Fabrication of vascularized tissue using microfabricated two-dimensional molds
US-9738860-B2 · Aug 22, 2017 · US
US11920114B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-11920114-B2 |
| Application number | US-202117176873-A |
| Country | US |
| Kind code | B2 |
| Filing date | Feb 16, 2021 |
| Priority date | Aug 26, 2015 |
| Publication date | Mar 5, 2024 |
| Grant date | Mar 5, 2024 |
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A culture module is contemplated that allows the perfusion and optionally mechanical actuation of one or more microfluidic devices, such as organ-on-a-chip microfluidic devices comprising cells that mimic at least one function of an organ in the body. A method for pressure control is contemplated to allow the control of flow rate (while perfusing cells) despite limitations of common pressure regulators. The method for pressure control allows for perfusion of a microfluidic device, such as an organ on a chip microfluidic device comprising cells that mimic cells in an organ in the body, that is detachably linked with said assembly, so that fluid enters ports of the microfluidic device from a fluid reservoir, optionally without tubing, at a controllable flow rate.
Opening claim text (preview).
The invention claimed is: 1. A system, comprising: a) a pressure manifold comprising a mating surface and a plurality of valves, each of said valves comprising a control feature, and b) a perfusion manifold configured to couple with said pressure manifold, said perfusion manifold comprising one or more reservoirs comprising fluid, said pressure manifold adapted to sense the presence of a coupled perfusion manifold and configured to apply pressure to said fluid in said reservoirs upon contact with said pressure manifold. 2. The system of claim 1 , wherein said perfusion manifold is engaged with a microfluidic device comprising cells. 3. The system of claim 1 , wherein said perfusion manifold comprises a cover above said one or more reservoirs. 4. The system of claim 3 , wherein said pressure manifold is configured to apply pressure to said fluid in said reservoirs through said cover. 5. The system of claim 3 , wherein said cover comprises ports. 6. The system of claim 5 , wherein the pressure manifold further comprises seals. 7. The system of claim 6 , wherein said seals of the pressure manifold are aligned with said ports. 8. The system of claim 1 , wherein said mating surface comprises spring shuttles, each of said spring shuttles comprising a first surface and a second surface, said first surface positioned on said mating surface, said second surface facing said control feature of one of said plurality of valves. 9. The system of claim 8 , wherein said control feature comprises a central pin. 10. A system, comprising: a) a pressure manifold comprising a mating surface and a plurality of valves, each of said valves comprising a control feature, said pressure manifold configured to accept a plurality of perfusion manifolds, and b) a perfusion manifold configured to couple with said pressure manifold, said perfusion manifold comprising one or more reservoirs comprising fluid, said pressure manifold adapted to sense the presence of a coupled perfusion manifold which opens one or more valves of said plurality of valves to enable the application of pressure to a perfusion manifold, wherein valves are closed where a perfusion manifold is absent, in order to prevent pressure leakage. 11. The system of claim 10 , wherein said perfusion manifold is engaged with a microfluidic device comprising cells. 12. A method, comprising: A) providing i) a pressure manifold, said pressure manifold comprising a mating surface and a plurality of valves, each of said valves comprising a control feature; and ii) a perfusion manifold comprising one or more reservoirs comprising fluid, and B) contacting the perfusion manifold with the mating surface of the pressure manifold under conditions such that said pressure manifold applies pressure to said one or more reservoirs of said perfusion manifold. 13. The method of claim 12 , wherein said perfusion manifold is engaged with a microfluidic device, said microfluidic device comprising one or more microchannels comprising living cells. 14. The method of claim 13 , wherein said pressure causes said fluid to flow from said one or more reservoirs into said one or more microchannels of said microfluidic device, thereby perfusing said cells. 15. The method of claim 12 , wherein said perfusion manifold comprises a cover above said one or more reservoirs. 16. The method of claim 15 , wherein said pressure manifold applies pressure to said fluid in said reservoirs through said cover. 17. The method of claim 15 , wherein said cover comprises ports. 18. The method of claim 17 , wherein the pressure manifold further comprises seals. 19. The method of claim 18 , wherein said seals of the pressure manifold are aligned with said ports. 20. The method of claim 12 , wherein said mating surface comprises spring shuttles, each of said spring shuttles comprising a first surface and a second surface, said first surface positioned on said mating surface, said second surface facing said control feature of one of said plurality of valves. 21. The method of claim 12 , wherein said control feature comprises a central pin. 22. A method, comprising: a) providing i) a pressure manifold comprising a mating surface and a plurality of valves, each of said valves comprising a control feature, said pressure manifold configured to accept a plurality of perfusion manifolds, and ii) a perfusion manifold configured to couple with said pressure manifold, said perfusion manifold comprising one or more reservoirs comprising fluid, said pressure manifold adapted to sense the presence of a coupled perfusion manifold; b) coupling said perfusion manifold with said pressure manifold, such that one or more valves of said plurality of valves open, whereupon pressure is applied to said perfusion manifold, wherein valves are closed where a perfusion manifold is absent, in order to prevent pressure leakage. 23. The method of claim 22 , wherein said perfusion manifold is engaged with a microfluidic device comprising cells. 24. The method of claim 23 , wherein pressure is applied to the fluid in said one or more reservoirs causing fluid to flow, thereby perfusing said cells. 25. The method of claim 24 , wherein negative pressure is applied.
by pressure · CPC title
for organ perfusion · CPC title
Preservation or perfusion media · CPC title
Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093) · CPC title
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