Microarray detector and methods

• US 7,354,389 B2
• Filed: 05/28/2003
• Issued: 04/08/2008
• Est. Priority Date: 05/28/2002
• Status: Expired due to Fees

• Current Assignee: Autogenomics
• Original Assignee: Autogenomics
• Inventors: Shen, Xiaohua, Mahant, Vijay K., Singh, Shailendra, Kureshy, Fareed
• Primary Examiner(s): Epperson; Jon D.
• Assistant Examiner(s): Lundgren; Jeffrey S.
• Application Number:
  US10/509,985
• Publication Number:
  US 20050118640A1
• Time in Patent Office: 1,777 Days
• Field of Search: None
• US Class Current: 506/37
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00673 of reagents
• CPC Class Codes: G01N 2035/00782 reprogrammmable code
• CPC Class Codes: G01N 2035/1025 Fluid level sensing
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 35/00732 Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/1016 Control of the volume dispensed or introduced

Abstract

A detector for optical analysis of a biochip determines the focal position of a plurality of analytes on the biochip using one or more registration markers on the biochip, wherein the analytes and the registration marker are illuminated by different light sources. Therefore, contemplated configurations will significantly reduce overall focusing time and automate proper positioning of the biochip, while allowing to determine a focal position without photobleaching or other undesirable effects on optically labile compounds. Thus, automated analyses can be performed without manual user intervention.

Claims

1. An analytic system for optical detection of a plurality of analytes that are bound to a biochip, the analytic system comprising:

a platform functionally coupled to a confocal microscope detector and movable along an x-coordinate, a y-coordinate, and optionally a z-coordinate relative to the detector, wherein the platform is configured to receive a biochip;

wherein the biochip has a plurality of registration markers and further has a plurality of analytes in predetermined positions relative to the registration markers;

a first light source that is configured to illuminate the registration markers at a first angle relative to the z-coordinate to generate registration marker signals, and further comprising a second light source that is configured to sequentially illuminate at least two of the plurality of analytes at a second angle relative to the z-coordinate to generate at least two individual analyte signals, respectively;

a computer configured to determine the position of the biochip with respect to a given x-coordinate value and a given y-coordinate value using the registration marker signals; and

wherein the first and the second angles are different.

2. The analytic system of claim 1 wherein the detector comprises an objective lens or an objective lens system with a numeric aperture that is sufficient to allow detection of the analyte signal without moving the platform along the z-coordinate.

3. The analytic system of claim 1 wherein the first light source has a wavelength maximum that is different from an absorption maximum of an optically detectable label of the at least one of the plurality of analytes.

4. The analytic system of claim 1 further comprising a third light source that illuminates the at least one of the plurality of analytes or another one of the plurality of analytes to generate a second analyte signal, and wherein the third light source has a wavelength maximum that is different from both, the wavelength maximum of the first light source and the absorption maximum of an optically detectable label of the at least one of the plurality of analytes or another one of the plurality of analytes.

5. The analytic system of claim 1 wherein the registration marker and the at least one of the analytes are illuminated at a different angle and a different wavelength by the first and the second light source, respectively.

6. The analytic system of claim 1 wherein the first light source is a laser or a light emitting diode, and wherein the second light source is a laser.

7. The analytic system of claim 1 wherein the registration marker comprises a fluorescent dye, a luminescent compound, a phosphorescent compound, or a reflective compound.

8. The analytic system of claim 1 wherein the analyte signal is a fluorescence signal, a chemiluminescence signal, or a phosphorescence signal.

9. The analytic system of claim 1 wherein the detector comprises a photo-multiplier tube or a charge-coupled device.

10. The analytic system of claim 1 further comprising a second and a third registration marker, and wherein a vertical focal position for detection of the analyte signals by the detector is determined by the analytic system using registration marker signals from the registration marker, the second registration marker and the third registration marker.

11. The analytic system of claim 1 wherein the analyte signal is normalized by the analytic system using a positive control marker on the biochip.

12. The analytic system of claim 1 further comprising a data transfer interface electronically coupled to the detector.

13. The analytic system of claim 12 wherein the data transfer interface is informationally coupled to a computer in a remote location.