Bioartificial liver
This document provides bioartificial liver (BAL) devices. Methods for making and using BAL devices also are provided.
1. A bioartificial liver device comprising a blood separation cartridge in fluid communication with a reservoir chamber, wherein said reservoir chamber is a cylindrical chamber having a top wall, a bottom wall, and a side wall and comprises a mixing chamber, a settling volume chamber, a funnel having an open spout, hepatocyte spheroids, and a means for mixing configured to maintain said hepatocyte spheroids in suspension, wherein said top wall of said reservoir chamber defines a top wall of said settling chamber, wherein said bottom wall of said reservoir chamber defines a bottom wall of said mixing chamber, wherein a portion of said side wall of said reservoir chamber defines a portion of a side wall of said settling chamber, and wherein a portion of said side wall of said reservoir chamber defines a portion of a side wall of said mixing chamber, wherein said mixing chamber is located below said settling volume chamber to allow said hepatocyte spheroids when present within said settling volume chamber to settle towards said mixing chamber and pass through said open spout, wherein said mixing chamber is separated from said settling volume chamber by said funnel, wherein at least a portion of said mixing chamber is defined by an outer surface of said funnel, wherein at least a portion of said settling volume chamber is defined by an inner surface of said funnel, wherein said mixing chamber is in fluid communication with said settling volume chamber via at least said spout, wherein said blood separation cartridge comprises a membrane configured to allow blood to be detoxified without said blood passing to said reservoir chamber, and wherein said bioartificial liver device is configured to deliver blood from a patient to said blood separation cartridge and to return detoxified blood to said patient,
wherein said means for mixing is arranged in the mixing chamber and below said open spout,
wherein said open spout is located from a bottom, inner surface of said mixing chamber at a distance configured to minimize loss of said hepatocytes spheroids out of the mixing chamber.
2. The bioartificial liver device of claim 1 , wherein said open spout is located less than 5 cm from said bottom, inner surface of said mixing chamber.
3. The bioartificial liver device of claim 1 , wherein said funnel comprises openings between 100 μm and 5 mm in diameter.
4. The bioartificial liver device of claim 1 , wherein said means for mixing is a magnetic stir bar within said mixing chamber.
5. The bioartificial liver device of claim 1 , wherein said mixing chamber comprises an inlet port.
6. The bioartificial liver device of claim 1 , wherein said settling volume chamber comprises an outlet port.
7. The bioartificial liver device of claim 1 , wherein said funnel comprises more than 25 openings.
8. The bioartificial liver device of claim 7 , wherein said openings are between 100 μm and 5 mm in diameter.
9. The bioartificial liver device of claim 1 , wherein said reservoir chamber comprises a sampling port.
10. The bioartificial liver device of claim 1 , wherein said reservoir chamber comprises temperature probe.