Cell culture device
A cell culture device comprises a well. A plurality of microwells are within the well, and a first common fluid volume is within the well above the microwells. A set of sub-microwells are within each microwell, and a second common fluid volume is within each microwell above the set of sub-microwells.
1. A cell culture device comprising:
a well defined by at least one well sidewall and a well bottom wall;
a plurality of microwells within the well, each microwell defined by at least one microwell sidewall extending upwardly from the well bottom wall and separating a microwell fluid volume from a microwell fluid volume of an adjacent microwell and a first common fluid volume within the well above the microwells, wherein microwell sidewalls between adjacent microwells converge to form an apex; and
a set of sub-microwells within each microwell for containing one or more cells within each sub-microwell, and a second common fluid volume within each microwell above the set of sub-microwells, each sub-microwell comprising a sub-microwell top portion, a sub-microwell bottom portion and at least one sub-microwell sidewall extending upwardly from the well bottom wall separating a sub-microwell fluid volume from a sub-microwell fluid volume of an adjacent sub-microwell.
2. The cell culture device of claim 1 , wherein each sub-microwell is further defined by a portion of one of the microwell sidewalls.
3. The cell culture device of claim 1 , wherein the well bottom wall is transparent or translucent.
4. The cell culture device of claim 1 , wherein each set of sub-microwells comprises four sub-microwells arranged in a 2×2 array.
5. The cell culture device of claim 1 , wherein each set of sub-microwells comprises sub-microwells arranged in a 2×1, 3×1, 3×2, 3×3 or larger array.
6. The cell culture device of claim 1 , wherein each sub-microwell tapers in cross-sectional area going from the sub-microwell top portion to the sub-microwell bottom portion.
7. The cell culture device of claim 1 , wherein each microwell is frustoconical or frustopyramidal.
8. The cell culture device of claim 1 , wherein each sub-microwell is frustoconical or frustopyramidal.
9. The cell culture device of any claim 1 , wherein each microwell comprises a microwell top portion and a microwell bottom portion, and each microwell tapers in cross-sectional area going from the microwell top portion to the microwell bottom portion.
10. The cell culture device of claim 1 , wherein the sub-microwells, microwells, and well are integrally formed.
11. The cell culture device of claim 1 , further comprising a magnetic or magnetizable member positioned below the sub-microwells.
12. The cell culture device of claim 11 , wherein the magnetizable member is a wire grid, the well is defined at least in part by a well bottom wall, and the wire grid is embedded within the well bottom wall.
13. The cell culture device of claim 1 , wherein each microwell has a microwell top portion and an opposed microwell bottom portion, and the top portion of each microwell has a microwell width of at least 100 microns.
14. The cell culture device of claim 13 , wherein each microwell has a microwell depth between the top portion and the bottom portion of at least 75 microns.
15. The cell culture device of claim 1 , wherein each microwell has a microwell top portion and a microwell bottom portion, and each microwell comprises a largest dimension at the microwell top portion, and a microwell depth between the microwell top portion and the microwell bottom portion, and the ratio of the largest dimension to the microwell depth is between 1.1:1 and 1.9:1.
16. The cell culture device of claim 1 , each microwell comprising a microwell top portion and a microwell bottom portion, each microwell comprising a largest dimension at the microwell top portion, and a microwell depth between the microwell top portion and the microwell bottom portion, wherein each microwell tapers in cross-sectional area going from the microwell top portion to the microwell bottom portion and the ratio of the largest dimension to the microwell depth is between 1.1:1 and 1.9:1.
17. The cell culture device of claim 16 , wherein the largest dimension is at least 140 microns.
18. The cell culture device claim 16 , wherein the microwell depth is at least 75 microns.
19. The cell culture device of claim 16 , wherein each microwell is frustoconical or frustopyramidal.
20. The cell culture device of claim 16 , wherein each sub-microwell is frustoconical or frustopyramidal.
21. The cell culture device of claim 16 , wherein the well is defined at least in part by at least one well sidewall, and a well bottom wall.
22. The cell culture device of claim 21 , wherein the well bottom wall is transparent or translucent.
23. The cell culture device of claim 16 , further comprising a magnetic or magnetizable grid positioned below the microwells.
24. The cell culture device of claim 23 , wherein the well is defined at least in part by a well bottom wall, and the grid is embedded within the well bottom wall.
25. The cell culture device of claim 16 , wherein the microwells and well are integrally formed.
26. The cell culture device of claim 16 , wherein the sub-microwells are integrally formed with the microwells and well.
27. The cell culture device of claim 16 wherein each set of sub-microwells comprises four sub-microwells arranged in a 2×2 array.
28. The cell culture device of claim 16 , wherein each sub-microwell tapers in cross-sectional area going from the sub-microwell top portion to the sub-microwell bottom portion.
29. The cell culture device of claim 16 , further comprising a second common fluid volume within each microwell above the set of sub-microwells.
30. The cell culture device of claim 16 , wherein the angle of the microwell sidewall with respect to the vertical is less than 30 degrees.