US 12,241,049 B2
Multi-compartment device containing human three-dimensional (3D) microtissues for toxicity testing
Kim Boekelheide, East Greenwich, RI (US); Jeffrey Morgan, Sharon, MA (US); Susan Hall, Saunderstown, RI (US); Hui Li, Cranston, RI (US); and Blanche Ip, Providence, RI (US)
Assigned to BROWN UNIVERSITY, Providence, RI (US)
Appl. No. 17/420,107
Filed by BROWN UNIVERSITY, Providence, RI (US)
PCT Filed Jan. 9, 2020, PCT No. PCT/US2020/012986
§ 371(c)(1), (2) Date Jun. 30, 2021,
PCT Pub. No. WO2020/146676, PCT Pub. Date Jul. 16, 2020.
Claims priority of provisional application 62/790,901, filed on Jan. 10, 2019.
Prior Publication US 2022/0081659 A1, Mar. 17, 2022
Int. Cl. C12M 3/00 (2006.01); C12M 1/00 (2006.01); C12M 1/32 (2006.01); C12M 1/42 (2006.01); G01N 33/50 (2006.01)
CPC C12M 21/08 (2013.01) [C12M 23/12 (2013.01); C12M 23/34 (2013.01); C12M 35/08 (2013.01); G01N 33/5014 (2013.01); G01N 33/5088 (2013.01)] 7 Claims
OG exemplary drawing
 
1. A device comprising at least a first compartment and a second compartment, with a central permeable wall between the first compartment and the second compartment; the permeable wall being a cell barrier that is impermeable to cells but permeable to small molecules, biomolecules, and proteins including hormones, without requiring a use of an impermeable wall with one or more capillary openings;
(a) wherein the first compartment is in an opening in a shape of a toroid, surrounding the central permeable wall acting as a molecule-permeable barrier, with a first floor and an outer wall adapted for containing three-dimensional (3D) metabolizing and hormone-producing microtissues, and wherein the first compartment can be seeded with cells from a cell population and the seeded cells will grow into one or more 3D microtissues surrounding the central cell barrier or permeable wall; the first compartment operative to accept a test compound, and the one or more 3D microtissues being capable of metabolizing the test compound;
(b) wherein the central permeable wall includes a hollow center with a second floor forming the second compartment surrounded by the central permeable wall;
(c) wherein the second compartment is adapted for containing cells of a selected target cell population that do not cross over to the first compartment, and wherein the second compartment can be seeded with cells, cells in a gel, or cells in a liquid from a selected target cell population and said cells are operative to grow into one or more target cells in a form of one or more microtissues, a two-dimensional (2D) attached monolayer of cells, and/or into a 3D spheroid; and
(d) whereupon if the 3D microtissue(s) metabolizes the test compound, metabolites and hormones resulting from one or more effects of the test compound on the 3D microtissues in the first compartment can passively diffuse through the central permeable wall to the one or more target cells in the second compartment and from the second compartment into the first compartment.