Horizontal fluid flow bioreactor for cancer research
A horizontal flow bioreactor facilitates continuous flow conditions to cells grown on a tissue engineered scaffold. More particularly, interstitial fluid flow conditions are mimicked around cells inside the body, thereby improving the mass transfer rates of cells and providing physical stimulus to the cells. Unlike the available perfusion based vertical bioreactors where flow is vertical through scaffolds, the horizontal flow reactor enables studies on attachment of cells to substrates, tissues, and bone mimetic scaffolds. The horizontal bioreactor further aides study of cell proliferation, cell migration, cell clustering, biology of cell growth, cell response, cell filtration techniques for capturing tumor cells, the testing of drugs, and drug delivery under flow conditions. The horizontal bioreactor can mimic in vivo conditions, epithelial to mesenchymal transition (EMT), and mesenchymal to epithelial transition (MET).
1 . A horizontal flow bioreactor comprising:
a primary site having cells, said primary site fluidly terminating at a media inlet or a surface of a transwell insert;
a scaffold placed between the media inlet and a media outlet;
a secondary site fluidly beginning at said media outlet;
a horizontal fluid path over and through said scaffolds for migrating said cells from the primary site to the secondary site;
wherein the primary site is an upper bioreactor chamber and the secondary site is a lower bioreactor chamber; and
wherein flow mimics interstitial fluid flow conditions around the cells.
2 . The horizontal flow bioreactor of claim 1 further comprising a drain.
3 . The horizontal flow bioreactor of claim 1 , wherein the cells are tumor cells.
4 . An incubator comprising:
a plurality the horizontal flow bioreactors of claim 1 ;
an epithelial to mesenchymal transition (EMT) test-bed comprising some of the horizontal flow bioreactors;
a multi-channel pump; and
a mesenchymal to epithelial transition (MET) test-bed comprising some of the horizontal flow bioreactors.
5 . The incubator of claim 4 wherein a number of horizontal flow bioreactors in the EMT test-bed and a number of horizontal flow bioreactors in the MET test-bed are identical, wherein the horizontal flow bioreactors within the EMT test-bed are fluidly arranged in parallel and the horizontal flow bioreactors within the MET test-bed are fluidly arranged in parallel.
6 . A method for modeling tumor growth and metastasis in vitro, the method comprising:
providing a horizontal flow bioreactor comprising a first bioreactor chamber; a second bioreactor chamber; a peristaltic pump that can regulate flow rate of a fluid; tubing for delivering the fluid between the pump, the first bioreactor chamber, the second bioreactor chamber; and an in-line injection port for sample insertion and/or sample extraction;
introducing tumor cells into the horizontal flow bioreactor;
flowing a medium from the first bioreactor chamber to the second bioreactor chamber, wherein the flow mimics interstitial fluid flow conditions around the cells.
7 . The method of claim 6 , wherein the first bioreactor chamber comprises a primary site scaffold, and wherein the second bioreactor chamber comprises a secondary site scaffold.
8 . The method of claim 7 , wherein the secondary site scaffold is a bone mimetic scaffold, a lung mimetic scaffold, a liver mimetic scaffold, or a brain mimetic scaffold.
9 . The method of claim 6 , wherein the introducing comprises seeding the tumor cells on a primary site scaffold in the first bioreactor chamber.