Title:  Method of delivering oxygen to cells by electrolyzing water

United States Patent:  6,368,592

Assignee:  Massachusetts Institute of Technology (Cambridge, MA)

Filed:  July 16, 1999

Oxygen is supplied to cells in vitro or in vivo by generating oxygen with an oxygen generator that electrolyzes water to oxygen and hydrogen. Oxygen can be generated substantially without generating free hydrogen using a multilayer electrolyzer sheet having a proton exchange membrane sandwiched by an anode layer and a cathode layer. The oxygen generator may be used to supply oxygen to cells contained by a culture plate, a culture flask, a microtiter plate or an extracorporeal circuit, or to cells in an encapsulating chamber for implanting in the body such as an immunoisolation chamber bounded by a semipermeable barrier layer that allows selected components to enter and leave the chamber. A bioactive molecule may be present with the cells. Oxygen can be delivered in situ to cells within the body such as by implanting the oxygen generator in proximity to cell-containing microcapsules in an intraperitoneal space, or by implanting a system containing the oxygen generator in proximity to an immunoisolation chamber containing cells.

SUMMARY OF THE INVENTION

The invention provides an oxygen generator device for delivering oxygen to cells or to a cell compatible fluid. The oxygen generator device disclosed herein has application for in vitro or in vivo use. In one aspect the device is placed in proximity to a cell compatible fluid. In another aspect, the oxygen generator is placed in proximity to cells for which supplemental oxygen is desired. In a further aspect of the invention, the oxygen generator is placed in proximity to a cell encapsulating device. The oxygen generator disclosed herein provides a system to deliver oxygen to cells in situ in the body of an organism.

In one embodiment of the invention, the oxygen generator is an electrolyzer device which electrolyzes water into oxygen and hydrogen. In another embodiment of the invention, the oxygen generator is in the form of a thin, multilayer electrolyzer sheet and is permeable to gas and water vapor but impermeable to liquids and dissolved material. In a further embodiment of the invention, the oxygen generator comprises a multilayer electrolyzer sheet having a proton exchange membrane sandwiched by an anode layer and a cathode layer. In a further embodiment of the invention, the device comprises a multilayer electolyzer sheet adapted for mating to a container containing cells.

In one embodiment of the invention, the oxygen generator is in communication with an energy source, such as a battery. In another embodiment of the invention, the battery is rechargeable transcutaneously. In a further embodiment of the invention, the battery is recharged using a transcutaneous energy transfer system (TET) system. In a further embodiment, the invention may be operated directly and continuously from a battery-powered TET system.

In one embodiment of the invention, the oxygen generator is provided in proximity to cells in vitro. The oxygen generator is provided, either within a container containing the cells, or as an integral part of the container. In one embodiment of the invention, the oxygen generator is provided, either within, or as an integral part of, a cell-containing cartridge in an extracorporeal circuit device.

In a further embodiment of the invention, the oxygen generator is provided as an in-line oxygenator through which blood, plasma, and other bodily fluids may flow. In this embodiment, the oxygen generator is mated to, contained within, or is an integral part of, a hollow tube through which blood, plasma, and other bodily fluids, or culture medium may flow.

In one embodiment, the invention provides a system for delivering oxygen in situ to cells within the body of an organism. In this embodiment of the invention, the system comprises an oxygen generator positioned in proximity to a cell encapsulating chamber and is implanted within the body of an organism. The cell encapsulating chamber comprises a containment space for cells bounded by a semipermeable barrier layer which acts as a selective diffusion layer, allowing selected components to enter and leave the cell encapsulating chamber.

In a further embodiment of the invention, the system includes an oxygen generator which comprises a multilayer electrolyzer sheet mated to a cell encapsulating chamber comprising two semipermeable membranes sealed together by a ring seal.

In another embodiment of the invention, the system for delivering oxygen in situ comprises a cell encapsulating chamber which defines an immunoisolation chamber. In this embodiment, the semipermeable barrier layer of the immunoisolation chamber immunoisolates cells contained within the chamber when the device is exposed to components of the immune system. In a further embodiment, the invention relates to a system implantable in the body of an organism for growing tissue in immunoisolation while providing supplemental oxygen to the tissue.

In another embodiment of the invention, the system for delivering oxygen in situ comprises an oxygen generator provided in proximity to, or mated with, a semipermeable membrane tube through which blood, plasma, and other bodily fluids may flow. In another embodiment of the invention, the membrane tube is surrounded by implanted tissue. In a further embodiment of the invention, the membrane tube and tissue is contained within a housing.

The invention also relates to a system for delivering oxygen in situ to cells which are not contained within a cell encapsulating device. In a one embodiment of the invention, the system for delivering oxygen in situ comprises an oxygen generator placed in proximity to cell-containing microcapsules which are free to migrate within an intraperitoneal space. In another embodiment of the invention, the system comprises an oxygen generator positioned in proximity to a cell-supporting, biocompatible, polymeric scaffold within the body of an organism. In this embodiment, the oxygen generator can be used to maintain, and support the growth of artificial tissues.

In a further embodiment of the invention, two oxygen generators are placed back to back with cells on both sides of the oxygen generator, maximizing the amount of oxygen that can be delivered to cells.

In another embodiment, the system is designed to deliver oxygen in situ to cells located at a distance from the oxygen generator. A tube with low oxygen permeability is attached to the oxygen generator. Generated oxygen is transferred through the tube to a flexible oxygen distributor fabricated from oxygen-permeable membranes. In one aspect of the invention, the oxygen distributor is placed in proximity to cells, tissues, or organs, for which supplemental oxygen is desired. In another aspect of the invention, the oxygen distributor is placed in proximity to a cell encapsulating device. The flexible oxygen distributor provides a means to deliver oxygen from an oxygen generator located at a distance to cells, tissues, or organs located anywhere, and having any shape, within the body of an organism.

In a further embodiment of the invention, the oxygen generator is an oxygen transfer device which electrochemically transfers oxygen from the cathode side to the anode side of the oxygen generator substantially without the generation of hydrogen.

The invention also relates to methods of delivering oxygen to cells in vitro comprising positioning an oxygen generator in proximity to the cells. In one embodiment of the invention, the method comprises delivering oxygen to cells contained within a container, such as a cell culture dish or a flask. In another embodiment of the invention, the method comprises placing an oxygen generator in proximity to the cells within a cell-containing cartridge in an extracorporeal circuit or in culture medium in a perfusion circuit. In another embodiment of the device, the oxygen generator is provided as an in-line oxygenator through which culture medium flows. In this embodiment, oxygenated culture medium flows through the cell-containing cartridge and is then discarded or recycled through the oxygenator for reoxygenation. In a further embodiment of the invention, the oxygenated culture medium is made to flow in and around an organ for transplantation, such as heart, kidney, liver, or pancreas, during the period when it is stored or shipped.

The invention also relates to a method of delivering oxygen in situ to cells within a body of an organism. In this embodiment of the invention, an oxygen generator is placed in proximity to cells which are free to migrate within an intraperitoneal space. In another embodiment of the invention, the method includes implanting a system within the body of an organism, the system comprising an oxygen generator which is in proximity to a cell encapsulating chamber, such as an immunoisolation chamber.

Claim 1 of 15 Claims

What is claimed is:

1. A method of delivering oxygen to a cell containment space, comprising:

selecting a cell container defining a cell containment space for containing cells in vitro, wherein the cell container comprises a semipermeable barrier layer bounding at least a portion of the cell containment space;

selecting an oxygen generator in communication with the containment space in proximity to the semipermeable barrier layer for generating oxygen from a fluid and delivering oxygen to the cell container, wherein the oxygen generator comprises an anode and a cathode, the anode and the cathode sandwiching a proton exchange membrane, the anode electrolyzes water to oxygen and hydrogen ions; and the cathode receives the hydrogen ions generated by the anode,

wherein the proton exchange membrane transports the hydrogen ions from the anode to the cathode and oxygen is generated substantially without the generation of free hydrogen;

initiating a chemical reaction comprising the electrochemical conversion of water in said fluid to oxygen; and

permitting said oxygen to diffuse to said cell containment space.

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