Devices and methods for sample analysis

• US 20010006417A1
• Filed: 01/22/2001
• Published: 07/05/2001
• Est. Priority Date: 07/22/1998
• Status: Active Grant

• Current Assignee: Molecular Devices
• Original Assignee: LJL Biosystems, Inc. (Molecular Devices)
• Inventors: Owicki, John C., Modlin, Douglas N., El-Hage, Amer
• Granted Patent: US 6,486,947 B2
• Time in Patent Office: Days
• US Class Current: 356/246
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

Devices and methods for containing and analyzing small sample volumes that are sandwiched between solid surfaces. The devices may include an automated drive mechanism that controls the relative positions of the surfaces and an environmental-control mechanism that controls the humidity, temperature, and/or other environmental conditions around the small sample volume. In some embodiments, at least one of the surfaces has a light-transmissive window for allowing optical analysis of a sample contained between the surfaces.

Claims

1. A multi-sample containment system comprising:

a microplate having an array of wells for containing samples, each well having a bottom surface; and

a cover member having a plurality of protrusions complementing the array of wells, each protrusion having a lower surface that contacts a sample opposite the bottom surface of a corresponding well.

2. The system of

claim 1

, wherein each protrusion is spring biased toward the bottom surface of a corresponding well.

3. The system of

claim 1

, wherein the lower surface of each protrusion is substantially planar.

4. The system of

claim 1

, wherein the lower surface of each protrusion is concave.

5. A method for modulating the number of unbound luminophores adjacent a surface during a luminescence surface assay, the method comprising:

providing a sample holder for holding a sample, the sample holder including at least one assay surface configured for performing a luminescence surface assay;

at least partially filling the sample holder with a fluid sample having a population of luminophores, the luminophores capable of binding to the assay surface or to a substrate adjacent the assay surface, so that the sample includes bound and unbound luminophores;

detecting luminescence from the sample, the detected luminescence including at least a portion from bound luminophores and at least a portion from unbound luminophores; and

positioning an excluder near the assay surface, so that the portion of the detected luminescence arising from the unbound luminophores may be modulated.

6. The method of

claim 5

, wherein the sample holder is a microplate well.

7. The method of

claim 6

, wherein the assay surface is a bottom wall of the microplate well.

8. The method of

claim 7

, wherein the assay surface is at least partially transparent.

9. The method of

claim 8

, wherein the step of detecting luminescence includes reading through the assay surface from below the bottom wall.

10. The method of

claim 9

, wherein the excluder includes carbon black to reduce autoluminescence.

11. The method of

claim 5

, the excluder being at least partially transparent, wherein the step of detecting luminescence includes reading through the excluder from above the bottom wall.

12. The method of

claim 11

, wherein the bottom wall includes carbon black to reduce autoluminescence.

13. The method of

claim 5

, wherein the substrate adjacent the assay surface includes cells.

14. The method of

claim 5

, wherein the step of detecting luminescence from the sample includes measuring the luminescence using a light detection device.

15. The method of

claim 14

, wherein the step of positioning an excluder includes placing the excluder within the depth of field of the light detection device.

16. The method of

claim 15

, the excluder having a displacement surface, wherein the excluder includes a stop element configured to set the minimum distance between the displacement surface and assay surface.

17. The method of

claim 5

further comprising mixing the sample by raising, lowering, or rotating the excluder.

18. The method of

claim 5

, the excluder including a displacement surface, wherein the assay surface and displacement surface are separated by at least about 10 micrometers.

19. The method of

claim 5

, the excluder including a displacement surface, wherein the assay surface and displacement surface are separated by no more than about 1 millimeter.

20. A method of analyzing a sample, the method comprising:

depositing a first sample on a first surface;

spreading the first sample across the first surface by robotically moving a second surface into contact with the first sample, where at least one of the first and second surfaces includes a light-transmissive window, and where the separation between the first and second surfaces defines a thin gap that is independent of the volume of the first sample;

depositing a second sample on a third surface;

spreading the second sample across the third surface by robotically moving a fourth surface into contact with the second sample, where at least one of the third and fourth surfaces includes a light-transmissive window, and where the separation between the third and fourth surfaces defines a thin gap that is independent of the volume of the second sample; and

performing an optical analysis on at least one of the first and second samples through at least one of the light-transmissive surfaces.