Engineering of a novel breast tumor microenvironment on a microfluidic chip

1. A microfluidic device, comprising:

a surface defining one or more microfluidic channels, wherein the surface extends beyond the one or more microfluidic channels;

a first three dimensional scaffold comprising one or more cancer cells that is not in direct contact with the one or more microfluidic channels;

a second three dimensional scaffold, at least a portion of which is directly contacting the one or more microfluidic channels and the first three dimensional scaffold, and which is in direct fluid communication with both the first three dimensional scaffold and the one or more microfluidic channels,

wherein the first three dimensional scaffold, the second three dimensional scaffold, or both comprise a gel matrix; and

wherein the extended surface underlies both the first and second three dimensional scaffolds.

2. The microfluidic device of claim 1 , wherein the one or more cancer cells are metastatic or tumorigenic cancer cells.

3. The microfluidic device of claim 1 , wherein the one or more cancer cells are breast cancer cells.

4. The microfluidic device of any of claim 1 , wherein the second three dimensional scaffold comprises one or more stromal cells.

5. The microfluidic device of claim 4 , wherein the one or more stromal cells are fibroblasts.

6. The microfluidic device of claim 1 , wherein the second three dimensional scaffold comprises one or more macrophages.

7. The microfluidic device of claim 1 , wherein one or more of the microfluidic channels comprises one or more endothelial cells.

8. The microfluidic device of claim 1 , wherein the gel matrix comprises one or more of the group consisting of collagen, fibronectin, hyaluronan, a hydrogel, a peptide gel, a gel-like protein or interpenetrating network hydrogels.

9. The microfluidic device of claim 1 , wherein the gel matrix comprises a collagen hydrogel.

10. The microfluidic device of claim 1 , wherein the surface further comprises microposts separating the one or more microfluidic channels from the second three dimensional scaffold.

11. The microfluidic device of claim 1 , further comprising one of more inlets for adding the first three dimensional scaffold, the second three dimensional scaffold, or both to the microfluidic device.

12. The microfluidic device of claim 1 , wherein one or more of the microfluidic channels comprises one or more fluidic inlets suitable for introducing a test agent into the microfluidic device.

13. The microfluidic device of claim 12 , comprising two microfluidic channels disposed along two opposite sides of the second three dimensional matrix.

14. The microfluidic device of claim 1 , wherein the one or more cancer cells are obtained directly from a cancer patient in need of treatment.

15. A method of assaying a test agent for anti-cancer activity, comprising:

introducing the test agent to the microfluidic device of claim 12 through the one or more fluidic inlets; and

observing the cancer cells within the microfluidic device to determine the effect of the test agent.

16. The method of claim 15 , wherein the cancer cells are obtained directly from a patient in need of treatment or commercially available cells lines.

17. A method of studying cancer or related cells, comprising:

observing one or more of the cancer cells or related cells within the microfluidic device of claim 1 .

18. The method of claim 17 , further comprising the steps of altering one or more microenvironments within the microfluidic device and determining the effect of the alteration on the one or more cancer cells or related cells.

19. A microfluidic device, comprising:

a surface defining two microfluidic channels and extending beyond the two microfluidic channels;

a first three dimensional scaffold comprising one or more cancer cells that is not in direct contact with the two microfluidic channels;

a second three dimensional scaffold, at least a portion of which is directly contacting the two microfluidic channels and the first three dimensional scaffold, and which is in direct fluid communication with both the first three dimensional scaffold and the two microfluidic channels;

wherein the surface underlies both the first and second three dimensional scaffolds; and

wherein the two microfluidic channels are disposed along two opposite sides of the second three dimensional scaffold.

20. A microfluidic device, comprising:

a surface defining two microfluidic channels and extending beyond the two microfluidic channels;

a first three dimensional scaffold comprising one or more breast cancer cells that is not in direct contact with the two microfluidic channels;

a second three dimensional scaffold comprising stromal cells, at least a portion of which is directly contacting the two microfluidic channels and the first three dimensional scaffold, and which is in direct fluid communication with both the first three dimensional scaffold and the two microfluidic channels;

one of more inlets for adding the first three dimensional scaffold, the second three dimensional scaffold, or both to the microfluidic device;

wherein the first three dimensional scaffold and the second three dimensional comprise a gel matrix;

wherein the surface further comprises microposts separating the one or more microfluidic channels from the second three dimensional scaffold

wherein the surface underlies both the first and second three dimensional scaffolds; and

wherein the two microfluidic channels are located on along two opposite sides of the second three dimensional scaffold.