Microarray detector and synthesizer

• US 6,545,758 B1
• Filed: 10/05/2000
• Issued: 04/08/2003
• Est. Priority Date: 08/17/2000
• Status: Expired due to Term

• Current Assignee: Gene Reader LLC (IPValuation Partners, LLC)
• Original Assignee: Able Signal Company, LLC
• Inventors: Sandstrom, Perry
• Primary Examiner(s): Evans, F. L.
• Application Number:
  US09/679,858
• Time in Patent Office: 915 Days
• Field of Search: 356/317, 356/318, 356/417, 250/458.1, 250/459.1, 250/461.1, 250/461.2
• US Class Current: 356/317
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00439 using micromirror arrays
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00576 fluorophore
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00639 the compounds being trapped in or bound to a porous medium
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 60/08 : Integrated apparatus specially adapted for both creating and screening libraries
• CPC Class Codes: G01J 3/02 : Details
• CPC Class Codes: G01J 3/021 : using plane or convex mirrors, parallel phase plates, or particular reflectors
• CPC Class Codes: G01J 3/0229 : using masks, aperture plates, spatial light modulators or spatial filters, e.g. reflective filters
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 : Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6456 : Spatial resolved fluorescence measurements; Imaging

Abstract

The present invention relates to novel systems, devices, and methods comprising spatial light modulators for use in the reading and synthesis of microarrays. For example, the present invention provides micromirror systems for synthesizing and acquiring data from nucleic acid microarrays and systems for collecting, processing, and analyzing data obtained from a microarray.

Claims

1. A system for detecting the presence of a sample on a microarray comprising:

a) a spatial light modulator capable of selectively optically interrogating a patterned microarray,

b) a synchronous detector system capable of detecting an optical signal obtained from said patterned microarray; and

c) a processor capable of performing repetitive comparative measurements of said optical signals from one or more sites on said patterned microarray.

2. The system of claim 1, wherein said synchronous detector system comprises an optical signal detector operated in analog mode.

3. The system of claim 1, wherein said synchronous detector system comprises an optical signal detector operated in photon-counting mode.

4. The system of claim 1, wherein said optical signal comprises fluorescence.

5. The system of claim 1, wherein said optical signal comprises luminescence.

6. The system of claim 1, further comprising a polychromatic light source.

7. The system of claim 6, wherein said polychromatic light source is selected from the group consisting of:

fluorescent lamps, mercury arc lamps, mercury-xenon arc lamps, xenon arc lamps, xenon flash lamps, and metal-halide lamps.

8. The system of claim 1, wherein said spatial light modulator comprises a micromirror device.

9. The system of claim 1, comprising a computer memory capable of storing processed data received from said processor.

10. A method for detecting optical signals generated from a microarray comprising:

a) providing;

i) a patterned microarray comprising a plurality of reaction sites;

ii) a light source;

iii) a spatial light modulator configured to optically interrogate said microarray;

iv) an optical detector system configured to receive light from the interrogated microarray

v) a signal processing system configured to synchronously control the spatial light modulator interrogation pattern and the sign of a multiplication factor of the signal from said optical detector;

b) controlling said spatial light modulator such that alternating patterns of reaction sites on said patterned microarray are interrogated to produce a time-varying detector signal from said optical detector;

c) controlling the multiplication factor of said optical detector signal synchronously with the alternating spatial light modulator interrogation pattern; and

d) producing an output signal by additively combining said synchronously multiplied optical detector signals over a time period encompassing one or more spatial light modulator alternation cycles.

11. The method of claim 10, further comprising a computer memory capable of storing an output signal from said signal processing system.

12. The method of claim 11, wherein said output signal comprises a bandwidth-limited signal representing the difference between two alternating spatial light modulator interrogation patterns.

13. The method of claim 10, wherein said light source comprises an excitation device.

14. The method of claim 13, wherein said excitation device comprises a polychromatic light source.

15. A microarray data acquisition system comprising:

a) a spatial light modulator configured to selectively interrogate one or more sites on a microarray;

b) a microarray detection system, wherein said microarray detection system is capable of generating a signal corresponding to hybridization at one or more sites on said microarray;

c) a signal path capable of passing signal from said microarray detector system with variable gain;

d) a processor capable of varying the gain of said signal path in a manner that is synchronous with the selection of interrogation sites on said microarray; and

e) a signal averaging system that produces an output signal representing a bandwidth-limited output from said variable-gain signal path.

16. The system of claim 15, wherein said variable-gain signal path comprises a processor-controlled switch to alternate between input signal phases in a manner that is synchronous with the selection of alternating interrogation patterns, such that an output representing the average difference between detector signals during alternating interrogation patterns is produced.

17. The system of claim 15, wherein said variable-gain signal path comprises a two-input multiplier where the polarity of one input signal is alternated by the processor in a manner that is synchronous with the selection of alternating interrogation patterns, such that an output representing the average difference between detector signals during alternating interrogation patterns is computed.

18. The system of claim 17, wherein said variable-gain signal path is implemented through digital calculation under programmed control.

19. The system of claim 15, wherein said signal averaging system is implemented through digital calculation under programmed control.

20. The system of claim 15, wherein said spatial light modulator comprises a micromirror device.