This application is directed to (1) the exchange of gasses between the ambient air and blood; (2) reducing the volume of a liquid solution by removing some of the solvent while maintaining the solute content intact and/or (3) extracting certain dissolved gases from a liquid while maintaining the rest of the liquid's constituents intact.
1: The main function of the lung is to exchange gasses between the ambient air and the blood. Within this framework O2 is transferred from the environment to the blood while CO2 is eliminated from the body. In a normal resting human these processes are associated with an O2 input of about 200-250 cm3/min and an output of about the same amount of CO2. This exchange is made through a surface area of 50-100 m2 of a 0.5-1 μm thick biological membrane separating the alveolar air from the pulmonary blood. This process is associated with the flow of similar volumes of blood and air—about 5 Liter/min. At the given flow rate the blood is in “contact” with the membrane through which diffusion takes place for a time period of ⅓-⅕ sec. In natural systems such as the lung the gas exchange is achieved by diffusion taking place across a thin biological membrane separating two compartments: the gases in the lung alveoli and the gases contained in the blood of the lung capillaries. The gases in the alveolar compartment are maintained at a composition close to that of ambient air or gas by moving the air or gases in and out of the lungs by respiratory movements. The gas exchange is achieved by diffusion through the surface area of the exchange membrane that is extremely large—about 70 m2. The driving force for diffusion of gases into and out of the blood is maintained by a very large blood flow through the lung capillaries.
2: in patients suffering from renal insufficiency or failure and hypervolemia, excess water may accumulate in a patient's blood (e.g., due to excess fluid administration). Failure to remove the excess fluid may result in heart failure, peripheral edema, including pulmonary edema which severely affects pulmonary blood gas exchanges, etc.
3: Ammonia and ammonium are highly toxic and therefore must be eliminated from the body. This is normally done by the liver where the blood dissolved ammonium is enzymatically transformed into urea which is less toxic. One of the main functions of the kidney is to eliminate the urea from the blood. However, in patients suffering from renal insufficiency or kidney failure, urea secretion is insufficient, and the patients must be continuously or frequently connected to an artificial kidney to eliminate the urea as well as other undesired compounds (e.g., ammonia) that accumulate.
One aspect of the invention is directed to a first method for removing excess water from blood. The first method comprises providing a plurality of fluid flow channels that are surrounded by hydrophobic nanotubes with diameters between 1 and 100 nm, with spaces between the nanotubes. Each of the channels has an outer boundary, an inflow end, and an outflow end, each of the channels is wide enough for blood to flow through, and the nanotubes are spaced close enough to each other to retain the blood within the channels when the blood is flowing through the channels. The first method also comprises passing the blood through the channels; and passing a gas through the spaces between the nanotubes outside the channels so that the gas comes into contact with the blood at the outer boundaries of the channels until the excess water in the blood evaporates into the gas.
Some instances of the first method further comprise determining whether a sufficient amount of water has been removed; and discontinuing the passing of the blood after a sufficient amount of water has been removed.
In some instances of the first method, the nanotubes are carbon nanotubes. In some instances of the first method, each of the channels has a diameter between 2 and 500 μm. In some instances of the first method, the nanotubes have a diameter between 5 and 20 nm. In some instances of the first method, the nanotubes are spaced on centers that are between 1.5 times the diameter of the nanotubes and 5 times the diameter of the nanotubes.
Another aspect of the invention is directed to a second method for removing excess solvent from a liquid. The second method comprises providing a plurality of fluid flow channels that are surrounded by hydrophobic nanotubes with diameters between 1 and 100 μnm, with spaces between the nanotubes. Each of the channels has an outer boundary, an inflow end, and an outflow end, each of the channels is wide enough for liquid to flow through, and the nanotubes are spaced close enough to each other to retain the liquid within the channels when the liquid is flowing through the channels. The second method also comprises passing the liquid through the channels; and passing a gas through the spaces between the nanotubes outside the channels so that the gas comes into contact with the liquid at the outer boundaries of the channels until the excess solvent in the liquid evaporates into the gas.
Some instances of the second method further comprise determining whether a sufficient amount of solvent has been removed; and discontinuing the passing of the liquid after a sufficient amount of solvent has been removed.
Another aspect of the invention is directed to a first solvent evaporation apparatus. The first apparatus comprises a field of at least one million hydrophobic nanotubes with diameters between 1 and 100 nm with spaces between the nanotubes though which gas can travel, with voids in the field positioned to form a plurality of fluid flow channels, each of which is surrounded by the nanotubes. The channels are wide enough for a liquid to pass through, and the nanotubes adjacent to the channels are spaced close enough to each other to prevent the liquid from escaping the channels. The first apparatus also comprises a gas pathway that passes through spaces between the nanotubes and extends from an input to the field of nanotubes to an output from the field of nanotubes; at least one sensor that generates data indicative of how much solvent has been removed from the liquid; and a controller that processes the data from the at least one sensor.
In some embodiments of the first apparatus, the liquid comprises blood and the solvent comprises water.
In some embodiments of the first apparatus, the liquid comprises blood and the solvent comprises water, and the apparatus further comprises a surface upon which the water condenses and a container for holding the condensed water. In these embodiments, the at least one sensor comprises a water level sensor that generates data indicative of how much water is in the container.
In some embodiments of the first apparatus, the liquid comprises blood and the solvent comprises water, and the at least one sensor comprises (a) a humidity sensor that outputs a first signal indicative of humidity of gas exiting the gas pathway and (h) a flow sensor that outputs a second signal indicative of flow of gas exiting the gas pathway. In these embodiments, the controller determines how much water has exited the gas pathway based on the first signal and the second signal.
Another aspect of the invention is directed to a third method for removing a specific molecule from a liquid. The third method comprises providing a plurality of fluid flow channels that are surrounded by hydrophobic nanotubes with diameters between 1 and 100 nm, with spaces between the nanotubes. Each of the channels has an outer boundary, an inflow end, and an outflow end, each of the channels is wide enough for the liquid to flow through, and the nanotubes are spaced close enough to each other to retain the liquid within the channels when the liquid is flowing through the channels. The third method also comprises passing the liquid through the channels; and passing a gas through the spaces between the nanotubes outside the channels so that the gas comes into contact with the liquid at the outer boundaries of the channels until the specific molecule in the liquid diffuses into the gas.
Some instances of the third method further comprise determining whether a particular amount of the specific molecule has been removed; and discontinuing the passing of the liquid after the particular amount of the specific molecule has been removed.
In some instances of the third method, the liquid is blood and the specific molecule is ammonia. In some instances of the third method, the nanotubes are carbon nanotubes. In some instances of the third method, each of the channels has a diameter between 2 and 500 μm. In some instances of the third method, the nanotubes have a diameter between 5 and 20 nm. In some instances of the third method, the nanotubes are spaced on centers that are between 1.5 times the diameter of the nanotubes and 5 times the diameter of the nanotubes.
Sonic instances of the third method further comprise analyzing the gas that has passed through the spaces between the nanotubes outside the channels to determine whether the specific molecule is present.
Some instances of the third method further comprise analyzing the gas that has passed through the spaces between the nanotubes outside the channels to determine how much of the specific molecule is present.
Another aspect of the invention is directed to a fourth method for introducing a specific molecule into a liquid. The fourth method comprises providing a plurality of fluid flow channels that are surrounded by hydrophobic nanotubes with diameters between 1 and 100 nm, with spaces between the nanotubes. Each of the channels has an outer boundary, an inflow end, and an outflow end, each of the channels is wide enough for the liquid to flow through, and the nanotubes are spaced close enough to each other to retain the liquid within the channels when the liquid is flowing through the channels. The fourth method also comprises passing the liquid through the channels; and passing a gas that includes the specific molecule through the spaces between the nanotubes outside the channels so that the gas comes into contact with the liquid at the outer boundaries of the channels until a desired quantity of the specific molecule diffuses into the liquid.
In some instances of the fourth method, the liquid is blood.
A first set of embodiments relate to a Gas Exchanger (“GE”) that will be described here within the framework of an artificial lung for efficient gas exchange (O2, CO2, etc.) between compartments such as human (or animal) blood and ambient air or some other gas. More specifically, the first set of embodiments are directed to an artificial lung and respiratory aid based on a structure made of nanotubes.
The GE system contains one or more gas exchange units 110 (GEU), and
The GE utilizes a plurality of hydrophobic nanotubes (NTs), e.g., carbon nanotubes. The NTs are highly hydrophobic, and the overall plurality of nanotubes may be referred to as a nanotuhe “field.” The NTs may be free standing; held together by Van der Waals forces; or mounted on a base made of, e.g., alumina, silicon, etc. Optionally, the structural integrity of the NTs can be enhanced by coating and infiltrating the NTs with an agent such as carbon (e.g., using well-known processes for forming vertically aligned carbon nanotubes). The field of NTs includes a large number of blood flow channels (BFCs) (“channels”) formed as discrete voids within the field of NTs. The field of NTs and the BFCs 2 therein may be constructed as described in U.S. Pat. Nos. 9,138,522 and 9,827,534, each of which is incorporated by reference in its entirety.
Each BFC is surrounded by NTs, which are shown in
The optimum distance between the NT centers will be related to the NT diameter, so that the NTs do not end up too far away from each other. More specifically, when thinner NTs are used, the NTs should preferably be packed more closely together. Preferably, the spacing between NTs will be not more than a few diameters of the NTs, and will more preferably be on the order of 1 diameter. For example, if NTs with 10 nm diameter are used, the NTs would preferably be spaced on centers of about 20 nm, which would mean that the spacing between adjacent NTs would be around one diameter. But if NTs with 20 nm diameter are used, the NTs would preferably be spaced further apart, on centers of about 40 nm. A suitable relationship between the NT diameter and the NT spacing is to space the NTs on centers that are between 1.5 times the diameter of the NT and 5 times the diameter of the NT. For example, if NTs with a diameter of 10 nm are used, the NTs should preferably be spaced on centers between 15 and 50 nm. In less preferred embodiments, the NTs are spaced centers between 1 times and 10 times the diameter of the NTs, or even between 0.5 times and 20 times the diameter of the NTs. Note that the NT packing or density affects the resistance to flow of the gas through the “forest” or “field” of NTs, which is an additional consideration that may be adjusted depending on the specific need. Note that the density of the NTs as well as the BFCs determine both (a) the exchange capacity and (b) the resistance to gas flow, and both of these parameters should be considered in selecting the layout and spacing of the NTs.
Methods for fabricating large masses of parallel carbon NTs, as depicted in
Collectively, the substrate, the field of NTs positioned on the substrate, and the voids within that field form a gas exchange “plate,” and this plate is used as a building block in the system described below. Each of the plates is formed from a very large number (e.g., millions or billions) of hydrophobic NTs with diameters between 1 and 100 nm. In some preferred embodiments, the NTs are vertically aligned carbon nanotubes (which are highly hydrophobic) that remain attached to the substrate on which they were formed. The NTs are positioned in a “field” with a large number (e.g., thousands or hundreds of thousands) of voids in that field that define vertical channels through which blood can pass. These channels are referred to herein as “blood-flow channels,” and the substrate has a hole that aligns with each of these blood-flow channels.
In alternative embodiments, each of these plates may be formed from a very large number (e.g., millions or billions) of interconnected NTs, with interconnections between the NTs that are sufficient to hold the plate together without requiring a substrate (in which case the substrate on which the NTs are originally grown can be removed). Examples of this variety of plate are described in “c-VACNT™ Enabled Fluid Reactor Innovations” by K. Strobl et al. (June 2019); “Vertically aligned carbon nanotube arrays as a thermal interface material” by L. Ping et al., APL Mater. 7, 020902 (2019); doi: 10.1063/1.5083868 (Feb. 2019); and in “Transfer of vertically aligned carbon nanotube arrays onto flexible substrates for gecko-inspired dry adhesive application” by Yang Li et al., RSC Advances, Issue 58 (May 2015). As in the previous variation, when this type of gas-exchange plate is used, a large number (e.g., thousands or hundreds of thousands) of preferably identical vertical blood-flow channels pass through the field of NTs.
The blood-flow channels are wide enough (e.g., between 2 and 500 μm) for the blood to flow through, and the NTs are spaced close enough together to retain the blood within the blood-flow channels, due to the hydrophobic nature of the NTs and the surface tension of the blood.
Returning to
The NT base 120 is preferably the substrate on which the NTs that surround the BFCs were fabricated, and the NT base 120 should have a hole or perforation 104 located at the center of each BFC. The NTs extend to the right from the NT base 120 and span a distance d2 to define the BFCs, which are oriented parallel to the direction of blood flow 107 and perpendicular to the gas flow direction 108. In some preferred embodiments, the distance d2 is between 0.1-1 cm. Because the NTs are grown on the NT base 120 and remain attached to it, no leakage near the base is expected. The NTs are held firmly in place by the extremely strong Van der Waals forces characterizing such nm scale structures. As a result of this configuration, blood that flows into the pool 105 will flow to the right through the perforations 104 in the NT base 120 and continue towards the right into and through the first set 20 of BFCs 2 in the first GEU.
A second NT base 120 is preferably positioned a short distance (e.g., between 0.1-4 mm in some embodiment or between 0.5 and 2 mm in some embodiments) away from the right end of the NTs that define the first set 20 of BFCs 2. When blood exits the first set of BFCs, it will flow into the gap between (a) the right end of the NTs that define the first set 20 of BFCs 2 and (b) the second NT base 120. The second GEU has a second set 20′ of BFCs 2 that is similar in construction to the first set 20 of BFCs 2, each BFC having an aligned perforation 104 in the NT base. The blood that enters the gap will then flow to the right through the perforations 104 in the second NT base 120 and continue towards the right, into and through the second set 20′ of BFCs 2 in the second GEU.
Note that when the blood exits the first set 20 of BFCs 2 and flows into the gap, surface tension of the blood (which is a water-based liquid) together with the hydrophobicity of the carbon NTs should prevent the blood from backing up into the very small spaces between the NTs that form the first set 20 of BFCs 2. Instead, the blood should flow to the right into the second set 20′ of BFCs 2 in the second GEU, because the diameter of the BFCs in the second GEU is orders of magnitude larger than the very small spaces between the NTs in the first GEU. The blood would then flow according to the pressure gradient through the second GEU (i.e., in the blood flow direction 107 through the holes in the second NT base 120 and then through the second set 20′ of BFCs 2 in the second GEU) rather than backwards. Note that the distance between adjacent NTs (i.e., less than a few diameters of the NTs, and preferably on the order of 1 diameter) is low enough to prevent blood plasma (or water) from penetrating the space between the NTs due to surface tension.
In alternative embodiments, additional stages (not shown) may be added in series. The blood eventually reaches the last GEU. A final support 100 is preferably positioned a short distance (e.g., between 0.1-4 mm in some embodiments, or between 0.5 and 2 mm in some embodiments) away from the right end of the NTs that define the last set 20′ of BFCs 2. When blood exits the last set of BFCs, it will flow into the gap between (a) the right end of the NTs that define the last set 20′ of BFCs 2 and (b) the final support 100. From there it will flow into the blood outflow channel 118.
While the blood is in the BFCs 2 in any of the stages, the blood has a chance to interact with the gases in the gas flow region 101. These gases flow in a gas flow direction 108 (i.e., up in
It is important note that, regardless of which variety of plate is used, the BFCs 2 have no coating or membrane to keep the blood from escaping the BFC. However, due to the high density (i.e., the close spacing) of the hydrophobic NTs surrounding the BFCs and the high surface tension of water, when a water-based fluid, such as blood, occupies or flows in the BFC, it will not leak out of the BFCs into the gas flow region 101. In other words, the NTs surrounding the BFC 2 form a virtual boundary for the liquid flow. The interactions between the blood and the gas occurs at this virtual boundary.
In addition, regardless of which variety of plate is used, the blood will travel through the blood-flow channels, while the gas that will exchange molecules with the blood permeates the spaces between the NTs (analogous to the way air permeates through a forest of trees). Because the NTs in the field are relatively densely packed, they can present significant resistance to horizontal flow of gas. So to ensure that the gas reaches the blood-flow channels, conduits that are free of NTs may optionally be included in the plate in some embodiments. In these embodiments, gas will permeate to the boundaries of the blood-flow channels by the combination of gas flowing through the conduits and diffusion from the conduits to nearby blood-flow channels.
Casing 111, a rigid biocompatible housing, seals the initial Blood Pool 105 as well as the one or more GEUs 110 contained within the casing 111. This permits gas exchange between the blood in the BFC and the air (or other gases) in the gas flow regions 101.
In this
For all of the embodiments described above, the blood in the inflow channel 106 is preferably venous blood that is low in oxygen and rich in CO2. The two blood gases undergo an exchange with the gas flowing in the gas flow region 101 around the BFCs in a direction 108 that is preferably normal to that of the BFC blood flow 107. This incoming gas is preferably rich in oxygen and has a low or zero concentration of CO2 so that the gas exchange is by diffusion along the concentration gradients. The blood in the outflow channel 118 will then be richer in O2 than the incoming blood.
The efficacy of the gas exchange is a function of the area of contact between the flowing blood and the flowing gas that may be oxygen or air. As mentioned above, in a normal pair of lungs this contact surface area is typically about 70 m2 while the blood flow is 5-7 L/min and air flow is similar. The amount of Oxygen or CO2 exchanged in normal human lungs is typically 200-250 cm3/min.
Let us now compute the parameters of gas exchange that satisfy the normal physiological requirements: The total BFC surface area that is needed for the gas exchange is a direct function of the BFC diameter and packing, i.e. the distance between the BFCs, and the total number of BFCs in the GE volume. For a GE having a total volume of 2 liters (e.g., 10 cm×10 cm×20 cm), the surface area available for exchange is independent of the arrangement of the GEUs within the GE, i.e. in series or in parallel, or their spatial configuration. For such a GE, if we assume that the BFC Radius is 10 μm, and the center-to-center distance of the BFCs is 40 μm, the total gas-blood exchange area is close about 80 m2, which is approximately equal to a typical pair of lungs. The Diffusion Capacity will therefore be over 2000 cm3 O2 per min (which exceeds the requirement of 250 cm3/min), and the Blood volume will be about 400 cm3 (which is comparable to that of the adult human respiratory system).
The overall GE preferably includes a plurality of GEUs connected together. The GEUs may be connected in series or in parallel to form the GE. Since connecting GEUs in series will increase the flow resistance, the number of GUIs that are connected in series should preferably be limited (e.g., to not more than ten). The GEUs may also be connected in a series/parallel combination. For example, three GEUs may be connected in series, and then the resulting set of three GEUs may be connected in parallel with five similar sets of three series-connected GEUs. Different series/parallel combinations may also be used.
The number of GEUs that are used in any given GE may vary, depending on the required surface area for diffusion. In some embodiments, a GE may contain between 2 and 20 GEUs connected in series, or between 2 and 10 GEUs connected in series.
Optionally, a plurality of GEUs may be combined into subsystems, and those subsystems may be connected in series, in parallel, or in series/parallel combinations to form the overall GE. When the BFCs are 20 μm in diameter and are spaced on 40 μm centers, 62,500 BFCs would fit in a 1 cm2 area, and would impose resistance to flow through the BFCs of 1.63·105 g/(s cm4). One example of suitable dimensions for a subsystem for use in a GE would be a width of 10 cm, a height of 10 cm, and a thickness of about 1.1 cm. The 1.1 cm thickness could be made of 10 GEUs that are each 0.1 cm thick, arranged in series as depicted in
In alternative configurations, the subsystems may be smaller e.g., 2 cm wide, 2 cm high, and about 1 cm thick, with similar internal construction to the 20×20×1.1 cm subsystems described above. These 2×2×1 cm subsystems can then be configured in parallel and/or in series to form the complete GE. In other alternative embodiments, the subsystems may be larger (e.g., 20 cm wide, 20 cm high, and about 2 cm thick).
Yet another possible configuration of GEUs for forming a GE would be to connect multiple (e.g., 2000) 1 cm2 units in parallel into a subsystem, and then connect 10 such subsystems in series. In such a GE system, the surface area of oxygen diffusion is sufficient for physiological quiet breathing and the resistance to flow in the BFCs would be only 815 g/(s cm4). This configuration would also have a pressure drop of less than 50 mmHg when 5-7 L/min of blood is flowing through the system.
Note that the diffusion capacity of the GEs discussed herein can be even higher than human lungs in which a 0.5-1 μm membrane (made up of living cells and a basal membrane) is interposed between the air and blood. In contrast, there is a direct air-blood contact in the GE. The continuous gas flow around the BFCs in the GE is also more efficient than the in/out air flow in the lungs during natural respiration.
We turn next to the efficacy of the Gas Exchanger with regards to CO2. The water Diffusion coefficients of CO2 and O2 are similar while the solubility of CO2 is about 24 times higher than that of O2. As the O2 and CO2 concentration difference between oxygenated and reduced blood are similar, the diffusion rate of CO2 is about 20 times that of O2. Thus, the CO2 transport in all the above processes is expected to be superior to that of O2.
Two examples of clinical applications are using the GE as an artificial lung and using the GE as a respiratory assist device.
Alternatively, air can be driven through the trachea and main bronchi via natural breathing as shown in
In any of these embodiments, the blood flow can be maintained by the natural pressure generated by the right ventricle or an appropriate blood vessel. Alternatively it can be driven by an external or implanted pump designed to generate blood flow for long periods of time. Such pumps are commercially available. The blood exiting the GE is returned to the body via a pulmonary vein 72 or veins, or any other appropriate blood vessel.
The flow rates for both blood and air are preferably adjustable to match the needs of the person, etc. this adjustment may be dynamic according to the changing need, for example during exercise. The adjustment may be controlled by sensors of a relevant physiological parameter such as the partial pressure of O2 and/or CO2 in the blood, Hb O2 saturation (oximetry), pH, etc. To supply the O2 (or other gas) needs, which amount to approximately 250 cm3/min for a resting adult man, a flow of about 5-7 L/min oxygenated blood is required; and this may need to be increased by a factor of up to 4-5 during exercise. An additional factor that should preferably be taken into consideration is the time the flowing blood is exposed to the gas diffusion process, the dwell time. In the normal resting human lung this duration is about ⅓-⅕ of a sec while the flow velocity is usually under 100 cm/s. The blood flow in the GE is compatible with these requirements. When the subject's heart is healthy, the blood flow may be powered by the patient's heart. Note that the series/parallel configuration of GEUs within the GE may be selected in advance to provide a desired flow resistance. To increase the resistance, the number of GEUs connected in series should be increased. To decrease the resistance, the number of GEUs connected in series should be reduced, and the number of parallel connections should be increased.
The corresponding air (or oxygen) flow is also about 5-8 L/min at rest and up to 5 times larger during exercise. When implanted, the Gas inlet 116 and Gas Outlet 114 (shown in
In certain circumstances, it may he beneficial to remove some of the water, or other liquid, from a solution without affecting the nature of the materials dissolved or suspended in it. For example, when excess water has accumulated in a patient's blood (e.g., in a patient with kidney failure, or in situations where too much fluid is administered to a patient), it would be desirable to remove some or all of the excess water from the patient's blood without affecting the other blood constituents.
A second set of embodiments is directed to a Fluid Reducer system designed to effectively remove water from blood (or other liquid). The hardware configuration of these embodiments is similar to the hardware configuration of the gas exchange are described above in connection with
Blood extracted from the patient flows through the BFCs 2, as described above in connection with
This arrangement provides an extremely large surface area for contact and molecular transfer between the blood (in the BFCs 2) and the gas flowing along the gas pathway, i.e., permeating through the field of NTs, and flowing around the virtual boundaries of the BFCs 2. For example, for a field that is 2 mm in height, with BFCs 2 having a radius of 25 microns spaced 25 microns apart, there are about 20,000 BFCs per square centimeter, and the total surface area of these 20,000 BFCs—i.e., area across which water molecules can be transferred to the gas—is about 30 square centimeters.
As explained above, the NTs surrounding the BFCs 2 form a virtual boundary for the blood flow. The interaction between the blood and the gas (e.g., the evaporation of the water from the blood into the gas) occurs at this virtual boundary. When the blood flows in the BFCs, the blood will be in direct contact with the flowing dry gas and some of the water in the blood will evaporate. This evaporation will transfer water molecules from blood in the BFCs 2 to the flowing gas, thereby lowering the water content of the blood in the BFCs. Lowering the water content of the blood (which also reduces blood volume) can be beneficial in a variety of contexts, including but not limited to extracorporeal oxygenation (e.g., ECMO or as described above in connection with the first set of embodiments).
The amount of water that is removed by evaporation can be controlled and adjusted by changing the flow rate of the blood and/or the gas. Such control may be applied using appropriate sensors, for osmolarity, flow, etc. located at a downstream end of the blood pathway (e.g., before the blood is returned to the patient's body). Control may be accomplished, e.g., using a needle valve or other regulator to adjust the rate at which gas exits a gas supply. The flow velocity of the gas, in turn, affects the evaporation rate of the water and hence the level of water removal. In alternative embodiments, the amount of water that is removed by evaporation can be controlled by varying the total surface area over which transfer of water molecules to the gas takes place (e.g. by providing multiple banks that each contain BFCs, and controlling the number of banks through which the blood and gas is routed).
In some embodiments, the amount of water that is removed from the blood by evaporation is measured directly, and the measured quantity of water may be used to control the system (e.g., by turning off the system once a predetermined quantity of water has been removed).
The gas that exits the gas exchanger 75 enters a water condensation subsystem 150, where the water vapor that was picked up in the gas exchanger 75 condenses into liquid water. A wide variety of conventional approaches for implementing the water condensation subsystem 150 will be apparent to persons skilled in the relevant arts, including but not limited to passing the humid gas over a cold surface with a high surface area. Moisture in the gas will condense into liquid water on the cold surface and is collected in a water container 152, and the water level in the water container 152 is measured by a water level sensor 154. The water level sensor 154 may be implemented using a wide variety of conventional approaches that will be apparent to persons skilled in the relevant arts, including but not limited to optical sensors, resistivity sensors, etc. The controller 156 receives a signal indicative of the water level from the water level sensor 154. When the amount of collected water reaches a set level, the controller 156 can stop the extraction of water from the blood by sending inappropriate signal to an actuator (not shown) that controls the gas valve 135 and/or an actuator (not shown) that controls the blood valve 140. Alternatively or additionally, the controller 156 can output an indication to healthcare personnel to disconnect the system or take another appropriate action.
The amount of water that has been removed from the blood by evaporation may also be determined indirectly, e.g., by tracking the humidity of the gas that exits the gas exchange unit over time, and estimating the amount of water that is been removed based on the tracked level of humidity. In this case, the estimated quantity of water that has been removed is used to control the system.
Note that while the fluid reducer embodiments are described above in the context of removing water from blood, these same embodiments may also be used to remove other solvents from other liquids. This can be accomplished by routing the other liquid from left to right through the gas exchanger 75 and routing gas from top to bottom through the gas exchanger 75 in either
Optionally, these Fluid Reducer embodiments can also heat the blood to a desired temperature. One example of a suitable configuration that may be used to heat is to coat both top and bottom surfaces, except for the openings of the BFCs 2, by a thin coating layer, which is preferably made from an electrically conducting material such as carbon. Such coating layer (not shown) may be made, for example, by vapor deposition, which leaves the BFCs 2 open. This arrangement is particularly suited to those embodiments where the plurality of NTs is arranged like a carpet-like field with the voids therein forming the fluid-flow channels (as depicted in
Because carbon NTs are conductive and a large number of carbon NTs span the distance between the upper and lower coating layers, heating in this embodiment can be accomplished by applying a voltage between the upper and lower coating layers via conductive leads. The applied voltage will cause a current to flow through the NTs, which will generate heat. As the electric resistance between the upper and lower surfaces of a typical NT carpet-like field is about 10 Ω per an area of 1 cm2, a 10 cm2 carpet-like field would function as a 1 Watt heater when activated by a 1 Volt potential difference. Changing the voltage will change the amount of heat that is generated. The amount of heat that is added to the system can be controlled by controlling the voltage that is applied to the leads or by controlling the current that passes through those leads.
In certain circumstances, it may be beneficial to remove certain dissolved gases from liquids such as water, or blood without affecting the nature of other materials dissolved or suspended in the liquid. For example, in patients suffering from renal insufficiency, it may be desirable to remove harmful dissolved gases (e.g., ammonia) from the patient's blood.
A third set of embodiments is directed to removing gasses (e.g., ammonia) dissolved in the blood by allowing its efficient diffusion into the gas or air that is brought into contact with the blood. The hardware configuration of these embodiments is similar to the hardware configuration of the Fluid Reducer system described above (i.e., the second set of embodiments
When ammonia gas is dissolved in water, some of it converts to ammonium ions:
H2O+NH3OH−+NH4+ (Equation No. 1)
Rapid and efficient elimination of ammonia (which is produced by protein degradation in living cells) from the blood will result in negligible concentrations of ammonia and ammonium in the blood and thus the quantity of urea synthesis by the liver will be markedly reduced. As the ammonia concentration is lowered the balance of equation (1) is moved to the left such that the ammonium is transformed to ammonia and is eliminated.
Effective removal is achieved by providing an extremely large area of contact between the blood and the gas. As in the Fluid Reducer embodiments, the NTs surrounding the BFC 2 form a virtual boundary for the blood flow. The interaction between the blood and the gas the diffusion of ammonia from the blood into the gas) occurs at this virtual boundary. When the blood flows in the BFCs it is in direct contact with the flowing gas such that the ammonia gas dissolved in the blood diffuses out to the flowing gas that contains no such molecules. The ammonia is carried away with the flowing gas. The blood ammonium and ammonia content is thus reduced. One can remove all the toxic material flowing in the blood and thus significantly reducing the amount of urea produced by the liver such that the amount of toxic material in the blood due to kidney failure is minimal.
The techniques described herein are not limited to removing ammonia from blood, and these same techniques can be used to remove any volatile molecule of interest from blood. More specifically, when blood is flowing through the BFCs 2, volatile molecules within the blood will diffuse out of the blood and into the flowing gas that originally contains no such molecules. This phenomenon can advantageously be utilized as a “diagnostic nose” by capturing the gas that exits the GEU and analyzing that gas to detect the presence and/or concentration of the molecules of interest. A diagnostic decision can then be made based on the detection and/or the concentration of the molecules of interest (or the absence of detected molecules).
Because there is direct blood-air contact, this type of “diagnostic nose” is superior to conventional artificial nose systems that rely on capturing air that is been exhaled from a person's lungs, and analyzing that exhaled air. This is because in the case of exhalation from the lungs, the relevant molecules in the blood must permeate the capillary and alveolar membranes before they can be detected. In contrast, the embodiments described herein provide direct blood-air contact, which increases the probability that the relevant molecule will be detected. The probability of detection is further increased because large quantities of blood will pass through the GEU.
Notably, the same hardware described above can also be used to introduce a specific molecule into a person's blood. Examples include introducing an anesthetic prior to surgery, introducing a pain killing compound, or adding various gases used for specific treatments (including but not limited to introducing CO2 to control blood pH, minute amounts of CO to affect Hb function, etc.). In these embodiments, the relevant molecules are added (in gas form) to the gas before the gas enters the GEU. When the relevant molecules come into contact with the blood (at the virtual boundary of the channels), the molecules will diffuse into the blood, where they can perform their intended function (e.g., anesthesia, pain relief, therapeutic treatment, etc.).
Furthermore, the techniques described herein are not limited to removing molecules that are dissolved in blood, detecting molecules that are present in blood, and adding molecules in controlled doses to blood. To the contrary, the techniques described herein can be used to remove molecules from any other liquid, detect molecules that are present in any other liquid, and add molecules in controlled amounts to any other liquid.
The embodiments above are described in the context of delivering O2 to blood and removing CO2 from blood, removing excess water from blood, and removing toxins from blood. But the invention is not limited to those contexts, and can be used to deliver other gases to blood, or remove other components from blood. For example, it may be used in connection with a body part that has a dedicated circulation (such as a leg, brain, kidney) to deliver any desired gas to that body part. This can be used to deliver a chemical such as an anesthetic or therapeutic gas intended to act locally. In such a case the gas will be inputted into the artery and outputted (eliminated) via the vein, etc.
Note also that the invention is not limited to medical uses, and can be used to exchange gases in other types of fluid flow systems, including industrial applications.
As additional use of the apparatuses described above is as a heat exchanger. Regardless of whether any gases are exchanged between the gas and liquid that flow through the device, heat transfer can still occur between the gas and the fluid. As a result, hot fluid can be used to heat the gas, cold fluid can be used to cool the gas, hot gas can be used to heat the fluid, or cold gas can be used to cool the fluid. The heat transfer is expected to be very effective relative to prior art devices because the contact surface area is very large, and there is no physical barrier between the gas and the fluid. Optionally, sensors and pumps may be used to control the exchange so as to maintain the desired temperature. These sensors and pumps may also be used when the primary purpose is gas exchange, as in the embodiments described above.
While the present invention has been disclosed with reference to certain embodiments, numerous modifications, alterations, and changes to the described embodiments are possible without departing from the sphere and scope of the present invention, as defined in the appended claims. Accordingly, it is intended that the present invention not be limited to the described embodiments, but that it has the full scope defined by the language of the following claims, and equivalents thereof.
This Application claims the benefit of U.S. Provisional Application 62/719,379 filed Aug. 17, 2018, which is incorporated herein by reference in its entirety.
Number | Date | Country | |
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62719379 | Aug 2018 | US |