Low fluid level detection device

Abstract

The portable housing for holding an organ or tissue for perfusion and transport includes a main chamber in which the organ or tissue and perfusion fluid may be placed, and also includes a secondary chamber (600) located within the main chamber. The volume of the secondary chamber is smaller than the volume of the main chamber, and the top of the secondary chamber is lower than the top of the main chamber. The secondary chamber may take the form of a standpipe, and is arranged such that the perfusion fluid exits the portable housing via an end of a tube located in the secondary chamber. During normal pumping conditions, the pumping removes perfusion fluid from the secondary chamber, and the secondary chamber is instantly refilled due to the wall of the standpipe being lower than the perfusion fluid level in the main chamber. During abnormal pumping conditions, such as a leak, the perfusion fluid level in the main chamber may drop below the wall of the standpipe, resulting in a reduction in the total amount of perfusion fluid in the standpipe. Thus, a large amount of air may be instantly drawn into the tube, which may cause an air alert and stop the perfusion. Thus, a preset amount of cold perfusion fluid is maintained in the main chamber, even during a leak.

Description

Technical Field

[0001] The present disclosure relates to devices and methods for storing, transporting, and / or perfusing one or more organs, tissues, etc., and monitoring, maintaining, and / or restoring the viability of those organs or tissues.

Background Art

[0002] The preservation of organs by machine perfusion using a perfusion fluid has been achieved at hypothermic temperatures, either with or without computer control. See, for example, Patent Document 1, Patent Document 2, Patent Document 3, Patent Document 4, Patent Document 5, and Patent Document 6. These are incorporated herein by reference. Hypothermic temperatures reduce the metabolism of the organ, lower the energy requirement, delay the depletion of high-energy phosphate storage and the accumulation of lactic acid, and prevent the morphological and functional decline associated with the interruption of blood supply.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Patent Document 8

Summary of the Invention

Problems to be Solved by the Invention

[0004] Certain types of mechanical perfusion devices achieve a low temperature for internal organs or tissues by cooling a reservoir of perfusion fluid that contacts the organ. By doing so, the cooled perfusion fluid reservoir can provide a backup function because it allows the device to be returned to static cold storage ("SCS") in the event of mechanical perfusion failure. However, if cold perfusion fluid leaks outside the container holding the organ, this SCS backup can also be damaged. Therefore, there is a need for a mechanical perfusion device that can more reliably ensure that SCS remains an executable backup option even in the event of leaks or similar failures.

Means for Solving the Problems

[0005] Accordingly, a portable housing for holding an organ or tissue for at least one of perfusion, storage, diagnosis, and transportation of the organ or tissue is disclosed herein. The portable housing can include a main chamber in which the organ or tissue and perfusion fluid for the organ or tissue can be disposed, and the portable housing can also include a secondary chamber that is within the main chamber and for holding perfusion fluid. The volume of the secondary chamber may be smaller than the volume of the main chamber, and the top of the secondary chamber may be lower than the top of the main chamber.

[0006] In combination with any of the above or below features, the volume of the main chamber can be 1.0 L to 2.0 L, and the volume of the secondary chamber can be 8 mL to 12 mL.

[0007] In combination with any of the above or below features, the top of the secondary chamber may be 1.3 inches to 2.1 inches lower than the top of the main chamber.

[0008] In combination with any of the above or below features, the secondary chamber can be disposed along the wall forming the main chamber.

[0009] Also disclosed is a device for holding an organ or tissue for at least one of perfusion, storage, diagnosis, and transportation of the organ or tissue. This device can include a portable housing having the above characteristics, and this device can also include a plurality of tubes for moving a perfusion fluid into and out of the portable housing. An end of a first tube among the plurality of tubes can be disposed within a secondary chamber.

[0010] In combination with any of the above or below characteristics, the device can be configured such that the perfusion fluid flows out of the portable housing via an end of the first tube that is at a fixed position within the secondary chamber.

[0011] In combination with any of the above or below characteristics, the device can include a pump for circulating the perfusion fluid to perfuse the organ or tissue, and the first tube provides an inlet to the pump for the perfusion fluid.

[0012] In combination with any of the above or below characteristics, the device can include a standpipe that forms a secondary chamber and includes a mounting portion for fixing the standpipe within the main chamber such that the position of the standpipe is controlled relative to the top of the main chamber.

[0013] In combination with any of the above or below characteristics, the mounting portion can include a hole through which the first tube protrudes before entering the secondary chamber.

[0014] In combination with any of the above or below features, the device can be configured to perfuse an organ or tissue with a perfusion fluid via a plurality of tubes and pumps, and during perfusion, the perfusion fluid flows from the main chamber to the secondary chamber and out of the portable housing via a first tube disposed within the secondary chamber. The device can further comprise a bubble detector configured to detect air in the perfusion fluid flowing out of the portable housing via an end of the first tube, and the device can be configured to stop perfusing the organ or tissue when the bubble detector detects air in the perfusion fluid flowing out of the portable housing via the end of the first tube.

[0015] In combination with any of the above or below features, the perfusion fluid can be cooled to a low temperature.

[0016] At least one method of perfusion, preservation, diagnosis, and transportation of an organ or tissue is also disclosed herein. The method can include placing the organ or tissue within the main chamber of the portable housing such that the perfusion fluid within the main chamber is higher than the top of the secondary chamber located within the main chamber, wherein the volume of the secondary chamber is smaller than the volume of the main chamber and the top of the secondary chamber is lower than the top of the main chamber. The method can further include perfusing the organ or tissue such that the perfusion fluid flows from the main chamber to the secondary chamber and the perfusion fluid flows out of the portable housing via the secondary chamber.

[0017] In combination with any of the above or below features, the perfusion fluid may flow out of the portable housing via a first tube of a plurality of tubes for moving the perfusion fluid into and out of the portable housing, and an end of the first tube is disposed within the secondary chamber.

[0018] In combination with any of the above or below features, the first tube can provide an inlet to a pump for circulating the perfusion fluid to perfuse the organ or tissue.

[0019] In combination with any of the above or below features, the method can further include stopping perfusion when an air bubble detector detects air in the perfusate flowing out of the portable housing via the first tube.

[0020] In combination with any of the above features, the method can further include stopping perfusion when the perfusate no longer exceeds the top of the secondary chamber.

[0021] These and other aspects of the present disclosure will be described with reference to the accompanying drawings and the following detailed description.

Brief Description of the Drawings

[0022]

Figure 1

Figure 2

Figure 3

Figure 4A

Figure 4B

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

BEST MODE FOR CARRYING OUT THE INVENTION

[0023] To generally understand the features of the present disclosure, reference is made to the drawings. In the drawings, like reference numerals are used throughout to indicate like elements.

[0024] In this specification, the invention is mainly described in connection with devices and methods involved in the transportation, storage, perfusion, and / or diagnosis of tissues and / or organs. However, the devices and methods of the present invention have many other applications, and thus, the various structures, devices, instruments, and methods of the present invention described herein should not be construed as being limited to a particular usage situation. The various features of the present disclosure are particularly suitable for use in connection with, and in combination with and / or related to, the features of the devices and methods disclosed in Patent Document 7 and Patent Document 8, and the entire disclosures of both of these are hereby incorporated by reference into this specification.

[0025] Figure 1 shows an external view of an organ transport and perfusion device 100. The device 100 can be sized and configured to perfuse a kidney, but perfusion of other organs, such as the liver, heart, and lungs, is also within the scope of the present invention. The device 100 can operate using a perfusate cooled to a low temperature that is passively maintained by an ice bath within the device. The device 100 can be designed to "carry" a kidney from a donor hospital to a recipient hospital while maintaining the viability of the donor kidney. During transport, the device 100, and thus the donor kidney, can be protected from changes in environmental conditions, such as temperature changes, and thus the device can ensure that the ambient environment around the perfused kidney remains stable. As previously explained, the fact that the kidney can also be immersed in the cooled perfusate during transport and perfusion ensures an optimal state.

[0026] More specifically, the device 100 of FIG. 1 can have a stable base that facilitates an upright posture and a handle 110 for carrying the device. The device 100 can also be equipped with shoulder straps and / or wheels to assist in transporting the device, and for example, a control panel 120 can be provided outside the device. The control panel 120 can display information such as, but not limited to, injection pressure, attachment of the tube frame (described later), power on / off, error or fault status, flow rate, flow resistance, injection temperature, bath temperature, pumping time, battery charge status, temperature profile (maximum and minimum values), opening and closing of the cover, history log or graph, and details and messages of additional status, and some or all of these can preferably be further transmitted to a remote location for data storage and / or analysis. Flow rate and pressure sensors or transducers within the device 100 can also be provided to calculate various organ characteristics such as the pump pressure and vascular resistance of the organ, store these in a computer memory, for example, enable analysis of the vascular resistance history, detect malfunctions of the device such as pressure increases, and display corresponding alerts or error status.

[0027] The device 100 can also have a latch 130 that requires a positive user action to open, thereby avoiding the possibility of the device 100 accidentally opening during transportation. The latch 130 can hold the top or cover 140 in a predetermined position. The top or cover 140 or a part thereof may be constructed of an optically transparent material to allow observation of the cassette (described below) and the organ perfusion state. The device 100 may be configured to include a cover opening detector that monitors whether the top or cover 140 is open or closed and displays it on the control panel 120. The device 100 may also be configured to have insulating exteriors of various thicknesses so that the user can configure or select an appropriate device 100 to change the range and distance of transportation. A compartment 150 may be provided and configured to hold patient and organ data such as charts, examination supplies, additional batteries, portable computing devices, etc., and / or to include means for displaying UNOS labels and / or identification and return information.

[0028] Figure 2 shows a cross-sectional view of apparatus 100 including cassette 65 and pump 210. Cassette 65 is preferably installable in or removable from apparatus 100 without removing the tubing set (described below) from cassette 65, thereby maintaining the sterility of the organs or tissues within the cassette. Sensors within apparatus 100 can detect the presence of cassette 65 within the apparatus and, depending on the sensor, can read the identification of the organs from a barcode or radio frequency, such as an RFID chip, or other "smart" tag attachable to or integrated with cassette 65. This enables automatic identification and tracking of the organs or tissues within cassette 65 and can be useful for monitoring and controlling the chain of custody. Adding a global positioning system integratable with cellular radio technologies, such as GSM, CDMA, or equivalents, to apparatus 100 and / or cassette 65 can facilitate global tracking and monitoring of the transporter and the internal organs, for example, via the Internet. Apparatus 100 can be interfacable to a computer network during transport by a hardwired connection to a local area network or by wireless communication. This interface can enable real-time tracking and display of data such as perfusion parameters, vascular resistance, and organ identification as well as the position of the transporter and cassette, or acquisition for future analysis.

[0029] The apparatus 100 also includes a filter 220 that removes precipitates and other particulate matter (preferably in the size range of 0.05 to 15 microns or more in diameter) from the perfusion fluid, thereby preventing clogging of the device or organ. The apparatus 100 can preferably also include a battery 230, which can be placed at the bottom of the device, under the pump 210, or any other location, but a location that is easily accessible for replacing the battery 230 is preferred. The battery 230 is preferably rechargeable outside or within the apparatus 100 and / or hot swappable one at a time. The battery 230 is preferably rapidly rechargeable without being fully discharged. The apparatus 100 can also provide additional storage space 240, for example, at the bottom of the device for a power cord, battery, and other accessories. Also, the apparatus 100 may include a power port for DC connection and / or AC connection to a vehicle such as an automobile or an airplane.

[0030] As shown in FIG. 2 and described in more detail below, the cassette wall CW is preferably configured to mate with the corresponding configuration of the device inner wall TW to maximize contact and thus heat transfer therebetween.

[0031] Figure 3 shows another cross-sectional view of the apparatus 100. In Figure 3, the apparatus 100 can have an outer enclosure 310 constructed of, for example, metal or preferably plastic or synthetic resin having sufficient strength to withstand penetration and impact. The apparatus 100 can include an insulator 320, preferably a thermal insulator made of, for example, glass wool or expanded polystyrene. The insulator 320 can be of various thicknesses in the range of 0.5 inches to 5 inches or more, preferably 1 to 3 inches, and even more preferably about 2 inches thick. The apparatus 100 can be cooled by a coolant 325, which can be, for example, an ice water bath or cryogenic material. When a cryogenic material is used, it may be designed to prevent freezing of the organ. When an ice water bath is used, the mixture of ice and water is preferably an initial mixture of about 1 to 1, although alternatively, the ice water bath may initially be a frozen solid. The apparatus 100 can be configured to hold various amounts of coolant, preferably up to 10 to 12 liters maximum. The ice water bath is inexpensive and may be preferred because generally the organ does not get as cold as to freeze. The coolant 325 preferably lasts for at least 6 to 12 hours, and more preferably at least 30 to 50 hours without replacement of the coolant. The level of the coolant 325 can be viewed, for example, through a transparent region of the apparatus 100 or automatically detected and monitored by a sensor. The coolant 325 is preferably exchangeable without stopping perfusion or removing the cassette 65 from the apparatus 100 and is preferably maintained within a watertight compartment 315 of the apparatus. For example, a transporter inner wall TW as shown in Figure 2 can be interposed between the coolant 325 of the device of Figure 3 and the cassette wall CW. The compartment 315 preferably prevents loss of the coolant 325 when the apparatus 100 is tilted or inverted. In use, heat can be conducted from the wall of the cassette 65 or the perfusion fluid reservoir therein to the coolant 325 to control the temperature within a desired range.Also, as described above, in the event of perfusion fluid loss due to power loss, electrical or computer failure, or leakage within the tubes of cassette 65, the coolant 325 can constitute a fail-safe cooling mechanism since apparatus 100 can automatically return to static refrigerated storage. Apparatus 100 can also be configured to include a heater for raising the temperature of the perfusion fluid.

[0032] Apparatus 100 can be powered by a battery such as battery 230 shown in FIG. 2, or by power supplied through plug 330. An electronic module 335 can also be provided within the apparatus. This electronic module 335, which can include a processor, a CPU, and / or memory such as RAM, ROM, etc., can control pump 210, various sensors, etc. that enable perfusion of the organ or tissue 350 within cassette 65 by the perfusion fluid, and control panel 120. The electronic module 335 can be cooled by ventilation air convection 370 and further by a fan. Preferably, the electronic module 335 can be disposed separately from the perfusion tube described below so as to prevent the electronic module from getting wet by the perfusion fluid and to avoid external heat being added from the electronic module to the perfusion fluid within the tube. As will be described later, pump 210 of the apparatus can deliver perfusion fluid 340 to organ or tissue 350 by supplying pressure to perfusion tube 460 of the tube set. Also, apparatus 100 and cassette 65 can accommodate various amounts of perfusion fluid 340, for example, up to 3 - 5 liters maximum. Preferably, about 1 liter of low-temperature perfusion fluid 340 is used to perfuse organ or tissue 350.

[0033] The cassette 65 and the device 100 are preferably constructed to fit or mate so as to enable efficient heat transfer. Preferably, the device 100 can include a compartment 215 for receiving the cassette and holding a coolant therein. The device 100 preferably relies on conduction to transfer heat from the cassette 65 to the coolant contained in the compartment 215. By this heat transfer, the device 100 can maintain the perfusate at a desired temperature. The geometric elements of the cassette 65 and the device 100 are preferably configured such that when the cassette 65 is disposed within the device 100, the contact area between the cassette 65 and the device 100 is as large as possible and they are fixed for transportation.

[0034] Figures 4A and 4B show an example of this geometry between the cassette 65 and the compartment 215 containing the coolant. The geometric shape of the interface between the cassette 65 and the compartment 215 is preferably designed such that the cassette 65 is pushed into the cavity formed by the compartment 215. Thus, the angles of the side walls are substantially the same, and thus all the side walls of the cassette 65 contact the side walls of the compartment 215 regardless of the shape of the cassette side or compartment side, such as flat or curved. By having substantially the same included angle, the surfaces of the cassette and the compartment 215 can contact even when affected by thermal expansion and contraction of the walls and mechanical tolerances.

[0035] The height of the cassette 65 above the compartment 215 is determined by the mating surface between the cassette 65 and the compartment 215. As shown in Figure 4B, the bottom of the cassette need not rest on the bottom of the compartment 215, but may do so in embodiments where the shape of the cassette 65 and the shape of the compartment 215 allow it. It will be understood that the shapes of the cassette 65 and the compartment 215 can be any shape that allows maximizing the contact between them, and thus maximizing the heat transfer between them, such as a frustum of a cone.

[0036] As described above, heat is conducted from the walls of the cassette 65 to the coolant within the compartment 215, thereby enabling control within a desired temperature range. The coolant can also provide a fail-safe cooling mechanism since in the event of a power outage, an electrical or computer failure, or a leakage of the perfusion fluid from the cassette tube, the apparatus 100 may automatically return to refrigerated storage. The apparatus 100 may also be configured to include a heater for raising the temperature of the perfusion fluid.

[0037] FIG. 5 shows a tube frame 400 that can be used to hold the aforementioned tube set. The tube frame 400 can be formed of a lightweight yet durable material, such as plastic, to facilitate carrying. The tube frame 400 can also be designed to hold the tubes of the tube set in desired positions. By disposing the tubes in predetermined positions, the installation and connection of apparatuses such as the cassette 65 shown in FIG. 6 are facilitated. Further, it is preferable that the cassette 65 and the tube frame 400 can be fitted to the apparatus 100.

[0038] When the tube frame 400 is fitted to the cassette 65, the tube set may already be connected to the cassette 65. For example, the tube 470 may provide an inlet to the pump 210 for the perfusion fluid stored within the cassette 65. The perfusion fluid may move through the tube 490, return from the outlet 480, and then pass through a filter that may be disposed, for example, inside or outside the cassette 65, such as beneath the cassette 65. After passing through the filter, the perfusion fluid moves to the tube 440 and then into the bubble trap 410. Providing the tube frame 400 with a sample port 495 enables liquid to be withdrawn from or injected into the tube 440. The perfusion fluid moves into the bubble trap 410 within the tube 440 and can then flow out of the bubble trap of the tube 460, thereby transporting the perfusion fluid into the cassette 65 to, for example, inject into and / or wash an organ or tissue within the cassette 65. The tube 450 can directly transport the liquid or gas exiting the bubble trap 410 into the cassette 65 and thus can bypass injection into the organ or tissue, although optionally it can wash the organ or tissue.

[0039] It will be appreciated that the tube frame 400 may hold other devices in addition to the tubes. For example, the tube frame 400 can hold a pressure sensor 420 that is used to control the bubble trap device 410 and the pump 210. It should also be understood that the tube frame 400 and the tube set can be connected to various devices such as the organ perfusion device 100 or an organ diagnostic device, as well as cassettes and / or transport devices.

[0040] The tube frame 400 is preferably attachable to a part of the device 100. For this purpose, the tube frame 400 can be connected to the device 100 and other devices by means of a snap 430 or other structures that securely fix the tube frame to the device. By providing sensors within the device 100, such as mechanical sensors or electrical sensors, the presence of the tube frame 400 within the device 100 can be detected. If the tube frame 400 is not properly attached to the device 100, the sensor may be configured to send an appropriate warning message to the control panel 120 to notify the user of the problem. If no measures are taken to properly attach the tube frame 400 within a predetermined time set automatically or programmed by the user, the device 100 may be programmed to prevent the start of perfusion. It should be understood that if perfusion starts and the tube frame 400 is not properly set, the device 100 can be programmed to stop the perfusion.

[0041] Another beneficial feature of the tube frame 400 is that it forms a stationary surface for tubes 450 and 460. These tubes can be used to directly route the perfusion fluid to an organ or tissue, or to bypass the organ and route it into the reservoir of the perfusion fluid within the cassette 65. It is desirable to place the tubes 450 and 460 in relatively fixed positions so that routing can be achieved by pinching the tubes to prevent the perfusion fluid from passing through. The tubes can be pinched, for example, by a solenoid (not shown) disposed on the device 100 that drives a blade that pinches the tube 450 and / or the tube 460 against the tube frame 400.

[0042] Figure 7 shows a simplified method of operating the apparatus 100. During the routine setup of the apparatus, by first priming the pump 210 with cooled perfusion fluid, all air can be removed from the perfusion circuit, including the tube set held by the tube frame 400. This can be done by a pre-programmed wash mode 510 followed by a prime mode 520 in the perfusion tube circuit of the apparatus. Sensors within the apparatus 100 can ensure that acceptable low-temperature conditions are met before inserting the cannula into the donor kidney (or other organ or tissue) via its renal artery (or other blood vessel depending on the type of organ or tissue) at step 530. The height of the perfusion fluid in the cassette 65 can depend on various factors such as the amount of perfusion fluid added to the cassette by the clinician and the volume of the organ within the cassette. Once the cannula is inserted into the kidney, a perfusion mode 540 can be initiated in which the perfusion fluid is pumped into the kidney or other organ or tissue. The perfusion during step 540 can occur over an extended period of time, and the apparatus 100 may be transported from one location to another during this time. Typically, during step 540, there are no functional problems with respect to performance over a range of perfusion flow rates and renal pressures, and as a result, the viability of the renal function prior to transplantation is improved. The clinician and technician can monitor some important variables such as renal pressure and the flow rate of the perfusion fluid, which are indicators of organ viability during step 540, and based on these and other variables, determine when to stop pumping the perfusion fluid by the pump 210 before proceeding with the surgical transplantation of the organ at step 550.

[0043] Under normal conditions during perfusion mode 540, there may be a problem where the sensors of device 100 detect small, incorrect air bubbles "in the line" of the perfusion tube circuit. An example of such a sensor is the air / bubble detector 485 shown in FIG. 5. As shown in that figure, the detector 485 may include a U-shaped channel, and within this U-shaped channel, a tube such as tube 440 or tube 460, for example, is arranged such that the wall of the tube fits tightly into the U-shaped channel. The detector 485 may be an ultrasonic sensor that is ultrasonically coupled by the tight fit of the tube within the U-shaped channel and the resulting compression. This arrangement eliminates the need for the detector 485 to interface with the interior of the perfusion fluid within the tube or the flow path in order to perform air / bubble detection. Thus, the detector 485 can perform its function without compromising the sterility of the perfusion fluid.

[0044] If the detector 485 detects air or bubbles, for example, due to an instantaneous density change in the perfusion fluid, the device can be programmed to automatically react to eliminate the risk of bubbles being injected into the renal artery of the kidney. For example, the device 100 can stop pumping the perfusion fluid by the pump 210 and then open a valve, such as a solenoid blade valve, to expel air from the system. If the air is automatically removed, the device 100 may be programmed to resume pumping the perfusion fluid by the pump 210 without intervention by the operator or clinician. As previously explained, if for some reason, such as a power outage or a leak in the cassette tubing, the device stops perfusion for an extended period, the device can enter a static cold storage ("SCS") mode, during which the kidney or other organ or tissue is maintained at a low temperature. During this time, the organ remains in fluid contact surrounded by the cold perfusion fluid within the cassette 65, thereby maintaining its low temperature and thus its viability. This situation is no worse than the conventional method of storing donor organs "on ice" for a short period, and if the low temperature is maintained, it does not prevent the organ from being transplanted into the recipient.

[0045] However, during the perfusion mode 540, if leakage of the perfusion fluid occurs within the perfusion circuit tube including the tube set of the tube frame 400, the kidney or other organs or tissues may lose protection from the cold perfusion fluid and the temperature may conversely increase. There is a possibility that the clinician may not notice this event, and even if only a short period of time has passed, the organ may be lost because the organ may warm up beyond the low temperature state. Also, during transportation that may last for several hours, there may be no monitoring by the clinician, so a failure such as leakage within the tube set may cause a fatal failure and damage the kidney or other organs or tissues. And during transportation, it is unlikely that the clinician can intervene to ensure that the donor organ remains within the SCS low temperature state, for example, stop the pumping of the pump 210 or add more perfusion fluid to the cassette 65.

[0046] Accordingly, as shown in FIG. 8 of the present application, the cassette 65 can include a low fluid level detection device or a standpipe 600 therein. The standpipe 600 can be a transparent, integral, injection-molded plastic part and there is a certain negative pressure during pumping by the pump 210. Thus, the perfusion fluid can be drawn out of the cassette 65 and into the tubing set and ultimately into a cannula that can be attached to the renal artery of the kidney. It can be disposed within the flow path of the cassette 65 near the tube 470. The standpipe 600 can have a constant vertical height relative to the height of the cassette 65 and can divide the interior of the cassette 65 into a secondary chamber 610 formed by the walls of the standpipe and a larger main chamber 66 constituted by the walls of the cassette 65. The standpipe 600 can be disposed along the wall of the cassette 65 and positioned such that the end of the tube 470 is disposed within the secondary chamber 610 of the standpipe. The end of the tube 470 can be positioned such that the opening of the tube is disposed as close as possible to the bottom of the secondary chamber 610 formed by the standpipe 600. Thereby, optimal performance can be ensured if leakage occurs within the tube. On the other hand, if the opening at the end of the tube 470 is higher relative to the bottom of the secondary chamber 610, the response can be faster and the time until pumping by the pump 210 is stopped can be shorter.

[0047] Figures 9 - 11 show the standpipe 600 in more detail. The standpipe can be constituted by a rear wall 612, a shorter front wall 614, and side walls 616 and 618. The standpipe can generally be divided into a lower part where the walls 612, 614, 616, and 618 form the secondary chamber 610, and an upper attachment part 650 by which the standpipe 600 can be fixed to the cassette 65. For example, the standpipe 600 can be fixed to the attachment part 650 by a tube 470 passing through a hole 655 in the rear wall 612. The width 620 of the standpipe 600 can be equal to or about 0.95 inches. The height 630 of the rear wall 612 of the standpipe 630 can be equal to or about 4.9 inches. The height 640 of the walls 614, 616, and 618 forming the secondary chamber 610, and thus the height of the secondary chamber 610, can be equal to or about 2.6 inches. As best shown in FIG. 10, the side walls 616 and 618 can project outward from the bottom of the standpipe 600 to a height 640. Thus, the depth 670 of the standpipe 600 at its bottom can be equal to or about 0.37, and the depth 660 of the standpipe 600 at the height 640 can be equal to or about 0.65 inches. The dimensions of the standpipe 600 can be selected such that the volume of the secondary chamber 610 is as small as possible relative to the volume of the main chamber. Thereby, for example, the amount of perfusion fluid lost in the event of a leak occurring within the tube outside the cassette 65 can be reduced. Also, the described dimensions and shape of the standpipe 600 may be preferred in order to enable the standpipe 600 to be formed by injection molding.

[0048] The relative volumes of the main chamber 66 and the secondary chamber 610 are very important for the safety performance functions described herein. To that end, the volume of the secondary chamber 610 can be between 8 mL and 12 mL, more preferably between 10 mL and 11 mL, and even more preferably equal to or about 10 mL, and the volume of the main chamber 66 can be between 1.0 L and 2.0 L, more preferably equal to or about 1.0 L. During use, the volume of the perfusion fluid in the main chamber 66 may be less than the volume of the main chamber 66. For example, the volume of the perfusion fluid can range from about 1.0 L to about 1.5 L. As schematically shown in FIGS. 13 and 14, the relative height of the cassette 65 and the standpipe 600 is similarly very important. To that end, distance 680 indicates the distance between the top 67 of the cassette 65 and the tops of the walls 614, 616, and 618 that form the secondary chamber 610. As used herein, "the top of the secondary chamber" as recited in the claims of the present application may refer to the tops of the walls 614, 616, and 618. This distance 680 can be between 1.3 inches and 2.1 inches, more preferably between 1.7 inches and 1.9 inches. This distance 680 positions the standpipe 600 in a fixed position locked relative to the height of the perfusion fluid in the main chamber 66.

[0049] FIG. 12 shows the steps of perfusion using the cassette 65 with the standpipe 600. During normal pumping state 810, the perfusion fluid level 700 in the cassette 65 can be above the walls 614, 616, and 618 of the standpipe 600, as shown in FIG. 13. This ensures that the secondary chamber 610 of the standpipe 600 is also filled with perfusion fluid. Thus, perfusion fluid can be removed from the secondary chamber 610 by pumping by the pump 210, but since the walls 614, 616, and 618 of the standpipe 600 are lower than the perfusion fluid level 700 in the cassette 65, the perfusion fluid is immediately refilled. As a result, when the perfusion fluid in the cassette 65 remains at its normal operating volume, the secondary chamber 610 remains filled even between high and low pressures and the resulting high and low pumping flow rates.

[0050] However, during an abnormal pumping state 820, such as leakage occurring somewhere in the perfusion circuit flow path tube outside the cassette 65, e.g., at the tube frame 400 or the filter circuit portion, the perfusion fluid in the cassette 65 may drop to a level 710 below the heights of the walls 614, 616, and 618, as shown in FIG. 14. Since the volume of the secondary chamber 610 is very small relative to the volume of the main chamber 66, when this occurs, while the perfusion fluid level in the main chamber remains at level 710, the amount of perfusion fluid in the secondary chamber may rapidly further decrease due to the pumping of the pump 210. Also, once the perfusion fluid is properly removed from the secondary chamber 610 and reaches a level 720 below the end of the tube 470, the secondary chamber 610 is in a fixed and locked position relative to the fluid height in the cassette 65 and thus cannot be refilled. Therefore, a large amount of air may be rapidly drawn into the tube 470, which may trigger an air alarm by the air / bubble detector 485 and cause the pump 210 to stop pumping. Since the perfusion fluid is cooled to a low temperature, in step 830, the device enters static refrigerated storage, which can be maintained until transplantation. Thus, even if perfusion fluid leaks outside the cassette 65, a preset amount of cold perfusion fluid can be maintained within the cassette 65, ensuring that the donor kidney or other organ or tissue remains in contact with the cold perfusion fluid in a cold state.

[0051] Accordingly, the standpipe 600 described herein can be completely passive in operation, does not require mechanical or electrical sensors, does not require additional software to operate and execute its function, and does not require intervention by a technician or clinician. As a result, the kidney or other tissue remains in a low temperature state, which is the baseline required to ensure that no damage occurs if leakage of the perfusate occurs. In fact, at simulated leakage rates exceeding 300 mL / hour, which is considered the maximum leakage rate for the worst-case scenario expected in the clinical setting, the level of the perfusate in the cassette 65 quickly drops below the tops of the walls 614, 616, and 618 of the standpipe 600, and as a result, air enters the tube 470. Depending on the magnitude of the leak and the flow rate and height of the perfusate in the cassette 65, it may take from seconds to minutes or longer for the level of the perfusate in the cassette 65 to drop below the upper wall of the standpipe. As described above, when air is detected by the system air bubble detector 485, the pump 210 immediately stops pumping to ensure that sufficient perfusate remains in the cassette 65 in contact with the kidney. Further tests at controlled simulated leakage rates have shown that the standpipe 600 rapidly allows air to flow into the tube 470 during a low renal pressure of 10 mmHg controlled by the pump 210, which is equivalent to a relatively low flow rate of the perfusate in the renal artery, resulting in the pump 210 stopping. Next, even at a high renal pressure of 65 mmHg controlled by the pump 210, which is equivalent to a relatively high flow rate in the renal artery, the device 100 rapidly stops the pump 210. Accordingly, in all performance scenarios of high and low renal pressures and high and low flow rates, it has been verified that the device 100 has entered the fail-safe SCS mode as a result of the "irreversible disorder state" caused by the loss of the perfusate. For comparison, if a leak occurs without the standpipe 600, the cold perfusate is depleted from the entire cassette 65, resulting in an increase in the temperature of the kidney or other organ or tissue.

[0052] Although the present invention has been described in connection with its specific embodiments, it will be apparent to those skilled in the art that many alternatives, modifications, and variations are possible. For example, although the present invention has been mainly described in connection with the perfusion of the kidneys, other organs and tissues such as the heart, liver, and lungs are also included within the scope of the present invention. Further, modifications to the present invention include using hydrophobic membranes incorporated into T-joints or molded joints with venturi restrictors, which can be more complex, may have higher implementation costs, and may be more difficult to manufacture to maintain performance quality. Accordingly, the embodiments of the present invention described herein are intended to be illustrative and not limiting. Various changes can be made without departing from the spirit and scope of the present invention.

Claims

1. A device for holding an organ or tissue for at least one of perfusion, storage, diagnosis, and transportation of the organ or tissue, the device including a portable housing, wherein the portable housing, a main chamber in which the organ or tissue and a perfusion fluid for the organ or tissue can be disposed, a secondary chamber within the main chamber for holding the perfusion fluid, the volume of the secondary chamber being smaller than the volume of the main chamber and the top of the secondary chamber being lower than the top of the main chamber, at least one tube for moving the perfusion fluid into and out of the portable housing, an end of a first tube of the at least one tube being disposed within the secondary chamber and the perfusion fluid flowing out of the portable housing via the end of the first tube, a pump for circulating the perfusion fluid from the first tube to perfuse the organ or tissue, a bubble detector configured to detect air in the perfusion fluid flowing out of the portable housing via the end of the first tube, and including, when the level of the perfusion fluid in the secondary chamber drops below the end of the first tube and the bubble detector detects air in the perfusion fluid, the device is configured to stop the perfusion of the organ or tissue, and a preset amount of the perfusion fluid is maintained within the main chamber to keep the organ or tissue in contact with the perfusion fluid, the device.

2. the volume of the main chamber is 1.0 L to 2.0 L, the volume of the secondary chamber is 8 mL to 12 mL, The device according to claim 1.

3. The top of the secondary chamber is 3.3 cm to 5.3 cm lower than the top of the main chamber. The device according to claim 2.

4. The secondary chamber is disposed along a wall forming the main chamber. The device according to claim 1.

5. The end of the first tube is at a fixed position within the secondary chamber. The device according to claim 1.

6. The first tube provides an inlet to the pump for the perfusion fluid, The device according to claim 1.

7. The apparatus according to claim 1, further comprising a standpipe, wherein an attachment portion is included to form the secondary chamber and fix the standpipe within the main chamber such that the position of the standpipe is controlled relative to the top of the main chamber.

8. The apparatus according to claim 7, wherein the attachment portion has a hole through which the first tube protrudes before entering the secondary chamber.

9. During the perfusion, the perfusion fluid flows from the main chamber into the secondary chamber and out of the portable housing via the first tube disposed within the secondary chamber. The apparatus according to claim 1.

10. The apparatus according to claim 1, wherein the perfusion fluid is cooled to a low temperature.

11. A method for at least one of perfusion, preservation, diagnosis, and transportation of an organ or tissue, comprising: placing the organ or tissue within the main chamber of the portable housing such that the perfusion fluid within the main chamber is higher than the top of a secondary chamber located within the main chamber, wherein the volume of the secondary chamber is smaller than the volume of the main chamber and the top of the secondary chamber is lower than the top of the main chamber; performing perfusion of the organ or tissue such that the perfusion fluid flows from the main chamber into the secondary chamber and out of the portable housing via an end of a first tube of at least one tube for moving the perfusion fluid within and out of the portable housing, through the first tube disposed within the secondary chamber; when the level of the perfusion fluid in the secondary chamber drops below the end of the first tube and an air bubble detector detects air in the perfusion fluid flowing out of the portable housing via the first tube, stopping the perfusion and maintaining a preset amount of the perfusion fluid within the main chamber while keeping the organ or tissue in contact with the perfusion fluid; The method includes.

12. The method according to claim 11, wherein the first tube provides an inlet to a pump for circulating the perfusion fluid to perfuse the organ or tissue.

13. The method according to claim 11, wherein the perfusion is stopped when the perfusion fluid no longer exceeds the top of the secondary chamber.

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