Microarray substrate with integrated photodetector and methods of use thereof

• US 20020004204A1
• Filed: 02/28/2001
• Published: 01/10/2002
• Est. Priority Date: 02/29/2000
• Status: Abandoned Application

• Current Assignee: Oʼkeefe, Matthew T.
• Original Assignee: Oʼkeefe, Matthew T.
• Inventors: OʼKeefe, Matthew T.
• Application Number:
  US09/796,932
• Publication Number:
  US 20020004204A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2533/101 Primer extension
• CPC Class Codes: C12Q 2565/501 : being an array of oligonucleotides
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof

Abstract

The present invention provides a microarray substrate comprising a plurality of photodetectors integrated therein. The invention further provides a detection device for use in conjunction with a microarray substrate of the invention, as well as methods of use of same.

Claims

1. A device comprising:

a solid substrate which provides a surface;

a plurality of different probe polymer sequences bound to the surface, wherein each different sequence is bound to a distinct area of the surface;

a plurality of photodetectors positioned in a manner such that a signal emitted from a distinct area of probe polymer sequences can be detected and differentiated from a signal of another distinct area of probe polymer sequences.

2. The device of claim 1, wherein the photodetector is selected from the group consisting of a photodiode, a charge-coupled device, a photoconductive cell, an avalanche photodiode, a photoresistor, a photoswitch, a phototransistor, a phototube, a photovoltaic cell, and a light-to-frequency converter.

3. The device of claim 1, wherein the photodetector is a photodiode.

4. The device of claim 3, wherein each photodiode is associated with a single distinct area.

5. The device of claim 1, wherein the substrate comprises a first layer and a second layer, wherein the first layer is detachably positioned on the second layer, wherein the first layer provides a surface to which a plurality of different probe polymer sequences are bound, wherein each different polymer sequence is bound to a distinct area of the surface, and wherein the second layer comprises a plurality of photodetectors positioned in a manner such that a signal emitted from a distinct area of probe polymer sequences on the first layer can be detected and differentiated from a signal of another distinct area of probe polymer sequences.

6. The device of claim 1, wherein the probe polymers are selected from the group consisting of single-stranded naturally-occurring nucleotide sequences, single-stranded modified nucleotide sequences, single-stranded synthetic nucleotide sequences, and single-stranded semi-synthetic nucleotide sequences.

7. The device of claim 1, further comprising a signal transmission means connected to the plurality of photodetectors.

8. The device of claim 7, further comprising a means for analyzing signals received from the signal transmission means.

9. The device of claim 1, wherein said substrate comprises a substance selected from the group consisting of silicon, GaAs, SiO₂, glass, and functionalized glass.

10. The device of claim 1, wherein at least one of said photodetectors comprises positional address information.

11. The device of claim 1, further comprising a means for regulating the temperature integrated within said solid substrate.

12. The device of claim 8;

further comprising a microprocessor for storing, managing, and processing information provided by an electronic signals received.

13. The device of claim 12, further comprising a light source;

and a means for directing the light source.

14. The device of claim 12, further comprising an the immobilizing element in the form of an x-y translation table.

15. The device of claim 1, further comprising a means for regulating the temperature within the device.

16. The device of claim 1, further comprising a radiant energy selection means.

17. The device of claim 16, wherein the radiant energy selection means is selected from the group consisting of an interference filter layer, an optical wave guide, a polarization layer, a time-resolved fluorescence means, and a grating.

18. A method of detecting a probe molecule in a microarray, comprising

a) allowing a labeled target molecule to hybridize to a probe molecule bound to a substrate, forming a probe-target hybrid;

and

b) detecting a signal from the probe-target hybrid using a photodetector positioned adjacent the probe molecule.

19. The method of claim 18, wherein the substrate is comprised of a plurality of distinct areas which each have bound thereto probe molecules and further wherein a plurality of photodetectors are positioned adjacent the distinct areas in a manner allowing for differentiating among signals received from the distinct areas.

20. The method of claim 18, further comprising analyzing signals received from the photodetectors.

21. A method of detecting a probe molecule in a microarray, comprising:

a) allowing an oligonucleotide primer molecule to hybridize to a probe molecule bound to a substrate, forming a probe-primer hybrid;

b) contacting the probe-primer hybrid with a DNA polymerase, forming a reaction mixture, under conditions that promote addition of a nucleotide to the 3′

end of the primer, such that a second polynucleotide strand is generated that comprises a nucleotide sequence complementary to the probe sequence such the second polynucleotide strand hybridizes to the probe, forming a probe-second polynucleotide strand hybrid, wherein the reaction mixture comprises a labeled nucleotide, and wherein the labeled nucleotide is incorporated into the second polynucleotide strand; and

c) detecting a signal from the second polynucleotide strand using a photodetector positioned adjacent the probe molecule,

wherein the substrate is comprised of a plurality of distinct areas which each have bound thereto probe molecules and further wherein a plurality of photodetectors are positioned adjacent the distinct areas in a manner allowing for differentiating among signals received from the distinct areas.