Light detection device with means for tracking sample sites

• US 6,310,687 B1
• Filed: 01/23/2001
• Issued: 10/30/2001
• Est. Priority Date: 07/07/1999
• Status: Expired due to Fees

• Current Assignee: Molecular Devices
• Original Assignee: LJL Biosystems, Inc. (Danaher Corporation)
• Inventors: Stumbo, David P., Modlin, Douglas N.
• Primary Examiner(s): EVANS, FANNIE L
• Application Number:
  US09/768,765
• Publication Number:
  US 20010033381A1
• Time in Patent Office: 280 Days
• Field of Search: 356/317, 356/318, 356/417, 250/458.1, 250/459.1, 250/461.1, 250/461.2, 422/63, 422/65, 422/82.05, 422/82.08
• US Class Current: 356/317
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/0405 manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
• CPC Class Codes: G01N 2035/0425 Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 2035/0462 Buffers [FIFO] or stacks [LIFO] for holding carriers between operations
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1011 Control of the position or alignment of the transfer device
• CPC Class Codes: G01N 35/1074 arranged in a two-dimensional array

Abstract

Apparatus and methods for optical detection with improved read speed and/or signal-to-noise ratio. These apparatus and methods may involve among others moving an sample substrate (108) while simulataneously detecting light transmitted from one or more sample sites (110) on the substrate (108) by sequentially tracking the sample sites (110) as they move. A stage (101), movable in a first direction, supports the substrate (108). A detector (118) detects light emanating from an examination region (102) delimited by a detection initiation position (106a) and a detection termination position (106b). An optical relay structure (122) transmit light from the examination region (102) to the detector (118). A scanning mechanism (120) simultaneously moves the optical relay structure (122) and the substrate in the first direction. The optical relay structure (122) tracks the substrate (108) between the detection initiation position (106a) and the detection termination position (106b).

Claims

1. An apparatus for detecting light transmitted from a substrate having a plurality of sample sites, the apparatus comprising:

a stage for supporting the substrate, the stage being configured to move the substrate in a first direction so that the sample sites pass sequentially through an examination region delimited by a detection initiation position and a detection termination position;

a detector configured to detect light;

an optical relay structure configured to transmit light from a sensed volume within the examination region to the detector, the sensed volume being smaller than the examination region; and

an automated scanning mechanism configured to move the sensed volume in the first direction between the detection initiation position and the detection termination position;

wherein the sensed volume tracks a first sample site as it moves between the initiation position and the termination position, so that light transmitted by the first sample can be detected by the detector.

2. The apparatus of claim 1, wherein the sensed volume returns to the initiation position after the first sample site passes the termination position to track the next sample site as it moves between the initiation position and the termination position.

3. The apparatus of claim 1 further comprising a light source, where the optical relay structure further is configured to transmit light from the light source to the sensed volume.

4. The apparatus of claim 1, wherein the sample sites move at a substantially constant speed through the examination region.

5. The apparatus of claim 1, wherein the time required for the sensed volume to return to the initiation position is less than the time required for the sensed volume to track a sample site as it moves between the initiation position and the termination position.

6. The apparatus of claim 1, wherein the scanning mechanism includes reflective optics.

7. The apparatus of claim 6, wherein the reflective optics is selected from the group consisting of a parabolic mirror, a polygonal mirror, and a galvanometer mirror.

8. The apparatus of claim 6, wherein at least a portion of the reflective optics undergoes translational motion to track the sample sites.

9. The apparatus of claim 6, wherein at least a portion of the reflective optics undergoes rotational motion to track the sample sites.

10. The apparatus of claim 1, wherein the scanning mechanism includes refractive optics.

11. The apparatus of claim 6, wherein the detector includes a wide area detection device, and the scanning mechanism includes a light blocking member having an aperture positioned between the detection device and the examination region so that sensed volume tracking through the examination region is facilitated by moving the light blocking member relative to the wide area detection device.

12. The apparatus of claim 1, wherein the substrate is selected from the group consisting of a microplate, a biochip, and a chromatography plate.

13. The apparatus of claim 12, wherein the substrate is a microplate and the sample sites are wells in the microplate.

14. The apparatus of claim 1, wherein the separation between the first and second sample sites exceeds the separation between the initiation position and the termination position.

15. The apparatus of claim 1 further comprising a housing configured to support and enclose a least a portion of the apparatus, where the initiation position and the termination position are referenced relative to a fixed portion of the housing.

16. The apparatus of claim 1, wherein the first sample site moves past the termination position before the second sample site moves into the initiation position.

17. The apparatus of claim 1, wherein the light transmitted from the substrate includes light selected from the group consisting of fluorescence, phosphorescence, and chemiluminescence.

18. The apparatus of claim 1, the composition being contained in a spatial volume lying between boundary interfaces located at different points along a Z-axis, wherein the Z-axis is substantially perpendicular to the stage.

19. The apparatus of claim 1, wherein the substrate further includes a third sample site, and wherein the sensed volume returns to the initiation position after the second sample site passes the termination position to track the third sample site as it moves between the initiation position and the termination position.

20. An apparatus for detecting light transmitted from a sample site, the apparatus comprising:

a stage for supporting a substrate containing the sample site;

a detector configured to detect light;

an optical relay structure positioned between the stage and the detector and configured to transmit light from a sensed volume to the detector; and

a support structure configured to support the stage, the detector, and the optical relay structure;

where the stage and the optical relay structure are configured to align the sample site and the sensed volume automatically and to maintain that alignment while moving the sample site relative to a fixed portion of the support structure, so that light transmitted from the sample site can be detected by the detector as the sample site is moved.

21. The apparatus of claim 20, wherein the optical relay structure includes an automated scanning mechanism that moves the sensed volume with the sample site relative to the fixed portion of the support structure.

22. The apparatus of claim 20, wherein the scanning mechanism includes reflective optics.

23. The apparatus of claim 22, wherein the reflective optics is selected from the group consisting of a parabolic mirror, a polygonal mirror, and a galvanometer mirror.

24. The apparatus of claim 22, wherein at least a portion of the reflective optics undergoes translational motion to track the sample sites.

25. The apparatus of claim 22, wherein at least a portion of the reflective optics undergoes rotational motion to track the sample sites.

26. The apparatus of claim 20, wherein the scanning mechanism includes refractive optics.

27. The apparatus of claim 22, wherein the detector includes a wide area detection device, and the scanning mechanism includes a light blocking member having an aperture positioned between the detection device and the examination region so that sensed volume tracking through the examination region is facilitated by moving the light blocking member relative to the wide area detection device.

28. The apparatus of claim 20, the sample site being a first sample site, where the substrate contains a plurality of sample sites, and where the stage and the optical relay structure are configured to align the sample sites serially with the sensed volume.

29. An apparatus for detecting light transmitted from a sample, the apparatus comprising:

a support structure having a stage for supporting a substrate containing the sample; and

means for detecting light from a sensed volume in the sample while the sensed volume and the sample move substantially together relative to the support structure.

30. A method of detecting light transmitted from a substrate having first and second sample sites, the method comprising:

moving the substrate in a first direction so that the first and second sample sites pass sequentially through an initiation position and a termination position;

aligning a sensed volume with the first sample site at the initiation position and maintaining the alignment while detecting light transmitted from the sensed volume as the first sample site moves from the initiation position to the termination position; and

aligning the sensed volume with the second sample site at the initiation position and maintaining the alignment while detecting light transmitted from the sensed volume as the second sample site moves from the initiation position to the termination position.

31. The method of claim 30, wherein each maintaining step includes the step of moving a reflective optics member.

32. The method of claim 31, wherein the reflective optics member is selected from the group consisting of a parabolic mirror, a polygonal mirror, and a galvanometer mirror.

33. The method of claim 30, wherein each maintaining step includes the step of rotating the reflective optics member.

34. The method of claim 30, wherein each maintaining step includes the step of moving a refractive optics member.