Hanging drop devices, systems and/or methods

• US 8,906,685 B2
• Filed: 01/28/2011
• Issued: 12/09/2014
• Est. Priority Date: 01/28/2010
• Status: Active Grant

• Current Assignee: 3D Biomatrix, Inc., Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: 3D Biomatrix, Inc., Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Takayama, Shuichi, Tung, Yi-Chung, Hsiao, Amy Yu-Ching, Jan, Edward
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US13/575,558
• Publication Number:
  US 20130040855A1
• Time in Patent Office: 1,411 Days
• Field of Search: None
• US Class Current: 435/383
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/141 Preventing contamination, tampering
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: B01L 3/50857 using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: B01L 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 25/01 Drops
• CPC Class Codes: C12N 5/0062 General methods for three-dimensional culture
• CPC Class Codes: G01N 2035/1046 Levitated, suspended drops
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates

Abstract

The present disclosure relates general to devices, systems, and methods of using such devices in creating and handling hanging drops of fluid. The present disclosure also relates to cell culture devices, methods and/or systems of using such devices as well as the use of cell culture devices, for example, for research and high throughput screening.

Claims

1. A hanging drop array plate comprising:

a top surface and a bottom surface, said top surface bounded by one or more edges,

a plurality of holes, each said hole extending from an opening in said top surface to an outlet at said bottom surface, said plurality of holes configured to accommodate a corresponding plurality of hanging drops formed by application of a liquid through said opening of each of said holes, wherein a single drop hangs from a respective one of each of said holes and distends under the influence of gravity beneath said outlet thereof to enable the culturing of cells therein,

said bottom surface including a plateau feature surrounding each of said holes, said plateau feature configured to restrain a hanging drop to a confined region about the respective said hole; and

said top surface including an upper reservoir configured to receive a body of liquid restricted from said plurality of holes for maintaining a substantially stable humidity above said plurality of holes, said upper reservoir disposed along one or more of said edges of said top surface.

2. The array plate of claim 1, wherein said upper reservoir substantially surrounds said plurality of holes.

3. The array plate of claim 1, wherein said top surface includes a peripheral rim disposed adjacent said one or more edges of said top surface, said peripheral rim having a rim height measured perpendicularly from said top surface.

4. The array plate of claim 3, further including a wall structure, said wall structure surrounded by said peripheral rim and inset therefrom with said upper reservoir formed in a space therebetween, said wall structure having a wall height measured perpendicularly from said top surface, said wall height being shorter than said rim height.

5. The array plate of claim 1, wherein each said hole is approximately 1.6 mm in diameter.

6. The array plate of claim 1, further including a tray configured to form an enclosed space below said bottom surface in spaced relation therefrom so as to maintain separation from the hanging drops.

7. The array plate of claim 6, wherein said tray includes at least one lower reservoir configured to receive a body of liquid for maintaining a substantially stable humidity below said plurality of holes.

8. The array plate of claim 7, wherein said tray is fabricated from an optically transparent material.

9. The array plate of claim 1, wherein said plateau comprises an annular ring structure.

10. A method of cell analysis, comprising:

a) inserting a plurality of hanging drops into the hanging drop array plate of claim 1; and

b) performing on one or more of the hanging drops an analysis method selected from the group consisting of cell culturing, cell maintaining, cell analysis, cell testing, and combinations thereof.