CN107183005A - The apparatus and method for of organ perfusion - Google Patents

Abstract

An organ perfusion device includes an inlet for connection to an organ, an outlet for connection to the organ, and a perfusion circuit. The perfusion circuit includes: a reservoir configured to store a perfusate; a liquid waste; and a plurality of fluid conduits. The plurality of fluid conduits are configured to define: a delivery fluid path connecting the reservoir to the inlet; a return fluid path connecting the reservoir to the outlet, the return fluid path being independent from the The delivery fluid path; the waste fluid path connecting the liquid reservoir and the waste liquid container. The organ perfusion apparatus further comprises: a first flow control device configured to selectively prevent or allow fluid flow from the reservoir to the organ via the delivery fluid path; a second flow control device configured to selectively actively prevent or allow fluid to flow from the reservoir to the waste via the waste fluid path.

Description

Apparatus and methods for organ perfusion

Cross References to Related Applications

This application claims priority to US Provisional Application 62/333467, filed May 9, 2016, and US Application 15/482015, filed April 7, 2017, the entire contents of which are incorporated herein by reference.

technical field

The present disclosure relates to the management of donor organs, and more particularly to an apparatus and method for organ perfusion.

Background technique

Donor organs such as lungs are highly perishable and must therefore be transplanted into the recipient as soon as possible after removal from the donor. The traditional approach is to simply freeze the donor organ before implanting it into the recipient. More recently, systems have been developed to perfuse organs prior to organ transplantation, which can extend the time window in which the organ remains viable. However, such systems are often complex and expensive, exacerbated by a heavy reliance on a number of disposable consumable parts. At the same time such systems are also difficult to transport.

Contents of the invention

In order to solve the above problems, the technical solutions provided by this disclosure are as follows:

An organ perfusion device includes an inlet for connection to an organ, an outlet for connection to the organ, and a perfusion circuit. The perfusion circuit includes: a reservoir configured to store a perfusate; a liquid waste; and a plurality of fluid conduits. The plurality of fluid conduits are configured to define: a delivery fluid path connecting the reservoir to the inlet; a return fluid path connecting the reservoir to the outlet, the return fluid path being independent from the The delivery fluid path; the waste fluid path connecting the liquid reservoir and the waste liquid container. The organ perfusion apparatus further comprises: a first flow control device configured to selectively prevent or allow fluid flow from the reservoir to the organ via the delivery fluid path; a second flow control device configured to selectively actively prevent or allow fluid to flow from the reservoir to the waste via the waste fluid path.

Advantageously, said priming circuit further comprises: a reservoir priming fluid path defined by said plurality of fluid conduits, said reservoir priming fluid path connecting an priming port to said reservoir.

Preferably, the perfusion circuit further comprises: an organ perfusion fluid path defined by the plurality of fluid conduits, the organ perfusion fluid path connecting the perfusion port and the organ; a third flow control device configured To selectively prevent or allow fluid to flow out of the infusion port via at least one of the reservoir infusion fluid path and the organ infusion fluid path.

Preferably, the perfusion circuit further comprises: a pump head module located on the delivery fluid path for receiving the perfusate from the reservoir; an adjustment module located on the delivery fluid path for receiving the perfusate from The pump head module receives the perfusate; the white blood cell filter located on the delivery fluid path is used to receive the perfusate from the adjustment module; the first flow control device is arranged on the pump head module and the between the white blood cell filters.

Preferably, said perfusion circuit further comprises a second leukocyte filter; an alternate delivery fluid path further defined by said plurality of fluid conduits, said alternate delivery fluid path being connected to said reservoir via said second leukocyte filter The liquid container and the inlet; the perfusion device further includes a third flow control device configured to selectively prevent or allow fluid to flow through the backup delivery fluid path.

Preferably, the perfusion device further comprises: an organ support; a drain located in the organ support; an organ support return fluid path further defined by the plurality of fluid conduits, the organ support return fluid path connecting The drain port and the liquid reservoir.

Preferably, the plurality of fluid conduits further define an organ stent waste fluid path, and the organ stent waste fluid path connects the drain port and the waste container; the perfusion device further includes a third flow control device, the third control device is configured to selectively prevent or allow fluid flow through the organ stent waste fluid path.

Preferably, the perfusion device further comprises: a controller, the controller stores a plurality of operating states, each operating state determines the position of each flow control device, and the controller is configured to communicate with the flow control device each in communication; a sensor configured to generate a measurement of a characteristic of the perfusate; the controller further configured to receive the measurement, automatically select one of the operating states based on the measurement, and based on the selected operating state state controls the flow control device.

Preferably, said perfusion device further comprises input means connected to said controller; said controller is further configured to receive a selected said operating state from said input device, and to control based on the selected operating state The flow control device.

Preferably, said first flow control device and said second flow control device have a disabled state configured to allow fluid to flow from said reservoir to said waste via said waste fluid path .

Preferably, said plurality of fluid conduits further defines an alternate return fluid path, said alternate return fluid path connecting said reservoir with said outlet; said priming circuit further comprising: and a third flow control device configured to selectively direct fluid flow through one of the return fluid path and the alternate return fluid path.

Preferably, said perfusion device further comprises: a disposable assembly comprising: said inlet; said outlet; said reservoir, said waste, and said plurality of fluid conduits of said perfusion circuit. and a reusable assembly comprising: a base configured to detachably support the disposable assembly in an operational state; the first flow control device; and the second flow control device; when the disposable assembly is When supported by the base, the first flow control device and the second flow control device are configured to selectively prevent or allow fluid flow through the delivery fluid path and the waste fluid path, respectively.

Preferably, said base includes a wall for supporting said disposable assembly; wherein said first flow control device and said second flow control device are supported by said reusable assembly for connection to adjacent said wall of the fluid conduit.

Preferably, the disposable assembly further includes a gas conduit connected to a gas inlet for connection to the organ; the reusable assembly further includes a ventilator; the disposable assembly and the reusable An assembly includes a matable mechanical interface configured to connect the ventilator and the gas conduit.

Preferably, said disposable assembly further includes a pump head module located on said delivery fluid path for receiving said perfusate from said reservoir; said reusable assembly further includes a pump drive module, said The pump driving module is used to drive the pump head module; the pump driving module and the pump head module are connected and run through the matching mechanical interface.

Preferably, said disposable assembly further comprises a conditioning module located on said delivery fluid path, said conditioning module comprising a heat exchanger and a gas exchanger. And the reusable assembly further includes: a heater configured to deliver heated fluid to the heat exchanger; and a gas storage device configured to deliver gas to the gas exchanger.

Description of drawings

Embodiments of the application are described below in conjunction with the following drawings:

Figure 1 is a schematic diagram of a perfusion device according to a non-limiting embodiment of the present disclosure;

FIG. 2 is a schematic diagram of the perfusion device in FIG. 1 in a disassembled state according to a non-limiting embodiment of the present disclosure;

3 is a schematic diagram of a perfusion circuit of the perfusion device of FIG. 1 , according to a non-limiting embodiment of the present disclosure;

4 is a schematic diagram of the perfusion circuit shown in FIG. 3 with some additional components of the perfusion apparatus of FIG. 1 , according to a non-limiting embodiment of the present disclosure;

5A and 5B are schematic diagrams of the flow control device of the perfusion device shown in FIG. 1 according to non-limiting embodiments of the present disclosure;

FIG. 6 is a schematic diagram of the ventilation circuit of the perfusion device of FIG. 1 , according to a non-limiting embodiment of the present disclosure;

Fig. 7 is a flowchart of the operation method of the perfusion device shown in Fig. 1 according to a non-limiting embodiment of the present disclosure;

FIG. 8 is a flow chart of a method for ending the operation of the perfusion device in FIG. 1 according to a non-limiting embodiment of the present disclosure;

Figure 9 is a schematic diagram of an example implementation of the perfusion circuit of Figure 3, shown according to a non-limiting embodiment of the present disclosure;

10A and 10B are schematic diagrams of a reservoir in the perfusion circuit of FIG. 3 , according to non-limiting embodiments of the present disclosure;

Figure 11 is a partial view of the embodiment of Figure 9 shown according to a non-limiting example of the present disclosure;

Figure 12 is an additional partial view of the embodiment of Figure 9, shown according to a non-limiting example of the present disclosure;

Figure 13 is another partial view of the embodiment of Figure 9, shown according to a non-limiting example of the present disclosure;

FIG. 14 is a schematic diagram showing the relative positions of certain components of the embodiment of FIG. 9 , according to a non-limiting example of the present disclosure.

detailed description

FIG. 1 shows a schematic diagram of an organ perfusion device 100 , which is simply referred to as device 100 herein. As will be described in detail below, device 100 may be used for at least one of evaluation, treatment, and transportation of donor organ 104 . In this embodiment, the donor organ is a pair of lungs (eg, human lungs) harvested from the donor and implanted in a recipient patient (patient not shown in Figure 1). The operation of device 100 for extracorporeal perfusion is described below, however, in other embodiments, device 100 may also be used for in vivo organ perfusion. It will also be apparent from the description below that device 100 or variations thereof may also be used in various other organs, such as the kidney, heart and liver.

Generally, device 100 is configured to provide a substantially sterile environment for organ 104 by providing a chamber that substantially isolates organ 104 from the outside. Apparatus 100 is also configured to allow perfusion of organ 104 with any suitable fluid (selected at least in part based on the properties of the perfused organ) to enable the above-mentioned evaluation and treatment of organ 104 and to extend the availability of organ 104 for transport. time. When the device 100 is applied to certain organs, such as the lung, it can also be configured to pass any suitable gas or mixed gas into the organ 104 so as to analyze and treat the organ 104 . When device 100 is applied to other organs, device 100 may also be configured to remove fluid (eg, urine in the kidney, bile in the liver).

Further, as described below, device 100 is configured to be transportable, for example, from a donor location to a vehicle (e.g., an aircraft), and from a vehicle to a recipient location (e.g., a hospital operating room). ). Still further, some components of device 100 are disposable, while other components are reusable.

In this embodiment, device 100 includes a disposable component 108 and a reusable component 112 . The disposable assembly 108 includes an organ support 114 , such as a tray in which the organ 104 can be placed, and a perfusion circuit capable of perfusing the organ 104 as mentioned above. It will be obvious to those skilled in the art that when the device 100 is applied to in vivo perfusion of the organ 104, the organ support 114 may not be used (in fact, may be omitted). When the device 100 is used for in vivo perfusion, the organ 104 is supported within the patient's body, thus no external organ support is required. Disposable assembly 108 also includes a protective dome 115 (in other embodiments, may also be non-dome-shaped) that may be attached to the upper portion of disposable assembly 108 to provide a substantially sealed cavity for receiving organ 104 room. The seal may or may not be hermetic. If not airtight, the seal is preferably watertight. When a ventilation circuit is present, the disposable assembly 108 also includes a portion of the ventilation circuit.

The reusable assembly 112 includes control equipment for the perfusion circuit and other components that will be described in detail below. Where a ventilation circuit is present, said other components may comprise the remainder of the ventilation circuit. The components of reusable assembly 112 may be housed within a housing (eg, having rigid walls and providing structural support for the components), which may also include wheels or other moving means to enable movement of device 100 .

As shown in FIG. 2 , the disposable assembly 108 can be separated from the reusable assembly 112, for example, to transport the reusable assembly 112 and organ 104 from the aforementioned means of transport to the recipient site, or simply to Disposable assembly 108 is removed and replaced after removal of organ 104 at 108 (eg, transplantation of organ 104 into a recipient patient).

Reusable assembly 112 includes a base 200 configured to releasably support disposable assembly 108 in an operational state (as shown in FIG. 1 ). Base 200 may include a variety of structural arrangements. In the embodiment shown in Figures 1 and 2, the base 200 includes three surfaces 200-1, 200-2 and 200-3. Each surface is in contact with a corresponding surface of the disposable assembly 108 when the device 100 is assembled and in operation. However, many other configurations can also be applied to the base 200 . For example, in other embodiments, base 200 may include a single surface, similar to surface 200 - 1 , for supporting disposable component 108 on reusable component 112 . As will be apparent from the following description, the structure of base 200 depends in part on the arrangement of physical connections between reusable assembly 112 and disposable assembly 108 to complete the ventilation circuit, control the perfusion circuit, and achieve other aspects of device 100. Function.

As noted above, the disposable set 108 includes a priming circuit. The perfusion circuit typically circulates the perfusate between the reservoir and the organ 104 to provide nutrients (e.g., glucose) to the organ 104, remove metabolic by-products from the organ 104, and optionally allow for multiple processes to be performed on the organ 104. assessment and treatment activities. Turning to Figure 3, the perfusion circuit is described in detail.

As shown in Figure 3, the perfusion circuit includes a reservoir 300 configured to store a perfusate. The perfusate may be any suitable fluid formulated to deliver nutrients to the organ 104 and excrete metabolic byproducts from the organ 104 . In other embodiments, the perfusate may be saline, water, or similar fluids, such as where delivery of nutrients is not desired, but metabolic byproduct removal is still desired. In this example, the perfusate was STEEN Solution ^™ . As will be described in detail below, the reservoir 300 may have a rigid outer wall or a flexible outer wall (or any suitable combination thereof) made of any suitable biocompatible and liquid-impermeable material , such as plastic. The size of the reservoir 300 depends on the application of the device 100 . In this embodiment, device 100 is configured for transporting lungs, reservoir 300 may have an internal volume of about 2L. However, it will be apparent that the reservoir may have various other suitable volumes in other applications.

The perfusion circuit also includes a waste vessel 304 configured to receive perfusate as described above under certain operating conditions, the waste vessel 304 will be described in detail below. The waste vessel 304 may have any suitable shape and configuration, including an outer wall of any suitable combination of flexible and rigid walls, which may be made of any suitable liquid-impermeable material, such as plastic.

The perfusion circuit also includes a plurality of fluid conduits 308-0, 308-1, 308-2, etc. (collectively referred to as fluid conduits 308), such as long flexible tubing (eg, silicone tubing, plastic tubing, or the like) that define a plurality of fluid paths. In some embodiments, some or all of fluid conduit 308 may be isolated, eg, sheathed with larger sized tubing.

The fluid pathways described in the present disclosure allow fluid to flow between two endpoints through any suitable combination of the aforementioned fluid conduits and other components. A fluid path is defined by the set of conduits 308 and other components along which liquid can flow between two endpoints. Thus, for example, if two endpoints (such as reservoir 300 and liquid waste 304) are connected by two sets of fluid conduits, the two endpoints are considered to be connected by two sets of fluid conduits even if some of the fluid conduits are shared by the two sets of conduits. Two different fluid paths are connected.

The fluid pathways described above include a delivery fluid pathway connecting the reservoir 300 and the inlet 312 of the organ support 114 . Inlet 312 may be, for example, a cannula connected to organ 104 to deliver perfusate thereto. In this embodiment, organ 104 is a pair of lungs, and inlet 312 may be a cannula connected to the main pulmonary artery (alternatively, in some embodiments, inlet 312 may be a pair of cannulas or a branched outlet). root cannula, connected to the left and right pulmonary arteries respectively). In this embodiment, the delivery fluid path is defined by fluid conduits 308-0, 308-1, 308-2, 308-3, 308-4, 308-5, and 308-6, each fluid conduit representing a Separate long tube. It will be apparent to those skilled in the art that various other catheter configurations may be used to define the delivery fluid path. The catheter configuration employed depends on the other components in the path of the conveyed fluid, as well as the distance between components.

Fluid conduit 308 in the perfusion circuit may also define a return fluid path that connects outlet 316 of organ support 114 and reservoir 300 . Outlet 316, similar to inlet 312, may be a single or a pair of cannulas connecting fluid conduit 308-7 to each of the left and right pulmonary veins of organ 104, respectively, or to the trunk of the pulmonary veins (which flow into the left atrium of the heart). ). The return fluid path and the delivery fluid path are independent of each other, that is, the return fluid path and the delivery fluid path do not share any fluid conduit 308 . As shown in Figure 3, the return fluid path is defined by fluid conduits 308-7, 308-8, 308-9, and 308-10.

Fluid conduit 308 may also define a waste fluid path that connects reservoir 300 and waste container 304 . As shown in Figure 3, the waste fluid path is defined by fluid conduit 308-0 (common to the delivery fluid path described above) and fluid conduit 308-11. It will be apparent to those skilled in the art that various other combinations of fluid conduits 308 may be used to provide the fluid pathways described above (and the fluid pathways described below). For example, the waste fluid path may not share fluid conduit 308-0 with the transfer fluid path. Instead, in some embodiments, reservoir 300 may provide an outlet exclusively for the waste fluid path so that fluid conduit 308-11 may be connected directly to reservoir 300 without branching to fluid conduit 308-0. catheter.

The perfusion circuit can include a number of other components, and the conduit 308 can define a number of additional fluid paths for connecting to a number of the other components. In particular, the perfusion circuit in this embodiment includes a pump head module 320 located in the delivery fluid circuit. Pump head 320 drives fluid received from reservoir 300 (via conduits 308-0 and 308-1) toward inlet 312 (ie, toward organ 104). More specifically, pump head 320 drives fluid to inlet 312 and also through a fluid conditioning module, such as a gas and heat exchange module 324 .

In this embodiment, the organ 104 is a pair of lungs, and the module 324 is used to remove oxygen from the perfusate flowing through the module 324 before the perfusate is delivered to the lungs. Deoxygenation can be achieved by injecting carbon dioxide (or any other suitable gas mixture) into the perfusate. The module 324 receives carbon dioxide through a gas supply line 326 which is connected to a mechanical interface 328 of the disposable assembly 108 . Module 324 may also be configured to control the temperature of the perfusate flowing through it via a heat exchanger. In some embodiments, the heat exchanger may be electrically powered. In this embodiment, heat exchange is accomplished by heated fluid being received from module 324 through input and output conduits 330 connected to port 328 , flowing through a heat exchanger within module 324 and out of module 324 . As will be described in detail below, module 324 may be used to heat the perfusate to a target temperature (eg, 37 degrees Celsius). In some embodiments, module 324 may also be operable to cool the perfusion circuit (eg, through operation of a thermoelectric cooler).

Obviously, in other embodiments, the gas exchange and heat exchange functions of the module 324 can be realized by separate devices (for example, an online electric heater can be provided upstream or downstream of the gas exchange module). In other embodiments, the gas exchange function may be omitted entirely, eg, when the organ 104 is an organ other than a lung or a pair of lungs, no gas exchange is required. In yet other embodiments, the gas exchange function may also be preserved when perfusing organs other than the lungs, albeit in a different manner than described here (eg, adding oxygen rather than carbon dioxide to the perfusion circuit).

Also included in the delivery fluid path is a leukocyte filter 332 downstream from the module 324 . It will be apparent to those skilled in the art that the leukocyte filter is configured to remove leukocytes from the perfusate that would otherwise return to the reservoir 300 for further fluid circulation through the organ 104 after the perfusate has passed through the organ 104 Accumulation (causes inflammation in organ 104).

The perfusion circuit may also include one or more additional leukocyte filters, such as secondary filter 334 . In some embodiments, secondary filter 334 may be omitted. In this embodiment, however, the secondary filter 334 is provided as a backup filter for the filter 332 . Depending on how long the device 100 is running, the filter 332 may become partially clogged with biological material, creating relatively high pressure on the pump head 320 to continue driving the perfusate toward the organ 104 . Therefore, filter 332 needs to be disabled and secondary filter 334 enabled. As will be apparent, the secondary filter 334 is located on an alternate delivery fluid path from the reservoir 300 to the inlet 312, which shares the same conduits as the aforementioned delivery fluid path, except for conduits 308-4 and 308-5. 308. In fact, alternate delivery fluid paths are defined by conduits 308-12 and 308-13.

Other components of the irrigation circuit may include a pressure control valve 336, such as a check valve, connected between conduits 308-8 and 308-9 (ie, on the return fluid path). In other implementations, the pressure control valve 336 can be located entirely within the fluid conduit such that conduits 308-8 and 308-9 can be replaced by a single conduit. In general, pressure control valve 336 is configured to maintain the pressure within conduit 308 (and thus within the blood vessels of organ 104) at a predetermined pressure level. For example, when organ 104 is a lung or a pair of lungs, the predetermined pressure level is approximately 5 mm Hg, so the cracking pressure of pressure control valve 336 is approximately 5 mm Hg. It will be apparent that other perfusate pressures may be used when device 100 (or variations thereof) is used in other organs.

The priming circuit may also include an alternate or secondary return path from outlet 316 to reservoir 300 . The alternate return path is defined by the same conduits as the return fluid path mentioned above, except fluid conduit 308-14 replaces conduits 308-8 and 308-9. In other words, the alternate return path allows perfusate to return to the reservoir 300 via a bypass of the pressure control valve 336, as will be described in detail below.

The perfusion circuit may include a number of additional fluid paths. Included are filter priming paths for connecting priming port 340 to filters 334 and 332 . Although an infusion port 340 (eg, possibly including a funnel) is shown below the organ 104, it should be apparent that the components in FIG. 3 are not shown in their actual physical arrangement. In practice, the infusion port 340 is located above all other components of the perfusion circuit, including the inlet 312 . A filter priming fluid path is defined by conduits 308-15, 308-5, and 308-12.

The fluid paths of the priming circuit may also include reservoir priming fluid paths. A reservoir priming fluid path is used to connect priming port 340 and reservoir 300 and is defined by conduits 308-16 and 308-17. It is foreseeable that the connection between the reservoir 300 and the conduit 308-0 is unobstructed so that the reservoir filling path can also flow to the pump head 320 and module 324 (i.e., the reservoir filling path is not limited to the reservoir Liquid container 300 liquid injection), will be described in detail below.

The fluid paths of the perfusion circuit may also include an organ stent return fluid path, via conduits 308-18, 308-19, and 308-17 connecting the organ stent 114 to the reservoir 300, and an organ stent waste fluid path, via conduit 308 -18 and 308-20 are connected to the organ holder 114 and the liquid waste container 304. Fluids (including perfusate and other biological fluids such as blood) may exit the organ 104 directly from the surface of the organ 104 while the device 100 is in operation, rather than through the outlet 316 . These fluids collect on the organ support 114, which may be connected to the conduit 308-18 by providing one or more drainage ports. The aforementioned organ stent return path and organ stent waste path allow these fluids to be recycled to the reservoir 300 or disposed of in the waste container 304, respectively. In some embodiments, one of the above paths may be omitted. For example, the organ stent waste path may be omitted and all fluid from the organ stent 114 may flow to the reservoir 300 . For another example, the return water path of the organ support can be omitted, and all the fluid from the organ support 114 can be diverted to the waste liquid container 304 .

The perfusion circuit can also be equipped with one or more sensors and sampling ports. In this embodiment, a flow sensor 342 and a temperature sensor 344 are provided on the delivery fluid path. A controller (not shown) of apparatus 100 may receive signals from sensors 342 and 344 to control the operation of pump head 320 and module 324 (or any other suitable heat exchanger used in place of module 324). Additionally, the perfusion circuit may include an oxygen partial pressure sensor 346 located proximate to one or both of the inlet 312 and outlet 316 . Finally, sampling ports may include upstream of inlet 312 (sampling port 348 ) and downstream of outlet 316 (sampling port 350 ), allowing perfusate samples to be withdrawn for testing outside of device 100 . In some embodiments, sampling ports 348 and 350 may be supplemented or replaced with additional in-line sensors, such as oxygen sensors, carbon dioxide sensors, and pH sensors.

Each component of the perfusion circuit that is interconnected by conduit 308 may have a vent passage (not shown) that allows air to escape from that component when the perfusion circuit is primed (ie, the perfusion circuit is first filled with perfusate). In some embodiments, one or more vent passages may be omitted. The actual arrangement of the components in the perfusion circuit and the relation of such arrangement to perfusion will be described in detail below.

Apparatus 100 also includes a plurality of flow control devices configured to selectively prevent or allow perfusate to flow along the aforementioned fluid paths. That is, the fluid pathways described above may be individually enabled or disabled by one or more flow control devices interacting with and selectively occluding the fluid conduit 308 . Device 100 thus includes multiple operating states, each of which is defined in terms of which fluid paths are enabled and which fluid paths are disabled.

A variety of flow control devices may be used in device 100 . For example, an inline valve may be placed within conduit 308 . In this embodiment, however, the flow control device is disposed outside the catheter 308 so that it does not come into contact with the perfusate. Additionally, in this embodiment, the flow control device is provided in the reusable assembly 112 , and the flow control device can be connected to a suitable conduit 308 when the disposable assembly 108 is installed into the base 200 .

Turning now to FIG. 4 , a perfusion circuit (disposed in the present embodiment within the disposable assembly 108 as described above) is shown together with certain components of the reusable assembly 112 , including a plurality of flow control devices 400 . In particular, in this embodiment, eight flow control devices 400-1, 400-2, 400-3, 400-4, 400-5, 400-6, 400-7 and 400-8 are shown. In other embodiments, other fluid conduit configurations requiring different numbers and arrangements of flow control devices 400 may be used to place device 100 in an operating state as described below.

Other components of the reusable assembly 112 are also shown in FIG. 4 , including a pump drive module 404 for activating the pump head 320 . The reusable assembly 112 may also include a complementary mechanical interface 408 configured to mate with the interface 328 of the disposable assembly 108, and to connect a source of perfusion gas 412 and a source of fluid heating (which may be simply referred to as a heater) via appropriate liquid or gas lines. 416 is connected to module 324 . In addition, the reusable assembly 112 includes a controller 420, which communicates with a pump drive module 404, a heater 416, and an input device 424 (such as a keyboard, mouse, touch screen, keypad, or the like) and a display device 428 (such as an LCD screen or the like). , in some embodiments, when the above-mentioned input device 424 includes a touch screen, it can be integrated with the input device 424) and connected to each other.

The controller 420 may also be connected to the sensors 342, 344 and 346 in a wireless or wired manner (not shown). Where the above connection is wired, it will be apparent that the connections may be made through interfaces 408 and 328, or through any suitable number of other complementary mechanical interfaces having electrical contacts. A controller 420 may also be connected to each of the flow control devices 400 described above for setting each control device 400 in an open or closed position, which will be described in detail below. The connection between the controller 420 and the control device 400 may be any suitable combination of wired and wireless.

Controller 420 may be implemented with any suitable microcomputer, including one or more integrated circuits, such as a non-transitory computer-readable storage medium in the form of memory (non-volatile, volatile, or a combination thereof). Processor (also known as central processing unit, or CPU).

Reusable assembly 112 also includes a power source (eg, one or more batteries or any other suitable power source). The power supply provides power to the controller 420, the input device 424, the display device 428, and any other electrically driven components. In this embodiment, the flow control device 400 is electrically driven, as is the pump driving module 404 and certain components of the module 324 (such as the thermoelectric cooler mentioned above). Inlet 312, outlet 316, leukocyte filters 332 and 334, pressure control valve 336, liquid reservoir 300, liquid waste container 304, organ holder 114, infusion port 340, etc. have been described in detail above in FIG. This will not be repeated.

Before further discussing the operation of the flow control device 400, the structure of the flow control device 400 is described in more detail. Figure 5A shows a flow control device 400 alone. The flow control device 400 includes a body 500 housing a solenoid assembly configured to drive a shaft (not shown) such that the shaft head 504 is in open and closed positions. Head 504 is configured to abut fluid conduit 308 . Thus, in the open position, the distal bulge of the head 504 is aligned with the direction of fluid flow through the corresponding conduit 308, thereby allowing fluid flow. In the closed position, the protrusion is substantially at a right angle to the direction of fluid flow, thereby blocking fluid flow. In embodiments utilizing a wired connection, the flow control device 400 also includes at least one electrical interface 508 for communicating power and control signals to the flow control device 400 .

FIG. 5B shows flow control device 400 including bracket 512 mountable to body 500 and adjacent to head 504 . Bracket 512 includes opposing openings 516 and 520 through which fluid conduit 308 passes. Bracket 512 also includes positioning structures, such as holes 524 , for positioning bracket 512 on body 500 . In this embodiment, bracket 512 is a component of disposable assembly 108 and is secured in place of fluid conduit 308 where flow control is desired. These selected positions enable each bracket 512 to be connected to the flow control device 400 when the disposable assembly 108 is seated on the base 200 (eg, precisely positioned through the holes 524). Accordingly, the head portion 504 of the flow control device 400 abuts the fluid conduit 308 and is capable of allowing or preventing fluid flow within the fluid conduit.

In the event that the flow control device 400 is powered off, it cannot be in a predetermined position (ie, open or close its corresponding fluid conduit 308). As described below, the predetermined failure locations of the flow control device 400 collectively define the fail-safe operating state of the device 100 in the event of a failure, such as a power outage.

Referring back to FIG. 4, as described above, each flow control device can selectively prevent or allow fluid to flow through one of the above-mentioned fluid paths. In particular, device 400-1 controls flow through the reservoir infusion fluid path; device 400-2 controls flow through the filter infusion fluid path; device 400-3 controls flow through the organ stent waste fluid path; device 400-4 controls flow via the return fluid path of the organ stent; device 400-5 controls flow via the waste fluid path; device 400-6 controls flow via the delivery fluid path; device 400-7 controls flow via the alternate delivery fluid path flow; and the device 400-8 controls flow via the alternate return fluid path.

Flow control device 400 may be individually controlled to enable or disable any combination of any number of the above-described fluid paths. Each combination of enabled (and thus disabled) fluid paths may be referred to as an operating state of device 100 . In this embodiment, the controller 420 is configured to store a plurality of operating states, each operating state being determined by a set of positions of the flow control device 400 . The controller 420 is further configured to select, based on any input data received via the input device 424 (e.g., from an operator of the apparatus 100) or based on an automatic determination by the controller 420 itself (e.g., based on data received from the aforementioned sensors), one of the stored operating states and send a control signal to the flow control device 400 to implement said operating state.

In some other embodiments, the storage of the operating state and its corresponding position of the flow control device 400 in the controller may be omitted. In these embodiments, controller 420 may be configured to accept input data from input device 424 specifying the position of each flow control device 400 . That is, in these embodiments, the operator of the plant 100 not only needs to select an operating state, but also needs to indicate to the controller 420 the location of each flow control device 400 . In still other embodiments, the above operation modes (ie, the controller 420 stores the running state and the operator manually manages the running state) can be combined. For example, the controller may store and enforce operating states as described above, or may switch to manual operating state management in response to predetermined inputs from input device 424, allowing the operator of apparatus 100 to exercise greater control over apparatus 100 (e.g. , make the device 100 run in the running state not stored by the controller 420).

Table 1 shows various operating states of the device 100 , in particular, there are eight operating states, and the corresponding positions of each flow control device 400 . Controller 420 may store the operational status in Table 1 (or, indeed, any desired operational status) in any suitable format, including, but not limited to, the tabular format shown below.

Table 1: Operating states defined by flow control device settings

As noted above, each operating state designates a position for each flow control device 400, thereby enabling or disabling each of the aforementioned fluid paths. Some operating states do not require specific flow control devices 400 to be assigned positions, thus allowing those flow control devices 400 to remain in their previous positions. For example, the fluid replenishment operating state does not require a particular location of the flow control devices 400-6 and 400-7. Therefore, when the operating state of the apparatus 100 is switched from the previous state to the fluid replenishing operating state, the positions of the fluid control devices 400-6 and 400-7 will not change.

As mentioned above, flow control device 400 cannot go to a predetermined position, for example in the event of a power outage. The emergency failure operating states described above indicate where each flow control device 400 fails. In other words, the fail-emergent operating state need not be actively selected (although it can be) by the controller 420 or the operator of the plant 100 . Conversely, the emergency fail-safe operating state may only be activated by powering down the device 100 . The "emergency failure" condition shown above may be activated automatically by the fail-safe position of the flow control device 400, or may be activated by the operator of the device 100 in response to any failure of one or two components of the device 100 or any failure of the device during operation. failure and manual activation to protect the organs in the device 100.

Before further discussing the operation of the perfusion circuit, additional components of the device 100 will be described as follows. In particular, as described above, the device 100 in this embodiment is configured for transporting and treating lungs and thus includes a ventilation circuit in addition to a perfusion circuit. Components of the ventilation circuit are shown in FIG. 6 . Although the perfusion circuit is omitted from FIG. 6 for clarity of view, it is apparent that both the perfusion circuit and the ventilation circuit are contained within the device 100 .

Generally speaking, the ventilation circuit is configured to connect (eg, underneath) the organ 104 to the ventilator 600, and the gas supply 604 supplies the ventilator 600 with a gas, such as pure oxygen, air, or the like. Ventilator 600 and gas supply 604 are contained in reusable assembly 112 and interface with gas conduits 608 (conduits 608-1, 608-2, and 608-3 as shown, which may also be exchanged with organ 104 using combination of any conduit for gas) connection. In this embodiment, the interface between ventilator 600 and catheter 608 is provided by mechanical interfaces 328 and 408, which were previously described in connection with the perfusion circuit. That is, interfaces 328 and 408 may support connection of a perfusion circuit and a ventilation circuit. In other embodiments, separate mechanical interfaces may be provided on the disposable assembly 108 and the reusable assembly 112 for the perfusion circuit and the ventilation circuit.

The ventilation circuit includes an exhaust valve 612 and a flow sensor 616, and the flow sensor 616 may be connected to the controller 420 in a wireless or wired manner. In some embodiments, flow sensor 616 may be implemented using one or more pitot tubes. Further, the ventilation circuit may include a bronchoscopy interface 620 that connects to catheter 608-3 and allows visualization of the lungs. On the other side, catheter 608-3 is connected to an endotracheal tube for connection to the trachea. The ventilation circuit may also include one or more regulating devices (eg, moisture heat exchangers) for controlling the temperature and moisture content of the gas delivered to the organ 104 . In this embodiment, these conditioning devices are included in the disposable assembly 108, since these conditioning devices typically include disposable air filters. In other embodiments, certain conditioning devices (eg, humidifiers) are reusable and thus placed in reusable assembly 112 .

Having described the internal components of device 100, the operation of device 100 will now be described. FIG. 7 shows a method 700 of initializing and running the device 100 . In block 702 , organ 104 is placed into device 100 . That is, when the organ 104 is a lung or a pair of lungs, the lungs are placed on the organ holder 114, the trachea is connected to the ventilation circuit, and the pulmonary artery and vein are connected to the perfusion circuit. The protective dome 115 is then placed over the lungs.

In block 705, the perfusion circuit is set to the priming state as shown in Table 1 above. As previously described, selection of an operating state may be performed by the control device in response to input data received from input device 424 specifying the operating state. In block 710 , perfusate is provided to the perfusion circuit through the perfusion port 340 . As apparent from FIG. 4 and Table 1 , the perfusate provided in block 710 flows into reservoir 300 , then through pump head 320 , module 324 and into filters 334 and 332 . Perfusate provided may also flow into filters 334 and 332 (via conduits 308-15, 308-5, and 308-12) in a direction opposite to the normal flow of fluid to ensure that filters 334 and 332 are completely filled. After the infusion of perfusate is complete (in this example approximately 2 liters of perfusate are provided, however other volumes of perfusate may be provided depending on the type and size of organ 104 ), method 700 proceeds to block 715 .

In block 715, the perfusion circuit is set to the perfusion operating state shown in Table 1. When the device 100 includes a ventilation circuit, as in the present embodiment, the ventilation circuit is also activated in block 715 . Additionally, the pump drive module 404 is also activated in block 715 . As a result, perfusate flows from reservoir 300 to organ 104 via the delivery fluid path, and fluid exiting organ 104 from outlet 316 returns to reservoir 300 via the return fluid path.

In block 720, a determination is made as to whether to renew the perfusate in the device 100. In some embodiments, block 720 (and in blocks 725 and 730, as described below) may be omitted. However, in the present example, certain isolated lung perfusion protocols allow for the removal and replacement of specific volumes of perfusate at predetermined intervals (eg, 500 ml after the first hour of surgery, and 250 ml every hour thereafter). Refreshing the perfusate dilutes any metabolic byproducts that may have accumulated in the reservoir and replenishes the supply of nutrients (especially glucose) in the perfusate. Renewing the perfusate may also dilute hormonal compounds (eg, produced by immune cells in the organ) in the perfusate. These compounds may cause unwanted inflammation if not diluted.

When the determination in block 720 is "Yes," execution of method 700 proceeds to block 725 where the perfusion circuit is set to the fluid removal state until the desired volume of perfusate has been transferred to waste 304 (eg, the predetermined length of time is selected based on a known flow rate along the waste liquid fluid path, or the predetermined length of time is selected based on a visual inspection of the liquid level in the liquid waste container 304 by the operator of the apparatus 100). It is apparent from Table 1 (and FIGS. 3 and 4 ) that the circulation of perfusate from reservoir 300 through organ 104 and back to reservoir 300 continues while block 725 is performed.

In block 730, after removing a predetermined volume of perfusate from the reservoir 300 to the waste container 304, the device 100 is set to the fluid replenishment operating state, and then further in the execution of block 710, the corresponding volume of perfusate is provided through the priming port 340 . In some embodiments, the corresponding volume of perfusate provided through infusion port 340 set in block 730 is equal to the volume of perfusate that flows to waste 304 in block 725 . However, in other embodiments, a greater or lesser volume of perfusate than was removed at block 725 may be configured to be replenished at block 730 . Execution of method 700 then re-arrives at block 715 .

When the determination in block 720 is no, a determination is next made in block 735 whether to remove fluid from the organ support 114 out of circulation. In certain circumstances, such as early in the operation of device 100, when other biological fluids (such as blood) are more likely to be present in the runoff collected by organ support 114, it may be desirable to remove fluid from organ support 114 rather than recirculating fluid to In the reservoir 300. When the determination in block 735 is "Yes", the perfusion circuit is set to perform the tray fluid removal operation for a selectable period of time (during which period, normal perfusate circulation to the organ 104 continues, Fluid flows from the organ rack drain port to the waste container 304, through the above-mentioned organ rack waste fluid path connecting the organ rack 114 and the waste container 304 by conduits 308-18 and 308-20), the tray fluid removal operation After the state is complete, the perfusion circuit then returns to the perfusion state at block 715 . It should be apparent that the decisions in blocks 720 and 735 can result in execution in the opposite direction to that shown in FIG. 7 . Similarly, execution of blocks 745 and 755, discussed below, need not occur in the order shown.

When the judgment in block 735 is "No", then a judgment is made in block 745 whether to switch from one white blood cell filter (such as filter 332) to another (such as filter 334). When the determination is affirmative, the perfusion circuit is set to the alternate perfusion state. In block 750, the alternate perfusion state (shown in Table 1) redirects the flow of perfusate from the delivery fluid path to the alternate delivery fluid path, and the remaining The state of the fluid path remains unchanged. When two leukocyte filters are provided, as in this embodiment, the operation of device 100 may be said to comprise two phases: a "ramp-up" phase using the first filter and a "normal" phase using the second filter .

When the determination in block 745 is "No", a determination is made in block 755 whether to end the operation of the device 100 . Since the device 100 has reached its destination and the organ 104 must be prepared for implantation into the recipient, a "Yes" decision must be made in block 755 . In other cases, the determination of block 755 may end unplanned, such as due to a component failure, loss of power, or the like. When the determination at block 755 is "NO", execution of method 700 continues at block 715 . When the decision in block 755 is "Yes", then operation of the device 100 will continue as shown in FIG. 8 .

FIG. 8 shows a method 800 for ending operation of device 100 . Method 800 may be performed differently depending on whether the end is planned (ie, not caused by a failure) or unplanned (ie, caused by a failure of device 100 ). When termination is planned, such as after successful transport of the organ 104 to the recipient patient's destination for transplantation, the purpose of the termination is to protect the organ 104 by reducing the metabolic rate of the organ 104 as the recipient patient prepares for transplantation.

In block 810, the perfusion circuit is set to an end state as shown in Table 1. As shown in Table 1, in the end state, the delivery fluid path is blocked (both filters 332 and 334 are prevented from receiving perfusate) and all remaining perfusate in the perfusion circuit is allowed to pass through reservoir 300 to waste 304. Additionally, operation of the pump driver 404 is also interrupted, and the ventilation circuit may also be disabled (eg, by shutting off the ventilator 600 and closing the airway 624 with a clip or other suitable implement). During initiation of the perfusion circuit drain in block 810 , in block 815 , a protection fluid (preferably a cooling protection fluid such as Perfadex ^™ ) is provided to the perfusion circuit through the infusion port 340 .

After the protection fluid is introduced, circulation of the protection fluid may be resumed in block 820 by returning the perfusion circuit to the priming state (thus activating the pump driver 404). Additionally, the heat exchanger of module 324 can be switched from a heating function to a cooling function. For example, when organ 104 is a lung or a pair of lungs, it is desirable to maintain the temperature of the protective fluid at about 10 degrees Celsius. As will be apparent, when the recipient patient is ready to receive the organ 104 , the final closing phase may be initiated by repeatedly performing block 810 without performing blocks 815 or 820 .

When operation of the device 100 ends in an unplanned manner (eg, due to a power outage or component failure), the perfusion circuit may be placed in an emergency failure state at block 820 by input from an operator or due to a failed position of the flow control device 400 . In block 830, as described in block 815, a protection fluid is supplied into the perfusion circuit. In block 835 , inlet 312 and outlet 316 are closed (eg, with clamps or caps, etc.) to ensure that some protective fluid remains within organ 104 . Additionally, at block 840, an external protective fluid may be supplied to the protective dome 115 through a cover (not shown) in the protective dome 115 such that the exterior of the organ 104 is at least partially surrounded by the protective fluid.

Having described the components and operation of device 100 above, the structure of certain components of device 100 and exemplary arrangements of these components will be described below. Referring to FIG. 9 , an exemplary embodiment of a disposable assembly 108 is shown. As shown in FIG. 9 , the disposable assembly 108 includes a support organ 104 (on a tray, not shown) and a housing 900 carrying the protective dome 115 . Housing 900 may include a window 904 that allows viewing of reservoir 300 therethrough. In addition to certain components of the disposable assembly 108, flow control devices 400 are also shown in FIG. The disposable assembly 108 is attached when the assembly 108 is mounted to the reusable assembly 112 . From the figures described below, it will be apparent that the flow control device 400 may be located at the three surfaces 200-1, 200-2, and 200-3 of the reusable assembly 112.

10A and 10B show a side view and a front view of the reservoir 300, respectively. As shown in FIGS. 10A and 10B , the reservoir 300 may include multiple inlets and outlets based on the configuration of the conduit 308 connected to the reservoir 300 . In this example, the reservoir 300 is a flexible bag (eg, made of any suitable plastic) that includes an outlet 1004 that connects to a conduit 308-0 and connects the reservoir 300 to a waste container 304 outlet 1008, ie, in the embodiment of FIG. 10, conduit 308-0 is replaced by two different conduits). Reservoir 300 also includes inlet 1012 for receiving perfusate from infusion port 340 or organ support 114 (shown in FIG. 3 ). Inlet 1016 receives perfusate through a return fluid path (ie, return from organ 104). Air escape port 1020 allows air to escape reservoir 300 during priming.

11 shows the arrangement of flow control devices 400-3 and 400-5 (located at surface 200-1 of base 200) and flow control devices 400-6 and 400-7 (located at surface 200-3 of base 200). . Also shown are reservoir 300 , pump head 320 , leukocyte filters 332 and 334 , infusion port 340 and mechanical interface 328 . In this embodiment, the mechanical interface 328 undertakes the connection of the module 324 , the ventilation circuit and the pump head 320 .

FIG. 12 is another view of the exemplary assembly shown in FIG. 11 , showing the remainder of the flow control device 400 . In particular, flow control devices 400 - 1 , 400 - 2 , and 400 - 4 are shown located at surface 200 - 2 of base 200 , while flow control device 400 - 8 is located at surface 200 - 1 of base 200 . The location of module 324 is also shown in FIG. 12 .

As shown in Figure 13, it can be seen that the fluid conduit 308 is routed from the parts of the disposable assembly 108 along one side of the disposable assembly 108 (for a detailed description and/or position of the fluid conduit, please refer to the description in Figure 3 ), which may allow an imaging platform 1300 (such as an x-ray panel) to be inserted between the organ 104 and the components. Thus, an imaging device positioned above organ 104 (orientation shown in FIG. 13 ) can capture images of organ 104 without interference from internal components of disposable assembly 108 .

Components of the disposable assembly 108 may be arranged to increase the priming efficiency of the priming circuit (eg, blocks 705 and 710 of method 700). As shown in Figure 14, the reservoir 300, pump head 320, leukocyte filters 332 and 334, and module 324 are positioned such that a hydrostatic gradient located above the organ 104), continues to the inlet 1012 of the reservoir 300, then continues to the outlet 1004 of the reservoir 300 and the pump head 320 (see FIG. 10B for a description of the inlet 1012 and outlet 1004). Although the module 324 is physically located above the pump head 320 , the pressure generated by the priming port 340 causes the module 324 to partially prime through the pump head 320 . Alternatively, filter 332 and filter 334, as well as the remainder of module 324, may pass through the aforementioned filter infusion fluid paths (i.e., conduits 308-15, 308-12, 308-5, 308-13, 308-4, and 308-3 , as shown in Figure 3) injection.

In the arrangement shown in the figures, during priming, fluid flow through conduits 308-15, 308-12, and 308-5 (shown in FIG. 3 ) to leukocyte filter 332 and leukocyte filter 334 may Not enough to completely fill filter 332 and filter 334 . In particular, the output ports of filters 332 and 334 (which serve as inputs during priming) may be located at the bottom of filters 332 and 334, and the priming may therefore not have sufficient hydrostatic pressure to fully Filter 332 and filter 334 are filled with liquid. Accordingly, filter 332 and filter 334 are partially primed in this embodiment through conduits 308-15, 308-12, and 308-5 (shown in FIG. 3). Priming of filters 332 and 334 is accomplished after pump head 320 is started to drive perfusate into filters 332 and 334 through conduits 308-3, 308-4, and 308-13 (shown in FIG. 3). Obviously, in other arrangements, the filter 332 and the filter 334 can be arranged to be activated by fluid injection from the infusion port 340 and flow through the conduits 308-15, 308-12, and 308-5 (as shown in FIG. 3 ). is fully infused. In other embodiments, priming of filter 332 and filter 334 may be accomplished through a separate filter outlet or a separate filter inlet. For example, in some embodiments, fluid may flow from infusion port 340 to the inlets of filters 334 and 332 (ie, the tops of the filters as shown in FIG. 14 ) through conduits 308-15 (shown in FIG. 3 ). , instead of flowing to the outlets of filter 332 and filter 334 via conduits 308-12 and 308-5 as shown in FIG.

Further, in some embodiments, a waste container 304 (not shown) is located below the outlet 1008 of the reservoir 300 so that any fluid in the perfusion circuit can be gravity transferred to the waste in the event of a power outage or other failure. in the liquid container.

In some embodiments, an organ perfusion device is provided, comprising: an inlet for connecting to the organ and an outlet for connecting to the organ; a perfusion circuit comprising: an infusion port configured to receive a perfusate; a reservoir a reservoir configured to store perfusate; a plurality of fluid conduits defining: a delivery fluid path connecting the reservoir to the inlet; a return fluid path connecting the reservoir to the outlet, the The return fluid path is independent of the delivery fluid path; the injection fluid path connects the injection port and the reservoir; the arrangement of the injection port and the reservoir creates a flow from the injection port Hydrostatic gradient to reservoir.

In some embodiments, the perfusion circuit further comprises: a pump head module located on the delivery fluid path for receiving the perfusate from the reservoir; the arrangement of the pump head module and the reservoir produces A hydrostatic gradient from the reservoir to the pump head module.

In some embodiments, the perfusion circuit further comprises: a leukocyte filter located between the pump head module and the inlet on the delivery fluid path; a filter inlet for connecting the pump head module and the leukocyte filter A first subset of fluid conduits and a second subset of fluid conduits for connecting the filter outlet of the leukocyte filter to the inlet; wherein the plurality of fluid conduits further define a Outlet filter priming fluid path.

In some embodiments, the filter infusion fluid path is defined by: a partial conduit of a second subset of fluid conduits; and a first infusion conduit connecting the infusion port to the The portion of the conduits of the second subset of fluid conduits.

In some embodiments, the perfusion circuit further comprises: a flow control device having: a flow control inlet connected to the first infusion conduit and receiving fluid from the infusion port; a first flow control outlet configured to deliver fluid to the first infusion conduit; The portion of the conduits of the second subset of fluid conduits, and the second flow control outlet, are configured to deliver fluid to the remaining conduits of the second subset of fluid conduits.

In some embodiments, the flow control device has: a first position configured to dispense fluid only to the first flow control outlet for priming the leukocyte filter through the filter outlet; a second position configured to dispense fluid only to the second flow control outlet for perfusing the organ through the inlet; and a third position configured to dispense fluid to both the first and second flow control outlets.

In some embodiments, the priming fluid path is separate from the filter priming fluid path.

In some embodiments, the priming fluid path is defined by a second priming conduit connecting the priming port and the reservoir.

In some embodiments, the perfusion circuit further comprises: an adjustment module located between the pump head module and the inlet on the delivery fluid path, for receiving the perfusate from the pump head module.

In some embodiments, the adjustment module is located between the pump head module and the leukocyte filter.

In some embodiments, the arrangement of the leukocyte filter and the regulation module creates a hydrostatic gradient from the infusion port, to the leukocyte filter, to the control module.

In some embodiments, there is provided a method of operating an organ perfusion apparatus, comprising: connecting an organ to a perfusion circuit, the perfusion circuit having: an infusion port; a fluid reservoir; a fluid waste container; a plurality of fluid conduits for defined by: an infusion fluid path connecting the infusion port and the reservoir; a return fluid path connecting the reservoir and the organ outlet, the return fluid path being independent of the delivery fluid a path; and a waste fluid path connecting the reservoir to the waste; controlling a plurality of flow control devices configured to selectively prevent or allow fluid to pass through the fluid conduit flow, the controlling comprising: setting a priming operating state to allow fluid to flow through the priming fluid path; in response to the set priming operating state, supplying perfusate via the priming port and the priming fluid path to Reservoir; sets a perfusion operating state to allow circulation of perfusate through the delivery, organ, and return fluid paths while preventing fluid flow through the perfusion and waste fluid paths; after setting the perfusion operating state , sets the Fluid Removal operating state to allow fluid to flow to the waste via the waste fluid path.

In some embodiments, the method further comprises: in response to removal of a predetermined volume of perfusate from the reservoir to waste, setting a supplemental operating state to allow fluid to flow through the perfusate fluid path to enable flow to the reservoir. Supplement with an additional predetermined volume of perfusate.

In some embodiments, the supplemental operating state further allows perfusate to circulate through the delivery fluid path, the organ fluid path, and the return fluid path while preventing fluid flow through the waste fluid path.

In some embodiments, installing the organ includes connecting the organ to each inlet and outlet.

In some embodiments, the organ may be a lung; and connecting the organ to the inlet includes connecting the inlet to a pulmonary artery of the organ; connecting the organ to the outlet includes connecting the outlet to a pulmonary vein of the organ.

In some embodiments, the plurality of fluid conduits further define an alternate delivery fluid path connecting the reservoir and the inlet; the controlling further comprises: setting an alternate perfusion state to allow perfusate to pass through the alternate delivery fluid pathway, the organ fluid pathway, and the return fluid pathway, while preventing fluid flow through the perfusion fluid pathway and the waste fluid pathway.

In some embodiments, the plurality of fluid conduits further define: an organ support return fluid path connecting the organ support to the reservoir, and an organ support connecting the drain port to the waste container waste fluid path; the controlling further comprising: setting the organ stent fluid removal operating state to allow perfusate to flow through the organ stent waste fluid path while preventing fluid flow through the organ stent return fluid path.

In some embodiments, setting the priming operating state includes activating a pump on the delivery fluid path.

In some embodiments, the method further includes setting an end-of-operation state to allow fluid flow through the return fluid path and the waste fluid path while preventing fluid flow through the transfer fluid path.

In some embodiments, the method further includes supplying the organ with protective fluid through the infusion port in response to draining the perfusate from the organ to a waste vessel.

In some embodiments, the method further includes closing the outlet and the inlet.

In some embodiments, the method further comprises supplying additional protective fluid to the exterior of the organ.

In some embodiments, a method of ending operation of an organ perfusion device is provided. The method includes: stopping circulation of a perfusate in a perfusion circuit connected to the organ through an inlet and an outlet; draining the perfusate from the organ to a waste vessel; and providing protective fluid to the organ through the perfusion port.

In some embodiments, the method of ending operation of an organ perfusion device further includes closing the outlet and the inlet.

In some embodiments, the method of ending operation of an organ perfusion device further includes supplying additional protective fluid to the organ.

The scope of the claims should not be limited by the specific examples set forth in the above examples, but should be given the broadest interpretation consistent with the entire specification.

Claims (16)

1. An organ perfusion device, characterized in that, comprising: an inlet for connection to said organ and an outlet for connection to said organ; Perfusion circuit, including: a reservoir configured to store a perfusate; waste container; A plurality of fluid conduits defining: a delivery fluid path connecting the reservoir and the inlet; a return fluid path, independent of the delivery fluid path, connecting the reservoir to the outlet; a waste fluid path connecting the reservoir and the waste container; a first flow control device configured to selectively prevent or allow fluid flow from the reservoir to the organ via the delivery fluid path; and A second flow control device configured to selectively prevent or allow fluid flow from the reservoir to the waste via the waste fluid path. 2. The perfusion device according to claim 1, wherein the perfusion circuit further comprises: A reservoir priming fluid path defined by the plurality of fluid conduits connects a priming port with the reservoir. 3. The perfusion device of claim 2, wherein the perfusion circuit further comprises: an organ perfusion fluid path defined by the plurality of fluid conduits, the organ perfusion fluid path connecting the perfusion port with the organ; A third flow control device configured to selectively prevent or allow fluid to flow out of the infusion port via at least one of the reservoir infusion fluid path and the organ infusion fluid path. 4. The perfusion device of claim 1, wherein the perfusion circuit further comprises: a pump head module positioned on the delivery fluid path for receiving the perfusate from the reservoir; a regulation module on the delivery fluid path for receiving the perfusate from the pump head module; A white blood cell filter located on the delivery fluid path is used for receiving perfusate from the regulation module; the first flow control device is arranged between the pump head module and the white blood cell filter. 5. The perfusion device of claim 4, wherein the perfusion circuit further comprises a second leukocyte filter; an alternate delivery fluid path further defined by the plurality of fluid conduits, the alternate delivery fluid path connecting the reservoir reservoir and the inlet via the second leukocyte filter; The perfusion device further includes a third flow control device configured to selectively prevent or allow fluid flow via the alternate delivery fluid path. 6. The perfusion device according to claim 1, further comprising: Organ stents; a drain located in the organ holder; An organ stent return fluid path further defined by the plurality of fluid conduits, the organ stent return fluid path connecting the drain and the reservoir. 7. The perfusion device of claim 6, wherein the plurality of fluid conduits further define an organ stent waste fluid path, the organ stent waste fluid path connecting the drain port and the waste fluid path. Liquid container; The perfusion apparatus further includes a third flow control device configured to selectively prevent or allow fluid flow through the organ stent waste fluid path. 8. The perfusion device according to claim 1, further comprising: a controller storing a plurality of operating states, each operating state determining the position of each flow control device, and configured to communicate with each of the flow control devices; a sensor configured to generate a measurement of a property of the perfusate; The controller is further configured to receive the measurement, automatically select one of the operating states based on the measurement, and control the flow control device based on the selected operating state. 9. The perfusion device of claim 8, further comprising an input device connected to the controller; The controller is further configured to receive a selected operating state from the input device and to control the flow control device based on the selected operating state. 10. The perfusion apparatus of claim 1, wherein the first flow control device and the second flow control device have a disabled state configured to allow fluid to pass through the waste fluid path Flow from the reservoir to the waste. 11. The perfusion apparatus of claim 1, wherein the plurality of fluid conduits further define an alternate return fluid path, the alternate return fluid path connecting the reservoir and the outlet; The perfusion circuit further comprises: a pressure control valve located in the return fluid path; and A third flow control device configured to selectively direct fluid flow through one of the return fluid path and the backup return fluid path. 12. The perfusion device of claim 1, further comprising: Disposable components, including: said entrance; said outlet; the fluid reservoir, the fluid waste, and the plurality of fluid conduits of the perfusion circuit; and Reusable components, including: a base configured to detachably support the disposable assembly in an operational state; said first flow control device; and said second flow control device; When the disposable assembly is supported by the base, the first flow control device and the second flow control device are respectively configured to selectively block or allow fluid to pass through the delivery fluid path and the waste fluid path flow. 13. The perfusion device of claim 12, wherein the base includes walls for supporting the disposable assembly; wherein the first flow control device and the second flow control device are supported by the reusable assembly for connection to the fluid conduit adjacent the wall. 14. The perfusion device of claim 12, wherein the disposable assembly further comprises a gas conduit connected to a gas inlet for connection to the organ; the reusable assembly further comprises a breathing machine; The disposable assembly and the reusable assembly include a matable mechanical interface configured to connect the ventilator to the gas conduit. 15. The perfusion device of claim 14, wherein the disposable assembly further comprises a pump head module positioned on the delivery fluid path for receiving the perfusate from the reservoir; The reusable assembly further includes a pump drive module for driving the pump head module; The pump driving module and the pump head module are connected and operated through the matable mechanical interface. 16. The perfusion device of claim 12, wherein the disposable assembly further comprises a conditioning module located on the delivery fluid path, the conditioning module comprising a heat exchanger and a gas exchanger; and The reusable components further include: a heater configured to deliver heated fluid to the heat exchanger; and A gas storage device configured to deliver gas to the gas exchanger.