Low background multi-well plates with greater than 864 wells for fluorescence measurements of biological and biochemical samples

• US 5,910,287 A
• Filed: 06/03/1997
• Issued: 06/08/1999
• Est. Priority Date: 06/03/1997
• Status: Expired due to Term

• Current Assignee: NEXUS Biosystems, Inc. (Azenta, Inc.)
• Original Assignee: Aurora Biosciences Corporation (Vertex Pharmaceuticals Incorporated)
• Inventors: Cassin, Peter J., Tsien, Roger Y., Pham, Andrew A., Harootunian, Alec Tate
• Primary Examiner(s): Pyon, Harold Y.
• Application Number:
  US08/868,049
• Time in Patent Office: 735 Days
• Field of Search: 422/82.05, 422/99, 422/101, 422/102, 422/104, 436/805, 436/809, 436/546, 436/800
• US Class Current: 422/553
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 9/523 for multisample carriers, e.g. used for microtitration plates
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10S 436/809 Multifield plates or multicontainer arrays

Abstract

The invention provides for multi-well plates with greater than 864 wells that comprise a layer of cycloolefin having low fluorescence and high transmittance. These multi-well plates are particularly well suited for fluorescence measurements.

Claims

1. A multi-well plate for fluorescence measurements of biological and biochemical samples, comprising:

more than 864 wells and each well comprising a wall and a bottom layer, said bottom layer with a low fluorescence and high transmittance portion comprising a cycloolefin copolymer, and

a frame, wherein said wells are disposed in said frame and said wells can hold ten microliters or less in volume,

wherein said multi-well plate is for detecting a fluorescence signal from a biological and biochemical sample and said multi-well plate has a footprint of a standard 96-well microtiter plate, and further wherein said low fluorescence and high transmittance portion is substantially all of said bottom layer.

2. The multi-well plate of claim 1, therein said multi-well plate has about 3456 or more wells.

3. The multi-well plate of claim 1, wherein said multi-well plate has wells with a well center to well center distance of less than about 2.5 mm.

4. The multi-well plate of claim 3, wherein said cycloolefin polymer has a thickness between about 20 and 200 microns.

5. The multi-well plate of claim 4, wherein said cycloolefin polymer has a thickness between about 30 and 80 microns thick.

6. The multi-well plate of claim 1, wherein said cycloolefin polymer has a thickness between about 20 and 200 microns.

7. The multi-well plate of claim 6, wherein said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm.

8. The multi-well plate of claim 7, wherein said frame is made of a cycloolefin polymer.

9. The multi-well plate of claim 6, wherein said multi-well plate is injection molded.

10. The multi-well plate of claim 9, wherein said bottom produces about 200 percent or less of the fluorescence compared to fused silica glass of 100 microns thickness at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 300 to 800 nm.

11. The multi-well plate of claim 9, wherein said wall comprises a pigment for background reduction.

12. The multi-well plate of claim 11, wherein said bottom ether comprises one member of a binding pair.

13. The multi-well plate of claim 11, wherein said bottom further comprises a plurality of living cells.

14. The multi-well plate of claim 11, wherein said walls are made of a cycloolefin compolymer.

15. A process for making a multi-well plate for fluorescence measurements of biological and biochemical samples with more than 864 wells and each well comprising a polymer wall, said process comprising:

injection molding said multi-well plate with a bottom layer with low fluorescence and high transmittance, comprising a cycloolefin copolymer, and

wherein said wells of said multi-well plate are disposed in a frame and said wells can hold ten microliters or less in volume, and said multi-well plate is for detecting a fluorescence signal from a biological or biochemical sample and said multi-well plate has a footprint of a standard 96-well microtiter plate, and further wherein said low fluorescence and high transmittance portion is substantially all of said bottom layer.

16. The process of claim 15, wherein said wells are made of a cycloolefin polymer.

17. The process of claim 15, injection molding yields a cycloolefin bottom between about 30 and 150 microns.

18. A kit, comprising:

a) reagents for an assay,

b) a multi-well plate for fluorescence measurements of biological and biochemical samples, comprising;

i) more than 864 wells and each well comprising a wall and a bottom layer, said bottom layer with a low fluorescence and high transmittance portion comprising a cycloolefin copolymer, and

ii) a frame, wherein said wells are disposed in said frame and said wells can hold ten microliters or less in volume;

wherein said multi-well plate is for detecting a signal from a sample and said multi-well plate has a footprint of a standard 96-well microtiter plate, and further wherein said low fluorescence and high transmittance portion is substantially all of said bottom layer.

19. The kit of claim 18, further comprising a detector.

20. A multi-well plate for fluorescence measurements of biological and biochemical samples, comprsing:

more than 864 wells in two dimensional linear arrays and each well comprising a wall and a bottom layer said bottom layer with a low fluorescence and high transmittance portion comprising a cycloolefin polymer, and

a frame, wherein said wells are disposed in said frame, and said wells can hold ten microliters or less in volume,

wherein said multi-well plate is for detecting a signal from a sample and said multi-well plate has a footprint of a standard 96-well microtiter plate, and further wherein said low fluorescence and high transmittance portion is substantially all of said bottom layer.

21. The multi-well plate of claim 20, wherein said multi-well plate is insert molded.

22. The multi-well plate of claim 21, wherein said bottom is between about 20 to 200 microns thick.