Gas Exchange Composite Membranes and Methods of Use Thereof

Patent metadata

Field	Value
Publication number	US-2017361007-A1
Application number	US-201515527590-A
Country	US
Kind code	A1
Filing date	Nov 18, 2015
Priority date	Nov 19, 2014
Publication date	Dec 21, 2017
Grant date	—

Abstract

Provided herein is a gas exchange composite membrane and methods of making the same. The gas exchange composite membrane may find use in a method of exchanging gas with blood in a subject in need of blood oxygenation support, which method is also disclosed. Also provided herein are systems and kits that find use in performing the methods of exchanging gas with blood.

First claim

What is claimed is:

1 . A gas exchange composite membrane comprising:
i) a non-porous, gas-permeable, polymeric membrane defining a first surface and a second surface opposite the first surface; and ii) a non-compliant, microporous membrane defining a third surface and a fourth surface opposite the third surface, wherein
the microporous membrane comprises one or more gas diffusion windows, each comprising a network of struts defining walls of a plurality of micropores, each micropore extending from the third surface to the fourth surface; and
the third surface is attached to the second surface,
wherein the first surface of the polymeric membrane provides an antithrombotic surface for gas exchange over the one or more gas diffusion windows, between blood flowing along the first surface and a gas at the second surface.

2 . The composite membrane of claim 1 , wherein the first surface is substantially flat over the one or more gas diffusion windows.

3 . The composite membrane of any of claims 1 and 2 , wherein the composite membrane has an oxygen gas permeability against air of 5 mL STP/cmHg/m 2 /min or more.

4 . The composite membrane of any of claims 1 to 3 , wherein the composite membrane has a carbon dioxide gas permeability against air of 20 mL STP/cmHg/m 2 /min or more.

5 . The composite membrane of any of claims 1 to 4 , wherein the composite membrane has an oxygen gas transfer rate against blood of 0.5 mL STP/cmHg/m 2 /min or more, at an average blood flow speed over the first surface in the range of about 1.0 to about 10 mm/sec.

6 . The composite membrane of any of claims 1 to 5 , wherein the composite membrane has a carbon dioxide transfer rate against blood of 2.0 mL STP/cmHg/m 2 /min or more, at an average blood flow speed over the first surface in the range of about 1.0 to about 10.0 mm/sec.

7 . The composite membrane of any of claims 1 to 6 , wherein the polymeric membrane has an average thickness in the range of 0.01 to 100 μm.

8 . The composite membrane of any of claims 1 to 7 , wherein the microporous membrane has an average thickness in the range of 0.01 to 100 μm.

9 . The composite membrane of any of claims 1 to 8 , wherein each of the one or more gas diffusion windows has a porosity in the range of 1 to 90%.

10 . The composite membrane of any of claims 1 to 9 , wherein the one or more gas diffusion windows overlie an area in the range of 1.0 mm 2 to 1.0 m 2 .

11 . The composite membrane of any of claims 1 to 10 , wherein a strut dividing adjacent micropores of the plurality of micropores have an average width in the range of 0.005 to 10.0 μm.

12 . The composite membrane of any of claims 1 to 11 , wherein the plurality of micropores is an array of micropores having substantially uniform dimensions.

13 . The composite membrane of claim 12 , wherein the array is a regular array of micropores.

14 . The composite membrane of any of claims 1 to 13 , wherein a micropore of the plurality of micropores has an average width in the range of 0.005 to 50 μm.

15 . The composite membrane of claim 14 , wherein the micropore has an average length in the range of 0.01 to 100 μm.

16 . The composite membrane of any of claims 1 to 15 , wherein the polymeric membrane is a polydimethylsiloxane (PDMS)-based polymeric membrane.

17 . The composite membrane of any of claims 1 to 16 , wherein the first surface is functionalized with an antifouling agent, an anticoagulant and/or an enzyme.

18 . The composite membrane of claim 17 , wherein the first surface is functionalized with polyethylene glycol, perfluorocarbon, heparin, polysulfobetaine methacrylate or carbonic anhydrase.

19 . The composite membrane of any of claims 1 to 18 , wherein the microporous membrane is a microporous polysilicon, silicon, silicon carbide, or silicon nitride membrane.

20 . The composite membrane of any of claims 1 to 19 , wherein the fourth surface comprises an anchoring strip that circumscribes each gas diffusion window, wherein the anchoring strip protrudes out relative to areas adjacent the anchoring strip on the fourth surface.

21 . The composite membrane of claim 20 , wherein the composite membrane further comprises a base substrate attached to the anchoring strip.

22 . A method of making a gas exchange composite membrane, comprising:
a) forming a non-compliant, microporous membrane defining a first surface; b) forming a multilayered membrane-supporting structure comprising a plurality of layers superposed among each other, wherein the multilayered membrane-supporting structure defines a second surface comprising a superficial layer of the plurality of superposed layers, and wherein the superficial layer comprises a non-porous, gas-permeable, polymeric membrane detachably disposed over an underlying layer; c) bonding the first surface to the second surface; and d) detaching the underlying layer from the non-porous, gas-permeable, polymeric membrane, thereby exposing a third surface of the non-porous, gas-permeable, polymeric membrane, wherein the third surface provides an antithrombotic surface for gas exchange across the composite membrane, between blood flowing along the third surface and a gas at a fourth surface of the non-compliant, microporous membrane opposite the first surface.

23 . The method of claim 22 , wherein the non-porous, gas-permeable, polymeric membrane is a PDMS membrane.

24 . The method of any of claims 22 and 23 , wherein the non-compliant, microporous membrane has an average thickness in the range of 0.01 to 100 μm.

25 . The method of any of claims 22 to 24 , wherein the non-porous, gas-permeable, polymeric membrane has an average thickness in the range of 0.5 to 10 μm.

26 . The method of any of claims 22 to 25 , wherein the non-compliant, microporous membrane is a microporous polysilicon, silicon, silicon carbide, or silicon nitride membrane.

27 . The method of any of claims 22 to 26 , wherein the bonding comprises plasma bonding, wet chemistry, or physical attachment of the first surface to the second surface.

28 . The method of any of claims 22 to 27 , wherein forming the non-compliant, microporous membrane comprises:
i) depositing a sacrificial layer over a fifth surface of a base substrate, wherein the sacrificial layer is patterned to create one or more anchor regions, each anchor region defining a window;
ii) depositing a non-compliant membrane on the patterned sacrificial layer;
iii) etching the non-compliant membrane deposited on the patterned sacrificial layer within an area defined by the window, to form a network of struts defining walls of a plurality of micropores in the non-compliant membrane;
iv) removing the base substrate over the area defined by the window; and
v) removing the sacrificial layer over the area defined by the window.

29 . The method of claim 28 , wherein the base substrate is a silicon or glass base substrate.

30 . The method of claim 29 , wherein the sacrificial layer is a silicon dioxide or silicon nitride layer.

31 . The method of any of claims 28 to 30 , wherein depositing the sacrificial layer comprises using thermal oxidation.

32 . The method of any of claims 28 to 31 , wherein the sacrificial layer has a thickness in the ra

Assignees

• Univ California

Inventors

• Roy Shuvo
• Yeager Torin
• Abada Emily
• Dharia Ajay S

Classifications

• B01D2257/104

  Oxygen · CPC title

• B01D2325/20

  Specific permeability or cut-off range · CPC title

• A61M1/1698 Primary

  Blood oxygenators with or without heat-exchangers (intracorporal A61M1/1678; manufacturing of membranes therefor B01D67/00; semi-permeable membranes for separation processes characterised by their properties B01D69/00; semi-permeable membranes characterised by their material B01D71/00) · CPC title

• A61M2209/088

  on the body · CPC title

• B01D53/228

  characterised by specific membranes · CPC title