Three-dimensional microfluidic platforms and methods of use thereof
Provided are methods and devices for formation and study of three-dimensional biological systems, including prokaryotic and eukaryotic cell migration, proliferation, and differentiation.
1. A microfluidic device, comprising:
an optically transparent material;
a substrate coupled to the optically transparent material; and
a scaffold having dimensions of at least 10 μm in three-dimensional space;
wherein
the substrate comprises a plurality of posts;
the scaffold contacts the substrate, the posts, and the optically transparent material;
the scaffold comprises a solid or semi-solid biological or biocompatible polymer;
the substrate comprises a first fluid-flow path and a second fluid-flow path;
the first fluid-flow path does not intersect with the second fluid-flow path;
the scaffold is disposed between the first fluid-flow path and the second fluid-flow path;
the posts are arranged in a staggered array; and
the staggered array of posts is disposed between the first fluid flow path and the second fluid flow path.
2. The device of claim 1 , wherein the first fluid-flow path and the second fluid-flow path are channels in the substrate.
3. The device of claim 1 , wherein the substrate comprises plastic.
4. The device of claim 1 , wherein the substrate comprises PDMS.
5. The device of claim 1 , wherein the substrate is modified.
6. The device of claim 5 , wherein the modified substrate is a result of exposure of the substrate to poly-D-lysine, or exposure of the substrate to plasma.
7. The device of claim 1 , wherein the scaffold comprises a first biological entity.
8. The device of claim 1 , further comprising a pressure regulator.
9. The device of claim 1 , wherein the first fluid-flow path or the second fluid-flow path comprises a resistance channel.
10. The device of claim 1 , wherein the first fluid-flow path has different dimensions than the second fluid flow path.
11. The device of claim 1 , wherein the scaffold comprises a solid or semi-solid biocompatible polymer; and the solid or semi-solid biocompatible polymer allows the passage of a second biological entity.
12. The device of claim 11 , wherein the scaffold comprises collagen, agarose, gelatin, fibronectin, fibrin, laminin, or a peptide; and the second biological entity comprises a eukaryotic cell.
13. The device of claim 11 , wherein the scaffold comprises collagen; and the second biological entity is selected from the group consisting of a growth factor, a cytokine, a hormone, an antibody, and an enzyme.
14. A method of measuring directed migration of a cell, comprising the steps of:
a) providing a device of claim 1 ;
b) introducing a cell into the first fluid-flow path;
c) introducing a biological entity into the second fluid-flow path; and
d) measuring the directed migration of the cell into the scaffold.
15. The method of claim 14 , wherein the biological entity is selected from the group consisting of prokaryotic cells, eukaryotic cells, growth factors, cytokines, hormones, antibodies, drugs, and enzymes.
16. The method of claim 14 , wherein the cell is a neutrophil, and the biological entity is an endothelial cell.
17. The method of claim 14 , wherein the cell is an endothelial cell; the biological entity is a second cell; the second cell is a tumor cell.
18. The method of claim 17 , wherein the cell and the second cell are obtained from the same subject.
19. A method of measuring blood vessel formation, comprising the steps of:
a) providing a device of claim 1 ;
b) introducing an endothelial cell or endothelial cell precursor into the first fluid-flow path;
c) introducing a biological entity into the second fluid-flow path; and
d) measuring the formation of a blood vessel in the scaffold.
20. The method of claim 19 , wherein the biological entity is selected from the group consisting of prokaryotic cells, eukaryotic cells, growth factors, cytokines, hormones, antibodies, drugs, and enzymes.
21. A method of measuring permeability, comprising the steps of
a) providing a device of claim 1 ;
b) introducing a first substance into the first fluid-flow path; and
c) measuring the permeability of the first substance into the scaffold.
22. The method of claim 21 , wherein the first substance is a fluid or a small molecule.
23. The method of claim 21 , wherein the scaffold comprises a cell monolayer.
24. The method of claim 21 , wherein the first substance comprises a cell.
25. The method of claim 24 , wherein the cell is an endothelial cell.
26. The method of claim 21 , wherein the scaffold comprises a second cell.
27. The method of claim 26 , wherein the second cell is a tumor cell.