WO2021183885A1

WO2021183885A1 - Integrated pump-gas exchange apparatus and methods

Info

Publication number: WO2021183885A1
Application number: PCT/US2021/022104
Authority: WO
Inventors: Israel Jessop
Original assignee: Vascular Perfusion Solutions Inc
Current assignee: Vascular Perfusion Solutions Inc
Priority date: 2020-03-13
Filing date: 2021-03-12
Publication date: 2021-09-16
Anticipated expiration: 2022-09-13

Abstract

A vascular perfusion device and system include a first fluid pathway, a second fluid pathway, and a pressure source configured to expand and collapse the second fluid pathway. The second fluid pathway can be at least partially disposed within the first fluid pathway, and the second fluid pathway can have an expanded state and a collapsed state, such that in the expanded state, the second fluid pathway displaces a fluid in the first fluid pathway. The first fluid pathway can be one of a perfusate pathway or a gas pathway, and the second fluid pathway can be the other. When a perfusate is disposed in the perfusate pathway, and a gas is disposed in the gas pathway, at least a portion of the gas crosses from the gas pathway to the perfusate pathway to mix with the perfusate when the second fluid pathway can displace the fluid.

Description

INTEGRATED PUMP-GAS EXCHANGE APPARATUS AND METHODS

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of priority to U.S. Provisional Patent

Application Serial No. 62/989,213 filed March 13, 2020, the contents of which are incorporated herein by reference in their entirety.

BACKGROUND

[0002] Vascular perfusion systems operate to pump an oxygen-enriched liquid or blood-based fluid through the vasculature of an organ, limb or other body tissue. The pumping and gas exchange actions are typically executed by a distinctly separate pump, and gas exchanger, respectively.

SUMMARY OF THE DISCLOSURE

[0003] The present disclosure provides devices, systems, and methods to perfuse vascularized tissue by combining the function of pump and gas exchanger into a single element, as part of a device which is both economical and easy to manufacture and operate. The device can include heat exchanger and gas exchanger elements, and the device adds pumping functionality to the exchanger by virtue of the cyclic expansion and contraction of a gas phase with respect to an elastic tubular or annular membrane. The pumping and oxygenation of perfusate (e.g., fluid carried through the system and delivered to tissue) can thus be accomplished by a single element, such as a tubular or annular membrane.

[0004] The tubular and substantially co-linear arrangement of two or more channels can allow for coiling, folding, or otherwise adapting the shape and arrangement of the entire device to fit various shape and size requirements. The device can achieve a high ratio of phase boundary surface area to volume due to the ability to coil, fold, or otherwise pack long lengths of membrane tubing into a small space, versus the use of a single planar membrane. [0005] The linear, flow-through design of the device can reduce the occurrence of unmixed volumes of perfusate. The entire device can be fabricated from readily available, standard parts, such as tubing, valves and connectors. The device can pump and oxygenate the perfusate using a small number of parts, for economical manufacture and simple, reliable operation.

[0006] In an example, a vascular perfusion device can include a first fluid pathway defined by a first material, a second fluid pathway defined by a second material, the second fluid pathway at least partially disposed within the first fluid pathway, and a pressure source fluidly coupled to the second fluid pathway. The second fluid pathway, when exposed to a first internal pressure can have an expanded state, and when exposed to a second internal pressure less than the first internal pressure, can have a collapsed state, such that in the expanded state, the second fluid pathway can displace a fluid disposed in the first fluid pathway. The first material can be resistant to expansion and contraction when exposed to the first internal pressure. The first fluid pathway can include one of a perfusate pathway or a gas pathway, and the second fluid pathway can include the other of the perfusate pathway or the gas pathway. When a perfusate is disposed in the perfusate pathway, and a gas is disposed in the gas pathway, at least a portion of the gas crosses from the gas pathway to the perfusate pathway to mix with the perfusate when the gas pathway can displace the fluid. The pressure source can be configured to expand and collapse the second fluid pathway when the first internal pressure and the second internal pressure are applied by the pressure source to the second fluid pathway.

[0007] In an example, a system for vascular perfusion can include a system pathway for delivery of one or more gases, and a gas source. The device can include a first fluid pathway defined by a first material, a second fluid pathway defined by a second material, the second fluid pathway at least partially disposed within the first fluid pathway, and a pressure source fluidly coupled to the second fluid pathway. The second fluid pathway, when exposed to a first internal pressure can have an expanded state, and when exposed to a second internal pressure less than the first internal pressure, can have a collapsed state, such that in the expanded state, the second fluid pathway can displace a fluid disposed in the first fluid pathway. The first material can be resistant to expansion and contraction when exposed to the first internal pressure. The first fluid pathway can include one of a perfusate pathway or a gas pathway, and the second fluid pathway can include the other of the perfusate pathway or the gas pathway. When a perfusate is disposed in the perfusate pathway, and a gas is disposed in the gas pathway, at least a portion of the gas crosses from the gas pathway to the perfusate pathway to mix with the perfusate when the gas pathway can displace the fluid. The pressure source can be configured to expand and collapse the second fluid pathway when the first internal pressure and the second internal pressure are applied by the pressure source to the second fluid pathway. The gas source can be fluidly coupled to the gas pathway via a pump, wherein the system is configured to be fluidly coupled to and perfuse a target tissue when the target tissue is coupled to the perfusate pathway.

[0008] In an example, a method of perfusing vasculature can include supplying oxygen through a second fluid pathway, wherein one of a first fluid pathway including a perfusate and the second fluid pathway comprises a rigid fluid pathway, and the other of the first fluid pathway and the second fluid pathway comprises an elastic fluid pathway configured to expand and contract with pressure, wherein at least a portion of the elastic fluid pathway resides within the rigid fluid pathway, and wherein a wall defining the rigid fluid pathway is less elastic than a wall defining the elastic fluid pathway; diffusing the oxygen from the second fluid pathway to the first fluid pathway into the perfusate to achieve a selected concentration of dissolved oxygen in the perfusate; and applying cyclical pressure to the elastic fluid pathway to pump the perfusate through the first fluid pathway.

BRIEF DESCRIPTION OF THE DRAWINGS [0009] In the drawings, which are not necessarily drawn to scale, like numerals may describe similar components in different views. Like numerals having different letter suffixes may represent different instances of similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

[0010] FIG. 1 illustrates a schematic diagram of a vascular perfusion system including a device capable of substantially simultaneous pumping and oxygenation.

[0011] FIGS. 2A-2F illustrate schematic diagrams of a perfusion device capable of substantially simultaneous pumping and oxygenation. FIGS. 2B- 2D show the device in different modes of operation. FIGS. 2E-2F shows a cross section of the device.

[0012] FIG. 3 illustrates a schematic diagram of a perfusion device including a heat exchange medium and multiple, nested gas pathways.

[0013] FIG. 4 illustrates a schematic diagram of a perfusion device including a line for heat exchange medium and multiple, parallel gas pathways. [0014] FIG. 5 illustrates a schematic diagram of a perfusion device including a filter.

[0015] FIGS. 6-7 illustrate schematic diagrams of a perfusion device with a helical fluid flow pattern.

[0016] FIG. 8 illustrates a schematic diagram of a perfusion device including a helical spacer element.

[0017] FIG. 9 is a flow diagram of a method according to various embodiments of the invention.

DETAILED DESCRIPTION

[0018] The present disclosure describes, among other things, a system and associated methods for perfusion of vasculature in organs or other tissue with oxygen-enriched liquid or blood-based fluid (“perfusate”). The system can include a device that both pumps and exchanges gas, allowing the substantially simultaneous pumping and oxygenation of perfusate cycling through the target tissue. “Substantially simultaneous” means, for the purpose of this document, that the device can engage in pumping and oxygenation activity at the same time, when it is operating. Pumping is accomplished using the cyclic expansion and contraction of a tubular or annular gas phase in an elastic membrane, such as a gas carrying flexible membrane.

[0019] FIG. 1 illustrates a schematic diagram of a vascular perfusion system 100 including a device capable of substantially simultaneous pumping and oxygenation. System 100 can include target tissue 102, carbon dioxide exhaust 110, an integrated pump and gas exchanger 112, fluidic switching valve 114, pressure regulator 115, gas source 116, a heat exchanger 118, and a filter 122.

[0020] In system 100, oxygen-depleted blood can exit the target tissue 102

(maintained at a substantially constant temperature by a temperature sensor) in a fluid flow pathway that moves toward a fluid reservoir. At the fluid reservoir, the fluid can be pressure regulated and new perfusate can be inserted into the stream. An exchange of fluid can occur as desired at fluid change (e.g., charge or drain) ports. Pump and gas exchanger 112 draws the perfusate along the fluid flow pathway. Gas exchange is regulated by a pressure regulator 115 and fed by gas from gas source 116 along with the fluidic logic switch 114, which oscillates between open and closed positions (to admit gas from the gas source 116 to the pump and gas exchanger 112), according to the feedback pressure supplied by the integrated pump and gas exchange device 112. In system 100, the fluid cycling in the fluid flow pathway can be a fluid carried through the system and delivered to tissue, such as a perfusate, including blood or some other fluid capable of carrying oxygen and other gases.

[0021] In some embodiments, oxygen is delivered to the pump and gas exchanger 112 using a microfluidic valve, or a fluidics monostable logic gate such as an OR gate or an OR/NOR gate, as the switching valve. Oscillation of the switching valve may be controlled electronically, or using feedback pressure from the organ container. One example of a switching valve that can use pressure feedback to induce oscillation, without electronic control, includes the V-5800 series vacuum piloted 3-way valve available from the Air Logic - Knapp Manufacturing, Incorporated of Racine, Wisconsin in the United States.

[0022] Examples of device 112 are discussed in more detail with reference to FIGS.

2-9 below. In gas exchange device 112, perfusate is oxygenated. Oxygenated perfusate can leave gas exchange device 112 and be filtered at filter 122 for particulates prior to entering target tissue 102. The flow of perfusate in system 100 can be regulated by, for example, check valves in line with the fluid pathway so as to prevent backwards fluid flow.

[0023] FIGS. 2A-2F illustrate schematic diagrams of a perfusion device 200 that is capable of substantially simultaneous pumping and oxygenation. FIGS. 2B-2D show the device in different modes of operation. FIG. 2E-2F show the device from a cross section. FIGS. 2A-2E will now be discussed together.

[0024] Device 200 can include two substantially co-linear pathways that may also be concentric pathways (e.g., lumens, tubes, channels, or other), where the inner pathway is defined by an elastic membrane (such as a gas carrying flexible membrane) separating the inner pathway from the outer pathway (such as a perfusate fluid pathway). A wall defining the inner pathway may comprise a gas-permeable, elastic membrane. A wall defining the outer pathway may comprise a relatively stiff, non-compliant tubing material such that the total volume of the system of gas plus liquid contained by the wall defining the outer pathway remains substantially constant. In some embodiments the elasticity of the wall defining the inner pathway is greater than the elasticity of the wall defining the outer pathway.

[0025] The gas and liquid phases can be separated by an elastic membrane that defines the inner pathway. In an example, as seen in FIG. 2B, the inner pathway can be filled with gas, such as oxygen, air, or other medical gases or gas mixtures that can be used to mix the gas with a perfusate. If the gas includes oxygen, the gas can be used to oxygenate the perfusate.

[0026] The outer pathway can be filled with perfusate, such as a blood, blood- containing, water, saline solution, or other liquid used to carry oxygen to a target tissue mass, such as an organ or limb. In an example, the inner pathway can be filled with perfusate, and the outer pathway can be filled with gas.

[0027] In either case, the gas can flow through the device in a pulsatile fashion, such as with periodic pressure cycling, resulting in a corresponding cycle of dilation and contraction of the elastic membrane. The periodic pressure can allow for flexing of the elastic membrane. In an example, as seen in FIG. 2C, the expansion of gas volume expands the inner, elastic membrane radially outward, pressurizing and displacing the liquid phase perfusate contained by the wall of the outer pathway, pumping the gas through a discharge port. The contraction of gas volume, as seen in FIG. 2D, can depressurize the liquid phase, pulling in fresh perfusate through an intake port.

[0028] Inter-pathway check valves on each end of the liquid-filled channel can be used to induce a one-way flow of perfusate, as shown in FIGS. 2C and 2D. A needle valve or other flow regulator can be employed in the gas-filled pathway to facilitate a net flow of gas through the device 200 in order to maintain appropriate partial pressures of both nutrient (e.g., oxygen) and waste (e.g., carbon dioxide) gases. Sweep gases, such as oxygen, carbon dioxide, nitrogen, or combinations thereof can be used to affect bulk motion of nutrient gases and waste gases through the device 200.

[0029] As perfusate moves over the elastic membrane surface, gas molecules are transported across the elastic membrane between the liquid and gas phases. Diffusion across the elastic membrane of gas molecules is driven by chemical gradient according to Fick’s law. During the lower (e.g., atmospheric) pressure phase of the pulsatile gas pressure cycle, a high oxygen partial pressure in the gas phase is greater than the lower pressure, and sufficient to drive oxygen across the membrane, to dissolve into the unsaturated perfusate. Likewise, waste carbon dioxide diffuses out from the carbon dioxide enriched perfusate, across the membrane, and into the gas phase which has a low partial pressure of waste gases due to the net flow of fresh gas into the device 200 and waste gases out of the device 200. [0030] During the higher-pressure phase of the pulsatile gas pressure cycle, oxygen transport from the gas phase into the liquid phase can be enhanced by the higher differential in chemical potential between the oxygen in the supply gas and dissolved oxygen in the elastic membrane. The higher oxygen pressure can result in higher oxygen concentrations on the gas-side of the membrane, higher gradients across the membrane, and ultimately more rapid transport across the membrane into the perfusate.

[0031] In some cases, such as shown in FIG. 2F, the relative locations of the gas and the perfusate can be switched from what is seen in FIGS. 2A-2E, so that the perfusate runs through the inner pathway, and the gas (e.g., oxygen) runs through the outer pathway. In this case, the inner pathway would still be defined by an elastic membrane through which oxygen could diffuse into the perfusate. The pumping of gas through the device 200 could accomplish diffusion in this case through a pulsatile gas pressure cycle, in a manner that is similar to prior examples, describing how the gas travels through the inner pathway - except in this case the gas travels mainly through the outer pathway, and the perfusate travels through the inner pathway.

[0032] FIG. 3 illustrates a schematic diagram of a perfusion device including a heat exchange medium (e.g., a temperature control material). FIG. 4 illustrates a schematic diagram of a perfusion device including a line for heat exchange medium. FIGS. 3 and 4 will now be discussed together.

[0033] FIGS. 3 and 4 illustrate multi -pathway, parallel arrangements of devices 300,

400, respectively. Multiple small pathways 301, 401 can be arranged within a single larger pathway defined by a substantially rigid wall, as shown. For example, the perfusate can fill the interstitial space between the small pathways 301, 401 of gas. The arrangement of locations for the liquid and the gas may also be reversed, wherein the perfusate is confined to the small tubes 301, 401 and the gas fills the interstitial space. In either case, the gas pressure and gas volume can vary cyclically depending on the cyclic pressure applied by the pumping action of the elastic membrane(s) disposed within the substantially rigid outer wall. The resultant influx and efflux of liquid combined with one-way inlet and outlet valves can operate to pump perfusate liquid through the device in a pulsatile fashion.

[0034] Additional fluid phases could be incorporated into the multi-pathway design to accomplish additional perfusion-related goals. For example, a heat exchange medium can be carried in one or more of the small pathways 302 to effect heat exchange across the perfusate, such as temperature regulation to induce cooling or heating of the perfusate.

[0035] Nested channels, as shown in FIG. 3, including three or more substantially concentric pathways, can also be used. Nested, concentric pathways can be used to increase either mass transport or heat transport by an approximate doubling of the phase boundary area for a given volume.

[0036] FIG. 5 illustrates a schematic diagram of a perfusion device 500 including a filter 501. The filter 501 can be nested inside the larger pathway on or near the smaller pathway defined by the elastic, gas-permeable membrane, so that as influx and efflux of liquid occurs, the filter 501 can capture particulate components that would otherwise interfere with perfusion. In some cases, a filter 501 can be placed outside of the device 500, but still form a part of the system flow pathway (e.g., fluid pathway 101 in FIG. 1) before or after the device 500 to protect the target tissue from particulate contaminants.

[0037] FIGS. 6-7 illustrate schematic diagrams of a perfusion device 600, 700, with a helical fluid flow pattern. FIG. 8 illustrates a schematic diagram of a perfusion device 800 including a helical spacer element. FIGS. 6-8 will now be discussed together.

[0038] A helical fluid flow pattern can be induced, for example, by helical patterns as shown in FIGS. 6 and 7. Tubing 600, 700, can include inner pathway 601, 701, outer pathway 602, 702, and helical patterns 603,703. Helical patterns 603, 703 can be formed into a surface of the outer or inner pathway along the length or for a portion of the device 600, 700. For example, the inner diameter of the outer pathway 602 can be rifled 603 to impart a helical flow of perfusate for convective mixing of the perfusate as it flows through the device 600. Alternatively, the outer diameter of the inner pathway 701 can be rifled 703 to impart helical flow of perfusate through the device 700.

[0039] Similarly, surface convolution can be induced by patterning various portions of the device 600, 700 (as well as device 200 in FIG. 2A). Helical convolution of the outer pathway can impart helical flow in the perfusate to enhance convective mixing of perfusate with the gas. Helical convolution also can also enhance the ability of the device to be coiled or bent to fit within confined spaces. This convoluted configuration can allow for increased flexibility in tubing. The convolution can impart accordion or bellows-like flexibility to tubing that could otherwise be too rigid to bend around smaller radii without kinking. [0040] In FIG. 8, instead of a groove pattern, a helical spacer 805 is used. The device

800 in FIG. 8 includes liquid perfusate 801, gas flow 802, rigid outer pathway 803, inner pathway 804, and helical spacer 805. The helical spacer 805 can be, for example, an additional piece of tubing situated between an outer wall of the inner pathway and an inner wall of the outer pathway. The helical spacer 805 can induce helical flow of fluid through the device but can also situate and secure the inner pathway inside the outer pathway.

[0041] FIG. 9 is a flow diagram of a method 1000 according to various embodiments of the invention. In method 1000, oxygen is supplied to a perfusate in a first pathway (block 1010). The first pathway can be one of two fluid pathways. Of the first and second pathways, one can be a relatively rigid fluid pathway, and one can be a relatively elastic fluid pathway. The elastic fluid pathway can be configured to expand and contract with cyclic pressure. The elastic pathway can reside within the rigid fluid pathway. The wall defining the elastic pathway can be more elastic than the wall defining the rigid pathway. One of the two pathways can be supplied with oxygen, the other can be supplied with a perfusate fluid.

[0042] The oxygen can be diffused across the membrane wall of the elastic pathway into the perfusate, oxygenating the perfusate fluid (block 1012). In some cases, the perfusate can be temperature regulated by bringing it into contact with heat exchange material (block 1013). Subsequently or simultaneously, a pump can apply cyclical pressure to the perfusate to induce movement of the perfusate through the pathway (block 1014). These actions can be repeated in a cyclical fashion as desired.

Various Notes & Examples

[0043] Each of these non-limiting examples can stand on its own or can be combined in various permutations or combinations with one or more of the other examples.

[0044] Example 1 can include a vascular perfusion device, comprising: a first fluid pathway defined by a first material; a second fluid pathway defined by a second material, the second fluid pathway at least partially disposed within the first fluid pathway, wherein the second fluid pathway, when exposed to a first internal pressure comprises an expanded state, and when exposed to a second internal pressure less than the first internal pressure, comprises a collapsed state, such that in the expanded state, the second fluid pathway can displace a fluid disposed in the first fluid pathway, wherein the first material is resistant to expansion and contraction when exposed to the first internal pressure, wherein the first fluid pathway comprises one of a perfusate pathway or a gas pathway, wherein the second fluid pathway comprises the other of the perfusate pathway or the gas pathway, and wherein, when a perfusate is disposed in the perfusate pathway, and a gas is disposed in the gas pathway, at least a portion of the gas crosses from the gas pathway to the perfusate pathway to mix with the perfusate when the second fluid pathway displaces the perfusate; and a pressure source to fluidly couple to the second fluid pathway and to expand and collapse the second fluid pathway when the first internal pressure and the second internal pressure are applied by the pressure source to the second fluid pathway.

[0045] Example 2 can include Example 1, wherein the second fluid pathway is substantially concentric with the first fluid pathway.

[0046] Example 3 can include any of Examples 1-2, further comprising a first valve in an inlet, and a second valve in an outlet, the first and second valves to regulate directional flow of fluid through the first fluid pathway.

[0047] Example 4 can include any of Examples 1-3, wherein the first fluid pathway comprises stainless steel.

[0048] Example 5 can include any of Examples 1-4, wherein the first material comprises a rigid material having a durometer of at least about Shore A 60.

[0049] Example 6 can include any of Examples 1-5, wherein the second material comprises an elastic material having a durometer of at least about Shore A 5.

[0050] Example 7 can include any of Examples 1-6, wherein when the second material expands diametrically from about 0.5% to about 5% per kPa of increased pressure, and wherein the first material expands diametrically by less than about 0.1% per kPa of increased pressure.

[0051] Example 8 can include any of Examples 1-7, wherein the first fluid pathway comprises a diameter of about 0.6 mm to about 18 mm, and wherein the second fluid pathway comprises a diameter of about 0.3 mm to about 15 mm.

[0052] Example 9 can include any of Examples 1-8, wherein the second material comprises silicone, polyisoprene, polyurethane, butyl rubber, or combinations thereof.

[0053] Example 10 can include any of Examples 1-9, wherein the perfusate pathway is to carry a fluid comprising blood.

[0054] Example 11 can include any of Examples 1-10, wherein the perfusate pathway is to carry an oxygen-enriched liquid.

[0055] Example 12 can include any of Examples 1-11, wherein the perfusate pathway further comprises an inlet valve regulating perfusate flow through an inlet, and an outlet valve regulating perfusate flow through an outlet.

[0056] Example 13 can include any of Examples 1-12, wherein the inlet valve and the outlet valve each comprise a check valve.

[0057] Example 14 can include any of Examples 1-13, wherein the gas pathway is to carry gas comprising oxygen.

[0058] Example 15 can include any of Examples 1-14, wherein the gas pathway comprises a plurality of gas pathways running substantially parallel to each other within the perfusate pathway.

[0059] Example 16 can include any of Examples 1-15, further comprising a heat exchange medium pathway at least partially disposed in the first fluid pathway.

[0060] Example 17 can include any of Examples 1-16, wherein the temperature control material pathway comprises a heat exchange medium.

[0061] Example 18 can include any of Examples 1-17, further comprising one or more filters in the first fluid pathway.

[0062] Example 19 can include any of Examples 1-18, wherein one of the first or second fluid pathways comprises a surface having one or more helical patterns, the helical patterns extending into or out of a surface defining at least one of the first or second pathways.

[0063] Example 20 can include any of Examples 1-19, further comprising a helical spacer between the second fluid pathway and the first fluid pathway, such that the helical spacer defines space between the inner wall of the first material, and the outer wall of the second material.

[0064] Example 21 can include any of Examples 1-20, further comprising a plurality of inter-pathway valves between the perfusate pathway and the gas pathway.

[0065] Example 22 can include any of Examples 1-21, wherein the pressure source is to apply a pulsatile pressure to the gas pathway, and wherein the pressure source further comprises or is coupled to a fluidic switch.

[0066] Example 23 can include a system for vascular perfusion, comprising: a system pathway for delivery of a perfusate; a vascular perfusion device comprising: a first fluid pathway defined by a first material; a second fluid pathway defined by a second material, the second fluid pathway at least partially disposed within the first fluid pathway, wherein the second fluid pathway, when exposed to a first internal pressure comprises an expanded state, and when exposed to a second internal pressure less than the first internal pressure, comprises a collapsed state, such that in the expanded state, the second fluid pathway can displace a fluid disposed in the first fluid pathway, wherein the first material is resistant to expansion and contraction when exposed to the first internal pressure, wherein the first fluid pathway comprises one of a perfusate pathway or a gas pathway, wherein the second fluid pathway comprises the other of the perfusate pathway or the gas pathway, and wherein, when a perfusate is disposed in the perfusate pathway, and a gas is disposed in the gas pathway, at least a portion of the gas crosses from the gas pathway to the perfusate pathway to mix with the perfusate when the second fluid pathway displaces the perfusate; and a gas source to fluidly couple to the gas pathway, wherein the system is to perfuse a target tissue when the target tissue is coupled to the perfusate pathway, when the gas source is fluidly coupled to the gas pathway and operates to expand and collapse the second fluid pathway when the first internal pressure and the second internal pressure are applied by the gas source to the gas pathway.

[0067] Example 24 can include any of Example 23, further comprising a fluid reservoir to fluidly couple to the system pathway upstream of the vascular perfusion device. [0068] Example 25 can include any of Examples 23-24, further comprising one or more pressure sensors coupled to the system pathway, to sense one or more pressures, respectively, when the one or more pressures are present within the system pathway.

[0069] Example 26 can include any of Examples 23-25, further comprising at least one oxygen sensor coupled to the system pathway.

[0070] Example 27 can include any of Examples 23-26, further comprising a filter coupled to the system pathway downstream of the vascular perfusion device.

[0071] Example 28 can include any of Examples 23-27, further comprising at least one fluid change port to fill or drain fluid disposed within the system pathway. [0072] Example 29 can include any of Examples 23-28, further comprising a pressure regulator coupled to the system pathway.

[0073] Example 30. can include any of Examples 23-29, wherein the vascular perfusion device further comprises a third fluid flow pathway.

[0074] Example 31 can include any of Examples 23-30, wherein the third fluid flow pathway comprises a heat exchange medium material.

[0075] Example 32 can include any of Examples 23-31, wherein the third fluid flow pathway comprises a second gas pathway for additional oxygen.

[0076] Example 33 can include a method of perfusing vasculature, comprising: supplying oxygen through a second fluid pathway, wherein a first fluid pathway comprises a perfusate, and one of the first fluid pathway and the second fluid pathway comprises an elastic fluid pathway configured to expand and contract with pressure, and another one of the first fluid pathway and the second fluid pathway comprise a rigid fluid pathway, wherein the elastic fluid pathway is at least partially disposed within the rigid fluid pathway, and wherein a wall defining the rigid fluid pathway is less elastic than a wall defining the elastic fluid pathway; diffusing the oxygen from the second fluid pathway to the first fluid pathway into the perfusate to achieve a selected concentration of dissolved oxygen in the perfusate; and applying cyclical pressure to the elastic fluid pathway to pump the perfusate through the first fluid pathway.

[0077] Example 34 can include Example 33, wherein applying the cyclical pressure comprises applying pressure pulses to the oxygen.

[0078] Example 35 can be any of Examples 33-34, wherein applying the cyclical pressure comprises applying pressure at a rate of about 30 to about 200 pulses per minute. [0079] Example 36 can be any of Examples 33-35, further comprising: oxygenating target tissue with the perfusate.

[0080] Example 37 can be any of Examples 33-36, wherein the target tissue comprises heart tissue, lung tissue, kidney tissue, or other tissue.

[0081] Example 38 can be any of Examples 33-37, further comprising regulating a temperature of the perfusate.

[0082] Example 39 can be any of Examples 33-38, wherein the selected concentration of dissolved oxygen in the perfusate comprises a partial pressure of oxygen of higher than about 150 mm Hg.

[0083] Example 40 can be any of Examples 33-39, wherein the selected concentration of dissolved oxygen in the perfusate comprises a partial pressure of oxygen of higher than about 500 mm Hg.

[0084] The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as “examples.” Such examples can include elements in addition to those shown or described. However, the present inventors also contemplate examples in which only those elements shown or described are provided. Moreover, the present inventors also contemplate examples using any combination or permutation of those elements shown or described (or one or more aspects thereof), either with respect to a particular example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

[0085] In the event of inconsistent usages between this document and any documents so incorporated by reference, the usage in this document controls.

[0086] In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In this document, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

[0087] The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description as examples or embodiments, with each claim standing on its own as a separate embodiment, and it is contemplated that such embodiments can be combined with each other in various combinations or permutations. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

CLAIMS What is claimed is:

1. A vascular perfusion device, comprising: a perfusate fluid pathway defined by a first material; a gas carrying flexible membrane defined by a second material, the gas carrying flexible membrane disposed within a portion of the perfusate fluid pathway; a valve coupled to the perfusate fluid pathway to ensure fluid flow in a first direction; a connection to a periodic gas source to drive oxygen into fluid in the fluid pathway and flex the flexible membrane to pump the fluid through the fluid pathway in the first direction.

2. The device of claim 1, wherein the first material is resistant to expansion and contraction when exposed to a first internal pressure.

3. The device of claim 1, wherein the first material comprises a rigid material having a durometer of at least about Shore A 60, or wherein the second material comprises an elastic material having a durometer of at least about Shore A 5.

4. The device of claim 1, wherein when the second material expands diametrically from about 0.5% to about 5% per kPa of increased pressure, or wherein the first material expands diametrically by less than about 0.1% per kPa of increased pressure.

5. The device of claim 1, wherein the perfusate pathway comprises at least one of an inlet check valve to regulate perfusate flow through a portion of the perfusate fluid pathway, or an outlet check valve to regulate perfusate flow through a portion of the perfusate fluid pathway.

6. The device of claim 1, wherein the gas carrying flexible membrane comprises a plurality of gas pathways running substantially parallel to each other within the perfusate fluid pathway.

7. The device of claim 1, further comprising a temperature control pathway at least partially disposed in the perfusate fluid pathway and a temperature sensor therein.

8. The device of claim 1, wherein at least one of the gas carrying flexible membrane and the perfusate fluid pathway comprises a surface having one or more helical patterns, the helical patterns extending into or out of a surface defining at least one of the first or second pathways.

9. The device of claim 1, wherein a space between an inner wall of the first material, and an outer wall of the second material is defined by a helical spacer between the perfusate fluid pathway and the gas carrying flexible membrane.

10. The device of claim 1, wherein the periodic gas source for applying a pulsatile pressure to the gas carrying flexible membrane, and the periodic gas source includes a fluidic switch.

11. A system for vascular perfusion, comprising: a system pathway for delivery of a perfusate; a vascular perfusion device comprising: a perfusate fluid pathway defined by a first material; a gas carrying flexible membrane defined by a second material, the gas carrying flexible membrane at least partially disposed within the perfusate fluid pathway, wherein the gas carrying flexible membrane, when exposed to a first internal pressure comprises an expanded state, and when exposed to a second internal pressure less than the first internal pressure, comprises a collapsed state, such that in the expanded state, the gas carrying flexible membrane can displace a fluid disposed in the perfusate fluid pathway, wherein the first material is resistant to expansion and contraction when exposed to the first internal pressure, wherein the perfusate fluid pathway comprises one of a perfusate pathway or a gas pathway, wherein the gas carrying flexible membrane comprises the other of the perfusate pathway or the gas pathway, and wherein, when the perfusate is disposed in the perfusate pathway, and a gas is disposed in the gas pathway, at least a portion of the gas crosses from the gas pathway to the perfusate pathway to mix with the perfusate when the gas carrying flexible membrane displaces the perfusate; and a gas source to fluidly couple to the gas pathway, wherein the system is to perfuse a target tissue when the target tissue is coupled to the perfusate pathway, when the gas source is fluidly coupled to the gas pathway and operates to expand and collapse the gas carrying flexible membrane when the first internal pressure and the second internal pressure are applied by the gas source to the gas pathway.

12. The system of claim 11, further comprising one or more pressure sensors coupled to the system pathway, to sense one or more pressures, respectively, when the one or more pressures are present within the system pathway.

13. The system of claim 11, further comprising at least one oxygen sensor coupled to the system pathway.

14. The system of claim 11, further comprising a filter coupled to the system pathway downstream of the vascular perfusion device.

15. The system of claim 11, further comprising a pressure regulator coupled to the system pathway.

16. The system of claim 11, wherein the vascular perfusion device further comprises a third fluid flow pathway comprising a heat exchange medium.

17. A method of perfusing vasculature, comprising: supplying oxygen through a gas carrying flexible membrane at least partially disposed within a perfusate fluid pathway; diffusing the oxygen from the gas carrying flexible membrane to the perfusate fluid pathway into a perfusate to achieve a selected concentration of dissolved oxygen in the perfusate; and applying periodic pressure to flex the gas carrying flexible membrane disposed within the perfusate fluid pathway to pump the perfusate through the perfusate fluid pathway.

18. The method of claim 17, wherein applying the periodic pressure comprises applying cyclical pressure at a rate of about 30 to about 200 pulses per minute.

19. The method of claim 17, further comprising oxygenating target tissue with the perfusate, wherein the target tissue comprises heart tissue, lung tissue, kidney tissue, or other tissue.

20. The method of claim 17, wherein the selected concentration of dissolved oxygen in the perfusate comprises a partial pressure of oxygen of higher than about 150 mm Hg.