Patent ID: 12220515

DETAILED DESCRIPTION

It will be readily understood that the components of the embodiments, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations in addition to the described example embodiments. Thus, the following more detailed description of the example embodiments, as represented in the figures, is not intended to limit the scope of the embodiments, as claimed, but is merely representative of example embodiments.

Reference throughout this specification to “one embodiment” or “an embodiment” (or the like) means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearance of the phrases “in one embodiment” or “in an embodiment” or the like in various places throughout this specification are not necessarily all referring to the same embodiment.

Furthermore, described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided to give a thorough understanding of embodiments. One skilled in the relevant art will recognize, however, that the various embodiments can be practiced without one or more of the specific details, or with other methods, components, materials, et cetera. In other instances, well known structures, materials, or operations are not shown or described in detail to avoid obfuscation.

As used herein and in the appended claims, the singular forms “a,” “an”, and “the” include plural references unless the context clearly dictates otherwise. Thus, for example, reference to “an impeller” includes a plurality of such impellers and equivalents thereof known to those skilled in the art, and so forth, and reference to “the impeller” is a reference to one or more such impellers and equivalents thereof known to those skilled in the art, and so forth. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each separate value and intermediate ranges are incorporated into the specification as if individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein otherwise clearly contraindicated by the text.

As used herein in reference to device10, the terms “axial”, “axially” or like terms refer generally to an axis around which a component (for example, fiber bundle300or impeller400) of device10is formed (although not necessarily symmetrically therearound). The term “radial” refers generally to a direction normal to such an axis. The terms “rear”, “rearward” or like terms refer generally to a direction along axis x ofFIG.1Aaway from or opposite the gas and fluid ports of device10. The terms “front”, “forward” or like terms refer generally to a direction along axis x toward the gas and fluid ports of device10. The terms “up”, “upward” or like terms refer generally to a direction along axis y ofFIG.1Atoward fiber bundle section200and away from pressurizing section122of base section100, while the terms “down”, “downward” or like terms refer to a direction along axis y away from fiber bundle section200and toward pressurizing section122of base section100. The terms “side”, “sideways” or like terms refer to a direction orthogonal to an up or down direction and orthogonal to an axial direction as described above. In general, terms related to direction and/or orientation as set forth herein are used to describe relative positions of the elements of the described embodiment and are not limiting unless otherwise indicated herein or otherwise clear from the text hereof.

In a number of embodiments, extracorporeal/paracorporeal ambulatory assist lung system hereof provide advantages in gas transfer efficiency and biocompatibility. The systems hereof may, for example, be designed for either central and/or peripheral cannulation and respiratory support of, for example, 1-3 months duration before device change-out may be required. Systems hereof are, for example, amenable to patients suffering from severe acute respiratory failure (ARDS) to chronic patients suffering from COPD or severe pulmonary hypertension (PH). Paracorporeal apparatuses, devices or systems are extracorporeal devices/systems generally located immediately adjacent to the body during use. In other words, paracorporeal devices or systems are “wearable” or ambulatory devices or systems. The apparatuses, devices and systems hereof are well suited for paracorporeal/ambulatory use as well as use as generally stationary extracorporeal use.

In many ambulatory devices or system under development, a blood pump is connected by one or more conduits (for example, lengths of tubing) to an oxygenator. While a number of systems have integrated blood pumps, the blood leaving the impeller unit of such devices typically travels through channels before being distributed by manifolds into the hollow fiber bundle compartment. Recently, devices which are less cumbersome than many other devices under development while providing for increased ambulatory respiratory assist were disclosed in PCT International Patent Application Publication No. 2016/210089, the disclosure of which is incorporated herein by reference. Such devices provide a highly integrated blood pump and lung, in which a pump mechanism such as an impeller pressurizes blood for flow through hollow gas permeable fibers (sometimes referred to herein as a fiber bundle). Such devices may, for example, be designed to be worn in a holster or vest paracorporeally. Moreover, such devices may, for example, provide for increased average or mean velocity through the fiber bundle as compared to other devices, which enhances gas exchange. The integrally formed extracorporeal systems for lung assist of PCT International Patent Application Publication No. 2016/210089 include an integrated housing having a blood flow inlet in fluid connection with a fiber bundle compartment and a pressurizing stator compartment.

In a number of embodiments as illustrated inFIGS.1A through4, device10includes a first, base or blood pressurizing section100(hereinafter referred to as base section100) and a modular or releasably connectible second, fiber bundle or gas exchange section200(hereinafter referred to as fiber bundle section200,200aetc.). In a number of embodiments, base section100and fiber bundle section200are releasably connectible so that a pressurizing system and the fiber bundle are encompassed within a relatively small form factor. As further described below, fiber bundle section200may be readily removed and replaced with another fiber bundle section such as fiber bundle section200aofFIG.1Bto provide a fiber bundle of, for example, a different size, a different configuration, a different surface treatment, a different fiber composition, etc. Device10may thereby provide for efficient and significant gas transfer rate in a number of different uses or treatments without inducing significant blood damage. Moreover, fiber bundle section such as fiber bundle section200or200amay be readily replaced with another like or identical fiber bundles section200or200a, respectively, in the case of, for example, damage, contamination or wear.

Fiber bundle section200includes a housing220which includes a fiber bundle compartment222as, for example, illustrated in, for example,FIGS.2B and3B. Fiber bundle compartment222houses a fiber bundle300and provides a gas pathway designed to uniformly perfuse the gas side of fiber bundle300with a sweep gas which may be oxygen or a gas mixture including oxygen.

As, for example, illustrated in the embodiments ofFIGS.2A and2B, systems5hereof may include a base section100and a plurality of different fiber bundle sections200,200aetc. Two fiber bundle sections200and200aare illustrated inFIGS.2A and2B, but more fiber bundle sections may be provided. In a number of embodiments, fiber bundle sections200and200a(and other fiber bundle sections hereof) are formed to have generally identically dimensions other than the length thereof. Elements of fiber bundle section200aare numbered similarly to corresponding elements of fiber bundle section200with the addition of the designation “a” thereto. Fiber bundle300amay, for example, be formed to have dimensions generally identically to fiber bundle300other than the length thereof. Upon formation, the gas exchanging portion of fiber bundle300(excluding any potting) had a diameter of 1.75 inches (0.044 meters) and a length of 1.52 inches (0.039 meters). Fiber bundle300ahad a diameter of 1.75 inches (0.044 meters) and a length of 3.20 inches (0.081 meters). In a number of embodiments, fiber bundle300had an overall surface area for gas exchange or total fiber surface area of 0.3 m2. Fiber bundle300included 96 PMP fiber layers. Fiber bundle300ahad an overall surface area for gas exchange or total fiber surface area of 0.65 m2. Fiber bundle300aincluded 200 PMP fiber layers.

In the embodiments of Figures IA through4E, numerous fiber bundle/device properties can be changed by switching between fiber bundle sections including, but not limited to, fiber bundle length (and, thereby, overall surface area for gas exchange), fiber bundle composition (for example, fiber bundle material, surface treatment), etc. The fiber bundle properties can vary over a wide range to be specifically adapted for a particular use or function, for a particular patient group, or even for a particular patient.

In the illustrated embodiment ofFIGS.1through4E, fiber bundle section200and associated fiber bundle300were, for example, designed for pediatric use, while fiber bundle section200aand associated fiber bundle300awere designed for adult use. In the case of each of fiber bundle sections200and200a, device10may, for example, be used for oxygenation and/or carbon dioxide removal. The integrated pump, including impeller400(a closed or enclosed impeller in a number of embodiments), draws venous blood from a patient via an inflow cannula (seeFIG.3B) placed within a blood vessel. Blood is pumped through the gas-exchanging fiber bundle, which is operable to transfer oxygen to and remove carbon dioxide from the blood. After the blood passes through the fiber bundle, the blood is returned to the patient's circulatory system via an outflow cannula (seeFIG.3B). The required levels of blood flow, pumping, and gas exchange provided by device10during respiratory support depends upon patient size (for example, a pediatric patient or an adult patient) as well as the nature of the respiratory insufficiency. In the case wherein carbon dioxide removal rather than oxygenation is the primary goal, lower blood flow rates and less invasive cannulation strategies may be used. When carbon dioxide is the primary goal, the methodology is typically referred to as extracorporeal carbon dioxide removal or ECCO2R.

In a number of embodiments, all gas and fluid inlets and outlets (collectively ports) are oriented in generally the same directions upon assembly of device10by connecting a fiber bundle section hereof to base section100(see, for example, Figures IA through2B). In the illustrated embodiment, the axes of gas inlet260, gas outlet264, fluid inlet130and fluid outlet250are generally parallel (for example, within less than 20, 10 or even 5 degrees of being parallel). In the embodiment ofFIGS.1through4C, the inlets and outlets are positioned on a forward or front side of device10. In the illustrated embodiment, such axes are generally coplanar (for example, within less than 20, 10 or even 5 degrees of being coplanar). By orientating all gas and fluid ports in generally the same direction, connection of tubing to such ports and wearing of device10hereof with attached tubing is facilitated. As set forth above, orientating all gas and fluid ports in generally the same direction indicates that the axes of each of the ports is within 20°, 10°, 5° or less of being colinear with all other axes.

In a number of embodiments, the dimensions of device10were no more than 13.2 cm (5.2 inches) in height (the y dimension inFIG.1A), no more than 11.4 cm (4.5 inches) in width (the z dimension inFIG.1A), and no more than 14 cm (5.5 inches) in length (the x dimension inFIG.1A). In a number of embodiments, the length of fiber bundle section varied between 6.9 cm (2.7 inches) and 11.2 cm (4.4 inches). The weight of device10with fiber bundle section200may, for example, be no greater than 550 g, or no greater than 500 g, while the weight of device10with fiber bundle section200amay be no greater than 620 g or nor greater than 570 g. In a number of embodiments, the priming volume of device10with fiber bundle section200was approximately 125 ml, and the priming volume of device10with fiber bundle section200awas approximately 160 ml. The form factor of device hereof may be further reduced by increasing pumping efficiency (for example, by further optimizing impeller design).

In that regard, a pressurizing mechanism such as a rotating element or an impeller400may be positioned within a pressurizing or pumping (impeller/stator) compartment124a housing120of base section100. In the illustrated embodiment, base section100includes a first or pressurizing section122which houses pumping or pressurizing compartment124and a second, or interface section140which extends at an angle from first section122to form an interface for connection with a fiber bundle section hereof. In the illustrated embodiment, extending section140extends at an angle of approximately 90° to the plane of rotation of impeller400as defined by pumping or pressurizing compartment124of first section122. Pumping or pressurizing compartment124was formed as an impeller stator/volute compartment of first section122. In the illustrated embodiment, first section122and pumping or pressurizing compartment124thereof were formed via connection of a first or upper housing section or portion120aand a lower or second housing section120bof base housing120. Lower or second housing section120bof base housing120(see, for example,FIG.4A) was sized to allow insertion of impeller400into impeller stator/volute compartment124of base housing120. Pumping or pressurizing compartment124houses impeller400and may be designed in accordance with traditional pump theory to maximize the pumping efficiency of impeller400. Impeller400rotates within pumping or pressurizing compartment124of housing120.

Fiber bundle section housing220and base section housing120are formed from rigid materials. In general, such rigid materials do not deform or flex significantly under the conditions of use. In a number of embodiments, fiber bundle section housing220and base section housing120are formed from polymeric materials and, typically, from the same polymeric material. The housing sections may, for example, be formed from extrusion.

The stator section of a centrifugal pump, after flow exits the impeller, is usually either a diffuser or a volute. The purpose of each of these two stator types is to efficiently diffuse velocity energy into pressure. Diffusers are characterized by a plurality of radially symmetric diffusing passageways surrounding the impeller. Either a volute-shaped or annular collector is used in tandem with the diffuser. Volutes are characterized by one or more scroll-shaped diffusing passageways (one in a number of embodiments hereof), depending on the pump configuration. A volute hereof receives fluid being pumped by the impeller, slowing down the fluid's flow rate and converting kinetic energy into pressure. The volute curves and increases in area as it approaches the discharge port.

Impeller400may, for example, be partially magnetically supported via one or more magnets positioned on or within impeller400. Impeller400, in the illustrated embodiment, is positioned within impeller volute compartment124such that the net hydrodynamic load on impeller400is upwards (in the orientation of the Figures). Thus, magnets used to support impeller400may exert a downward force on impeller400. As, for example, discussed in PCT International Publication No. WO2014/085620, one or more magnets may be seated in one or more seating of impeller400and (in cooperation with another magnet which may be within or external to impeller volute compartment124) is operable to apply force offset the combined hydrodynamic and coupling magnet forces, thereby minimizing the axial forces applied to the bearings, and improving overall system durability. Top and bottom pivot bearings412aand412b(seeFIG.4A), respectively, may, for example, be ultra-high-molecular-weight polyethylene (UHMWPE) pivot and cup type bearings housed in a stainless steel shell, which maximizes their resistance to wear.

FIG.2Cillustrates fluid (blood) flow (solid arrows) and sweep gas flow (dashed arrows) through device10. In that regard, a fluid such as blood is drawn into the central portion of impeller400via a fluid inlet130formed in base section100and centrifugally spun outwards via impeller vanes410(see, for example,FIGS.3C and5A) as indicated by the radially outward oriented solid arrows inFIG.2C. Blood is then channeled to fiber bundle300as shown in, for example,FIGS.1B and3C. As, for example, illustrated inFIG.3C, a channel126extends from impeller volute compartment124to a flow channel142. At the point that channel126extends from impeller volute compartment124, flow channel142may, for example, extend the height (that is, the vertical dimension in the orientation ofFIG.2C) of impeller400to, for example, maximize washing on the underside of impeller400, as this is a common area for thrombus deposition in pivot pumps. In the illustrated embodiment, channel126extends generally tangentially (for example, within 5 degrees of tangentially therefrom) from impeller volute compartment to connect to flow channel142. In a number of embodiments, flow channel142had a circular cross-section. Channel126extends rearward at an angle to approximately a centerline of impeller400where channel126connects to flow channel142.

Flow Channel142may be incorporated into base housing120(that is, within extending section140) in a manner that it does not further increase the form factor of fiber bundle300and, thereby, fiber bundle section200. In the illustrated embodiment (see, for example,FIGS.2B,2C and4C), flow channel142travels vertically upward (in the orientation of the drawings) and at an angle of approximately 90° (that is approximately perpendicularly or perpendicularly) to the plane of rotation of impeller400through extending section140of base section100and enters a fluid/blood inlet volume or manifold144portion formed in a forward-facing portion of extending section140where the fluid/blood contacts a second or rearward surface of fiber bundle300. Providing rounded or arced corners/ends in flow channel142may assist in, for example, reducing or minimizing hemolysis and thrombosis. In a number of embodiments, flow channel142has a round or circular cross-sectional shape.

In a number of embodiments, the blood enters the second or rearward end of fiber bundle300from manifold144and passes around the hollow fibers thereof. After passing through fiber bundle300, blood exits system10via an outlet volume or manifold224, which is in fluid connection with a first or forward end of fiber bundle300at a first end thereof and with a blood/fluid outlet250at a second end thereof. The liquid/fluid flow path may be separated from the gas flow path through device10by abutment/sealing between (i) the periphery of the rear face of fiber bundle300and surface146and (ii) the periphery of the front face of fiber bundle300and fiber bundle housing220.

In the illustrated embodiment, fiber bundle section200includes an interface270(a fiber bundle section200aincludes a like interface270a) which connects to a cooperating interface170of extending section140of base section100. Each fiber bundle section hereof may include a like or identical interface which cooperates with interface170to form a sealed connection between one of the fiber bundle sections hereof and base section100. Fiber bundle sections hereof are thus each readily connectible to and removable from base section100hereof for devices10of differing flow and/or mass exchange properties (as well as differing dimensions, volume and/or weight). As illustrated schematically in the representative embodiment ofFIG.2C, fiber bundle section200amay include an interface270ahaving a connector272awhich cooperates with a cooperating connector172on interface170to form a sealed connection between interface270aof fiber bundle section200aand interface170of base section100. Other fiber bundle sections hereof may similarly include like connectors to cooperate with cooperating connector172. Connector272a(and like or identical connectors of other fiber bundle sections hereof) may cooperate with cooperating connector172via sliding fits, snap fits, threaded fits, Luer lock connection fits etc. as known in the mechanical/medical connection arts. A sealing connection between interface270aand interface170may, for example, be facilitated by a seal180such as an O-ring, which is seated in a seating formed in forward surface146of the illustrated embodiment.

The gas pathway in device10may, for example, be relatively simple. Gas flows in through a gas inlet port260into a channel262on one side of fiber bundle300and out through a gas outlet port264in fluid connection with a channel266on the other side of fiber bundle300. Thus, gas flow through fiber bundle300is in the average or bulk direction of the dashed arrows inFIG.2C. Channel262is the inlet to the gas pathway and channel266is the outlet. The sweep gas passes through262across (that is radially across) the lumens of the fibers into channel266. Channel262is sealed from channel266, for example, by sealing contact between an inner surface of housing220and fiber bundle300or by sealing contact with a sealing member which extends between an inner surface of housing220and fiber bundle300. In a number of embodiments, the height of channels262and266were approximately 0.8 cm (0.3 inches). The width may, for example, be chosen to assist in uniformly perfusing all of the fibers in fiber bundle300. The direction of gas flow may, for example, be such that it is generally along or assisted by the direction of gravity when device10is worn by the patient, so that any condensation that is built up will be cleared as a result of the effect of gravity.

FIG.4Aillustrates a perspective, disassembled or exploded view of device10including smaller, pediatric fiber bundle section200.FIG.4Billustrates a side view of device10with larger, adult fiber bundle200aconnected to base section100.FIG.4Cillustrates a rear view of device10with a rear panel removed to illustrate channel142extending from the pressurizing section122to manifold144(through extending section140). As described above, in the illustrated embodiment, channel142is incorporated into base housing120within extending section140in a manner that it does not further increase the form factor of fiber bundle300and, thereby, fiber bundle section200. As described above, channel142travels in a plane that is orthogonal to or perpendicular to the plane of rotation of impeller400through extending section140of base section100and enters a fluid/blood inlet volume or manifold144portion.

FIG.4Dillustrates a side view of another embodiment of paracorporeal ambulatory assist lung device10′ hereof that is similar in design and operation to device10with larger, adult fiber bundle section200aconnected to base section100′. In describing device10′, elements of device10′ include reference numbers similar to corresponding elements of device10with the addition of the designation “′”.FIG.4Eillustrates a rear view of device10′ with a rear panel removed to illustrate flow path channel142′ which extends from pressurizing section122′ into a manifold144′. Similar to flow channel142of device10, flow channel142′ extends upward from pressurizing section122′, through extending section140, in a plane generally perpendicular to the plane of rotation of impeller400′. However, flow channel142′ does not extend generally linearly and vertically upward through extending section140′, but travels in a curvilinear path through extending section140′ to manifold144′. Once again, providing rounded or arced corners/ends in flow channel142′ may assist in, for example, reducing or minimizing hemolysis and thrombosis. In a number of embodiments, flow channel142′ may, for example, have a round or circular cross-sectional shape. As seen in a comparison ofFIGS.4E and4C, the from factor of extending section140′ is larger than that of extending section140, resulting in device10′ having a slightly larger form factor and being a slightly heavier than device10′. The path or shape of flow channels such as channels142and142′ may, for example, be readily optimized based upon variables such as impeller design, pressure requirements, hemolysis limits, device form factor, etc. using known engineering principles.

Similar to device10, all gas and fluid inlets and outlets (collectively ports) maybe oriented in generally the same direction upon assembly of device10′. In the illustrated embodiment, the axes of gas inlet260′, gas outlet264′, fluid inlet130′ and fluid outlet250′ are generally parallel and positioned on one side of device10′. As described above, by orientating all gas and fluid ports in generally the same direction, connection of tubing to such ports and wearing of device10′ hereof with attached tubing is facilitated.

Fiber bundle300may, for example, be manufactured in accordance with methods described in PCT International Publication No. WO2014/085620, the disclosure of which is incorporated herein by reference. In a number of embodiments, fiber bundle300was a generally cylindrical bundle of hollow fiber membranes (for example, fiber arrays, membranes or fabrics as described above) stacked in layers at, for example, 5-15 degree angles to one another and aligned generally perpendicular to the principal direction of blood flow (that is, generally perpendicular to axis A of fiber bundle300—seeFIGS.2B and2D)) to maximize gas exchange. In a number of representative embodiments studied herein, fiber bundle300was a generally cylindrical bundle of hollow fiber membranes stacked in layers at approximately 14 degree angles to one another. In that regard, the fibers were cut into round sheets and stacked at a 14 degree angle between adjacent sheets into a potting mold. The ends of the hollow fibers were potted into semi-circular gas manifold channels (gas inlet manifold channel262and gas outlet manifold channel266). Polyurethane glue was injected into the mold by using centrifugal force generated by spinning the mold in a lathe. The polyurethane binds all the fibers into fiber bundle300. The thickness of the potting glue was roughly 0.25 in and was chosen to provide adequate mechanical support.

Aligning the hollow fibers generally perpendicular (for example, within no more 5 degrees from perpendicular or even within nor more than 2.5 degrees of perpendicular) to axis A can significantly decrease volume (that is, improve compactness) as compared to systems in which hollow fibers are generally parallel to the axis of the housing/blood flow.

In a number of embodiments, fiber bundle300was sealed to axially extending sealing sections formed on an inner wall of fiber bundle compartment222to form generally semi-circular (in cross-section) manifolds. The sealing sections may, for example, extend radially inward to contact and form a sealing connection with fiber bundle300. Two sealing section may be used to form generally semi-circular (that is, extending approximately 180 degrees) manifolds. Additional sealing sections may, for example, be used to create manifolds that extend around the inner circumference of fiber bundle compartment222less than 180 degrees.

Fiber bundle300may, for example, be wound and positioned within a four-piece reusable mold made from, for example, acetal (Delrin) for potting. During potting, two-part polyurethane adhesive (available from Cas Chem, of Bayonne, NJ) is injected into the mold. The mold is then centrifuged to assure even distribution around the periphery without any voids. Once the adhesive has cured, the potted fibers are removed and trimmed. This procedure establishes a common gas pathway between all fibers.

As described above, the fibers used in the studies of devices10were provided in array, fabric or membrane form. Approaches to improving thromboresistance include the use of zwitterionic molecular species attached (for example, covalently) to the surface of the fibers without significantly affecting gas transport across the fiber surface. Carbonic anhydrase may, for example, be immobilized on or in the vicinity of fiber surfaces to enhance carbon dioxide removal. See, for example, U.S. Pat. No. 7,763,097, the disclosure of which is incorporated herein by reference. Furthermore, blood flow paths and patterns in device10may be optimized using for example computational fluid dynamics or CFD for improved hemocompatibility. The ultimate anticoagulation requirements for device10may also be further reduced because blood exiting device10flows through the patient's lungs, which can continue to act as a filter of small emboli.

As described above, blood enters device10through fluid flow inlet or blood flow inlet port130and is pumped by impeller400. In a number of studied embodiments, impeller400was supported by two pivot bearings412aand412bmounted into housing120and aligned with and cooperate with extending members414aand414bon the central axis of radial impeller400. As known in the bearing arts, extending member414aand414bmay, for example, include a rounded end that is rotatable relative to a bearing cup of bearings412aand412b(for example, similar to a ball and socket joint). The bearing cups may, for example, be formed from ultrahigh molecular weights polyethylene and are available, for example, from Modern Plastics of Shelton, Connecticut. The use of pivot bearings412aand412beliminates the need for seals and bearings. The pivot bearings maintain impeller400axially and radially aligned within system10. Also, secondary saline infusion used in some systems to keep blood from contacting friction/heat generating components are not required. Fresh blood enters device10and flows across the pivot bearings, flushing the area with fresh fluid.

Magnetically suspended or levitated impellers without bearings may, for example, be used to further increase longevity. However, device10, in a number of embodiments, may require periodic change-out (for example, every 1-3 months) as a result of fouling in the lung compartment. A simpler and less complex approach of magnetic coupling of impeller400, but not magnetic levitation, was chosen in a number of embodiments. In the illustrated embodiment, magnets450, which are seated in seatings460(seeFIG.5A-5C) on rotating impeller400couple magnetically to rotating magnets on an external motor drive (shown schematically inFIG.2A) to maintain a hermetic seal. System10may, for example, be powered by a power module (seeFIG.2A) including one or more batteries. In the illustrated embodiment, six relatively small (0.75″ diameter by 0.25″ thick) magnets450are used as “coupling magnets” to maintain a magnetic couple between the motor drive and impeller400. One or more magnets may also be used to stabilize the hydrodynamic force.

Operation of device10is further discussed below for device10including fiber bundle section200. However, operation with other fiber bundle sections hereof will be essentially the same. During operation, an oxygen-containing “sweep gas” (for example, oxygen) flows into gas inlet channel262via gas flow inlet260and is distributed through the lumens of the individual fiber membranes of fiber bundle300. Oxygen (O2) diffuses out of the fibers into the flowing blood (flowing around the fibers and generally perpendicular to the orientation thereof) as carbon dioxide (CO2) diffuses from blood into the fibers and is carried by the sweep gas to outlet channel266and therethrough to gas flow outlet264. As described above, the blood then leaves device10via blood flow outlet250. Oxygen and carbon dioxide exit the lumens of the fibers into gas outlet channel266. As, for example, illustrated inFIG.3B, the ends of fiber bundle300contacts a first end of fiber bundle compartment222of fiber bundle section housing220and form gas inlet channel262and gas outlet channel266. Blood is thereby prevented from directly flowing into gas inlet channel262and/or gas outlet channel266. The potting of fiber bundle300prevents blood from flowing radially out of fiber bundle300and into gas inlet channel262and/or gas outlet channel266.

Devices10used in studies hereof were not fully optimized. Further optimization may be effected, for example, using a number of tools including CFD, bench testing and/or in vivo studies. Operating between 1000-1800 RPM, device10, including fiber bundle section200could deliver flows from 1 to 3 liters per minute or LPM while generating pressure heads up to 280 mmHg. Operating between 700-2100 RPM, device10, including fiber bundle section200acould deliver flows from 0.25 to 4 liters per minute or LPM while generating pressure heads up to 410 mmHg. These dynamic ranges enable devices10hereof to be attached using peripheral and/or central placement modes using either access cannula or directly connecting grafts.

Velocity in fiber bundle300or300agoverns the gas exchange efficiency as mass transfer in general is enhanced in high velocity environments. However, attaining relatively high velocities can induce hemolysis if not well controlled. In device10, velocity is controlled by specifying frontal/cross-sectional area of fiber bundles hereof to flow. This area is specified by the fiber bundle diameter. As described above, flow is normal to fibers. Fiber bundle diameters below 3 inches (or below 2.5 inches) may increase efficiency. A generally cylindrical bundle having a diameter of 3 inches corresponds to a frontal area or cross-sectional area of 7.07 in2, while a diameter of 2.5 inches corresponds to a frontal area or cross-sectional area of 4.9 in2. In a number of embodiments, the diameter may be no more than 2 inches (cross-sectional area of 3.14 in2). In a number of studies, the diameter of fiber bundles300and300awas each 1.75 inch, corresponding to a frontal or cross-sectional area of 2.41 in2, which provides an increased level of efficiency. As diameter is decreased, fewer fibers are able to fit in a single layer of fibers. Thus the number of fiber layers must be increased, which increases the height of a particular bundle, to achieve a predetermined rate of gas exchange. As described above, in a number of embodiments, the diameter of the fiber bundle is maintained constant between different fiber bundle sections. The length of fiber bundle may be determined for a particular use to provide sufficient fiber bundle surface area for that use. The diameter of a fiber bundle hereof may, for example, be chosen based on the desired mean velocity of blood through fiber bundle. Based on the predetermined diameter and fiber density of the fiber bundle, the number of sheets or the length of the fiber bundle may be chosen to obtain a desired surface area. Mean velocity, as used herein, is defined as flowrate through device10divided by the cross-sectional area of the fiber bundle.

Polymethyl Pentene (PMP) fibers used in studies hereof had an outer diameter or OD of 380 micron and an inner diameter or ID of 200 micron. Many other materials can be used for the fibers hereof (for example, polymeric materials such as polypropylene, silicone, etc.). Such fibers may be coated and/or functionalized with a wide variety of materials. These fibers were manufactured as arrays, membranes or fabrics of hollow fibers, wherein a plurality of fibers is fabricated as an integral, generally planar array having generally the same fiber orientation. In forming fiber bundle300and other fiber bundles hereof, such arrays, membranes or fabrics are cut into sheets that were placed one on top of the other in stack of multiple layers as described above. The porosity of fiber bundle was maintained at approximately 0.5.

FIG.6Aillustrates a study of volume oxygenation rate (mL/min) as a function of blood flow rate (mL/min) for device10including fiber bundle section200and fiber bundle section200a. As expected, the lower total fiber surface area (0.3 m2) of fiber bundle300of fiber bundle section200results in lower oxygenation than fiber bundle300a(having a total fiber surface area of 0.65 m2) of fiber bundle section200a. Device10with fiber bundle section200a(designed for adult use) provides favorably comparable performance with existing devices designed for adult use, while device10with fiber bundle section200(designed for pediatric use) provide favorably comparable performance with existing devices for pediatric use.

FIG.6Bprovides the results of in-vitro hemolysis studies in the form of a normalized index of hemolysis or NIH (g/100 L) for a device hereof with a pediatric fiber bundle section200as illustrated inFIG.1Aand for a commercially available control system (that is, the LILLIPUT2pediatric oxygenator available from Sorin Group of Modena, Italy with a CENTRIMAG® blood pump available from Thoratec Corporation of Pleasanton, California) at a flow rate of 2.5 L/min.

In hemolysis studies, samples were drawn every 30 min to measure hematocrit (HCT) and plasma-free hemoglobin (pfHb). Plasma was isolated from whole blood in two centrifuge spins (15 min at 800 g, 10 min at 7200 g), and absorbance at 540 nm was measured spectrophotometrically (Genesys 10S UV-Vis; Thermo Scientific. Waltham, MA). PfHb concentration was calculated from absorbance using a standard curve developed from a linear-fit of serially diluted whole blood with 100% hemolysis versus absorbance.

The normalized index of hemolysis (NIH) was calculated for circuit comparisons:
NIH(g/100 L)=ΔpfHb/Δt×V×(100−HCT)/100×100/Q

Where NIH=normalized index of hemolysis in grams of hemoglobin released into the blood per 100 L of flow through the circuit (g/100 L); ΔpfHb=increase in pfHb over the sampling time interval (g/L); V=circuit volume (L); HCT=hematocrit (%); Δt=sampling time interval (min); Q=average blood flow rate (L/min).

FIGS.6C through6Hillustrate further pumping and gas exchange studies of devices hereof with pediatric fiber bundle section200and adult fiber bundle section200a. The pump testing was performed using a blood analog solution (a carboxymethyl cellulose solution) that has a similar viscosity to blood. These benchtop results ofFIGS.6C through6Hdemonstrate that the devices hereof are capable of producing suitable flow rates and gas exchange over a wide variety of lung treatment scenarios.FIG.6Cillustrates a study of pressure as a function of flow rate for a device hereof with a pediatric fiber bundle section200assuming an 18 Fr (French) venous cannula, a 14 Fr arterial cannula and an outflow (pulmonary artery) pressure of 50 mmHg as a result of pulmonary hypertension.FIG.6Dillustrates a study of pressure as a function of flow rate for a device hereof with an adult fiber bundle section200aassuming a 27 Fr (French) dual-lumen cannula.FIG.6Eillustrates a study of pressure as a function of flow rate for a device hereof with an adult fiber bundle section200aassuming a 15.5 Fr (French) dual-lumen cannula.FIGS.6C through6Edemonstrate that the devices hereof are able to produce adequate blood flow rates for use in a variety of applications. For example,FIG.6Cdemonstrates that the devices10hereof (including pediatric fiber bundle section200) are able to generate the required pressure for flow rates and cannula sizes that would typically be used for pediatric respiratory support. Similarly,FIG.6Ddemonstrates that the devices10hereof (including adult fiber bundle section200a) are able to generate the required pressure for flow rates and cannula sizes that would typically be used for adult respiratory support.FIGS.6F through6Hdemonstrate that the devices hereof can achieve targeted oxygen and CO2transfer rates for a variety of applications. In that regard,FIG.6Fillustrates a study of oxygen transfer rate as function of blood flow rate for a device hereof with a pediatric fiber bundle section200.FIG.6Gillustrates a study of oxygen transfer rate as function of blood flow rate for a device hereof with an adult fiber bundle section200a. The data ofFIGS.6F and6Gare also set forth inFIG.6Afor comparison.FIG.6Hillustrates a study of normalized CO2removal rate as function of blood flow rate for a device hereof with an adult fiber bundle section200a.

A blood/test fluid flow loop used in gas exchange (oxygenation/CO2removal) studies hereof is illustrated inFIG.7A, while a blood flow loop used in hemolysis studies hereof is illustrated inFIG.7B. In vitro oxygen exchange rates were, for example, measured in bovine blood using the experimental circuit ofFIG.7A. Prior to use, blood was filtered (40-μm filter, Pall Biomedical Inc., Fajardo, PR) and treated with heparin (15 IU/mL) and gentamicin (0.1 mg/mL). Blood was first pre-conditioned to venous conditions (O2saturation=65±5%, pCO2=45±5 mmHg) via recirculation through a deoxygenator. Once venous blood conditions were achieved, sweep gas to the deoxygenator was discontinued and tubing was clamped to produce single-pass blood flow through the test device for oxygen exchange rate measurements. Blood temperature was maintained at 37±1 C throughout the experiment via a heat exchanger. Oxygen exchange rates were evaluated at varying blood flow rates and impeller rotation rates. Pure oxygen was used as the sweep gas and controlled using a GR series mass flow controller (Fathom Technologies, Georgetown, TX). Blood samples were taken at the inlet and outlet of the test device and analyzed using a RAPIDPoint 405 blood gas analyzer with co-oximetry (Siemens Healthcare Diagnostics Inc., Tarrytown, NY). Oxygen exchange rates were calculated from inlet and outlet oxygen partial pressures and saturations using the following equation
{dot over (V)}Q2=Q[aQ2(PQ2out−PQ2in)+10CtHgb(SQ2out−SQ2in)]
where {dot over (V)}Q2is the oxygen exchange rate (mL/min), Q is the blood flow rate (L/min), aQ2is the solubility of oxygen in blood [3E-2 mL O2/(L blood·mmHg)], PQ2out−PQ2inis the oxygen partial pressure difference across the device (mmHg), Ctis the hemoglobin binding capacity (1.34 mL O2/g), Hgb is the hemoglobin concentration (g/dL), and SQ2out−SQ2inis the fractional oxygen saturation difference across the device.

Blood damage was evaluated at varying flow rates using bovine blood. Prior to use, blood was filtered (40-μm filter, Pall Biomedical Inc., Fajardo, PR) and treated with heparin (15 IU/mL) and gentamicin (0.1 mg/mL). Evaluation was performed using a continuous flow circuit (schematic shown below) consisting of the test device connected to an 800-mL compliant blood reservoir via the intended use cannulas. The compliant reservoir was submerged within a heated water bath during testing to maintain a blood temperature of 37±1 C. For each operating condition evaluated, blood (hematocrit=30%) was circulated for a period of 6 hours during which blood samples were collected every 30 minutes. Plasma was isolated from whole blood in two centrifuge spins (15 min at 800 g, 10 min at 7200 g), and absorbance at 540 nm was measured spectrophotometrically (Genesys 10S UV-Vis; Thermo Scientific, Waltham, MA). PfHb concentration was calculated from absorbance using a standard curve developed from a linear-fit of serially diluted whole blood with 100% hemolysis versus absorbance.

Unlike many devices, devices10hereof may be used in both relatively high flow rate respiratory support/oxygenation and relatively lower flow rate carbon dioxide removal. In the case of pediatric respiratory support with fiber bundle section200, the blood flow rate may, for example, be in the range of approximately 1 to approximately 2.5 L/min. An 18-22 Fr (French) venous cannula or a 12-16 Fr arterial cannula may be used. In the case of adult respiratory support with fiber bundle section200a, the blood flow rate may, for example, be in the range of approximately 1 to approximately 3.5 L/min. A 27 Fr dual lumen cannula may be used. In the case of low flow carbon dioxide removal or ECCO2R with fiber bundle section200a, the flow rate may, for example, be less than 1 L/min. Further a 15.5 Fr dual lumen cannula may be used. A clinician may, for example, begin a patient with a cannula and a flow rate for ECCO2R and later discover that further intervention (oxygenation) is required. Full respiratory support, including oxygenation and carbon dioxide removal, may, for example, be initiated by changing the cannula to a larger cannula and increasing flow rate without the necessity of using a different device or the necessity of changing the fiber bundle section of the device. The devices hereof thus span the range of low flow rate to provide carbon dioxide removal to high flow rate to provide oxygenation and carbon dioxide removal without changing either the base section (including the pumping mechanism) of the fiber bundle section, thereby providing use among different patients as well as changing course of treatment for a particular patient.

The foregoing description and accompanying drawings set forth a number of representative embodiments at the present time. Various modifications, additions and alternative designs will, of course, become apparent to those skilled in the art in light of the foregoing teachings without departing from the scope hereof, which is indicated by the following claims rather than by the foregoing description. All changes and variations that fall within the meaning and range of equivalency of the claims are to be embraced within their scope.