological polymer and an associated fluorescent label located inside said cell;
- optics constructed and arranged to deliver said excitation beam to a region of said first surface and cause emission of fluorescent radiation emitted from said label having a second wavelength different from said first wavelength;
- a detector constructed and arranged to detect said fluorescent radiation emitted from said cell and generate a signal representing said fluorescent radiation;
- and
- a processor constructed and arranged to process said signal and generate an image corresponding to said fluorescent radiation detected from said first surface.
Dependencies are inferred from the claim text.