Micromachined bilayer unit of engineered tissues

• US 20050202557A1
• Filed: 11/05/2004
• Published: 09/15/2005
• Est. Priority Date: 04/28/2000
• Status: Active Grant

• Current Assignee: Charles Stark Draper Laboratory Incorporated, Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Charles Stark Draper Laboratory Incorporated
• Inventors: Barnard, Edward S., Kaazempur-Mofrad, Mohammad R., Orrick, Brian K., Borenstein, Jeffrey, Vacanti, Joseph P., Krebs, Nicholas J., Pritchard, Eleanor M., Weinberg, Eli, Marentis, Theodore
• Granted Patent: US 7,776,021 B2
• Time in Patent Office: Days
• US Class Current: 435/369
• CPC Class Codes: A61M 1/1678 intracorporal peritoneal dialysis A61M1/28
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

Methods and materials for making an apparatus which duplicates the functionality of a physiological system id provided.

Claims

1. An apparatus which duplicates the functionality of a physiological system, comprising:

a) a first mold defining upper and lower surfaces, wherein at least one surface of the first mold includes microchannels formed thereon;

b) a second mold defining upper and lower surfaces, wherein at least one surface of the second mold includes microchannels formed thereon;

c) a semi-permeable membrane defining an upper surface and a lower surface,

wherein the upper surface of the membrane is secured adjacent to the lower surface of the first mold and the lower surface of the membrane is secured adjacent to the upper surface of the second mold.

2. The apparatus of claim 1, further comprising nutrient supply and excretion removal conduits in fluid communication with the apparatus.

3. The apparatus of claim 2, further comprising pumping means for circulating fluid through the apparatus.

4. The apparatus of claim 1, further comprising additional molds stacked upon the first and second molds to form about 8 to about 2000 layers.

5. The apparatus of claim 1, wherein the semi-permeable membrane is made of a material selected from the group consisting of cellulose, PolyDiMethylSiloxane, PolyMethylMethacrylate, PolyEtherSulfone, PolySulfone, PolyCarbonate, PolyLactide-co-Glycolide, PolyCaproLactone and Biorubber.

6. The apparatus of claim 1, wherein the microchannels are connected beginning from one or more inlets, expanding into more channels, and then converging back into one or more outlets.

7. The apparatus of claim 1, wherein there is a pattern of microchannels in each of the first and second molds and the pattern in the first mold is identical to the pattern in the second mold.

8. The apparatus of claim 1, wherein there is a pattern of microchannels in each of the first and second molds and the pattern in the first mold is non-identical to the pattern in the second mold.

9. The apparatus of claim 1, further comprising a coating on at least one surface that includes a blood clot-preventing compound.

10. The apparatus of claim 1, wherein microchannels of the first mold are endothelialized.

11. The apparatus of claim 1, wherein microchannels of the second mold are endothelialized.

12. The apparatus of claim 1, wherein the semi-permeable membrane is biodegradable.

13. The apparatus of claim 1, wherein the semi-permeable membrane has pores of between about 0.01 and about 20 μ

m.

14. The apparatus of claim 1, wherein at least one of the molds comprises through-holes.

15. The apparatus of claim 1, wherein the first and second molds are fastened by a spin-glue process.

16. The apparatus of claim 1, wherein the first and second molds are fastened by a plasma bonding process.

17. A method of fastening a semi-permeable membrane having an upper surface and a lower surface to a polymeric mold having microchannels defined on a surface thereof to form an apparatus which duplicates the functionality of a physiological system, comprising the steps of:

a) exposing the membrane and a polymeric film to oxygen plasma to attach the membrane and film to each other;

b) separating the polymeric film from the membrane; and

c) exposing the membrane and the mold to oxygen plasma to attach the surface of the mold having microchannels defined thereon to the upper surface of the membrane.

18. The method according to claim 17, further comprising the step of:

d) exposing the membrane and a second mold to oxygen plasma to attach the surface of the mold having microchannels defined thereon to the lower surface of the membrane.

19. A method of fastening a semi-permeable membrane having an upper and an lower surface to a polymeric mold having microchannels defined on a surface thereof to form an apparatus which duplicates the functionality of a physiological system, comprising the steps of:

a) exposing the surface of the polymeric mold having microchannels defined thereon to the liquid state of the polymer used to form the polymeric mold;

b) spinning the polymeric mold with the polymer liquid thereon;

c) bringing the membrane in contact with the surface of the polymeric mold having microchannels defined thereon; and

d) allowing the polymeric liquid in contact with the mold and membrane to set.

20. The method according to claim 19, wherein the step of allowing the polymeric liquid in contact with the mold and membrane to set further comprising elevating the surrounding temperature.

21. An apparatus for the filtration of small molecules, comprising a first mold, a semi-permeable membrane, a second mold and a pumping means, wherein the first mold is fastened to the second mold and the semi-permeable membrane is disposed between the first and second molds, and wherein the first and/or second molds have means defining flow control patterns, and a pumping means for circulating fluid through the device.

22. The apparatus of claim 21, wherein the first mold comprises a microvascular network and the second mold comprises parenchymal cells.

23. The apparatus of claim 22, wherein small molecules are removed from the microvascular network and passed to the parenchymal cells.

24. The apparatus of claim 23, wherein the parenchymal cells are kidney cells.

25. The apparatus of claim 21, wherein the flow control patterns are microchannels.

26. The apparatus of claim 21, wherein flow control patterns of the first mold are endothelialized.

27. The apparatus of claim 21, wherein flow control patterns of the second mold are endothelialized.