JP2005535293A - Equipment that can be used in medicine - Google Patents

Abstract

An organ culture device for culturing viable organs (1) is disclosed. This device uses a pump (3) to provide a culture medium for culturing viable organs. The pump has a pump chamber (45) disposed between the inlet and the outlet. The pump achieves the pulsed pumping action of the culture medium by repeatedly deforming the elastic tubular side wall (44) of the pump chamber with compressed gas. The flow path of the culture medium may be a circulation type or a non-circulation type. The device has a reservoir (70, 80) for the culture medium and a collection container (74, 84). Gas transfer to and from the culture medium is also performed. Also disclosed is a gas pressure control device that supplies the pump itself and pulsed pressurized gas, for example to the pump.

Description

  The present invention relates to an organ culture apparatus for culturing viable organs, particularly organs composed of or containing living cells. The present invention can be applied to the organ culture apparatus of the present invention and can be applied to other applications, in particular, a liquid pump and a pulsed pressurized air supply. It also relates to a gas pressure control device.

  A “viable organ” as used herein means a natural or synthetic organ that consists of or contains a living cell. Cells need to be cultured so that they are at least viable and selectively grow. Such viable organs are used in medicine, veterinary medicine, and other biology and biotechnology fields. A viable organ may be, for example, a natural organ removed from an organism for transplantation or other purposes, or an organ that is at least partially synthesized. For example, the synthetic structure may have a synthetic substrate of biologically compatible material in which cells are present. Organs may be stored or cultured to grow cells, for example, in a synthetic structure that is adapted to grow and mimic natural organs. Applicant's international patent application GB02 / 01183, filed March 26, 2002 and published as WO 02/077336, describes a rigid viable organ containing cells and its manufacture. doing.

Numerous methods and devices are known that maintain cells in a viable state for storage and / or growth by maintaining the culture medium and contacting the cells.
International Publication No.02 / 077336

  The inventor has recognized that there is a need for a simple organ culture device for culturing viable organs that are easily maintained during storage and / or transport.

  Viable organs used in the present invention may be in the form of sheets, tubes or hollow organs and usually comprise bound cells and an extracellular matrix, and preferably a layer of endothelial cells on at least one surface. Or a sheet, tube, or hollow structure thereof. The cells bound by the external matrix are usually smooth muscle cells or fibroblasts. The following is an example.

Sheet:
Skin structure: sheet hollow organ of fibroblast and extracellular matrix (ECM) with epithelial cell layer (in the form of a tube):
Bladder: smooth muscle / ECM tube + transitional epithelium Gastric: smooth muscle / ECM + special gastric epithelial tube:
Parts of the digestive tract (e.g. esophagus, small intestine, colon, rectum):
Esophageal-smooth muscle / ECM + squamous epithelium Small intestine / colon / rectum-smooth muscle / ECM + columnar epithelium + goblet vascular or arteriovenous shunt: smooth muscle cell / ECM, with endothelial cell layer Urethra or ureter-smooth muscle / ECM + transitional epithelium A viable organ may be, for example, a surgically implantable artificial structure containing living cells.

  Manufacture of artificial structures in the form of sheets or tubes, possibly containing living cells, was filed on March 26, 2002 and published as WO 02/077336 “cured tubes and UK patent application filed on Jan. 27, 2003, as described in Applicant's co-pending PCT application entitled “Methods and Apparatus for Forming Hardened Tubes and Sheets” It is also described in No. 0301834.8. A supply assembly supplying such a structure or organ is a book entitled “Delivery Assembly for Use in Surgery” which claims priority from UK patent application No. 0207416.9. As described in the applicant's co-pending application. The contents of these patent applications are incorporated herein by reference.

  In organs such as the gastrointestinal tract, eg, structures that become part of the esophagus, stomach, small intestine, colon, rectum, it is desirable that the smooth muscle cell tube has a multilayer structure, eg, two or three layers. A method for forming such a multilayer is disclosed in WO 02/077336.

  According to the present invention, in one aspect, a chamber containing a viable organ disposed along a liquid flow path for the flow of culture medium through the chamber and a culture medium provided along the liquid flow path The pump has a pump chamber with a net flow direction of the culture medium passing through it, and repeats the deformable wall of the pump chamber arranged on the side of the net flow direction An organ culture device for culturing viable organs that can obtain a pulse pumping action by being deformed is provided.

  The pumping action of the pump makes it possible to create advantageous conditions in the chamber containing the organ. In particular, pulsed culture media are believed to help maintain and form certain forms of tissue by mimicking conditions in the body. For example, if the tissue being cultured is vascular tissue, the culture medium that is pulsed may help culture the appropriate endothelial cell layer.

  By placing the deformable wall transverse to the net flow direction of the culture medium through the pump chamber, the wall can be deformed substantially transverse to the net flow direction.

  This arrangement of deformable walls is advantageous because the flow characteristics of the pump, and thus the flow characteristics within the chamber in which the organ is located, can be improved compared to other pump configurations. In particular, the wall having the same stroke volume and stroke speed, but the deformable wall is arranged in another position, e.g. facing towards the net flow direction or away from the net flow direction. Turbulent flow can be reduced compared to a conventional pump.

  The deformable wall is preferably an elastically deformable wall. The wall is deformed by external forces, such as pressure acting on its outer surface. When this pressure is removed, the wall absorbs its undeformed shape due to the elasticity of the wall. This helps to allow the culture medium to flow into the pump chamber so that it can be pumped out in subsequent strokes of the pump.

  In this device, the liquid flow path allows the culture medium to flow or circulate over the surface of a viable organ. The device shall allow gas transfer via gas transfer means between the outside and circulating culture medium, for example transfer of oxygen and, if necessary, carbon dioxide to the culture medium and removal of carbon dioxide. Is preferred.

  The gas transfer means is preferably operated by gas diffusion in the gas permeable wall. Typically, the device includes a conduit that forms part of the liquid flow path. Thus, the apparatus may include a gas transfer chamber having a wall that is a gas permeable wall of the conduit and confining gas diffused through the gas permeable wall.

  The pump of the organ culture device is preferably operated with pressurized gas. This is advantageous when it is desired that the organ culture device does not require power while transporting viable organs between hospitals, for example. A simple gas-power pump is described below.

  Gas driven pumps are cheaper and easier to dispose than electric pumps. If the organ culture device has to be disposable, the ease of disposal (to avoid the risk of cross contamination between patients) is an important factor.

  In a pump, the pumping action is preferably obtained by repeatedly deforming the wall with pressurized gas outside the wall. The pressurized gas may be a gas that provides gas transfer to the culture medium, and the elastically deformable wall of the pump is itself gas permeable, and thus gas transfer occurs through the wall. Is most preferred. By combining the pumping action and the gas exchange action, a simple, economical and easily disposable device can be obtained.

  In other possible embodiments, the pressurized gas that operates the pump can exchange gas in a separate chamber within the culture medium circuit.

  Typically, the pump has an inlet and an outlet on both sides of the pump chamber. These can be located on the longitudinal axis of the pump chamber. The deformable wall is preferably disposed between the inlet and the outlet substantially parallel to the longitudinal axis.

  The wall preferably deforms inwardly toward the longitudinal axis of the pump chamber. It is undesirable for the wall deformation to proceed along the wall parallel to the longitudinal axis of the pump chamber. However, such a peristaltic pumping action may be possible.

  The elastically deformable wall preferably includes first and second portions. Alternatively, there may be first and second elastically deformable walls of the pump chamber. Preferably, the first and second portions, or the first and second walls, face the pump chamber laterally or face each other diagonally across the pump chamber. Thus, these elements can exert a pumping action from various directions on the liquid contained in the pump chamber. This reduces the “dead” volume in the pump chamber, that is, by reducing the dead volume of liquid that remains substantially stationary in the pump chamber even after repeated pump strokes. Can be pumped out.

  More preferably, the elastically deformable wall extends substantially circumferentially around the pump chamber. In this way, the various portions of the deformable wall are substantially deformable toward the longitudinal axis (aligned in the net flow direction) of the pump chamber. Usually, the deformable wall is a deformable tube. Such a structure makes it possible to reduce the “dead” volume in the pump chamber for the same reasons as described above.

  The pump chamber tube with inlet and outlet at both ends allows pumping while suppressing turbulence. In particular, if the length of the pump chamber (and preferably the deformable wall) is long compared to its width, a sufficient stroke volume of the pump can be displaced by relatively slight deformation of the wall. This helps to minimize turbulence.

  The apparatus may include a reservoir that supplies a culture medium that is pumped toward the chamber. The liquid flow path or a portion thereof can extend from the reservoir toward the pump and optionally through the pump chamber.

  The flow path may be non-circulating. If the flow path is completely non-circulating, the culture medium is not recirculated. In that case, the culture medium in the pump chamber is obtained only from the reservoir. In the case of a non-circulating channel, a culture medium collecting means, for example a bag, is arranged downstream of the chamber. The collecting means and the chamber are preferably in communication via a flow regulating valve that can increase the back pressure in the chamber so that the organ can easily receive the pulsed flow from the pump.

  Alternatively, the flow path may be circulating or partially circulating. In that case, at least some of the culture medium is recirculated from the chamber to the pump and sent back to the chamber. The culture medium can be replenished from the reservoir (eg, intermittently or continuously) when the reservoir is present. In that case, the culture medium collecting means is required to accommodate the outflow volume of the culture medium in the flow path.

  The device preferably includes a sampling port for sampling and analyzing the culture medium from the flow path, for example during use of the device.

  In both non-circulating and circulating devices, the device is preferably sealed in a liquid-tight manner, i.e. the culture medium from the reservoir or the culture medium in the device is not exposed to the outside. This helps to reduce the risk of infection or contamination of the culture medium and organs.

  The entire organ culture device of the present invention can be made of a material suitable for irradiation after its manufacture and assembly, for example to sterilize the device using gamma radiation.

  In a second aspect, the present invention provides a liquid pump that is suitable for use in the organ culture apparatus of the present invention described above, but also has other possible uses.

  In this aspect, the present invention provides for a deformable pump chamber for liquid having a net flow direction in the pump chamber for pumped liquid and a pump chamber disposed laterally in the net flow direction. There is provided a liquid pump having a wall shaped pump member acting on the liquid, the deformable wall pumping under the action of a pulsed supply of pressurized gas.

  Such a pump is particularly useful and effective when handling relatively small amounts of liquid. Thus, the pump chamber of the pump has a volume of 1 liter or less, or 100 ml or less, or even 10 ml or less. The volume of the pump chamber is usually the volume between the inlet and outlet directional devices, such as a one-way valve, provided in the pump.

  The pump according to the invention may comprise means for generating a pulsed pressurized gas, eg a gas cylinder, from a pressurized gas supply such as a reservoir. An apparatus suitable for generating such a pulsed flow of pressurized gas will be described below.

  Preferred features of the pump will be described in relation to the pump of the first aspect of the invention described above. The preferred features described below can be incorporated into the first or third aspect of the present invention.

  The deformable wall of the pump chamber is preferably elastically deformable. The deformable wall may be a tube containing the liquid to be pumped during use. In this case, the structure of the device is simplified. In order to transfer gas to and / or from the liquid being pumped, the deformable wall may be gas permeable. In this way, for example, a gas such as oxygen can be fed into the liquid being pumped, in which case oxygen treatment is required. When the gas pressure acting on the deformable wall is pulsed, the gas transfer speed is improved by the movement of the gas.

  The pumps of the present invention can be applied to other medical and veterinary applications and devices, and the present invention extends to such applications. This pump, which is simple and does not require power, can be used, for example, to pump blood in a cardiac assist technology that assists the heart from outside the body. When oxygen transfer is performed in the pump, the pump can simultaneously perform oxygen treatment of blood.

  According to the present invention, in a third aspect, a gas accumulator chamber having an inlet and an outlet connected to a source of pressurized gas and elastically expandable by moving a movable wall of the chamber is provided. Having a valve member movable between a closed position for closing the outlet and an open position for allowing the outlet flow to pass through the outlet, actuated by movement of the movable wall of the accumulator chamber; Means for moving the valve member from a closed position to an open position when a predetermined pressure is reached in the accumulator chamber, and a valve when the accumulator chamber contracts after a volume of gas has been released from the accumulator chamber There is provided a gas pressure control device for supplying a pulsed pressurized gas having means for returning the member to a closed position.

  The device is self-circulating and does not require external control, i.e. no external power source other than the pressurized gas supplied.

  The elastically expandable accumulator chamber may be a piston and cylinder assembly, the piston forming the movable wall of the chamber. The piston may include an actuating member that initiates movement away from the closed position of the valve member. The apparatus may include deflecting means that act on the valve member as the valve member moves from the closed position, so that after eliminating the pressure differential across the valve member when the valve member opens, the valve member is deflected means. Is moved to the open position. The deflecting means may be a component arranged to exert a tension between the movable wall of the accumulator chamber and the valve member and bias the valve member toward its open position when the valve member opens. .

  This gas pressure control device is particularly applicable to the control of the gas pumps described above, but can also be applied to medicine, and the present invention is directed to the use of such devices in medical and veterinary processes and devices. Expanded. The gas pressure control device can be used to supply pulsed supply air to a patient, for example, in a positive pressure ventilation system where the patient is supplied with pulsed supply air by mouth or nose.

  The present invention is an organ culture device as described herein in a form capable of receiving a viable organ, for example by forming a viable organ in the culture device, wherein the viable organ Further provided is a device that has been previously sterilized so that it can be stored in a sealed enclosure that maintains its sterilized condition.

  The present invention further provides a method of maintaining a viable organ so that it can be transported and stored using the organ culture apparatus of the first aspect.

  Embodiments of the present invention will now be described through non-limiting examples with reference to the accompanying drawings.

  In the drawings, the same reference numerals are used for the same or corresponding parts.

  An organ culture device embodying the present invention shown in FIG. 1 is embedded in a matrix of sodium alginate hardened by contact with a calcium chloride solution contained in a cylindrical chamber or cavity 8 in housing 2. It has a viable organ in the form of a tube 1 with living biological cells. The nature of the tube 1 and the housing 2 and the method of forming the tube 1 in situ within the housing 2 was filed on March 26, 2002, the contents of which are incorporated herein by reference. This is described in detail in the applicant's international patent application GB02 / 01183 (International Publication No. 02/077336).

  A modification of the embodiment of FIG. 1 is shown in FIGS. The common features are described below.

  The housing 2 shown in FIG. 1 has a body part 13 which is a rectangular block with a central recess 13a whose surface is located at the cross-sectional line of FIG. It has a semicircular groove 14 that forms half of the cylindrical cavity 8. The housing 2 is not shown in FIG. 1 and has a corresponding groove that fits hermetically in the recess 13a of the body 13 and forms the other half of the cylindrical cavity 8 containing the tube 1. It has a main body. This cylindrical cavity extends into the bores of the larger ends 15, 16 of the body 13. As will be described later, the second main body portion is disposed at a predetermined position on the main body portion 13 when the tube 1 is formed, and remains at a predetermined position when the tube 1 is cultured. The surgeon uses the cultured tube 1 It is only removed by the surgeon at the time of surgery for the patient who desires.

  In order to form the tube 1 in situ in the housing, a slider member 18 is initially present at the lower end of the cavity 14 located on the sleeve 21 (shown in FIG. 1 at the final position of the slider member 18). Have been). The slider 18 has a recess at its lower end where a narrow tube 22 is placed at the upper end of the sleeve 21.

  The sleeve 21 is sealed in the cavity 14 in the end 16 of the body 13 by an O-ring (not shown) and the slider 18 is shown in FIG. It is held by a block 25 so that it can be moved to a certain position.

  A sodium alginate solution containing biological cells (which may later be extracted from a patient into which tube 1 is surgically inserted) is placed sideways to fill cavity 14 (from one of ports 23, 24 described below). Inject through passage 20. Next, the block 25 and the sleeve 21 holding the slider 18 are pushed upward to the position shown in FIG. A calcium chloride solution is injected into the sleeve 21 through the conduit 28. The calcium chloride solution emerges from the tube 22 and drives the slider member 18 that acts as an adjustment valve. The slider member 18 has an outer diameter that is smaller than the inner diameter of the cavity 14, so that as the slider member moves, a thin layer of alginic acid is left behind and immediately comes into contact with the calcium chloride solution to form a compact. It is chemically cured to a sufficient extent (this compact is tube 1 and not rigid). The shaped body therefore consists of a matrix of hardened alginate containing living cells. The slider member rests at a position beyond the branch point with the lateral passage 11 as shown in FIG. During the movement of the slider 18, excess alginate solution appears through the cap 12.

  In the block 25, the conduit 28 connects to the side tube 26 ending in the connector 27. Before and after forming the tube 1, the lateral passage 11 and the side tube 26 are connected by a continuous conduit 9 to form a closed and sealed complete circuit including the cylindrical cavity 14 containing the tube 1. In order to maintain the sealing / sealing performance of the circulation path, the end cap 12, the lateral passage 20, and the conduit 28 must be closed. In FIG. 1, conduit 9 has an inlet 23 and an outlet 24 with valves that allow simultaneous injection and removal of liquid to and from the closed circuit as needed to change or refill the circuit. doing. Thereby, the circulation path is washed to remove the alginic acid solution and the calcium chloride solution, and then a culture medium having properties suitable for maintaining and promoting the growth of the cells in the tube 1 is added. Suitable culture media for this are known in the art and need not be described here.

  The embodiment of FIG. 1 uses a fully recirculating liquid flow path, ie a closed circuit. In contrast, the embodiment of FIG. 2 uses a non-recirculating liquid flow path. In FIG. 2, the culture medium reservoir 70 is attached to the upstream side of the pump 3 in the liquid flow path via a pipe and a flow rate adjustment valve. The culture medium flows into the pump 3 by gravity. The flow regulating valve 72 may be variable to allow various flow rates from the reservoir 70 to the pump 3 depending on the culture medium flow rate required through the cavity 14.

  The culture medium flows from the pump 3 through the cavity 14 to the downstream side of the lateral passage 11. A culture medium collection container 74 is connected to the lateral passage 11 via a flow rate adjusting valve 76. The culture medium flowing along the lateral passage 11 is discharged into a container 74 which may be a bag, for example. Note that FIG. 2 is schematic and the container 74 can be positioned lower than the reservoir 70 so that the flow of culture medium can be partially moved by the hydrostatic head due to the height difference.

  The flow regulating valve 76 allows the back pressure to increase within the cavity 14 and throughout the flow path. Therefore, the pulse pumping action by the pump 3 makes it possible to guide the pressure wave along the flow path. Such pressure waves are thought to aid cell culture and growth.

  The embodiment of FIG. 3 shows an apparatus that allows partial recirculation of the culture medium. A liquid flow circuit can be defined in that there is a liquid flow path from the pump 3 through the conduit 9, the cavity 14 and back to the pump 3 along the transverse path 11. However, a culture medium reservoir 80 that communicates with the conduit 9 via the flow rate regulating valve 82 is provided. The culture medium reservoir 80 can communicate with the downstream side of the pump 3. This is because sufficient culture medium is recirculated to operate the pump 3 to a satisfactory extent.

  A culture medium collection container 84 is provided on the downstream side of the cavity 14. This is in communication with the lateral passage via the flow regulating valve 86. In operation, the container 84 collects the same volume of culture medium that is supplied from the reservoir 80 to the circulation.

  In this case as well, the container 64 can be arranged at a lower height than the reservoir 80 to allow gravity flow of the culture medium along the flow path.

  A sampling port may be provided in the passage 88 for sampling and analyzing spent culture media, for example. Similarly, a sampling or injection port can be provided, for example, in the passage 90 to sample the culture medium into the reservoir 80, dilute the culture medium in the reservoir 80, or replenish the culture medium.

  The flow path formed by the cavity 94 and the conduit 9 includes the pump 3 shown in detail in FIGS. The pump 3 is gas driven using gas from a compressed gas cylinder 5 supplied to the control device 4 via an adjustable valve 7 and a pipe 6 to give the pumped pressurized gas to the pump 3 . The control device 4 is shown in detail in FIG.

  By means of a pump 3, which requires neither mechanical power nor power, the culture medium flows along the flow path, so that the culture medium passes over at least the inner surface of the tube 1 (actually, the tube 1 passes through the So that the culture medium passes over both surfaces of tube 1). Since the pump 3 operates in a pulsed output that is considered advantageous for culturing the cells in the tube 1, when the cells in the natural state are accustomed to the pulse supply flow, the flow of the culture medium is pulsed to some extent Is done.

  The pump shown in FIGS. 4 and 5 is a molded synthetic plastic material in which each end member has a connection 33, 34 hermetically connected to an adjacent portion of the conduit 9 and includes a one-way valve A rigid composite 30 comprising the two end members 31, 32. The one-way valve has a valve seat 35 and a valve member which is in the form of a ball 36 and is biased to contact the valve seat by a compression spring 37. These valves thus allow a one-way flow through the pump 3 in the direction of the arrow 38.

  The two end members 31, 32 are connected by a rigid cylindrical body 39, which is also molded from a plastic material and has an inlet 40 and an outlet 41 for pressurized drive gas. Within the main body 39, the end members 31, 32 are sealed with a cylindrical silicone rubber tube 42 having a circumferential recess 43 in the axial central region of the outer surface. The recess 43 extends around the tube 42 and forms a circumferential chamber that communicates with both the inlet 40 and the outlet 41. Thus, the central region of the tube 42 has a thin wall 44 that is elastically deformable and deforms much more easily than the rest of the tube 42. Outlet 41 includes a bleed orifice (not shown) that restricts the flow of gas from chamber 43.

  The pump shown in FIG. 4 is driven only by a pulsed pressurized gas fed to the inlet 40 and generated as described below. The pressure pulse in the chamber 43 elastically deforms the thin wall 44 inward as shown in FIG. This allows a portion of the liquid contained in the valve member 45 to be pushed out through the one-way valves 35, 36, 37 on the right side of the pump, as can be seen in FIGS. When the pressure pulse drops due to leakage from the outlet 41, the thin wall 44 returns to its cylindrical state and a volume of liquid is drawn into the chamber 45 through a one-way valve at the left end of the pump.

  Each “stroke”, ie the volume pumped by each pressure pulse, can be altered by changing the dimensions of the thin wall 44 and changing the pressure fluctuations during the pressure pulse. The pumping speed can also be changed by changing the speed of the pressure pulse.

  Any suitable gas can be used to drive the pump, and no mechanical power source or power source is required. With the exception of the spring 37, the entire pump can be made of a synthetic plastic material and is therefore suitable for sterilization, for example by gamma radiation.

  In a modified version of the pump, a rigid cylinder of plastic material with a number of openings in the wall is inserted into the cavity 43 and pressed against the end wall of the cavity 43, so that the thin wall 44 is in tension. Maintained. This improves the elasticity of the wall 44 and the return to the cylindrical state.

  The silicone rubber tubing used for tube 42 is a conventional tubing material (AltiSil silicone tubing from Altec, Bude, Cornwell, England) and has been shown to allow gas permeation for gas diffusion. This allows gas diffusion into or out of the liquid in the pump chamber 45. In particular, if the pumped gas used to drive the pump is oxygen and / or carbon dioxide or contains oxygen and / or carbon dioxide, oxygen and / or carbon dioxide can be pumped into the liquid in the chamber 45. Is possible. Thus, when this pump is used in the organ culture apparatus of FIG. 1, FIG. 2, or FIG. 3, the necessary exchange of oxygen and carbon dioxide with the flowing culture medium can be easily and conveniently performed. Alternatively, a separate gas diffusion device can be provided in another portion of the flow path, for example, a gas permeable silicone tube. The gas used in the individual gas diffusion device may actually be the gas used to drive the pumps of FIGS.

  To drive the pump, it is necessary to provide pressurized gas that is pulsed. In the devices of FIGS. 1, 2 and 3, this is realized by the control device 4 shown in FIG. Similar to the pumps of FIGS. 4 and 5, this device is driven only by the pressurized gas supplied to it and no other external power is required.

  The apparatus of FIG. 6 has a cylindrical body 50 having a peripheral gas inlet 51 and an axial outlet 52 in the end wall 53. The piston 54 is slidable in the axial direction along the cylinder 50 and is sealed to the cylinder by an O-ring 55. The piston 54 extends through the opening in the second end wall 57 and holds a rod 56 that stabilizes the piston 54. The opening and rod 56 are shaped to allow gas to enter and exit the space to the left of the piston 54, as can be seen in FIG. In this space is a compression spring 58 that biases the piston 54 towards the end wall 53.

  The piston 54 holds an axially protruding sleeve 59 on the front face of the piston 54 having a central bore that opens at the forward end and a closed end slot 60 that allows lateral access to the bore. ing. A rod 61 having a pin 62 protruding into the slot 60, which holds an O-ring 64 and a valve member 63 sealed to a valve seat 65 around the inlet of the outlet 52 at the forward end And slide in the bore above. Around the rod 61 there is a coil spring 66 connected to the valve member 63 and the sleeve 59 and acting as a tension spring when extended and acting as a compression spring when compressed.

  The device 4 operates as follows. The gas supplied to the inlet 51 under pressure drives the piston 54 to the left against the action of the compression spring 58 and fills the cylinder chamber 67 on the right side of the piston 54 with the compressed gas. The valve member 63 is held in contact with the valve seat 65 by the gas pressure difference over the whole. Thus, the pin 62 slides along the slot 60 and the spring 66 is extended, but the tension applied by the spring 66 is not sufficient to lift the valve member 63 from the valve seat 65. When the pin 62 reaches the right end of the long hole 60, the sleeve 59 pulls the rod 61, so that the valve member 63 is lifted from the valve seat 65 at this time. This eliminates the pressure differential across the valve member 63, so this time the spring 66 rapidly pulls the valve member 63 and the rod 61 to the left, the outlet 52 is fully open and supplies a pulsed compressed gas from the device. It becomes possible.

  Due to the pressure drop in the chamber 67, the compression spring 58 moves the piston 54 to the right, bringing the valve member into contact with the valve seat 65 again. This contact is ensured by the pin 62 reaching the left end of the slot 60. The spring 66 is configured such that the pin 62 is in the center region of the slot 60 in a balanced state.

  The cycle of filling chamber 67 and releasing gas through outlet 52 is then repeated.

  The outflow speed of the gas from the outlet 52 when the outlet 52 is open must be faster than the inflow speed from the inlet 51. This can be achieved by appropriate bleed orifices or by adjusting the control of the valve 7 shown in FIGS. The pressure differential across the device 4 can also adjust the stroke speed of the device 4. Process speed and stroke volume can be adjusted by changing the characteristics of the springs 58 and 66 and the length of the rod 61.

  Except for the spring 66, the entire device of FIG. 6 can be made of a synthetic plastic material that can be sterilized by gamma radiation.

  The device 4 of FIG. 6 is shown as a separate unit, but can be incorporated into the structure of the pump 3 to form a single pumping device. One or both of these devices can be incorporated into the main body 2 to form a unitary structure.

  As described above, the constituent members 2, 3, and 4 do not require an external power source other than the pressurized gas supply source, and are more suitable for sterilization. Each component, such as the body 2, conduit 9 and pump 3, and optionally the valve 4 assembly, can be inserted into a sterilizable packaging enclosure of the type used in many surgical devices, The enclosure is then sealed. A suitable packaging material is Rexam Medical Packaging Integra® Form medical thermoforming film. The device inside the sealed package can then be sterilized in a known manner, for example by gamma radiation. In this form, the device is conveniently stored and, in use, transported to the laboratory for the initial stage of preparing a viable organ such as tube 1. After the tube 1 is formed, the device can immediately start the culture phase by circulating the culture medium through the closed circuit without having to install liquid piping and other devices. Contamination can be easily avoided throughout the entire culture period of organs, which can require weeks of time.

  It is advantageous to use a pressurized gas sealed from the circulating culture medium for driving the device. This is because gas consumption is relatively low and is easily provided by a suitable compressed gas canister or cylinder. The filling state of such a cylinder or canister is easily monitored by a pressure gauge. Electric devices that are not easy to sterilize and are relatively effective are avoided. When transporting organ culture devices, for example between hospitals, it is advantageous not to require a power source.

  With the exception of pressurized gas cylinders or canisters, the organ culture apparatus shown in FIGS. 1-6 can be made almost entirely of parts made of synthetic plastic material by injection molding. Therefore, this device is inexpensive to manufacture and is advantageous when the device is disposable. The device also meets the standards currently set for disposable medical devices.

  Although the drawings show an organ culture device that includes a viable organ in the form of a tube formed in-situ within the device, the present invention is not so limited. The principle of operation of the device can be applied to the storage and transport of other viable organs, including natural organs such as kidneys and blood vessels.

  As described above, the pump shown in FIGS. 4 and 5 and the controller for generating the pulsed pressurized gas of FIG. 6 are used in many other medical devices and other devices, as well as in the medical field. It can be used for other purposes.

1 is a schematic partial cross-sectional view of an organ culture device according to a first embodiment of the present invention. FIG. 5 is a schematic partial cross-sectional view of an organ culture device according to a second embodiment of the present invention. FIG. 5 is a schematic partial cross-sectional view of an organ culture device according to a third embodiment of the present invention. FIG. 4 is a schematic cross-sectional view of a pump that is an embodiment of the present invention and that is used in the organ culture apparatus of FIGS. 1, 2, and / or 3. FIG. 5 is a schematic cross-sectional view of the pump of FIG. FIG. 4 is a schematic cross-sectional view of a pressurized gas flow control device used in the organ culture device of FIGS. 1, 2, and / or 3 according to an embodiment of the present invention.

Claims (33)

An organ culture device for culturing viable organs,
A chamber containing a viable organ disposed along a liquid flow path for the flow of culture medium through the chamber;
A pump provided along the liquid flow path for pumping the culture medium;
The pump has a pump chamber with a net flow direction for the culture medium passing through it, and pulsed pumping by repeatedly deforming the deformable walls of the pump chamber located on the side of the net flow direction. A device that can obtain the action.   The device of claim 1, wherein the deformable wall is elastic.   3. The apparatus according to claim 1, further comprising gas transfer means for feeding gas into or out of the culture medium.   4. The apparatus of claim 3, wherein the gas transfer means operates by diffusing gas through a gas permeable wall.   5. A device according to any one of the preceding claims, wherein the repeated deformation of a deformable wall can be obtained by a pressurized gas outside the wall.   6. The apparatus according to claim 5, wherein the pressurized gas performs gas transfer to the culture medium.   7. The apparatus of claim 6, wherein the deformable wall of the pump is gas permeable and therefore gas transfer occurs through the wall.   8. A device according to any one of the preceding claims, wherein the deformable wall extends substantially circumferentially around the pump chamber.   The apparatus of claim 8, wherein the deformable wall is tubular.   The pump has an inlet and an outlet located at opposite ends of the pump chamber and disposed on the longitudinal axis of the pump chamber, and the deformable wall is disposed between the inlet and the outlet; 10. A device according to any one of claims 1 to 9, which is substantially parallel to the longitudinal axis.   11. A device according to any one of the preceding claims, wherein the liquid channel or part of the liquid channel extends from a reservoir that supplies the culture medium pumped towards the chamber.   12. The apparatus according to any one of claims 1 to 11, further comprising a culture medium collecting means disposed downstream of the chamber.   The apparatus of claim 12, wherein the chamber and the collecting means are in communication via a flow regulating valve.   14. A device according to any one of claims 1 to 13, wherein the liquid channel or part of the liquid channel forms a liquid flow circuit and at least some of the culture medium is recirculated in use.   15. Apparatus according to any one of the preceding claims, comprising a sampling port located downstream of the chamber for sampling the culture medium.   16. Apparatus according to any one of claims 1 to 15, wherein in use, the chamber contains viable organs and circulates in the liquid flow circuit through a culture medium.   17. A method of maintaining viable organs so that they can be transported and stored using the organ culture apparatus of any one of claims 1-16.   18. A device according to any one of the preceding claims, pre-sterilized to contain viable organs and placed in a sealed enclosure to maintain the sterilized state of the device.   Further comprising a gas pressure control device that controls the gas flow to provide a pulsed flow of compressed gas to the pump, the organ culture device is pre-sterilized to accommodate viable organs and maintains the sterilized state of the device 7. An organ culture device according to claim 4, 5 or 6, which is placed in a sealed enclosure for the purpose. A pump for liquids,
A pump chamber for the liquid having a net flow direction therein for the pumped liquid;
Having a pumping member acting on the liquid in the shape of a deformable wall of the pump chamber, arranged laterally in the net flow direction;
The deformable wall is a liquid pump that pumps in response to a pulse of pressurized gas.   21. A pump according to claim 20, wherein the deformable wall is elastic.   22. A pump according to claim 20 or 21, wherein the deformable wall extends substantially circumferentially around the pump chamber.   23. A pump according to any one of claims 20 to 22, wherein the deformable wall is tubular.   24. A pump according to any one of claims 20 to 23, having means for generating a pulsed flow of pressurized gas from a reservoir of pressurized gas.   25. A pump according to any one of claims 20 to 24, wherein the deformable wall is gas permeable and provides gas transfer between the pumped liquid and the pressurized gas. A gas pressure control device for supplying pressurized gas to be pulsed,
A gas accumulator chamber having an inlet and an outlet connected to a source of pressurized gas and elastically expandable by movement of the movable wall of the chamber;
A valve member movable between a closed position for closing the outlet and an open position for generating an outflow through the outlet;
Means actuated by moving the movable wall of the accumulator chamber, thereby moving the valve member from the closed position to the open position when a predetermined pressure is reached in the accumulator chamber;
Means for returning the valve member to a closed position when the accumulator chamber contracts after a volume of gas has been released from the accumulator chamber.   27. The apparatus of claim 26, wherein the accumulator chamber is a piston and cylinder assembly.   28. An apparatus according to claim 26 or 27, wherein the movable wall holds an actuating member that initiates movement of the valve member in a direction away from the closed position.   Having a deflecting means acting on the valve member when the valve member is moved from the closed position, thereby eliminating the pressure difference across the valve member when the valve member is opened; 29. The device according to any one of claims 26 to 28, wherein the device is moved to.   30. Use of a pump according to any one of claims 20 to 25 or a device according to any one of claims 26 to 29 in medicine relating to humans or animals.   21. The organ culture device according to claim 1, comprising the pump according to claim 20 as the pump of the device.   32. The organ culture device according to claim 31, comprising the gas pressure control device according to any one of claims 26 to 29, wherein pressurized gas supplied in a pulsed manner is supplied to the pump. The pump according to any one of claims 20 to 25, comprising the gas pressure control device according to any one of claims 26 to 29, wherein the pressurized gas supplied in pulses is supplied to the pump.

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