Sample analysis systems

• US 6,982,431 B2
• Filed: 08/13/2002
• Issued: 01/03/2006
• Est. Priority Date: 08/31/1998
• Status: Expired due to Fees

• Current Assignee: Molecular Devices
• Original Assignee: Molecular Devices
• Inventors: Owicki, John C., Modlin, Douglas N., Edwards, Glenn R., Taylor, Michael T., Marquiss, Samuel A.
• Primary Examiner(s): LE, QUE TAN
• Application Number:
  US10/218,897
• Publication Number:
  US 20030127609A1
• Time in Patent Office: 1,239 Days
• Field of Search: 250/576, 250/573, 250/574, 250/225, 250/461.2, 250/338.5, 356/343, 356/317, 356/318, 356/417, 422/63, 422/82.08
• US Class Current: 250/573
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6445 Measuring fluorescence polarisation
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates

Abstract

Systems, and components thereof, for analyzing samples. These systems include apparatus and methods for generating, transmitting, detecting, and/or analyzing light, including without limitation high-throughput optical screening devices for analyzing samples at one or more assay sites. These systems also include apparatus and methods for supporting samples for analysis, including without limitation multiwell sample holders such as microplates.

Claims

1. An apparatus for detecting light emitted from a composition, comprising:

a stage for supporting a composition in an examination site, the composition being contained in a spatial volume lying between boundary interfaces located a different points along a Z-axis, wherein the Z-axis is substantially perpendicular to the stage;

an automated registration device that automatically brings successive compositions, held in adjacent wells of a microplate, and the examination site into register for successive analysis of the composition;

an arc lamp light source positioned to deliver light to the composition in the examination site;

a detector positioned to receive light transmitted from the composition in the examination site;

an optical relay structure located between the light source and the detector, the optical relay structure being capable of transmitting light substantially from a sensed volume of the composition, wherein the sensed volume is spaced away from at least one of the boundary interfaces of the composition; and

an automated Z-axis optical adjustment device that automatically adjusts the position of the sensed volume along the Z-axis between and spaced away from the boundary interfaces.

2. The apparatus of claim 1, the optical relay structure including confocal optics elements substantially contained within an optics head positioned above or below the stage, wherein the Z-axis optical adjustment device includes a drive mechanism that moves the optics head relative to the Z-axis.

3. The apparatus of claim 1, wherein the sensed volume is spaced substantially away from all the boundary interfaces.

4. The apparatus of claim 1, the sensed volume having a waist region in a sample plane, and a Z-pick-up, wherein the diameter of the waist region is approximately half the dimension of the Z-pick-up.

5. The apparatus of claim 1, wherein the optical relay structure includes an aperture substantially centered about the Z-axis and contained in an image plane conjugate to a sample plane intersecting the sensed volume.

6. The apparatus of claim 1, further comprising an automated registration device controller for preprogramming the relative movement into registration of successive compositions and the examination site.

7. The apparatus of claim 1, the light source being one of a plurality of light sources positioned at a source station, further comprising a switching mechanism for interchangeably connecting different light sources, selected from among the plurality of light sources, to the optical relay structure for different applications.

8. The apparatus of claim 1, wherein the detector is a photomultiplier tube, or a photodiode, or a charge-coupled device.

9. The apparatus of claim 1, wherein the sensed volume is diffraction limited.

10. The apparatus of claim 1, wherein the light source produces high-intensity, high-color temperature light.

11. The apparatus of claim 1, wherein the optical relay structure includes a first aperture and a first lens positioned along a light path between the light source and the examination site or between the detector and the examination site.

12. The apparatus of claim 11, wherein the optical relay structure includes a second aperture and a second lens, the first aperture and the first lens being positioned along a light path between the light source and the examination site, the second aperture and the second lens being positioned along a light path between the detector and the examination site, so that light is transmitted substantially to and from the same sensed volume in a composition at the examination site.

13. The apparatus of claim 11, the optical relay structure including at least one fiber optic element, wherein the first aperture is defined by the dimension of an end of the fiber optic element.

14. The apparatus of claim 11, the optical relay structure including a second aperture, the first and second apertures having different dimensions, further comprising an aperture switching mechanism for interchangeably positioning a selected aperture in the light path leading to or from a sensed volume in a composition at the examination site, so that the size of the sensed volume can be altered by switching between the first and second apertures.

15. The apparatus of claim 11, wherein the diameter of the first aperture is adjustable.

16. The apparatus of claim 11, wherein the first aperture and the first lens are contained in a first optics head positioned near the stage.

17. The apparatus of claim 16, the first optics head being positioned above the stage, wherein the optical relay structure includes a second optics head positioned below the stage, each optics head having a light entrance port optically connected to the light source, and a light exit port optically connected to the detector, and a switch control mechanism capable of interchangeably configuring any one of the following light transmission routes to and from a sensed volume in a composition located at the examination site:

(a) top-illumination and top-detection, (b) top-illumination and bottom-detection, (c) bottom-illumination and top-detection, and (d) bottom-illumination and bottom-detection.

25. The apparatus of claim 1, the light source having a positive contact and a negative contact, further comprising a power supply having an ignition circuit adapted to generate a voltage pulse to trigger ignition of the arc lamp, wherein the ignition circuit includes a ground, and positive and negative lamp outputs adapted to connect to the positive and negative contacts, respectively, on the lamp, and wherein the positive and negative lamp outputs are ground referenced.

26. The apparatus of claim 1, wherein the arc lamp light source includes a xenon arc lamp light source.

18. An apparatus for measuring the polarization of light emitted from a composition, comprising:

a stage for supporting the composition at an examination site;

an automated registration device that automatically brings successive compositions and the examination site into register for successive analysis of the compositions;

a continuous high color temperature light source;

an excitation optical relay structure having an excitation polarizer, wherein the excitation optical relay structure directs light from the light source through the excitation polarizer toward the composition;

a detector; and

an emission optical relay structure having an emission polarizer, wherein the emission optical relay structure directs light emitted from the composition through the emission polarizer toward the detector.

19. The apparatus of claim 18, wherein the continuous high color temperature light source has a color temperature of at least about 3500 Kelvin.

20. The apparatus of claim 18, wherein the continuous high color temperature light source is a xenon arc lamp.

21. The apparatus of claim 18, wherein the apparatus is capable of detecting light transmitted substantially from a sensed volume of the composition.

22. The apparatus of claim 21, the composition being contained in a spatial volume lying between boundary interfaces, wherein the sensed volume is spaced substantially away from at least one of the boundary interfaces.

23. The apparatus of claim 18, further comprising a second light source, wherein the high color temperature light source is configured for steady-state polarization assays, and wherein the second light source is configured for time-resolved polarization assays.

24. The apparatus of claim 18, further comprising a modulator mechanism configured to vary the intensity of light incident on the composition without varying the intensity of light produced by the light source.

27. The apparatus of claim 18, wherein the continuous high color temperature light source includes a light-emitting diode.