Medical device comprising a gas transfer membrane

Abstract

A medical device for transferring a gas component between a sweep gas flow and a biological liquid flow, comprising: a gas transfer membrane which is permeable for the gas component but impermeable for the biological liquid, the gas transfer membrane comprising a liquid contact surface arranged to face the biological liquid flow and transfer the gas component between the biological liquid and the sweep gas flow beneath the liquid contact surface, wherein the gas transfer membrane comprises a highly porous solid layer having a porosity in the range of 70-99%.

Description

[0001] MEDICAL DEVICE COMPRISING A GAS TRANSFER MEMBRANE

[0002] Technical Field

[0003] The present disclosure relates to devices for transferring a gas component between a sweep gas flow and a biological liquid, such as blood. More particularly, the present disclosure concerns gas transfer membranes used in such devices.

[0004] Background

[0005] Gas exchange in blood is a physical process by which gases move through a membrane, such as the blood-air barrier in the alveoli of a mammal lung, to allow oxygen to be taken up by the blood and carbon dioxide to be released from the blood.

[0006] In cases of respiratory failure or bypass, an external gas exchange device may be used to support or replace the function of a patient’s lungs. Such external gas exchange devices, more commonly known as membrane oxygenators, typically use a sweep gas to enrich the patient’s blood with oxygen and to remove carbon dioxide. Following the principle of the lung, a membrane forms a barrier between the patient's blood and the sweep gas containing the gases necessary for blood oxygenation. For this reason, most membrane oxygenators are equipped with hollow fibers acting as the oxygenation membrane.

[0007] Two types of membrane currently in commercial use are porous hollow fiber membranes and diffusive hollow fiber membranes.

[0008] In the porous hollow fiber membranes, for example Oxyphan(TM) (3M, USA), the membrane is formed by hydrophobic polypropylene (PP) hollow fibers. The membrane is permeable to gases, but not permeable to blood due to its hydrophobic material properties. These membranes are less suited for long-term use since over time plasma leakage may occur.

[0009] In the diffusive hollow fiber membranes, for example Oxyplus(TM) (3M, USA), the membrane is formed by hydrophobic polymethylpentene (PMP) hollow fibers. Due to the manufacturing process, the porous hollow fibers have a dense outer skin. Thanks to the high gas permeability of the PMP material, gas permeates through the outer skin of the membrane by diffusion. The dense outer skin functions as a diffusion barrier, allowing diffusion of gas, while effectively blocking the transfer of liquids such as blood plasma or water into the pores, even over extended periods of use. These membranes are therefore suitable for both short-term and long-term applications.

[0010] The hollow fibers are typically knitted into mats held in shape by polyester warp threads. The mats are then either wound or stacked in order to reach the desired gas exchange area.

[0011] Another gas transfer principle that has been contemplated but is not yet in commercial practice is using vertically aligned carbon nanotube (VACNT) membranes with a pattern of small channels. The blood flows through the channels and due to the super hydrophobic properties does not enter the carbon nanotubes. Gases on the other hand can easily penetrate the carbon nanotubes, allowing gases to be transferred between the blood flow and a sweep gas flow. The patterns and channels can be arranged in various configurations in order to reach the desired gas exchange area. Advantages of this technology appear to include low resistance to flow resulting in a low pressure drop over the device and reduced damage to the blood.

[0012] Drawbacks of the hollow fiber type membranes include limited permeability for gases, that they may become permeable to liquid over time, and that they create a relatively high flow resistance or pressure drop for the blood flow due to the length of the path the blood has to travel. The VACNT membranes may eliminate some of these problems. They may for example provide reduced flow resistance or pressure drop for the blood flow. However, they also introduce new drawbacks, such as problems with hemocompatibility issues as well as a high cost of production.

[0013] Therefore, there is a need for improved and alternative techniques for transferring gases between a sweep gas flow and a biological liquid flow in a circulatory system of a patient, which eliminate or ameliorate at least some of the drawbacks of the existing techniques.

[0014] Summary

[0015] In view of the above, the present disclosure provides an improved or alternative technology having the features set out in the independent claims. More specifically, the present disclosure provides an improved medical device comprising a gas transfer membrane which eliminates or ameliorates at least some of the drawbacks of existing gas transfer membranes.

[0016] Hence, according to a first aspect, there is provided a medical device for transferring a gas component between a sweep gas flow and a biological liquid flow. The medical device comprises a gas transfer membrane which is permeable for the gas component but impermeable for the biological liquid. The gas transfer membrane comprises a liquid contact surface arranged to face the biological liquid flow and transfer the gas component between the biological liquid and the sweep gas flow beneath the liquid contact surface. The gas transfer membrane comprises a highly porous solid layer having a porosity in the range of 70-99%.

[0017] Medical devices for transferring a gas component between a sweep gas flow and a biological liquid flow are also referred to as, for example, gas exchange devices or membrane oxygenators. This type of device plays a critical role in scenarios like cardiopulmonary bypass surgery, extracorporeal membrane oxygenation (ECMO), and other medical treatments requiring the transfer of gas components (such as oxygen and carbon dioxide) between biological liquid (typically blood) and a sweep gas.

[0018] The gas transfer membrane is key to the function of the device. The gas transfer membrane should be permeable for the gas component but impermeable for the biological liquid. In other words, the gas transfer membrane is semi-permeable. The gas transfer membrane allows specific gases to pass through, while blocking others and maintaining separation between the blood and the gas phases.

[0019] The present inventors have found that a gas transfer membrane which is permeable for the gas component but impermeable for the biological liquid, and which comprises a highly porous solid layer having a porosity in the range of 70-99% is useful as a gas transfer membrane in a medical device.

[0020] The term “porous” refers to a characteristic of a solid material that contains pores (voids). A porous material may allow for the passage of gases, liquids, or even solids through these interconnected or isolated pores. The structure may vary from highly ordered to random and can be either natural or engineered. The presence and arrangement of these pores may influence the properties of the material such as density, permeability, and strength. The term “porosity” refers to a measure of the volume fraction of void spaces (pores) within a solid material. It is typically expressed as a percentage of the total volume of the material that is occupied by these pores. Porosity is an intrinsic property that describes how much empty, or void, space is present within a solid matrix. This property is important in determining the mechanical and transport behaviours of a material, such as resistance to flow of gases through the material.

[0021] The term “highly porous solid layer” as used herein refers to a comprising or consisting of a highly porous solid material, wherein the layer has a high porosity, specifically a porosity in the range of 70-99%. In some embodiments, the highly porous solid layer has a porosity in the range of 80-99%, and preferably in the range of 90-99%.

[0022] The highly porous solid layer may have an open pore structure, a closed pore structure or a combination thereof. An open pore structure may provide lower resistance to gas flow than a closed pore structure. In some embodiments the highly porous solid layer has an open pore structure. In some embodiments the highly porous solid layer has a combination of open and closed pore structures.

[0023] The highly porous solid layer preferably has sufficient structural integrity to serve as a gas transfer membrane in the inventive medical device. In some embodiments, the highly porous solid layer has sufficient structural integrity to serve as a gas transfer membrane in the inventive medical device on its own, i.e. without an additional support layer or carrier layer. Thus, in some embodiments, the highly porous solid layer is self-supporting. In some embodiments, the highly porous solid layer has sufficient structural integrity to serve as a gas transfer membrane in the inventive medical device when a plurality of gas transfer membranes are combined in a stacked arrangement.

[0024] The highly porous solid layer may also preferably be capable of serving as a support structure for another layer of the gas transfer membrane, for example a thin polymeric barrier layer which is permeable for the gas component but impermeable for the biological liquid. This allows for an advantageous combination of a highly porous solid layer having very low resistance to gas flow but sufficient structural integrity, with another layer, which is permeable for the gas component but impermeable for the biological liquid, but which due to low structural integrity could not be used as a gas transfer membrane on its own.

[0025] Highly porous solid layers as used in the medical device of the present disclosure, having a porosity in the range of 70-99% and having sufficient structural integrity to serve as a gas transfer membrane in the inventive medical device have been realized by the development of a group of materials called aerogels.

[0026] Aerogels are a class of porous solid materials derived from a gel in which the liquid component of the gel is replaced with a gas. This process results in a material characterized by an extremely low density and a high degree of porosity. Aerogels are known for their ultra-lightweight nature, exceptional thermal insulation properties, and high surface area. The internal structure of aerogels typically comprises a network of interconnected nano-sized pores, which contributes to their low thermal conductivity and makes them highly effective as insulators.

[0027] Aerogels can be composed of a variety of materials including, but not limited to, silica, metal oxides, carbon, and organic polymers, each conferring specific properties suitable for diverse applications ranging from thermal insulation in buildings and aerospace components to applications in electronics, optics, and environmental cleanup.

[0028] The defining characteristic of aerogels lies in their method of production, typically involving the use of a supercritical fluid drying process which allows the liquid in the gel to be removed without causing the gel structure to collapse, thereby preserving the three-dimensional network of the original gel. This provides aerogels with a combination of structural integrity and material properties which differs from other porous materials.

[0029] Aerogels are functionalizable and may be hydrophilic or hydrophobic. Owing to the fact that the manufacturing process for the aerogels is relatively expensive, aerogels have not found wide application in the industry up to now. However, in recent years intensive research has led to new developments of the aerogel materials as well as their manufacturing processes.

[0030] Polymeric aerogels were developed relatively recently compared to their silica counterparts. The development of polymeric aerogels began gaining momentum in the early 2000s. These materials extended the aerogel group by incorporating organic polymers, rather than just inorganic bases such as silica. The development of polymeric aerogels was driven by the desire to create aerogels with specific properties like flexibility, resilience, and functionality that are not typical of traditional silica aerogels. Examples of polymeric aerogels include, but are not limited to, aerogels formed from polymers such as polyurethane, polyimide, polystyrene, polyacrylate, resorcinol-formaldehyde, and melamine-formaldehyde.

[0031] Thus, in some embodiments, the highly porous solid layer comprises an aerogel. In some embodiments, the highly porous solid layer consists of, or substantially consists of, an aerogel. In some embodiments, the highly porous solid layer is formed of an aerogel.

[0032] In some embodiments, the highly porous solid layer comprises a polymeric aerogel. In some embodiments, the highly porous solid layer consists of, or substantially consists of, a polymeric aerogel. In some embodiments, the highly porous solid layer is formed of a polymeric aerogel.

[0033] In some embodiments the polymeric aerogel is selected from polyurethane aerogels, polyimide aerogels, polystyrene aerogels, polyacrylate aerogels resorcinolformaldehyde aerogels, and melamine-formaldehyde aerogels, and combinations thereof. In some embodiments the polymeric aerogel is selected from polyurethane aerogels and polyimide aerogels. In some embodiments the polymeric aerogel is a polyimide aerogel.

[0034] The highly porous solid layer may be further characterized by the size of its pores. In some embodiments, essentially all of the pores of the highly porous solid layer have a pore size in the range of 2-2000 nm, preferably in the range of 2-1000 nm, and more preferably in the range of 2-500 nm. In some embodiments, at least 90%, preferably at least 95%, and more preferably at least 98% of the pores of the highly porous solid layer have a pore size in the range of 2-2000 nm, preferably in the range of 2-1000 nm, and more preferably in the range of 2-500 nm.

[0035] The gas transfer membrane and the highly porous solid layer have a sheet like structure, i.e. thin and flat, and typically extending considerably in length and width relative to its thickness. In some embodiments, the highly porous solid layer has a thickness in the range of 10-1000 pm, preferably in the range of 25-500 pm, and more preferably in the range of 40-200 pm. The highly porous solid layer may be hydrophobic or hydrophilic. In some embodiments, the highly porous solid layer is hydrophobic. A hydrophobic highly porous solid layer is preferred in embodiments wherein the highly porous solid layer is arranged to be in direct contact with the biological liquid flow, i.e. when a surface of the highly porous solid layer serves as the liquid contact surface arranged to face the biological liquid flow.

[0036] Highly porous solids having a high porosity in the range of 70-99% will have a low resistance to flow of gases through the material. In a medical device as described herein, this means that gas components present in a sweep gas flow or a biological liquid flow flowing on opposite sides of the gas transfer membrane can quickly pass through the highly porous solid layer thereof, to or from the liquid contact surface. In some cases, the high porosity of the highly porous solid layer may even allow for the highly porous solid layer to serve as a flow path for the sweep gas flow itself, i.e. the sweep gas flow passes the device travelling through the highly porous solid material of the highly porous solid layer.

[0037] In some embodiments, the gas transfer membrane consists of the highly porous solid layer. In such embodiments, the highly porous solid layer is preferably hydrophobic in order to resist permeation of water from the biological liquid flow into the highly porous solid layer. Embodiments wherein the gas transfer membrane consists of the highly porous solid layer may be particularly useful in short-term applications.

[0038] In some embodiments, the gas transfer membrane further comprises one or more additional layers in addition to the highly porous solid layer. Particularly, a continuous liquid barrier layer on the highly porous solid layer of the gas transfer membrane may be useful since it may allow for a broader range of highly porous solids to be used in the highly porous solid layer. The outer surface of the continuous liquid barrier layer then forms the liquid contact surface. A liquid barrier layer on the highly porous solid layer of the gas transfer membrane allows for the highly porous solid layer to be either hydrophobic or hydrophilic. A liquid barrier layer on highly porous solid layer of the gas transfer membrane may also help to extend the lifetime of the membrane, e.g. by providing improved resistance to accumulation of biological matter, including blood debris, clot formation etc., on the liquid contact surface. Thus, in some embodiments, the gas transfer membrane further comprises a continuous liquid barrier layer on the highly porous solid layer of the gas transfer membrane, wherein the liquid barrier layer is permeable for the gas component but impermeable for the biological liquid. The outer surface of the continuous liquid barrier layer then forms the liquid contact surface.

[0039] The liquid contact surface of the gas transfer membrane is preferably biocompatible or hemocompatible. The term biocompatible in the present context refers to the ability of a material to perform with an appropriate host response when applied as part of a medical device. This means that the material does not produce a harmful or toxic response when placed in the body and can coexist with biological tissues or systems without causing adverse effects. Biocompatible materials are non- carcinogenic, non-toxic, and do not cause significant inflammation or immune rejection. The term hemocompatible in the present context relates specifically to the compatibility of a material with whole blood. A hemocompatible material does not adversely affect blood or its components when it comes into contact with them. This includes not causing hemolysis (destruction of red blood cells), not triggering coagulation (blood clotting) in an uncontrolled manner, and not activating the body’s complement system (part of the immune system that enhances the ability to clear microbes and damaged cells).

[0040] In embodiments, wherein the gas transfer membrane comprises a continuous liquid barrier layer on the highly porous solid layer of the gas transfer membrane, the liquid barrier layer is preferably biocompatible or hemocompatible.

[0041] The continuous liquid barrier layer is preferably polymer based. In some embodiments, the continuous liquid barrier layer consists of, or substantially consists of, a polymer. Silicone polymers have been found to be very useful for the continuous liquid barrier layer. Other polymers that may be used in the continuous liquid barrier layer include, but are not limited to, fluoropolymers, such as polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF), polyacrylates and polymethacrylates, polyurethanes, and polyamides.

[0042] In some embodiments the continuous liquid barrier layer comprises a silicone polymer. In some embodiments, the liquid barrier layer consists of, or substantially consists of, a silicone polymer. In some embodiments, the liquid barrier layer is formed of a silicone polymer. Due to their good biocompatibility and hemocompatibility properties, the silicone polymers are widely used in medical devices. Silicone polymers are impermeable for biological liquids, and have, as compared to other polymers, a very high gas permeability.

[0043] For maximum gas permeability the liquid barrier layer should preferably be as thin as possible. In some embodiments, the liquid barrier layer has a thickness in the range of 0.05-10 pm, preferably in the range of 0.1-5 pm, and more preferably in the range of 0.1 -2.5 pm. Such thin silicone polymer layers cannot be used unsupported as a membrane, and thus the highly porous solid layer serves as a support structure for the liquid barrier layer.

[0044] In embodiments thereof, the medical device may further be provided with a gas inlet for receiving an inlet sweep gas and a gas outlet for expelling an exhaust sweep gas, wherein a sweep gas flow path is formed between said gas inlet and said gas outlet.

[0045] In embodiments thereof, the medical device may further be provided with a liquid inlet for receiving an inlet biological liquid and a liquid outlet for expelling an exhaust biological liquid, wherein a biological liquid flow path is formed between said liquid inlet and said liquid outlet. In some embodiments, the medical device comprises a housing in which the gas transfer membrane is arranged.

[0046] The gas transfer membrane of the medical device is preferably arranged between a biological liquid flow path and a sweep gas flow path of the device.

[0047] The gas transfer membrane may be arranged between the biological liquid flow path and a sweep gas flow path of the device in many different ways.

[0048] In some embodiments, the medical device comprises a plurality of gas transfer membranes in a stacked arrangement. The plurality gas transfer membranes may be stacked directly on top of each other, or they may be separated by a spacer arranged between the adjacent gas transfer membranes.

[0049] An advantage of the gas transfer membranes used in the medical devices of the present disclosure is that they can be manufactured in various physical shapes, either by forming directly in the manufacturing process or by downstream processing (e.g., by laser ablation). For example, the gas transfer membranes can be manufactured with grooves on at least one of its surfaces. When a plurality of such gas transfer membranes are stacked, the grooves form channels between gas transfer membranes arranged adjacent to each other. These channels are useful as flow paths either for the biological liquid or for the sweep gas.

[0050] In some embodiments, the device comprises a plurality of gas transfer membranes in a stacked arrangement, wherein a biological liquid flow path is formed between a first gas transfer membrane and a second gas transfer membrane arranged adjacent to each other.

[0051] In some embodiments, the device comprises a plurality of gas transfer membranes in a stacked arrangement, wherein a sweep gas flow path is formed between a third gas transfer membrane and a fourth gas transfer membrane arranged adjacent to each other.

[0052] In some embodiments, the second gas transfer membrane and the third gas transfer membrane are one and the same.

[0053] In some embodiments, the second gas transfer membrane and the third gas transfer membrane are arranged adjacent to each other.

[0054] In some embodiments, the biological liquid flow path and / or the sweep gas flow path is formed in the surface of at least one of the adjacent gas transfer membranes.

[0055] In some embodiments, the biological liquid flow path and / or the sweep gas flow path is formed by a spacer arranged between the adjacent gas transfer membranes.

[0056] In some embodiments, the biological liquid flow path and the sweep gas flow path are arranged transversely, angled, or perpendicularly, in relation to each other.

[0057] In some embodiments, the medical device disclosed herein is a device for oxygenation of blood, a device for removal of carbon dioxide from blood, a device for continuous renal replacement therapy (CRRT), a device for removal of carbon monoxide from blood, a device for removal of nitrogen from blood (e.g. diving sickness therapy), or a device for adding nitric oxide to blood, or a combination of two or more thereof. In some embodiments, the medical device disclosed herein is a device for oxygenation of blood. According to a second aspect, there is provided a system for transferring a gas component between a sweep gas flow and a biological liquid flow, the system comprising: a medical device according to the first aspect, and an extracorporeal circuit configured to circulate a biological liquid from a patient through the medical device by means of a circulation unit, and a sweep gas supply circuit configured to lead a sweep gas from a sweep gas source through the medical device.

[0058] In the context of the present disclosure, the term “sweep gas flow” or “sweep gas flow rate” typically refers to how the sweep gas is moved through the system. The flow rate may either refer to the total flow rate of gas supplied to the medical device or exhausted by the medical device, or to the flow rate of the sweep gas in a particular part of the medical device. The flow rate may generally be understood as a term describing the quantity of a gas moving through a given cross-sectional area per unit time and can be measured in terms of either volume or mass.

[0059] In the context of the present disclosure, the term “biological liquid flow” or “biological liquid flow rate” typically refers to how the biological liquid is moved through the system. The flow rate may either refer to the total flow rate of biological liquid supplied to the medical device or exhausted by the medical device, or to the flow rate of the biological liquid in a particular part of the medical device. The flow rate may generally be understood as a term describing the quantity of a biological liquid moving through a given cross-sectional area per unit time and can be measured in terms of either volume or mass.

[0060] In the context of the present disclosure, the term “biological liquid” refers to any fluid of biological origin that is produced by or contained within living organisms. These liquids are primarily composed of water, dissolved biologically active solutes (including but not limited to salts, proteins, enzymes, hormones, and nutrients), and may contain cells, cellular fragments, or other macromolecules. Biological liquids are essential for various physiological functions such as transport, regulation, protection, and communication between systems and organs within the body. Examples of biological liquids include, but are not limited to, blood and blood plasma. The second aspect may generally have the same features and advantages as the first aspect. It is further noted that the disclosure relates to all possible combinations of features, unless explicitly stated otherwise.

[0061] Brief Description of the Drawings

[0062] The above, as well as additional object, features, and advantages of the present disclosure will be better understood through the following illustrative and nonlimiting detailed description of examples of the present disclosure, with reference to the appended drawings, where the same reference numerals will be used for similar elements, wherein:

[0063] Figure 1 shows a system according to an example, comprising a medical device coupled to an extracorporeal circuit.

[0064] Figure 2 is a schematic illustration of a gas transfer membrane according to an example.

[0065] Figures 3a-3c are a schematic illustrations of gas transfer membranes according to examples.

[0066] Figures 4a-4c are a schematic illustrations of medical devices according to examples.

[0067] Figure 5 is a schematic illustration of a medical device according to an example.

[0068] Figure 6a-6b are schematic illustrations of a medical device according to an example.

[0069] As illustrated in the figures, the sizes of the elements and features may be exaggerated for illustrative purposes and, thus, are provided to illustrate the general structures of the examples. Like reference numerals refer to like elements throughout.

[0070] Detailed Description

[0071] Figure 1 shows by way of example a system 100 for transferring a gas component between a sweep gas flow and a biological liquid flow. In this embodiment, the biological liquid is blood in a circulatory system of a patient 10. The system 100 comprises a medical device 110 configured to provide oxygen-rich blood by exposing oxygen-poor blood of the patient 10 to oxygen provided by an inlet gas and to allow passage of excess oxygen to an exhaust gas.

[0072] Examples of systems 100 according to the present disclosure include cardiopulmonary bypass machines (heart-lung machine) providing circulatory and respiratory support in the operating theatre while the heart is stopped for surgery, extracorporeal membrane oxygenator (ECMO) devices providing circulatory and respiratory support in intensive care units, and extracorporeal carbon dioxide removal (ECCO2R) devices removing excess carbon dioxide from the blood. Although the system will be described herein mainly with reference to transferring a gas component between a sweep gas flow and blood in a circulatory system of a patient, it is noted that the system may be applied more generally to for transferring a gas component between a sweep gas flow and a biological liquid flow. Examples of applications for the medical device and systems comprising the medical device include, but are not limited to, oxygenation of blood, removal of carbon dioxide from blood, continuous renal replacement therapy (CRRT), removal of carbon monoxide from blood, removal of nitrogen from blood (e.g. diving sickness therapy), or adding nitric oxide to blood, or a combination of two or more thereof.

[0073] In the present example, the medical device 110 is arranged in an extracorporeal circuit 105 in which blood of the patient is circulated through the medical device 110 by means of a circulation unit 107 or by passively by the patient itself in pumpless arteriovenous (AV) mode (e.g., in AV-ECMO). The extracorporeal circuit 105 typically comprises fluid lines, or circuit tubing, for connecting the various components of the extracorporeal circuit and carrying the patient’s blood through the medical device 110.

[0074] The circulation unit 107 may, for example, comprise a displacement pump, typically a roller pump, or a rotational pump, typically a centrifugal pump, depending on the specific type of system 100. Roller pumps typically comprises a rotating roller compressing a flexible tube or membrane. As the roller rotates, it squeezes the tube, creating a flow of blood. Centrifugal pumps, on the other hand, use a rapidly rotating impeller to create a centrifugal force which pushes the blood outwards to generate a substantially continuous blood flow. The sweep gas may be provided from a gas source 118, which may be a gas outlet of a central medical gas system of a hospital facility, a pressurised gas cylinder, or any other type of gas source suitable for delivering gas, for example oxygen or air, for medical applications. In its simplest form ambient air may also be drawn through the device by means of negative pressure, e.g. by a fan commected to the gas outlet.

[0075] The sweep gas from the gas source 118 is supplied to the gas inlet 111 of the medical device 110. Valve arrangements (not shown) may be configured to adjust the gas concentration and flow rate of the inlet gas according to the patient’s needs, allowing the healthcare professionals to control the gas levels delivered to the patient. The valve arrangements may be electronically controlled, and in some examples configured to utilise sensor input to achieve the accurate gas composition and flow rate.

[0076] The medical device 110 may be arranged to release the exhaust sweep gas via a gas outlet 112 to the open air, to a gas capture device, or a gas evacuation arrangement (not shown). The gas capture device, or gas evacuation arrangement, may be employed to recycle components of the exhaust gas or to prevent e.g. anaesthetic agents and hyperbaric oxygen to accumulate in the surrounding air.

[0077] The medical device 110 is configured to facilitate exchange of gas components between the patient’s blood and a sweep gas passing through the medical device 110. Typically, the medical device is configured to allow oxygen to pass from the sweep gas into the blood, thereby oxygenating the blood, and to allow carbon dioxide to be released from the blood and pass into the sweep gas. It will be appreciated that other types of gas and substances may be exchanged in a similar way, including anaesthetic agents and nitric oxide.

[0078] The medical device 110, which in some examples may be referred to as an oxygenator, may comprise a sweep gas flow path 113 and a biological liquid flow path 116 separated by a gas transfer membrane 120. The blood may be circulated through the biological liquid flow path 116 via a liquid inlet 114 and a liquid outlet 115 by the circulation unit 107, whereas the sweep gas may flow through the sweep gas flow path 113 via a gas inlet 111 and a gas outlet 112. At the gas inlet 111, the sweep gas may be referred to as an inlet sweep gas, whereas the gas leaving the medical device 110 may be referred to as an exhaust sweep gas. Due to a partial pressure gradient, or a concentration difference, between individual components of the sweep gas and the corresponding component in the blood, this component may be transferred through the gas transfer membrane 120 from the sweep gas flow path 113 into the biological liquid flow path 116 or vice versa. In particular, oxygen may be passed from the sweep gas flow path 113 into the biological liquid flow path 116 through the gas transfer membrane 120, so that the oxygen-poor blood is oxygenated into oxygen-rich blood. Vice versa, carbon dioxide may be passed from the biological liquid flow path 116 into the sweep gas flow path 113 through the membrane 120, so that carbon dioxide is removed from the flow of blood.

[0079] Figure 2 shows by way of example a gas transfer membrane 120 useful in the medical device. The gas transfer membrane 120 is permeable for the gas component s) but impermeable for the biological liquid. The gas transfer membrane 120 comprises a liquid contact surface 121 arranged to face the biological liquid flow and transfer the gas component between the biological liquid and the sweep gas flow beneath the liquid contact surface. The gas transfer membrane comprises a highly porous solid layer 122 having a porosity in the range of 70-99%. The highly porous solid layer 122 may be formed of an aerogel. The aerogel can be composed of a variety of materials including, but not limited to, silica, metal oxides, carbon, and organic polymers. The highly porous solid layer 122 may for example be formed of a polymeric aerogel. The polymeric aerogel may for example be selected from polyurethane aerogels, polyimide aerogels, polystyrene aerogels, polyacrylate aerogels resorcinol-formaldehyde aerogels, and melamine-formaldehyde aerogels, and combinations thereof. In some embodiments the polymeric aerogel is selected from polyurethane aerogels and polyimide aerogels. In some embodiments the polymeric aerogel is a polyimide aerogel.

[0080] Polymeric aerogel films can be prepared according to methods known in the art. As an example, a method for preparing a polyimide aerogel film will now be described.

[0081] Polymer Synthesis: The process begins with the synthesis of the polyimide precursor, typically a polyamic acid (PAA), which is derived from the reaction of dianhydrides and diamines. The specific types of dianhydrides and diamines can be varied depending on the desired properties of the final polyimide aerogel, such mechanical strength, and water resistance.

[0082] Solution Preparation: The synthesized polyamic acid is dissolved in a suitable solvent, often an aprotic solvent like N,N-dimethylacetamide (DMAc), N-methyl-2- pyrrolidone (NMP), or dimethyl sulfoxide (DMSO), to form a viscous solution. This solution may also contain a porogen (pore-forming agent), which helps in creating the porous structure in the final aerogel.

[0083] Gelation: The polyamic acid solution undergoes gelation. This can be induced by chemical means such as the addition of a chemical cross-linker or by thermal curing. During this step, the polyamic acid partially converts to polyimide through imidization, and a three-dimensional gel network is formed.

[0084] Aging and Imidization: The gel is aged under controlled conditions to enhance cross-linking and complete the imidization process. Imidization can be accelerated by heating, which converts the remaining polyamic acid to polyimide, thereby stabilizing the gel structure.

[0085] Solvent Exchange: To prepare for drying, the solvent within the gel is replaced with another solvent that has a lower surface tension and is easier to remove. This step is crucial to maintain the structure of the aerogel during drying.

[0086] Drying: The drying should be performed in a way that preserves the gel’s nanostructure:

[0087] Supercritical Drying: This involves replacing the solvent with supercritical carbon dioxide, which is then vented off at conditions above its critical temperature and pressure, minimizing capillary stresses that could collapse the gel structure.

[0088] Ambient Pressure Drying: An alternative to supercritical drying, this method involves slowly drying the gel at ambient pressure after replacing the original solvent with one that evaporates more gently, such as pentane or hexane.

[0089] Post-processing: The dried polyimide aerogel film can then be further processed, for example, by machining or by adding other functional materials to enhance its properties. Surface treatments might also be applied to modify its interaction with other substances. Characterization: Finally, the aerogel films are characterized to confirm their properties such as porosity and mechanical strength. This ensures they meet the specifications required for their intended applications.

[0090] The highly porous solid layer 122 may be characterized by the size of its pores. In some embodiments, essentially all of the pores of the highly porous solid layer have a pore size in the range of 2-2000 nm, preferably in the range of 2-1000 nm, and more preferably in the range of 2-500 nm. In some embodiments, at least 90%, preferably at least 95%, and more preferably at least 98% of the pores of the highly porous solid layer have a pore size in the range of 2-2000 nm, preferably in the range of 2-1000 nm, and more preferably in the range of 2-500 nm.

[0091] The gas transfer membrane 120 and the highly porous solid layer 122 have a sheet like structure, i.e. thin and flat, and typically extending considerably in length and width relative to its thickness. In some embodiments, the highly porous solid layer has a thickness in the range of 10-1000 pm, preferably in the range of 25-500 pm, and more preferably in the range of 40-200 pm.

[0092] The highly porous solid layer 122 may be hydrophobic or hydrophilic. In some embodiments, the highly porous solid layer is hydrophobic. A hydrophobic highly porous solid layer is preferred in embodiments wherein the highly porous solid layer is arranged to be in direct contact with the biological liquid flow, i.e. when a surface of the highly porous solid layer serves as the liquid contact surface arranged to face the biological liquid flow.

[0093] The gas transfer membrane in Figure 2 further comprises a continuous liquid barrier layer 123 on the liquid contact side of the highly porous solid layer 122, wherein the liquid barrier layer is permeable for the gas component but impermeable for the biological liquid. The outer surface of the continuous liquid barrier layer 123 then forms the liquid contact surface 121.

[0094] Although the gas transfer membrane 120 in Figure 2 is shown with a continuous liquid barrier layer 123 on the highly porous solid layer 122 it is noted that the gas transfer membrane may in alternative embodiments consists of the highly porous solid layer 122 as such. In such embodiments, the highly porous solid layer is preferably hydrophobic in order to resist permeation of water from the biological liquid flow into the highly porous solid layer. An outer surface of the highly porous solid layer 122 then forms the liquid contact surface 121.

[0095] In the example shown in figure 1, the continuous liquid barrier layer 123 is formed of a silicone polymer. Due to their good biocompatibility and hemocompatibility properties, the silicone polymers are widely used in medical devices. Silicone polymers are impermeable for biological liquids, and have, as compared to other polymers, a very high gas permeability. For maximum gas permeability the liquid barrier layer should preferably be as thin as possible. In some embodiments, the liquid barrier layer 123 has a thickness in the range of 0.05-10 pm, preferably in the range of 0.1-5 pm, and more preferably in the range of 0.1-2.5 pm. A thin silicone polymer layer cannot be used unsupported as a membrane, and thus the highly porous solid layer 122 serves as a support structure for the liquid barrier layer 123.

[0096] The continuous liquid barrier layer 123 can be applied to the liquid contact surface of the gas transfer membrane according to methods known in the art. As an example, a method for preparing a silicone polymer barrier layer will now be described. A liquid solution or suspension of the silicone polymer in a solvent or carrier is applied to the liquid contact surface using a suitable liquid application technique, for example brushing, rolling, spraying, dip coating, or spin coating. The applied coating is then dried and cured at room temperature or at elevated temperature, converting from a liquid to a solid state as it sets. The curing time can vary based on the type of silicone, thickness of the film application, and curing conditions.

[0097] As shown in Figure 3 a, a gas transfer membrane 120 in the form of a highly porous solid layer, for example a polyimide aerogel layer having a thickness of 125pm, can be provided in sheet form. The highly porous solid layer sheets can be manufactured in various physical shapes, either by forming directly in the manufacturing process or by downstream processing (e.g., by laser ablation). For example, the highly porous solid layer can be manufactured with grooves on at least one of its surfaces. When a plurality of gas transfer membranes prepared from such highly porous solid layers are stacked, the grooves form channels between gas transfer membranes arranged adjacent to each other useful as flow paths either for the biological liquid or for the sweep gas.

[0098] Figure 3b shows a gas transfer membrane 120’ consisting of a highly porous solid layer 122’, for example a polyimide aerogel layer, with grooves 124 formed directly in the manufacturing process. Depending on the aerogel material (hydrophobicity, pore size, etc.), the highly porous solid layer can be used either as a gas transfer membrane by itself, or as a support structure for a continuous liquid barrier layer, for example a thin silicone polymer layer.

[0099] Figure 3c shows a gas transfer membrane 120” consisting of a highly porous solid layer 122”, for example a polyimide aerogel layer, with grooves formed directly in the manufacturing process, and a continuous liquid barrier layer 123, for example a thin silicone polymer layer on the grooved surface of the highly porous solid layer.

[0100] In the example illustrated in figure 1, the membrane 120 is schematically illustrated as a single sheet but in many applications, it may be preferred to combine a plurality of gas transfer membranes in a stacked arrangement or gas transfer membrane assembly. The plurality gas transfer membranes may be stacked directly on top of each other, or they may be separated by a spacer arranged between the adjacent gas transfer membranes.

[0101] Figure 4a shows a gas transfer membrane assembly 126’ where two gas transfer membranes 120’ as described with reference to Figure 3b are arranged in a stacked arrangement such that the grooves 124 form channels between gas transfer membranes arranged adjacent to each other useful as flow paths either for the biological liquid or for the sweep gas.

[0102] Figure 4b shows a gas transfer membrane assembly 120” where two gas transfer membranes 120” as described with reference to Figure 3c are arranged in a stacked arrangement to form a gas transfer membrane assembly such that the grooves 124 form channels between gas transfer membranes arranged adjacent to each other useful as flow paths for the biological liquid. In a gas transfer membrane according to this example, the continuous liquid barrier layer 123, for example a thin silicone polymer layer may also act as an adhesive for binding the two gas transfer membranes together. Figure 4c shows a gas transfer membrane assembly 126”’ where two gas transfer membrane assemblies 126” as described with reference to Figure 4b are arranged in a stacked arrangement with a spacer 128 arranged between the adjacent gas transfer assemblies such that a channel is formed between the between gas transfer assemblies useful as a flow path for the sweep gas.

[0103] In the gas transfer membrane assemblies 126’, 126 ”, 126’” described with reference to Figures 4a-c the gas transfer membranes or membrane assemblies are arranged transversely, angled, or perpendicularly, in relation to each other. Accordingly, the biological liquid flow paths and the sweep gas flow paths are also arranged transversely, angled, or perpendicularly, in relation to each other. This facilitates the introduction of the biological liquid and sweep gas into the structure since all inlets and outlets of the flow paths for the biological liquid will be positioned on a first pair of opposing faces of the device, and all inlets and outlets of the flow paths for the sweep gas will be positioned on a second pair of opposing faces of the device.

[0104] A plurality of gas transfer membranes or gas transfer membrane assemblies can be stacked in order to obtain a required gas transfer membrane surface area. Figure 5 schematically shows a gas transfer membrane assembly having a stack of a plurality of gas transfer membrane assemblies as described with reference to Figure 4c separated by spacers. All inlets and outlets of the flow paths for the biological liquid are positioned on a first pair of opposing faces of the device, and all inlets and outlets of the flow paths for the sweep gas are positioned on a second pair of opposing faces of the device. The medical device may therefore readily be provided with ports or connectors (not shown) for directing biological liquid and sweep gas into their respective flow paths. Via such ports or connectors the medical device may be connected to a system for transferring a gas component between a sweep gas flow and a biological liquid flow, for example a system 100 as described herein with reference to Figure 1. In alternative embodiments different sections of the stack of gas transfer membrane assemblies may be used for the transfer of different gas components. For example, one section of the stack of gas transfer membrane assemblies may be used for the transfer of oxygen to the biological liquid, and another section of the stack of gas transfer membrane assemblies may be used for the transfer of nitric oxide to the biological liquid. In such embodiments, the medical device may be provided with additional ports or connectors (not shown) for directing different sweep gases into the flow paths of the respective sections. The medical device may further comprise a housing (not shown) in which the stack of gas transfer membrane assemblies is arranged.

[0105] Figure 6a shows an alternative gas transfer membrane assembly 130, wherein the grooves 134 in the gas transfer membranes 132 are oblique to increase mixing of blood and make it more tolerant to alignment of the membranes. Figure 6b shows schematically how a plurality of the gas transfer membrane assemblies 130 described with reference to Figure 6a can be stacked in order to obtain a required gas transfer membrane surface area.

[0106] The gas transfer membranes and medical devices comprising the gas transfer membranes described herein provide many advantages including, but not limited to:

[0107] - Possibility to optimize the geometry of the biological liquid flow path, which may lead to lower hemolysis when the biological liquid is blood.

[0108] - Lower pressure drop due to the high porosity (e.g., enabling pumpless arteriovenous (AV) circulation mode).

[0109] - Potentially smaller foreign surface area and / or smaller filling volume, and consequently smaller products, due to the improved gas diffusion.

[0110] - Simplified manufacturing processes.

[0111] - Possibility of a modular design using smaller gas transfer modules connected in parallel.

[0112] - Possibility for the realization of a lung implant.

[0113] Additionally, variations to the disclosed embodiments can be understood and effected by the skilled person in practising the claimed invention, from a study of the drawing, the disclosure, and the appended claims. Moreover, in the drawings and specification, there have been disclosed preferred examples of the invention and, although specific terms are employed, they are used in a generic and descriptive sense only and not for the purpose of limitation. The scope of the invention is set forth in the following claims, in which the word ‘comprising’ does not exclude other elements or steps, and the indefinite article ‘a’ or ‘an’ does not exclude a plurality. The term ‘beneath’ as used herein with reference to the liquid contact surface is not intended to imply any specific orientation or arrangement of the components of the medical device, but only to distinguish one side of the liquid contact surface from the opposite side of the liquid contact surface. The term ‘substantially consists of as used herein with reference to a component of a material or part of the medical device, e.g. the highly porous solid layer and the continuous liquid barrier layer, generally means that material or part comprises at least 90% by weight, preferably at least 95% by weight, and more preferably at least 98% by weight, of the component.

Claims

CLAIMS1. A medical device for transferring a gas component between a sweep gas flow and a biological liquid flow, comprising: a gas transfer membrane which is permeable for the gas component but impermeable for the biological liquid, the gas transfer membrane comprising a liquid contact surface arranged to face the biological liquid flow and transfer the gas component between the biological liquid and the sweep gas flow beneath the liquid contact surface, wherein the gas transfer membrane comprises a highly porous solid layer having a porosity in the range of 70-99%, wherein the highly porous solid layer comprises an aerogel.

2. The device according to claim 1, wherein the highly porous solid layer has a porosity in the range of 80-99%, and preferably in the range of 90-99%.

3. The device according to any one of the preceding claims, wherein the highly porous solid layer has an open pore structure.

4. The device according to any one of the preceding claims, wherein the highly porous solid layer is self-supporting.

5. The device according to any one of the preceding claims, wherein the highly porous solid layer comprises a polymeric aerogel.

6. The device according to any one of the preceding claims, wherein the highly porous solid layer is formed of an aerogel, preferably a polymeric aerogel.

7. The device according to any one of the preceding claims, wherein essentially all of the pores of the highly porous solid layer have a pore size in the range of 2-2000 nm, preferably in the range of 2-1000 nm, and more preferably in the range of 2-500 nm.

8. The device according to any one of the preceding claims, wherein the highly porous solid layer has a thickness in the range of 10-1000 pm, preferably in the range of 25-500 pm, and more preferably in the range of 40-200 pm.

9. The device according to any one of the preceding claims, wherein the highly porous solid layer is hydrophobic.

10. The device according to any one of the preceding claims, wherein the gas transfer membrane further comprises a continuous liquid barrier layer on the highly porous solid layer, wherein the liquid barrier layer is permeable for the gas component but impermeable for the biological liquid.

11. The device according to any one of the preceding claims, wherein the liquid barrier layer is biocompatible or hemocompatible.

12. The device according to any one of the preceding claims, wherein the liquid barrier layer comprises a silicone polymer.

13. The device according to any one of the preceding claims, wherein the liquid barrier layer is formed of a silicone polymer.

14. The device according to any one of the preceding claims, wherein the liquid barrier layer has a thickness in the range of 0.05-10 pm, preferably in the range of 0.1-5 pm, and more preferably in the range of 0.1-2.5 pm.

15. The device according to any one of the preceding claims, wherein the gas transfer membrane is arranged between a biological liquid flow path and a sweep gas flow path of the device.

16. The device according to any one of the preceding claims, wherein the device comprises a plurality of gas transfer membranes in a stacked arrangement, andwherein a biological liquid flow path is formed between a first gas transfer membrane and a second gas transfer membrane arranged adjacent to each other.

17. The device according to any one of the preceding claims, wherein the device comprises a plurality of gas transfer membranes in a stacked arrangement, and wherein a sweep gas flow path is formed between a third gas transfer membrane and a fourth gas transfer membrane arranged adjacent to each other.

18. The device according to claims 16 and 17, wherein the second gas transfer membrane and the third gas transfer membrane are one and the same.

19. The device according to claims 16 and 17, wherein the second gas transfer membrane and the third gas transfer membrane are arranged adjacent to each other.

20. The device according to any one of the claims 16-19, wherein the biological liquid flow path and / or the sweep gas flow path is formed in the surface of at least one of the adjacent gas transfer membranes.

21. The device according to any one of claims 16-20, wherein the biological liquid flow path and / or the sweep gas flow path is formed by a spacer arranged between the adjacent gas transfer membranes.

22. The device according to any one of the preceding claims, wherein the medical device is a device for oxygenation of blood, a device for removal of carbon dioxide from blood, a device for continuous renal replacement therapy (CRRT), a device for removal of carbon monoxide from blood, a device for removal of nitrogen from blood (e.g. diving sickness therapy), or a device for adding nitric oxide to blood, or a combination of two or more thereof, preferably a device for oxygenation of blood.

Images