Abstract:
An organ perfusion apparatus and method monitor, sustain and/or restore viability of organs and preserve organs for storage and/or transport. Other apparatus include an organ transporter, an organ cassette and an organ diagnostic device. The apparatus and methods include the cassette and transporter with heat transfer surfaces arranged to transfer heat between a cooling source in said transporter and the heat transfer surfaces of the cassette.

Description:
[0001]    This is a Continuation of application Ser. No. 10/815,853 filed Apr. 2, 2004, which claims the benefit of U.S. Provisional Application No. 60/459,986 filed Apr. 4, 2003. The disclosure of the prior applications is hereby incorporated by reference herein in its entirety. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    The invention relates to apparatus and methods for perfusing one or more organs, tissues or the like (hereinafter generally referred to as organs) to monitor, sustain and/or restore viability of the organs. This invention further relates to allowing effective heat transfer to or from the contents of a portable cassette. 
         [0003]    Preservation of organs by machine perfusion has been accomplished at hypothermic temperatures with or without computer control with crystalloid perfusates and without oxygenation. See, for example, U.S. Pat. Nos. 5,149,321, 5,395,314, 5,584,804, 5,709,654, 5,752,929 and 5,827,222 to Klatz et al., which are hereby incorporated by reference. Hypothermic temperatures provide a decrease in organ metabolism, lower energy requirements, delay depletion of high energy phosphate reserves and accumulation of lactic acid and retard morphological and functional deterioration associated with disruption of blood supply. 
         [0004]    Ideally organs would be procured in a manner that limits their warm ischemia time to essentially zero. Unfortunately, in reality, many organs, especially from non-beating heart donors, are procured after extended warm ischemia time periods (i.e., 45 minutes or more). The machine perfusion of these organs at low temperature has demonstrated significant improvement (Transpl Int 1996 Daemen). Further, prior art teaches that the low temperature machine perfusion of organs is preferred at low pressures (Transpl. Int 1996 Yland) with roller or diaphragm pumps delivering the perfusate at a controlled pressure. Numerous control circuits and pumping configurations have been utilized to achieve this objective and to machine perfuse organs in general. See, for example, U.S. Pat. Nos. 5,338,662 and 5,494,822 to Sadri; U.S. Pat. No. 4,745,759 to Bauer et al.; U.S. Pat. Nos. 5,217,860 and 5,472,876 to Fahy et al.; U.S. Pat. No. 5,051,352 to Martindale et al.; U.S. Pat. No. 3,995,444 to Clark et al.; U.S. Pat. No. 4,629,686 to Gruenberg; U.S. Pat. Nos. 3,738,914 and 3,892,628 to Thorne et al.; U.S. Pat. Nos. 5,285,657 and 5,476,763 to Bacchi et al.; U.S. Pat. No. 5,157,930 to McGhee et al.; and U.S. Pat. No. 5,141,847 to Sugimachi et al. 
         [0005]    WO 88/05261 to Owen discloses an organ perfusion system including an organ chamber that is supplied with an emulsion fluid or physiological electrolyte that is transported through a perfusion system. The chamber contains a synthetic sac to hold the organ. Perfusate enters the organ through a catheter inserted into an artery. The perfusate is provided by two independent fluid sources, each of which includes two reservoirs. 
       SUMMARY OF THE INVENTION 
       [0006]    The present invention focuses on avoiding damage to an organ during perfusion while monitoring, sustaining and/or restoring the viability of the organ and preserving the organ for storage and/or transport. The invention is directed to apparatus and methods for perfusing an organ to monitor, sustain and/or restore the viability of the organ and/or for transporting and/or storing the organ. 
         [0007]    In perfusion, gross organ perfusion pressure may be provided by a pneumatically pressurized medical fluid reservoir controlled in response to a sensor disposed in an end of tubing placed in the organ, which may be used in combination with a stepping motor/cam valve or pinch valve which provides for perfusion pressure fine tuning, prevents over pressurization and/or provides emergency flow cut-off. Alternatively, the organ may be perfused directly from a pump, such as a roller pump or a peristaltic pump, with proper pump control and/or sufficiently fail-safe controllers to prevent over pressurization of the organ, especially as a result of a system malfunction. Substantially eliminating over pressurization prevents and/or reduces damage to the vascular endothelial lining and to the organ tissue in general. 
         [0008]    Apparatus of the invention may be used for various organs, such as the kidneys, and may be adapted to more complex organs, such as the liver, having multiple vasculature structures, for example, the hepatic and portal vasculatures of the liver. 
         [0009]    An organ diagnostic apparatus may also be provided to produce diagnostic data such as an organ viability index. The organ diagnostic apparatus includes features of an organ perfusion apparatus, such as sensors and temperature controllers, as well as cassette interface features, and provides analysis of input and output fluids in a perfusion system. Typically, the organ diagnostic apparatus is a simplified perfusion apparatus providing diagnostic data in a single pass, in-line perfusion. 
         [0010]    Embodiments of the invention also provide an organ cassette which allows an organ to be easily and safely moved between apparatus for perfusing, storing, analyzing and/or transporting the organ. The organ cassette may be configured to provide uninterrupted sterile conditions and efficient heat transfer during transport, recovery, analysis and storage, including transition between the transporter, perfusion apparatus and organ diagnostic apparatus, and/or other apparatus. 
         [0011]    Embodiments of this invention also provide an organ transporter which allows for transportation of an organ, particularly over long distances. The organ transporter may include features of an organ perfusion apparatus, such as sensors and temperature controllers, as well as cassette interface features. 
         [0012]    Embodiments of this invention provide a cooling source in the transporter. 
         [0013]    Embodiments of this invention provide the cassette and a compartment of the transporter with one or more heat transfer surfaces which contact and allow effective heat transfer to or from the contents of the cassette. 
         [0014]    Embodiments of this invention provide the cassette and the compartment of the transporter with substantially complementary mating configurations. 
         [0015]    Embodiments of this invention provide for planar and non-planar heat transferring surfaces. 
         [0016]    These and other features and advantages of this invention are described in, or are apparent from, the following detailed description of various exemplary embodiments of systems and methods according to this invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0017]    The above and other aspects and advantages of the invention will become apparent from the following detailed description of embodiments when taken in conjunction with the accompanying drawings, in which: 
           [0018]      FIG. 1  is an organ perfusion apparatus according to the invention; 
           [0019]      FIG. 2  is a schematic diagram of an apparatus of  FIG. 1 ; 
           [0020]      FIG. 3  is a diagram of the electronics of the apparatus of  FIG. 2 ; 
           [0021]      FIGS. 4A-4D  show perspective views of various embodiments of an organ cassette according to the invention; 
           [0022]      FIG. 5  is a schematic diagram of an organ perfusion apparatus configured to simultaneously perfuse multiple organs; 
           [0023]      FIGS. 6A and 6B  show an embodiment of an organ cassette of the present invention; 
           [0024]      FIG. 7  shows an exterior perspective view of an organ transporter according to the present invention; 
           [0025]      FIG. 8  shows a cross section view of an organ transporter of  FIG. 7 ; 
           [0026]      FIG. 9  shows an alternative cross-section view of an organ transporter of  FIG. 7 ; 
           [0027]      FIG. 10  shows the mating of a cassette with a compartment according to the present invention; 
           [0028]      FIG. 11  shows a tube frame with a tube set according to the present invention; and 
           [0029]      FIG. 12  shows a tube frame connected to a cassette according to the present invention. 
       
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0030]    For a general understanding of the features of the invention, reference is made to the drawings. In the drawings, like reference numerals have been used throughout to designate like elements. 
         [0031]    The invention is described herein largely in the context of apparatus and methods involved in transport, storage, perfusion and diagnosis of tissues and organs. However, the inventive apparatus and methods have many other applications, and thus the various inventive structures, devices, apparatus and methods described herein should not be construed to be limited to, particular contexts of use. Various features of the disclosed invention are particularly suitable for use in the context of, and in conjunction and/or connection with the features of the apparatus and methods disclosed in U.S. patent application Ser. No. 09/645,525, the entire disclosure of which is hereby incorporated by reference herein. 
         [0032]      FIG. 1  shows an organ perfusion apparatus  1  according to the invention.  FIG. 2  is a schematic illustration of the apparatus of  FIG. 1 . The apparatus  1  is preferably at least partially microprocessor controlled, and pneumatically actuated. A microprocessor  150  connection to the sensors, valves, thermoelectric units and pumps of the apparatus  1  is schematically shown in  FIG. 3 . Microprocessor  150  and apparatus  1  may be configured to and are preferably capable of further being connected to a computer network to provide data sharing, for example across a local area network or across the Internet. 
         [0033]    The organ perfusion apparatus  1  is preferably capable of perfusing one or more organs simultaneously, at both normothermic and hypothermic temperatures (hereinafter, normothermic and hypothermic perfusion modes). All medical fluid contact surfaces are preferably formed of or coated with materials compatible with the medical fluid used, more preferably non-thrombogenic materials. As shown in  FIG. 1 , the apparatus  1  may include a housing  2  which includes front cover  4 , which is preferably translucent, and a reservoir access door  3 . The apparatus preferably has one or more control and display areas  5   a ,  5   b ,  5   c ,  5   d  for monitoring and controlling perfusion. 
         [0034]    As schematically shown in  FIG. 2 , enclosed within the housing  2  is a reservoir  10  which preferably includes three reservoir tanks  15   a ,  15   b ,  17 . Two of the reservoir tanks  15   a ,  15   b  are preferably standard one liter infusion bags, each with a respective pressure cuff  16   a ,  16   b . A pressure source  20  can be provided for pressurizing the pressure cuffs  16   a ,  16   b . The pressure source  20  is preferably pneumatic and may be an on board compressor unit  21  supplying at least 10 LPM external cuff activation via gas tubes  26 , 26   a , 26   b , as shown in  FIG. 2 . The invention, however, is not limited to use of an on board compressor unit as any adequate pressure source can be employed, for example, a compressed gas (e.g., air, CO 2 , oxygen, nitrogen, etc.) tank (not shown) preferably with a tank volume of 1.5 liters at 100 psi or greater for internal pressurization. Alternatively, an internally pressurized reservoir tank (not shown) may be used. Reservoir tanks  15   a ,  15   b ,  17  may, in embodiments, be bottles or other suitably rigid reservoirs that can supply perfusate by gravity or can be pressurized by compressed gas. 
         [0035]    Gas valves  22 - 23  may be provided on the gas tube  26  to allow for control of the pressure provided by the onboard compressor unit  21 . Anti-back flow valves  24   a ,  24   b  may be provided respectively on the gas tubes  26   a ,  26   b . Pressure sensors P 5 , P 6  may be provided respectively on the gas tubes  26   a ,  26   b  to relay conditions therein to the microprocessor  150 , shown in  FIG. 3 . Perfusion, diagnostic and/or transporter apparatus may be provided with sensors to monitor perfusion fluid pressure and flow in the particular apparatus to detect faults in the particular apparatus, such as pressure elevated above a suitable level for maintenance of the organ. Gas valves GV 1  and GV 2  may be provided to release pressure from the cuffs  16   a ,  16   b . One or both of gas valves GV 1  and GV 2  may be vented to the atmosphere. Gas valve GV 4  in communication with reservoir tanks  15   a ,  15   b  via tubing  18   a ,  18   b  may be provided to vent air from the reservoir tanks  15   a ,  15   b  through tubing  18 . Tubing  18 ,  18   a ,  18   b ,  26 ,  26   a  and/or  26   b  may be configured with filters and/or check valves to prevent biological materials from entering the tubing or from proceeding further along the fluid path. The check valves and/or filters may be used to prevent biological materials from leaving one organ perfusion tubeset and being transferred to the tubeset of a subsequent organ in a multiple organ perfusion configuration. The check valves and/or filters may also be used to prevent biological materials, such as bacteria and viruses, from being transferred from organ to organ in subsequent uses of the perfusion apparatus in the event that such biological materials remain in the perfusion apparatus after use. The check valves and/or filters may be provided to prevent contamination problems associated with reflux in the gas and/or vent lines. For example, the valves may be configured as anti-reflux valves to prevent reflux. The third reservoir tank  17  is preferably pressurized by pressure released from one of the pressure cuffs via gas valve GV 2 . 
         [0036]    The medical fluid may be blood or a synthetic fluid and may, for example, be a simple crystalloid solution, or may be augmented with an appropriate oxygen carrier. The oxygen carrier may, for example, be washed, stabilized red blood cells, cross-linked hemoglobin, pegolated hemoglobin or fluorocarbon based emulsions. The medical fluid may also contain antioxidants known to reduce peroxidation or free radical damage in the physiological environment and specific agents known to aid in tissue protection. An oxygenated (e.g., cross-linked hemoglobin-based bicarbonate) solution is preferred for a normothermic mode while a non-oxygenated (e.g., simple crystalloid solution preferably augmented with antioxidants) solution is preferred for a hypothermic mode. The specific medical fluids used in both the normothermic and hypothermic modes may be designed or selected to reduce or prevent the washing away of or damage to the vascular endothelial lining of the organ. For a hypothermic perfusion mode, as well as for flush and/or static storage, a preferred solution is the solution disclosed in U.S. Pat. No. 6,492,103, the entire disclosure of which is incorporated herein by reference. Examples of additives which may be used in perfusion solutions for the present invention are also disclosed in U.S. Pat. No. 6,046,046 to Hassanein, the entire disclosure of which is incorporated by reference. Of course, other suitable solutions and materials may be used, as is known in the art. 
         [0037]    The medical fluid within reservoir  10  is preferably brought to a predetermined temperature by a first thermoelectric unit  30   a  in heat transfer communication with the reservoir  10 . A temperature sensor T 3  relays the temperature within the reservoir  10  to the microprocessor  150 , which adjusts the thermoelectric unit  30   a  to maintain a desired temperature within the reservoir  10  and/or displays the temperature on a control and display areas  5   a  for manual adjustment. Alternatively or in addition, and preferably where the organ perfusion device is going to be transported, the medical fluid within the hypothermic perfusion fluid reservoir can be cooled utilizing a cryogenic fluid heat exchanger apparatus such as that disclosed in filed U.S. Pat. No. 6,014,864, which is hereby incorporated by reference. 
         [0038]    An organ chamber  40  is provided which supports a cassette  65 , as shown in  FIG. 2 , which holds an organ to be perfused, or a plurality of cassettes  65 , as shown in  FIG. 5 , preferably disposed one adjacent the other. Various embodiments of the cassette  65  are shown in  FIGS. 4A-4D . The cassette  65  is preferably formed of a material that is light but durable so that the cassette  65  is highly portable. The material may also be transparent to allow visual inspection of the organ. 
         [0039]      FIG. 4A  shows a cassette  65  which holds an organ  60  to be perfused. Various embodiments of such a cassette  65  are shown in  FIGS. 4A-4D ,  6 A,  6 B,  10  and  12 . The cassette  65  is preferably formed of a material that is light but durable so that the cassette  65  is highly portable. The material may also be transparent to allow visual inspection of the organ. 
         [0040]    Preferably the cassette  65  includes side walls  67   a , a bottom wall  67   b  and an organ supporting surface  66 , which is preferably formed of a porous, perforated or mesh material to allow fluids to pass there through. The cassette  65  may also include a top  67   d  and may be provided with an opening(s)  63  for tubing (see, for example,  FIG. 4D ). The opening(s)  63  may include seals  63   a  (e.g., septum seals or o-ring seals) and optionally be provided with plugs (not shown) to prevent contamination of the organ and maintain a sterile environment. Additionally, the cassette  65  may be provided with tubing for connection to an organ and/or to remove medical fluid from the organ bath, and a connection device(s)  64  for connecting the tubing to, for example, tubing  50   c ,  81 ,  82 ,  91  and/or  132 , (see, for example,  FIG. 4D ) of an organ storage, transporter, perfusion and/or diagnostic apparatus. 
         [0041]    The cassette  65 , and/or the organ support, opening(s), tubing(s) and/or connections(s), may be specifically tailored to the type of organ and/or size of organ to be perfused. Flanges  67   c  of the side support walls  67   a  can be used to support the cassette  65  disposed in an organ storage, transporter, perfusion and/or diagnostic apparatus. The cassette  65  may further include a handle  68  which allows the cassette  65  to be easily handled, as shown, for example, in  FIGS. 4C and 4D . Each cassette  65  may also be provided with its own mechanism (e.g., stepping motor/cam valve  75  (for example, in the handle portion  68 , as shown in  FIG. 4C )) for fine tuning the pressure of medical fluid perfused into the organ  60  disposed therein, as discussed in more detail below. Alternatively, pressure may, in embodiments, be controlled by way of a pneumatic chamber, such as an individual pneumatic chamber for each organ (not shown), or by any suitable variable valve such as a rotary screw valve or a helical screw valve. 
         [0042]    Cassette  65  may be provided with a closeable and/or filtered vent  61  (see, for example,  FIG. 4D ). Vent  61  preferably includes a filter device, and provides for control and/or equalization of pressure within the cassette without contamination of the contents of the cassette. For example, organs are frequently transported by aircraft, in which pressure changes are the norm. Even ground transportation can involve pressure changes as motor vehicles pass through tunnels, over mountains, etc. It is often desirable to provide for pressure equalization of the cassette under such circumstances. However, free flow of air to achieve pressure equalization might introduce contaminants into the cassette. Thus, a filtering vent  61  is preferably provided to allow the air flow without permitting introduction of contaminants into the cassette. 
         [0043]    The filter preferably will let clean air pass in both directions but will not allow dirt, dust, liquids and other contaminants to pass. The pore size in the filters can be any size desired and can be small enough to prevent bacteria from passing. A pressure control valve can optionally be associated with vent  61  as well. Such a valve may be configured or controlled to restrict the rate at which external pressure changes are transmitted to the inside of the cassette, or even to prevent pressure increases and/or decreases, as desired. 
         [0044]      FIGS. 6A-6B  show an alternative embodiment of cassette  65 . The cassette  65  is a portable device and is provided with a lid, preferably two lids, an inner lid  410  and an outer lid  420 . As such, the one or more lids  410  and  420  can create a substantially airtight seal with the cassette  65 . This air tight seal can create a pressure difference between the inside and outside of cassette  65 . Pressure sensors that control perfusion of the organ may be referenced to the atmospheric pressure. In such embodiments, it is desirable that the air space around the organ in cassette  65  is maintained at atmospheric pressure. 
         [0045]    Accordingly, the cassette may also include one or more devices for controlling the pressure. The devices for controlling pressure can be an active or passive device such as a valve or membrane. Membranes  415  and  425 , for example, can be located in the inner lid  410  and outer lid  420 , respectively. It should be appreciated that any number of membranes can be located in the cassette (including its lid(s)) without departing from the spirit and scope of the invention. The membranes  415  and  425  are preferably hydrophobic membranes which help maintain an equal pressure between the inside and the outside of the cassette. A pressure control valve can optionally be associated with membranes  415  and  425 . Such a pressure control valve may be configured or controlled to restrict the rate at which external pressure changes are transmitted to the inside of the cassette, or even to prevent pressure increases and/or decreases, as desired. 
         [0046]    The membranes  415  and  425 , if sufficiently flexible, can be impermeable or substantially impermeable. Alternatively, they may include filters that will let clean air pass in both directions, however, the membranes  415  and  425  will not allow dirt, dust, liquids and other contaminants to pass. The pore size in the filters can be any size desired, and preferably, the pore size of the membranes  415  and  425  can be small enough to prevent bacteria from passing. The actions of the membranes  415  and  425  and corresponding filters help maintain the sterility of the system. 
         [0047]    Preferably, cassette  65  is made of a sufficiently durable material that it can withstand penetration and harsh impact. The lids  410  and  420  may be removable or may be hinged or otherwise connected to the body of cassette  65 . Clasp  405 , for example, may provide a mechanism to secure lids  410  and  420  to the top of cassette  65 . Clasp  405  may additionally be configured with a lock to provide further security and stability. A biopsy and/or venting port  430  may additionally be included in inner lid  410  or both inner lid  410  and outer lid  420 . Port  430  may provide access to the organ to allow for additional diagnosis of the organ with minimal disturbance of the organ. Cassette  65  may also have an overflow trough  440  (shown in  FIG. 6B  as a channel present in the top of cassette  65 ). When lids  410  and  420  are secured on cassette  65 , overflow trough  440  provides a region that is easy to check to determine if the inner seal is leaking. Perfusate may be poured into and out of cassette  65  and may be drained from cassette  65  through a stopcock or removable plug. 
         [0048]    In  FIG. 6A , cassette  65  is shown with tubeset  400 . Tubeset  400  can be connected to perfusion apparatus  1  or to an organ transporter or an organ diagnostic apparatus, and allows cassette  65  to be moved between various apparatus without jeopardizing the sterility of the interior of cassette  65 . Preferably, cassette  65  is made of a sufficiently durable material that it can withstand penetration and harsh impact. As shown in  FIG. 6A , the tube set may be connected to a bubble trap device BT. A preferred such device is described in detail in a U.S. provisional patent application filed simultaneously herewith entitled “Device for separating bubbles from a liquid path” (attorney docket no. 115624). 
         [0049]    Cassette  65  and/or its lid(s) may be constructed of an optically transparent material to allow for viewing of the interior of cassette  65  and monitoring of the organ and to allow for video images or photographs to be taken of the organ. A perfusion apparatus or cassette  65  may be wired and fitted with a video camera or a photographic camera, digital or otherwise, to record the progress and status of the organ. Captured images may be made available over a computer network such as a local area network or the internet to provide for additional data analysis and remote monitoring. Cassette  65  may also be provided with a tag that would signal, e.g., through a bar code, magnetism, radio frequency, or other means, the location of the cassette, that the cassette is in the apparatus, and/or the identity of the organ to perfusion, storage, diagnostic and/or transport apparatus. Cassette  65  may be sterile packaged and/or may be packaged or sold as a single-use disposable cassette, such as in a peel-open pouch. A single-use package containing cassette  65  may also include tubeset  400  and/or tube frame  200 , discussed further below. 
         [0050]    Cassette  65  is preferably configured such that it may be removed from an organ perfusion apparatus and transported to another organ perfusion and/or diagnostic apparatus in a portable transporter apparatus as described herein or, for example, a conventional cooler or a portable container such as that disclosed in U.S. Pat. No. 6,209,343, or U.S. Pat. No. 5,586,438 to Fahy, both of which are hereby incorporated by reference in their entirety. 
         [0051]    In various exemplary embodiments according to this invention, when transported, the organ may be disposed on the organ supporting surface  66  and the cassette  65  may be enclosed in a preferably sterile bag  69 , as shown, for example, in  FIG. 4A . When the organ is perfused with medical fluid, effluent medical fluid collects in the bag  69  to form an organ bath. Alternatively, cassette  65  can be formed with a fluid tight lower portion in which effluent medical fluid may collect, or effluent medical fluid may collect in another compartment of an organ storage, transporter, perfusion and/or diagnostic apparatus, to form an organ bath. In either case, the bag  69  would preferably be removed prior to inserting the cassette into an organ storage, transporter, perfusion and/or diagnostic apparatus. Further, where a plurality of organs are to be perfused, multiple organ compartments may be provided. Alternatively, cassette  65  can be transported in the cassette and additionally carried within a portable organ transporter. 
         [0052]      FIG. 7  shows an external view of an embodiment of a transporter  1900  of the invention. The transporter  1900  of  FIG. 7  has a stable base to facilitate an upright position and handles  1910  for carrying transporter  1900 . Transporter  1900  may also be fitted with a shoulder strap and/or wheels to assist in carrying transporter  1900 . A control panel  1920  is preferably also provided. Control panel  1920  may display characteristics, such as, but not limited to, infusion pressure, attachment of the tube frame, power on/off, error or fault conditions, flow rate, flow resistance, infusion temperature, bath temperature, pumping time, battery charge, temperature profile (maximums and minimums), cover open or closed, history log or graph, and additional status details and messages, some or all of which are preferably further transmittable to a remote location for data storage and/or analysis. Flow and pressure sensors or transducers in transporter  1900  may be provided to calculate various organ characteristics including pump pressure and vascular resistance of an organ, which can be stored in computer memory to allow for analysis of, for example, vascular resistance history, as well as to detect faults in the apparatus, such as elevated pressure. 
         [0053]    Transporter  1900  preferably has latches  1930  that require positive user action to open, thus avoiding the possibility that transporter  1900  inadvertently opens during transport. Latches  1930  hold top  1940  in place on transporter  1900  in  FIG. 7 . Top  1940  or a portion thereof may be constructed with an optically transparent material to provide for viewing of the cassette and organ perfusion status. Transporter  1900  may be configured with a cover open detector that monitors and displays whether the cover is open or closed. Transporter  1900  may be configured with an insulating exterior of various thicknesses to allow the user to configure or select transporter  1900  for varying extents and distances of transport. In embodiments, compartment  1950  may be provided to hold patient and organ data such as charts, testing supplies, additional batteries, hand-held computing devices and/or configured with means for displaying a UNOS label and/or identification and return shipping information. 
         [0054]      FIG. 8  shows a cross-section view of a transporter  1900 . Transporter  1900  contains cassette  65  and pump  2010 . Cassette  65  may preferably be placed into or taken out of transporter  1900  without disconnecting tubeset  400  from cassette  65 , thus maintaining sterility of the organ. In embodiments, sensors in transporter  1900  can detect the presence of cassette  65  in transporter  1900 , and depending on the sensor, can read the organ identity from a barcode or radio frequency or other “smart” tag that may be attached or integral to cassette  65 . This can allow for automated identification and tracking of the organ and helps monitor and control the chain of custody. A global positioning system may be added to transporter  1900  and/or cassette  65  to facilitate tracking of the organ. Transporter  1900  may be interfaceable to a computer network by hardwire connection to a local area network or by wireless communication while in transit. This interface may allow data such as perfusion parameters, vascular resistance, and organ identification and transporter and cassette location to be tracked and displayed in real-time or captured for future analysis. 
         [0055]    Transporter  1900  also preferably contains a filter  2020  to remove sediment and other particulate matter, preferably ranging in size from 0.05 to 15 microns in diameter or larger, from the perfusate to prevent clogging of the apparatus or the organ. Transporter  1900  preferably also contains batteries  2030 , which may be located at the bottom of transporter  1900  or beneath pump  2010  or at any other location but preferably one that provides easy access to change batteries  2030 . Batteries  2030  may be rechargeable outside of transporter  1900  or while within transporter  1900  and/or are preferably hot-swappable one at a time. Batteries  2030  are preferably rechargeable rapidly and without full discharge. Transporter  1900  may also provide an additional storage space  2040 , for example, at the bottom of transporter  1900 , for power cords, batteries and other accessories. Transporter  1900  may also include a power port for a DC hookup, e.g., to a vehicle such as an automobile or airplane, and/or for an AC hookup. 
         [0056]    As shown in  FIG. 8 , the cassette wall CW is preferably configured to mate with a corresponding configuration of inner transporter wall TW to maximize contact, and thus heat transfer, there between as discussed in more detail below. 
         [0057]      FIG. 9  shows an alternative cross-section of transporter  1900 . In  FIG. 9 , the transporter  1900  may have an outer enclosure  2310  which may, for example, be constructed of metal, or preferably a plastic or synthetic resin that is sufficiently strong to withstand penetration and impact. Transporter  1900  contains insulation  2320 , preferably a thermal insulation made of, for example, glass wool or expanded polystyrene. Insulation  2320  may be various thicknesses ranging from 0.5 inches to 5 inches thick or more, preferably 1 to 3 inches, such as approximately 2 inches thick. Transporter  1900  may be cooled by coolant  2110 , which may be, e.g., an ice and water bath or a cryogenic material. In embodiments using cryogenic materials, the design should be such that organ freezing is prevented. An ice and water mixture is preferably an initial mixture of approximately 1 to 1, however, in embodiments the ice and water bath may be frozen solid. Transporter  1900  can be configured to hold various amounts of coolant, preferably up to 10 to 12 liters. An ice and water bath is preferable because it is inexpensive and generally can not get cold enough to freeze the organ. Coolant  2110  preferably lasts for a minimum of 6 to 12 hours and more preferably lasts for a minimum of 30 to 50 hours without changing coolant  2110 . The level of coolant  2110  may, for example, be viewed through a transparent region of transporter  1900  or be automatically detected and monitored by a sensor. Coolant  2110  can preferably be replaced without stopping perfusion or removing cassette  65  from transporter  1900 . Coolant  2110  is preferably maintained in a watertight compartment  2115  of transporter  1900 . For example, an inner transporter wall TW as shown in  FIG. 8  can be interposed between the coolant  2110  and cassette wall (CW) in the apparatus of  FIG. 9 . Compartment  2115  preferably prevents the loss of coolant  2110  in the event transporter  1900  is tipped or inverted. Heat is conducted from the walls of the perfusate reservoir/cassette  65  into coolant  2110  enabling control within the desired temperature range. Coolant  2110  is a failsafe cooling mechanism because transporter  1900  automatically reverts to cold storage in the case of power loss or electrical or computer malfunction. Transporter  1900  may also be configured with a heater to raise the temperature of the perfusate. 
         [0058]    Transporter  1900  may be powered by batteries or by electric power provided through plug  2330 . An electronics module  2335  may also be provided in transporter  1900 . Electronics module  2335  may be cooled by vented air convection  2370 , and may further be cooled by a fan. Preferably, electronic module  2335  is positioned separate from the perfusion tubes to prevent the perfusate from wetting electronics module  2335  and to avoid adding extraneous heat from electronics module  2335  to the perfusate. Transporter  1900  preferably has a pump  2010  that provides pressure to perfusate tubing  2360  (e.g. of tube set  400 ) to deliver perfusate  2340  to organ  2350 . Transporter  1900  may be used to perfuse various organs such as a kidney, heart, liver, small intestine and lung. Transporter  1900  and cassette  65  may accommodate various amounts to perfusate  2340 , for example up to 3 to 5 liters. Preferably, approximately 1 liter of a hypothermic perfusate  2340  is used to perfuse organ  2350 . 
         [0059]    Cassette  65  and transporter  1900  are preferably constructed to fit or mate such that efficient heat transfer is enabled. Preferably, the transporter  1900  contains a compartment  2115  for receiving the cassette. The transporter  1900  preferably relies on conduction to move heat from the cassette  65  to coolant  2110  contained in compartment  2115 . This movement of heat allows the transporter  1900  to maintain a desired temperature of the perfusion solution. The geometric elements of cassette  65  and transporter  1900  are preferably constructed such that when cassette  65  is placed within transporter  1900 , the contact area between cassette  65  and transporter  1900  is as large as possible and they are secured for transport. 
         [0060]      FIG. 10  shows an example of this geometry between cassette  65  and compartment  2115  containing coolant  2110 . The interface geometry between cassette  65  and compartment  2115  is preferably designed so that cassette  65  will wedge into a cavity created by compartment  2115 . Accordingly, the angles of the side walls are substantially equal and thus, all side walls of cassette  65  make contact with the side walls of compartment  2115  regardless of the shape of the cassette sides or compartment sides, such as flat or curved. Having the included angles substantially equal allows the surfaces of cassette  65  and the compartment  2115  to make contact even when influenced by the thermal expansion and contraction of the walls and mechanical tolerances. 
         [0061]    The height of cassette  65  above compartment  2115  is determined by the mating surfaces of cassette  65  and compartment  2115 . As shown in  FIG. 10  the bottom of the cassette does not have to rest on the bottom of compartment  2115 , but can rest at the bottom in embodiments in which the shape of cassette  65  and compartment  2115  allow it. It should be appreciated that the shape of cassette  65  and compartment  2115  in these embodiments can be any shape, such as for example a truncated cone, that allows for maximum contact and therefore maximum heat transfer between them. 
         [0062]    As discussed above, heat is conducted from the walls of the perfusate reservoir/cassette  65  into coolant  2110  of compartment  2115  enabling control within the desired temperature range. Coolant  2110  can provide a failsafe cooling mechanism because transporter  1900  automatically reverts to cold storage in the case of power loss or electrical or computer malfunction. Transporter  1900  may also be configured with a heater to raise the temperature of the perfusate. 
         [0063]      FIG. 11  shows a tube frame  200  of embodiments of the invention, which may be used for holding tube set  400  discussed with respect to  FIG. 6A . Tube frame  200  is preferably formed of a material that is light but durable, such as for example plastic, so that tube frame  200  is highly portable. The tube frame  200  is designed to hold the tubing of the tube set  400  in desired positions. In  FIG. 11 , tube frame  200  is shown holding the tubes of tube set  400  of  FIG. 6A . It should be appreciated that there may be other numbers of tubes that comprise tube set  400 . Having the tubing in set positions allows for easier installation and connection with devices such as cassette  65  as shown in  FIG. 12 . The cassette  65  and tube frame  200  are then preferably mated with transporter  1900 . 
         [0064]    When tube frame  200  is mated with cassette  65 , the tube set  400  is preferably already connected with the cassette  65 . For example, tube  270  provides an inlet to a pump  2010  from the stored liquid at the bottom of cassette  65 . The liquid travels through tube  290  and back out outlet  280  through a filter which may, for example, be located inside or outside, for example, below, cassette  65 . After traveling through the filter, the liquid will travel to tube  240  and into the bubble trap  210 . A sample port  295  may be provided with tube frame  200  to allow for drawing liquid out of or injecting liquid into the tube  240 . Liquid travels into the bubble trap  210  in tube  240  and travels out of bubble trap  210  in tube  260 , which carries the liquid into the cassette, for example, to infuse and/or wash the organ. Tube  250  will carry liquid or gas leaving the bubble trap  210  into cassette  65  bypassing infusion of, but optionally washing, the organ. 
         [0065]    It should be appreciated that tube frame  200  can hold other devices in addition to tubes. For example, tube frame  200  can hold a bubble trap device  210  and a pressure sensor  220  used to control pump  2010 . It should also be appreciated that tube frame  200  and tube set  400  can be connected to a variety of devices such as the organ perfusion device  1  or an organ diagnostic device, as well as a cassette and/or transporter. 
         [0066]    In various exemplary embodiments, tube frame  200  is preferably attachable to a portion of the transporter  1900 . The tube frame  200  may be connected to transporter  1900 , and other devices, by way of snaps  230  or other structure that will securely hold the tube frame to the device. Sensors, for example mechanical or electrical sensors, in transporter  1900 , or other devices, can be provided to detect the presence of tube frame  200  in transporter  1900 . If the tube frame  200  is not properly attached to the transporter, the sensors may be configured to send an appropriate alert message to control panel  1920  for notifying the user of a problem. If no action is taken to properly attach tube frame  200  in a given amount of time automatically set or programmed by the user, transporter  1900  can be programmed to prevent the beginning of perfusion. It should be appreciated that if perfusion has begun and tube frame  200  is not appropriately set, the transporter can be programmed to stop perfusion. 
         [0067]    Another valuable feature of the tube frame is that makes the stationary surface for the tube  250 , and tube  260 . These tubes are used to route perfusion solution either directly to the organ or, bypassing the organ, into the reservoir. It is desirable to have tube  250  and tube  260  located in a relatively fixed position so that the routing may be done by pinching the tubing so that no liquid can pass. The tubes may, for example, be pinched by a solenoid (not shown) located on transporter  1900  that drives a blade that pinches tube  250  and/or tube  260  against the tube frame  200 . 
         [0068]    While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations may be apparent to those skilled in the art. Accordingly, the embodiments of the invention as set forth herein are intended to be illustrative, not limiting. Various changes may be made without departing from the spirit and scope of the invention.