Apparatus for holding small volumes of liquids

• US 6,027,695 A
• Filed: 04/01/1998
• Issued: 02/22/2000
• Est. Priority Date: 04/01/1998
• Status: Expired due to Term

• Current Assignee: Bristol-Myers Squibb Pharma Company (Bristol-Myers Squibb Company)
• Original Assignee: DuPont Performance Elastomers L (Bristol-Myers Squibb Company)
• Inventors: Oldenburg, Kevin R., Chung, Thomas D. Y., Hollis, Gregory F.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US09/053,287
• Time in Patent Office: 692 Days
• Field of Search: 422/61, 422/102, 436/172, 436/174, 436/809, 435/288.3, 435/288.4, 435/305.1, 435/305.2, 356/244
• US Class Current: 506/39
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0893 having a very large number of wells, microfabricated wells
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: C40B 60/14 for creating libraries

Abstract

An apparatus for holding liquid, such as a microtiter plate, in which a plurality of wells are formed. Each of the wells have side walls that intersect in an edge that defines the boundary between adjacent wells. The edge boundary prevents liquid from collecting between the wells, thereby causing all of the liquid applied to the plate to enter one of the wells. The microtiter plate can be formed from a material having a reflectance and/or fluorescence that is optimized for the particular application in which the microtiter plate will be used. Microtiter plates for use in fluorescence measurement applications are made from material having low fluorescence, such as a liquid crystal polymer, while microtiter plates for use in luminescence measurements are made from material having a high reflectance. Microtiter plates for spectrophotometric applications are made with wells having clear bottoms and opaque walls. Such clear bottomed wells can be made by incorporating a photobleachable dye into the plate material so as to render it essentially opaque and then irradiating the bottoms of the wells so as to render them transparent. Such wells can also be made by forming the plate from an essentially transparent material and then irradiating the sidewalls with a beam of light so as to render them essentially opaque.

Claims

1. An apparatus for holding a liquid during assay, comprising a plate in which a plurality of adjacent wells are formed, each of said wells having (i) a bottom, (ii) at least one side wall, said side walls of adjacent wells intersecting so as to form an upward facing edge, and (iii) an opening for receiving a liquid, said openings of adjacent wells being separated by a boundary defined by said edge.

2. The apparatus according to claim 1, wherein the width of each of said edges is no greater than approximately 250 microns.

3. The apparatus according to claim 2, wherein each of said edges forms an arcuate surface having a radius of curvature no greater than approximately 150 microns.

4. The apparatus according to claim 1, wherein the maximum width of any horizontal surface formed on said edges is less than approximately 80 microns.

5. The apparatus according to claim 1, wherein a first portion of each of said side walls is disposed adjacent said upward facing edge, and wherein said first side wall portions are inclined at an angle with respect to the vertical direction.

6. The apparatus according to claim 5, wherein a second portion of each of said side walls extends in essentially the vertical direction.

7. The apparatus according to claim 5, wherein each of said first portions of said well side walls forms a conical surface.

8. The apparatus according to claim 7, wherein each of said side walls further comprises a second portion, said second side wall portions being cylindrical.

9. The apparatus according to claim 7, wherein said conical surface forms an included angle of no greater than approximately 90°

.

10. The apparatus according to claim 9, wherein said included angle is no greater than approximately 60°

.

11. The apparatus according to claim 5, wherein said first side wall portions of each of said wells forms an angle of no greater than approximately 45°

with respect to the vertical direction.

12. The apparatus according to claim 11, wherein said angle said first side wall portions form with respect to the vertical direction is no greater than 30°

.

13. The apparatus according to claim 1, wherein each of said wells is a microwell.

14. The apparatus according to claim 13, wherein the volume of each of said microwells is no greater than approximately 5 microliters.

15. The apparatus according to claim 14, wherein the volume of each of said microwells is no greater than approximately 0.5 microliters.

16. The apparatus according to claim 1, wherein at least approximately 2400 microwells are formed in said plate.

17. The apparatus according to claim 16, wherein at least approximately 9600 microwells are formed in said plate.

18. The apparatus according to claim 1, wherein said plate is formed from a liquid crystal polymer.

19. The apparatus according to claim 1, wherein each of said well bottoms is flat.

20. The apparatus according to claim 1, wherein each of said well bottoms is arcuate.

21. The apparatus according to claim 1, wherein said plate is formed from a transparent material, and further comprising a photochromic film bonded to said side walls.

22. An apparatus according to claim 1, wherein said plate is formed from a material having essentially no fluorescence in the range of wave lengths in the 300 nm to 650 nm range.

23. The apparatus according to claim 22, wherein said material is a liquid crystal polymer.

25. The method according to claim 23, wherein said beads are from a combinatorial chemistry library.

24. A method of screening an agent for biological activity, comprising the steps of:

a) suspending a plurality of beads in a solvent so as to form a bead containing suspension;

b) pouring said suspension onto a plate having a plurality of microwells formed therein, each of said microwells having (i) a bottom, (ii) at least one side wall, said side walls of adjacent microwells intersecting so as to form an upward facing edge, and (iii) an opening for receiving said suspension, said openings of adjacent microwells being separated by a boundary defined by said edge, whereby a portion of said solvent enters each of said microwells;

c) allowing said suspended beads to settle into said microwells so that each of said beads is suspended in said portion of said solvent in one of said microwells;

d) removing said solvent; and

e) applying said agent onto said plate.