U.S. patent application number 15/338841 was filed with the patent office on 2017-02-16 for organ perfusion systems.
The applicant listed for this patent is Organox Limited. Invention is credited to Philip David Canner, Constantin C. Coussios, Peter John Friend, Stuart Brian William Kay, David George Robinson, Leslie James Russell, Peter Alan Salkus.
Application Number | 20170042141 15/338841 |
Document ID | / |
Family ID | 47172815 |
Filed Date | 2017-02-16 |
United States Patent
Application |
20170042141 |
Kind Code |
A1 |
Kay; Stuart Brian William ;
et al. |
February 16, 2017 |
ORGAN PERFUSION SYSTEMS
Abstract
A disposable set of components for an organ perfusion system
comprising a fluid supply duct for supplying fluid to the organ, a
fluid removal duct for removing fluid from the organ, and a
surrogate organ removably connected between the fluid supply duct
and the fluid removal duct so as to form a fluid circuit, so that
fluid can be circulated in the circuit in preparation for
connection of the organ.
Inventors: |
Kay; Stuart Brian William;
(Cambridge, GB) ; Robinson; David George;
(Cambridge, GB) ; Canner; Philip David;
(Cambridge, GB) ; Salkus; Peter Alan; (Cambridge,
GB) ; Russell; Leslie James; (Oxford, GB) ;
Friend; Peter John; (Oxford, GB) ; Coussios;
Constantin C.; (Oxford, GB) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Organox Limited |
Oxford |
|
GB |
|
|
Family ID: |
47172815 |
Appl. No.: |
15/338841 |
Filed: |
October 31, 2016 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
14357118 |
May 8, 2014 |
|
|
|
PCT/GB2012/052782 |
Nov 8, 2012 |
|
|
|
15338841 |
|
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A01N 1/0247 20130101;
Y10T 83/04 20150401; A01N 1/021 20130101 |
International
Class: |
A01N 1/02 20060101
A01N001/02 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 10, 2011 |
GB |
GB 1119418.0 |
Nov 10, 2011 |
GB |
GB1119419.8 |
Claims
1. A method of preparing an organ perfusion system for use in
perfusing a bodily organ, the method comprising: providing a
disposable set of components for the organ perfusion system, the
set comprising a fluid supply duct for supplying fluid to the
bodily organ, a fluid removal duct for removing fluid from the
bodily organ, a surrogate organ removably connected between the
fluid supply duct and the fluid removal duct so as to form a fluid
circuit, a priming reservoir containing perfusion fluid, a priming
duct, and a connector, wherein the connector connects the fluid
circuit to the priming reservoir via the priming duct; arranging
the disposable set such that the connector is positioned at a
lowest point of the fluid circuit; and filling the fluid circuit
with the perfusion fluid from the priming reservoir via the
connector thereby causing the perfusion fluid to flow upwards
through the whole fluid circuit.
2. The method of claim 1 further comprising circulating the
perfusion fluid in the fluid circuit in preparation for connection
of the bodily organ.
3. The method of claim 1 wherein the organ perfusion system further
comprises a fluid reservoir having a top, the priming reservoir is
moveably attached to the fluid circuit, and filling the circuit
with perfusion fluid comprises raising the priming reservoir a
level that is higher than the top of the fluid reservoir thereby to
cause the perfusion fluid to flow from the priming reservoir into
the fluid circuit.
4. The method of claim 3 wherein the organ perfusion system
comprises an air vent located above the fluid reservoir, and air is
vented from the system through the vent as the fluid circuit is
filled with the perfusion fluid.
5. The method of claim 2 wherein the organ perfusion system further
comprises an oxygenator connected to the fluid supply duct and the
fluid removal duct, and the method comprises adding oxygen into the
perfusion fluid as the perfusion fluid is circulated in the fluid
circuit.
6. The method of claim 2 wherein the organ perfusion system further
comprises a measuring duct connected between the fluid supply duct
and the fluid removal duct, and the method comprises measuring the
content of at least one component of the perfusion fluid in the
measuring duct as the perfusion fluid is circulated in the fluid
circuit.
7. The method of claim 1 wherein the organ perfusion system further
comprises a pump arranged to pump fluid round the fluid circuit,
the pump comprising a pump head which is independently movable, and
the method comprises tapping the pump head to remove gas trapped
therein.
8. The method of claim 2 further comprising disconnecting the
surrogate organ from the fluid circuit and connecting the bodily
organ into the fluid circuit for perfusion.
9. The method of claim 1 wherein the surrogate organ comprises an
inlet duct and an outlet duct, and connecting the surrogate organ
into the fluid circuit comprises connecting the inlet duct to the
fluid supply duct and connecting the outlet duct to the fluid
removal duct.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the priority benefit of U.S. patent
application Ser. No. 14/357,118 filed May 8, 2014; International
PCT Application PCT/GB2012/052782 filed Nov. 8, 2012 and published
under PCT 21(2) in the English language; Great Britain Patent
Application Serial No. 1119418.0 filed Nov. 10, 2011; and Great
Britain Patent Application Serial No. 1119419.8 filed Nov. 10,
2011, all of which are incorporated by reference herein.
FIELD OF INVENTION
[0002] The present invention relates to perfusion systems for
bodily organs, for example human organs, such as the liver,
pancreas, kidney, small bowel, but also other organs including
non-human organs.
BACKGROUND OF THE INVENTION
[0003] It is known, for example from EP 1 168 913, to provide a
system for extracorporeal organ perfusion, in which a human or
non-human organ can be preserved, for example prior to transplant
into a patient. The system typically comprises a reservoir for
perfusion fluid, which may be blood or another perfusion solution,
and a circuit for circulating the fluid through the organ.
SUMMARY OF THE INVENTION
[0004] The present invention provides a set of components for an
organ perfusion system, the set comprising a fluid supply duct for
supplying fluid to the organ, a fluid removal duct for removing
fluid from the organ, and a surrogate organ removably connected
between the fluid supply duct and the fluid removal duct so as to
form a fluid circuit, so that fluid can be circulated in the
circuit in preparation for connection of the organ. The set may be
disposable. For example it may be arranged for a single use.
[0005] The fluid supply duct and the fluid removal duct may be
arranged for connection, directly, or indirectly, to an oxygen
adding means so that oxygen can be added into fluid in the
circuit.
[0006] The set may further comprise a measuring duct, which may be
connected between the fluid supply duct and the fluid removal duct,
or may be connected between two other suitable places in the
circuit, and measuring means arranged to measure the content of at
least one component of the fluid. The measuring duct may be
arranged to bypass the organ. The measuring duct may be of a
smaller diameter than the supply duct and the fluid removal
duct.
[0007] The set may further comprise a pump arranged to pump fluid
round the circuit. This may be located, for example, in the fluid
removal duct.
[0008] The set may further comprise a fluid reservoir arranged to
contain fluid for circulation in the circuit. The set may further
comprise a pressure control duct arranged to connect the reservoir
to a return port of an oxygen adding means.
[0009] The set may further comprise a fluid return duct arranged to
return fluid produced by the organ or fluid, which may be perfusion
fluid leaked, by the organ into the circuit. If the organ is a
liver, the fluid may be ascites. For other organs the fluid may be
a different fluid. The fluid return duct may be arranged for
connection to the reservoir, whether the reservoir is part of the
set or not. The set may further comprise a pump arranged to pump
fluid in the fluid return duct. The set may comprise a fluid level
sensor arranged to measure the level of the fluid produced by the
organ. The set may comprise a sump, to which the fluid return duct
is connected, for collecting the fluid produced by the organ.
[0010] The set may further comprise a collection system for
collecting fluid produced by the organ. This may be a different
fluid. For example, in the case of a liver it may be bile, or in
the case of a kidney it may be urine. The set may further comprise
measurement means for measuring the volume of the fluid produced by
the organ.
[0011] The set may further comprising a further fluid supply duct
removably connected to the surrogate organ. This is appropriate,
for example, for perfusion of a liver, whereas other organs, such
as the pancreas, only require one fluid supply duct. The further
fluid supply duct may be arranged for connection to a reservoir,
whether or not that forms part of the set.
[0012] The set may further comprise a connector for connection to a
fluid supply. The connector may be arranged to be at the lowest
point of the circuit when the circuit is in use. For example it may
be in the fluid removal duct.
[0013] The set may further comprise an air vent. The air vent may
be arranged to be located above the reservoir. The air vent can be
used to vent air from the system as the circuit is filled with
fluid.
[0014] The whole system may be arranged such that there are no, or
substantially no, air traps within it. For example the whole of the
perfusion circuit may be arranged to slope upwards from the
connector for the fluid supply to the air vent, so that fluid can
fill the circuit from the supply, no air pockets will be trapped in
the circuit, and all air in the circuit will be vented out and
replaced by fluid.
[0015] The set may further comprise a support panel arranged to
support at least one of the ducts, which may be in the form of
flexible tubing.
[0016] The support panel, an organ container and a pump may form
separate units of the set. The units may be connected together by
one or more of the ducts, which may be flexible. This may allow the
units to be moved between a folded state for storage and an
unfolded state for use, whilst connected together.
[0017] Indeed the present invention further provides a set of
components for an organ perfusion system, the set comprising a
support panel supporting a component, such as at least one flexible
tube, forming part of the system, an organ container, and a pump,
wherein the support panel, the organ container and the pump form
separate units of the set which are connected together by one or
more flexible tubes, so that the units can be moved between a
folded state for storage and an unfolded state for use, whilst
connected together. The flexible tube or tubes may form part of a
perfusion circuit of the system.
[0018] The support panel may have a channel formed therein, in
which the at least one flexible tube or duct is located. The
support panel may further comprise a tab, which may be formed
integrally with the panel, and may be arranged to retain the tube
or duct in the channel. The channel may be divided into two channel
sections which are spaced apart. The panel may have an aperture
through it. The aperture may extend around three sides of the tab.
The two channel sections may open into the aperture. This may
enable a portion of the flexible tube or duct to be bent, fitted
through the aperture, and then straightened so as to be retained in
the channel by the tab.
[0019] The present invention further provides a support panel for
supporting a length of flexible tubing or other flexible member,
the panel having a channel formed therein, wherein the channel is
divided into two channel sections which are spaced apart, and the
panel has an aperture through it, between the channel sections,
which extends around three sides of a portion of the panel which
forms a tab, the two channel sections opening into the aperture so
that a portion of the flexible member can be bent, fitted through
the aperture, and then straightened so as to be retained in the
channel by the tab.
[0020] The panel on either side of each of the channel sections may
lie in a common flat plane. The tab may be flat and may be formed
in the same plane. The depth of the channel may be greater than the
sum of the diameter of the flexible member and the thickness of the
tab, so that the flexible member can be straightened completely
within the two channel sections.
[0021] The panel may comprise a recess arranged to receive an
oxygenator in it. The panel may comprise a recess arranged to
receive a fluid reservoir in it.
[0022] The present invention further provides a method of making a
support panel according to the invention, the method comprising
providing the panel with the two channel sections formed in it, and
cutting the aperture through the panel so as to leave the tab.
[0023] At least one of the two channel sections may be formed with
an end wall. The cutting step, or a separate cutting or other
removal step, may remove the end wall.
[0024] The present invention further provides a perfusion system
for the perfusion of an organ, the system comprising a perfusion
fluid circuit for circulating perfusion fluid through the organ,
the circuit comprising a fluid supply duct for supplying fluid to
the organ and a fluid removal duct for removing fluid from the
organ, the system further comprising a surrogate organ arranged to
be connected between the fluid supply duct and the fluid removal
duct so that fluid can be circulated in the circuit in preparation
for connection of the organ.
[0025] The present invention further provides a method of preparing
an organ perfusion system for perfusion of an organ, the method
comprising providing a perfusion system with a surrogate organ
connected into it, circulating perfusion fluid through the system
including the surrogate organ in preparation for connection of the
organ. The perfusion system may be any system according to the
invention as described above. The perfusion system may comprise any
set of components according to the invention as described
above.
[0026] Preferred embodiments of the present invention will now be
described by way of example only with reference to the accompanying
drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 is a schematic diagram of a perfusion system
according to an embodiment of the invention;
[0028] FIG. 2 is an enlargement of part of FIG. 1;
[0029] FIG. 3 is a cross section through a connector forming part
of the system of FIG. 1;
[0030] FIG. 4 is a perspective view of a surrogate organ and its
connections forming part of the system of FIG. 1;
[0031] FIG. 5 is a perspective view of a support structure forming
part of the system of FIG. 1;
[0032] FIG. 6 is a perspective view of a support panel forming part
of the structure of FIG. 5;
[0033] FIG. 7 is a front view of part of the panel of FIG. 6 during
its manufacture;
[0034] FIG. 8 is a perspective view of the same part of the panel
of FIG. 6 during its manufacture;
[0035] FIG. 9 is a plan view of the same part of the panel of FIG.
6 at a subsequent stage of its manufacture;
[0036] FIG. 10 is a front view of part of the panel of FIG. 6
arranged to retain disposable tubing on the panel; and
[0037] FIG. 11 is a perspective view of the same part of the panel
as FIG. 10;
[0038] FIG. 12 is a perspective view of parts of the system of FIG.
1 in a folded condition;
[0039] FIG. 13 is a schematic view of an organ connected into the
system of FIG. 1;
[0040] FIG. 14 is a schematic diagram, similar to FIG. 1, of the
system modified for perfusion of a different organ.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0041] Referring to FIGS. 1 and 2, a perfusion system according to
an embodiment of the invention generally comprises a sling 10 in
which an organ can be supported, a fluid reservoir 12, an
oxygenator 14, and a perfusion circuit 16 arranged to circulate
fluid between the reservoir, the organ, and the oxygenator during
perfusion. A controller 18 is arranged to control the functioning
of the system as will be described in more detail below.
[0042] The sling 10 is of moulded plastics or other suitable
material and designed to be compliant so as to enable non-traumatic
support of the organ whilst providing a degree of shock absorption
during transport. The sling 10 has a perforated base 19 through
which fluids leaking from the organ can flow out, and side walls 20
extending upwards from the base 19, and a rim 22 extending around
the top of the side walls 20. A fluid sump 24 which, where the
organ is a liver, forms an ascites sump, is located beneath the
sling 10, and comprises a concave base 26 that tapers downwards to
a drainage hole 28, which is formed through its lowest point. The
sump 24 is arranged to catch fluid leaking through the base 19 of
the sling. The sump 24 also comprises side walls 30 that extend
upwards from the base 26, around the side walls 20 of the sling,
and have a flange 32 around their top which supports the rim 22 of
the sling 10. A removable cover 34, which is of moulded plastics,
fits over the top of the sling 10 and has a rim 36 around its lower
edge which fits against the rim 22 of the sling.
[0043] The sling 10 is supported within an organ container 40 which
has the ascites sump 24 and a bile sump 42 supported in its base
44, and in this embodiment formed integrally with it. The organ
container 40 has side walls 46 extending upwards from its base 44
and a removable cover 48. The bile sump 42 is about twice as deep
as the ascites sump 24 and generally narrow and tubular in shape,
and extends downwards from the base 44 of the container 40 with its
rim 52 level with the rim 32 of the ascites sump 24 and the rim 22
of the sling.
[0044] The bile sump 42 is formed in two parts, an upper part 42a
and a lower part 42b, both of which are integral with the base 44
of the organ container. The lower part 42b has a bile inlet port 54
formed in its side, towards its upper end 56, and a bile overflow
port 58 formed in its upper end. A bile outlet port 60 is formed in
the base 44 of the organ container close to the top of the bile
sump, with an upper connector 60a for connection via a cannula to
the liver, and a lower connector 60b for connection to a bile
measurement system 62. The bile measurement system 62 is arranged
to measure the volume of bile secreted by the liver before allowing
it to flow into the bile sump 42.
[0045] As can best be seen in FIG. 2, the bile measurement system
62 comprises a bile receiving duct 64 having its upper end
connected to the lower connector 60b, and its lower end connected
to a T-piece connector 66, a bile outlet duct 68 having its upper
end connected to the connector 66 and its lower end connected to
the bile inlet port 54, and an overflow duct 70 having its lower
end connected to the connector 66 and its upper end connected to a
further port 69 formed in the base 44 of the container. An overflow
pipe 72 connects the top of the further port 69 to the bile
overflow port 58 in the top of the lower part 42b of the sump. A
liquid level sensor 74 is arranged to measure the level of fluid in
the overflow duct 70 and to output a signal indicative of the fluid
level to the controller 18. In this embodiment the liquid level
sensor 74 is arranged to detect when the liquid level in the
overflow duct 70 reaches a predetermined height, and send a signal
indicative of this to the controller 18. A flow control valve,
which in this embodiment comprises a pinch valve 76, in the bile
outlet duct 68 is switchable between a closed state in which it
closes the outlet duct 68 so that bile can build up on the
measurement system 62 and an open state in which it allows bile to
drain from the measurement system 62 into the bile sump 42. The
controller 18 is arranged to control the flow control valve 76.
[0046] The controller 18 is arranged to measure the rate at which
bile is secreted by the liver by closing the pinch valve 76 so that
bile builds up in the outlet duct 68, and then in the bile
receiving duct 64 and overflow duct 70. When the level sensor 74
detects that the bile has reached the predetermined level, it is
arranged to send a signal to the controller 18 which responds by
opening the pinch valve 76, for example for a predetermined period,
to allow the bile to drain out of the measurement system into the
sump, and then closes it again so that bile can start to collect in
the measurement system again. The controller 18 is also arranged to
record in memory the times at which the bile reaches the
predetermined level, and therefore the times at which the
measurement system is filled. This information, together with the
known volume of the system when it is filled to the predetermined
level, allows the rate at which bile secreted over time to be
monitored. For example the controller 18 may be arranged to
calculate a flow rate each time the valve 76 is opened from the
known volume of the system and the time interval between the valve
opening and the previous valve opening. That flow rate can be
displayed on the GUI 17, being updated each time a new calculation
of flow rate is recorded. Alternatively, the controller 18 may be
arranged to store this flow rate information in memory, so that
flow rate data for the whole perfusion process can be stored and
then output or displayed via the GUI 17. As a further alternative,
the controller may not perform any calculation but may generate an
output which varies with the flow rate, and the GUI may be arranged
to respond to the output by generating a display, such as a line
graph, which is indicative of the flow rate, for example by having
appropriately marked axes. It will be appreciated that, for organs
other than the liver, this measurement system can be arranged to
measure other fluids leaking from, or excreted by, the organ during
perfusion, and to record and display the measured volume. For
example the organ may be a kidney and the fluid may be urine.
[0047] Referring back to FIG. 1, an ascites duct 80 is connected at
one end to the drainage hole 28 in the bottom of the ascites sump
26 and at the other end to an ascites return port 82 in the top of
the fluid reservoir 12. The ascites duct 80 has a central portion
80a that is the lowest part of the duct 80, being below the level
of the ascites sump 26, as well as below the level of the reservoir
12. An ascites pump 84 is provided in the central portion 80a of
the ascites duct 80 to pump ascites from the sump 26 back up into
the reservoir 12. An ascites measurement tube 86 extends vertically
upwards from the central portion 80a of the ascites duct, adjacent
to, and upstream of, the pump 84, and has a fluid level sensor 88
in it. This level sensor 88 is arranged to detect, and output a
signal, when fluid in the measurement tube 86 reaches a
predetermined level that is below the base 19 of the sling 10, and
in this embodiment above the drainage port 28 in the ascites sump.
The fluid level sensor 88 is connected to the controller 18 which
receives the signals from it, and can therefore detect when the
level of ascites in the sump reaches a predetermined level. In
response to this the controller 18 is arranged to activate the
ascites pump 84, for example for a predetermined time, to reduce
the level of ascites in the sump 26. The speed of the pump 84 may
be variable and the controller 18 may be arranged to control the
speed of the pump, or the duty ratio of the pump, or the average
speed of the pump, on the basis of the measured fluid level. In
other embodiments the ascites level sensor can be located within
the sump 26. Indeed any suitable system for measuring the volume of
accumulated ascites can be used as feedback to control the
operation of the pump 84. For example a pressure sensor located
close to the pump 84 could be used to measure accumulated ascites
volume. In still other embodiments the ascites pump 84 can simply
be arranged to operate for fixed periods with no measurement of
ascites volume.
[0048] In a modification to this embodiment, there is a further
ascites level sensor in addition to the sensor 88, so that the
sensors can detect when the ascites level reaches upper and lower
levels. The controller 18 is arranged to start the ascites pump 84
when the ascites is detected as reaching the upper level, and to
step the ascites pump 84 when the ascites level drops to the lower
level. The controller is then arranged to record the timing of each
time the pump is turned on, and this provides an indication of the
total volume of ascites and the flow rate of ascites during
perfusion. This information can be stored and displayed on the GUI
17 in the same way as the bile measurements. It will be appreciated
that, for other organs, this measurement system can be used to
measure the total volume or flow rate of other fluids leaking from,
or excreted by, the organ during perfusion. This measurement can
also be provided with only one ascites level sensor as shown in
FIG. 1, for example if the pump 84 is arranged to operate until it
has pumped all of the ascites that is upstream of the pump 84,
which can be assumed to be a fixed volume.
[0049] The perfusion circuit 16 further comprises a first fluid
supply duct 100, which when used for perfusion of a liver forms a
portal duct, a second fluid supply duct 102, which when used for
perfusion of a liver forms a hepatic artery duct, and a fluid
removal duct 104, which when used for perfusion of a liver forms an
inferior vena cava (IVC) duct. The system and its operation will
now be described for perfusion of a liver, but it will be
appreciated that it can equally be used for other organs. The
portal duct 100 has one end connected to an outlet port 106 in the
fluid reservoir and the other end attached to a portal vein
connector 108. The portal duct 100 extends through a port 110 in
the side wall 46 of the organ container 40 so that the portal vein
connector 108 is located inside the container. A flow control valve
112, in the form of a pinch valve, having a variable degree of
opening, is provided in the portal duct 100 and is connected to the
controller 18. The controller 18 is arranged to vary the degree of
opening of the pinch valve 112 so as to control the rate of flow of
fluid from the reservoir 12 to the portal vein of a liver. A portal
flow sensor 113 is provided in the portal duct 100 and is arranged
to output a signal indicative of the flow rate of fluid in the
portal duct 100. The output of the flow sensor 113 is connected to
the controller 18 which can therefore monitor the flow rate in the
portal duct. The controller 18 is also arranged to determine from
the flow sensor 113 signal when the flow of fluid from the
reservoir ceases due to the reservoir being empty. In response to
detection of an empty reservoir the controller 18 is arranged to
close the flow control valve 112 so as to prevent air from reaching
the organ. The hepatic artery duct 102 has one end connected to a
first outlet port 114 of the oxygenator 14 and the other end
attached to a hepatic artery connector 116. The hepatic artery duct
102 extends through a port 118 in the side wall 46 of the organ
container 40 so that the hepatic artery connector 116 is located
inside the container. The IVC duct 104 has one end attached to an
IVC connector 120, which is located inside the container 40, and
extends out through a port 122 in the base 44 of the organ
container 40, having its other end connected to an inlet port 124
of the oxygenator 14. A pump 123 is provided in the IVC duct 104
having its inlet connected by a part of the IVC duct 104 to the IVC
connector 120, and its outlet connected to the inlet port 124 of
the oxygenator 14. The pump 123 is, arranged to pump fluid from the
IVC duct 104 into the oxygenator 124. The pump 123 is a variable
speed pump and is connected to, and controlled by, the controller
18. An IVC flow sensor 125 is arranged to measure the rate of fluid
flow rate in the IVC duct 104 and is arranged to output a signal
indicative of the flow rate of fluid in the vena cava duct 104. The
output of the flow sensor 125 is connected to the controller 18
which can therefore monitor the flow rate in the IVC duct 104.
[0050] Each of the connectors 108, 116, 120 is a quick-release
connector arranged to allow the duct to which it is attached to be
connected, either via a cannula to the appropriate vein or artery
of the liver, or to a surrogate organ 126 which is arranged to
complete the perfusion circuit prior to connection of the real
organ. The surrogate organ 126 comprises two inlet ducts 128, 130
for connection to the portal duct 100 and the hepatic artery duct
102, and one outlet duct 132 for connection to the IVC duct 104. In
this embodiment the surrogate organ is in the form of a simple
Y-piece connector 134 which connects the two inlet ducts 128, 130
to the outlet duct 132 so that, when it is connected into the
circuit, fluid can flow through it from the portal duct 100 and the
hepatic artery duct 102 to the IVC duct 104.
[0051] Each of the portal duct 100, the hepatic artery duct 102 and
the IVC duct 104 has a pressure sensor 136, 137, 138 in it,
arranged to measure the pressure of fluid in the duct 100, 102,
104. Each of these pressure sensors 136, 137, 138 is arranged to
measure pressure at a point close to the respective connector 108,
116, 120, and to output a signal indicative of the pressure at that
point. Referring to FIG. 3, the pressure sensor 136 in the portal
duct 100 will now be described, but those 137, 138 in the hepatic
artery duct 102 and IVC duct 104 are identical. The duct 100 is
split into two sections 100a, 100b, and the pressure sensor 136 is
located in a moulded plastics sensor housing 300 which forms part
of a connector 302 arranged to connect the two sections 100a, 100b
of the duct together. The connector 302 comprises a tubular body
304, with the sensor housing 300 formed on one side, centrally
between its two ends 306, 308. Each end of the tubular connector
body has a stepped outer diameter, having a thicker part 310 at the
end, and a thinner part 312 between the thicker part 310 and the
sensor housing 300. A step 313 is formed between the two parts 310,
312. The thicker part 310 is tapered, getting thinner towards the
end of the body. The portal duct sections 100a, 100b are formed of
plastics tubing which have an inner diameter which is similar to
the outer diameter of the thinner parts 312 of the connector 302.
The tubing can therefore be stretched over the thicker parts 310 of
the connector and the step, so that they will grip, and be held in
place, on the connector.
[0052] The port 118 in the organ housing 40 has a cylindrical wall
314 surrounding it on the outer side of the housing 40. The wall is
thicker at its base than at its outer end, so that its inner
diameter decreases from its outer end to its inner end. This inner
diameter is slightly greater than the thicker parts 310 of the
connector body, so that one end of the connector body, with the
tubing pushed over it, can be pushed into the aperture within the
cylindrical wall 314, so that the tubing is held between the
cylindrical wall 314 and the thicker part 310 of the connector, as
shown in FIG. 3. The tubing can then be pulled from inside the
housing 40 to secure the connector 302 and tubing in place.
[0053] Referring to FIG. 4, the surrogate organ 126 is supported on
a moulded support 400, designed to provide upwards sloping of the
surrogate organ to avoid air entrapment during priming. The support
has a circular raised turret 402 formed in it which has a Y-shaped
groove 403 formed in its top surface in which the Y-shaped
connector 134 of the surrogate organ 126 can be located. The
support 400 has a further raised turret or strip 404 which has two
recesses 405 across its top surface in which the ends of the two
inlet ducts 128, 130 of the surrogate organ can be located. The
support has a further raised turret 406 having a recess 407 across
its top surface in which the end of the outlet duct 132 of the
surrogate organ can be located. Each of the connectors 108, 116,
120, which connect the surrogate organ 126 to the two main inlet
ducts 100, 102 and the main outlet duct 104, comprises a pipe stub
410 arranged to fit into one of the ducts 128, 130, 132 of the
surrogate organ 126, another pipe stub 412 arranged to fit into the
end of one of the inlet ducts 100, 102 or the outlet duct 104, and
a bellows 414 connecting the two pipe stubs 410, 412 together in a
flexible manner so that the connectors can each accommodate a
degree of misalignment between the two tube sections they connect
together.
[0054] Three clamps 420 are provided, one on each of the two inlet
ducts 128, 130 of the surrogate organ, and one on the outlet duct
132 of the surrogate organ. Each of these clamps 420 is ratchet
clamp that can be closed so as to pinch the duct and seal it to
prevent the flow of fluid through it. The ratchet 422 on the clamp
retains it in this closed position, but can be released to release
the clamp and open the duct. Three similar ratchet clamps 424 are
provided, one on each of the main inlet ducts 100, 102 and one on
the outlet duct 104, close to the respective connector 108, 116,
120, and between the connector 108, 116, 120 and the pressure
sensors 136, 137, 138. These six clamps can be used to seal the
ends of the various ducts when the surrogate organ is being
connected into, or disconnected from, the perfusion circuit.
[0055] Referring back to FIG. 1, the oxygenator 14 has a second
outlet port 140 which is connected by a pressure control duct 142
to a pressure control port 144 in the fluid reservoir 12. A flow
control valve, in the form of a pinch valve 146, having a variable
degree of opening, is provided in the pressure control duct 142 and
is connected to the controller 18 so that the controller can vary
the degree of opening of the pinch valve 146 thereby to control the
return flow of fluid from the oxygenator 14 to the reservoir 12.
This, together with the speed of the pump 123, is controlled by the
controller 18 to control the pressure of fluid flowing to the organ
through the hepatic artery duct 102, as well as the pressure of the
fluid in the vena cava duct 104 flowing away form the organ. A vent
duct or pipe 158 is connected at its lower end to a fluid through
duct in the oxygenator 14 and extends upward so that its upper end
is approximately level with the top of the reservoir 12. This vent
158 is closable, and is arranged to be opened during filling of the
fluid circuit to vent air from the oxygenator, but is closed during
perfusion.
[0056] Referring still to FIG. 1, a nutrient control circuit 170
comprises a set of syringes 172, in this case four, each containing
a respective nutrient, and a nutrient feed duct 174 which has one
end connected to a separate fluid reservoir 176 and the other end
connected to a nutrient inlet port 178 in the top of the main fluid
reservoir 12. Each of the syringes 172 is connected to the nutrient
feed duct 174 by a respective nutrient input duct 180. A nutrient
pump 182 is arranged in the nutrient feed duct 174 to pump fluid
through the nutrient feed duct from the nutrient feed reservoir 176
into the main reservoir 12 via the nutrient inlet port 178. The
pump 182 and the syringes 172 are controlled by the controller 18
so that the rate at which each of the nutrients is fed into the
reservoir 12 is controlled.
[0057] A small diameter fluid analysis duct 190 has one end
connected to the IVC duct 104, upstream of the pump 123, and in
this case downstream of the IVC flow sensor 125, and the other end
connected to the pressure control duct 142, upstream of the
pressure control valve 146, so that fluid can flow through the
fluid analysis duct 190 from the pressure control duct 142 to the
IVC duct 104, bypassing the organ. A measurement system, in this
case in the form of a blood gas analyser (BGA) 192 is arranged to
measure various parameters of the fluid flowing through the fluid
analysis duct 190. In this embodiment the BGA 192 is arranged to
measure the oxygen content and the carbon dioxide content of the
fluid flowing through it. Other parameters can also be measured and
monitored. The BGA 192 is connected to the controller 18 and
arranged to output signals each of which is indicative of the value
of one of the parameters it measures, and the controller 18 is
arranged to receive those signals so that the parameters can be
monitored by the controller 18. The signals therefore include an
oxygen level signal, a CO.sub.2 level signal, and a glucose level
signal in this embodiment.
[0058] A priming bag or reservoir 194 is supported at a level which
is above the top of the reservoir 12, and connected by a priming
duct 196 to the perfusion circuit at a priming point which is in
the vena cava duct 104 at its lowest point 104a. This is also the
lowest point of the perfusion circuit 16, which allows the whole
circuit 16 to be filled from the bottom, as will be described in
more detail below.
[0059] Referring to FIG. 5, a support structure for the perfusion
system comprises a housing 500 the front face 502 of which has an
aperture 504 behind which the controller 18 and GUI 17 are located,
another aperture 506 within which the nutrient syringes 172 are
located, and a large aperture in which a disposable support panel
or cartridge 508 is located which supports many of the disposable
components of the system. A pump support housing 509 is located on
the base of the structure to support the perfusion pump 123.
[0060] Referring to FIG. 6, the cartridge 508 comprises a
thermoformed plastics panel which has a recessed reservoir support
region 510 in its upper half through which a pair of apertures 512,
514 are formed, an oxygenator support area 516 in its lower half
which also has a recess formed in it, which may comprise an
indentation or an aperture 518 or both, in which the oxygenator can
be supported, two control valve apertures 520, 522 in which the
pinch valves 112, 146 can be located, and a series of channels 524
formed in it, which are open to the rear, in which the flexible
tubing of the fluid circuit ducts can be located. At various points
along the channels 524 there is a break in the channel, with a
retaining tab 526 which serves to retain the tubing in the channel
524. The formation of the panel so as to include these tabs will
now be described.
[0061] Referring to FIGS. 7 and 8, the first stage of production of
the cartridge 508 is thermoforming which is used to form a series
of formations in the panel, which is flat prior to the
thermoforming. The formations are raised or convex on the front
side and hollow or concave on the rear side. The channels 524 are
mainly formed in this way, being of generally U-shaped cross
section. Where a retaining tab 526 is to be formed, the channel 524
is divided into two separate sections 524a, 524b each of which has
an end wall 528, the two end walls 528 facing each other and being
separated by a gap 530. Because the panel was flat before being
thermoformed, the areas to either side of each of the channel
sections are flat and in a common plane. The area 532 of the panel
between these end walls 528 is also left flat, and lies in the same
plane, i.e., the plane of the original flat panel. Referring to
FIG. 9, a cutting step is then performed which removes both of the
end walls 528, and part of the area 532 of the panel between them,
leaving a tab 526 which is formed from a part of that area 532. The
tab 526 extends in a direction perpendicular to the length of the
channel 524, having two sides and its free end formed by the
cutting step. An aperture 534 is formed through the panel, by the
cutting step, which extends around the two sides and the free end
of the tab. The ends of the two channel sections 524a, 524b open
into that aperture 534 on either side of the tab 526. As can best
be seen in FIG. 11, the tubing 540, which forms part of the
perfusion circuit, is placed into the channel 524 from the back of
the cartridge 508. Where one of the tabs 526 is formed, the tubing
can be bent into a U-shape so that it can be pushed through the
aperture 534 around the tab 526, and then straightened behind that
tab 526 so that the tab 526 retains it in the channel 524. The
depth of the channel 524 is greater than the sum of the diameter of
the tubing 540 and the thickness of the tab 526 (which is the same
thickness as that of the rest of the panel), so that the tubing can
be straightened completely within the two channel sections 524a,
524b and across the gap 530 between them.
[0062] In other embodiments the cartridge is shaped from a flat
panel by methods other than thermoforming, and in still further
embodiments, the cartridge is not shaped from a flat panel, but is
moulded in a form similar to that of FIGS. 7 and 8 and then
cut.
[0063] Referring back to FIG. 1, and to FIG. 12, much of the system
is formed as a disposable set of components which can be connected
to the rest of the system, used once, and then disposed of. The
main components of the disposable set of this embodiment are shown
in FIG. 12. In this embodiment, the disposable set includes the
surrogate organ 126, each of the inlet ducts 100, 102 and the
outlet duct 104. The flow control valves 112, 146 in the inlet
ducts 100, 102 can be re-used, as they are arranged to fit around
the flexible tubing forming the respective ducts and to compress
it, and therefore do not come into contact with the perfusate. The
connectors 300 with integral pressure sensors also form part of the
disposable set, although in other embodiments they may be
re-usable. The pump 123 in the outlet duct 104 can also be arranged
to be disconnected and re-used, but can, as in this embodiment, be
connected into the system as part of the disposable set. The sling
10 and sump 24 form part of the disposable set. The whole of the
ascites drainage system forms part of the disposable set, including
the ascites pump 84, although in other embodiments the pump 84 can
be disconnected and re-used. The components of the bile measurement
system, including the bile inlet duct 64, the bile overflow duct 70
and overflow pipe 72, the bile outlet duct 68 and the connector 66,
all form part of the disposable set. The organ container 40 also
forms part of the disposable set. The bile sump, in this case
including the lower part 42b and the upper part 42a, forms part of
the disposable set. The analysis duct 190 and BGA 192 form part of
the disposable set. The nutrient control circuit 170 also forms
part of the disposable set. This may include the nutrient pump 182,
or that may be dis-connectable and reusable. The priming reservoir
194 and duct 196 form part of the disposable set. The reservoir 12
forms part of the disposable set. All of the ducts of the
disposable set are formed of flexible plastics tubing. The vent 158
also forms part of the disposable set.
[0064] As shown in FIG. 12, the disposable set also includes the
cartridge 508, together with the components it supports, which form
one unit of the set, the organ container 40 and its lid 48 together
with the sling 10 and sump 26, and bile measurement system and
sump, which form another unit of the set, as well as the pump 123
which forms a third unit of the set. The units are connected to
each other via the flexible tubing, and can therefore be folded
down for storage and transport and unfolded for use. When stored
and delivered for use, the cartridge 508 is folded down over the
organ container 40, and the pump 123 is connected into the outlet
duct 104, but not rigidly supported. This also allows the pump to
be moved, or gently tapped, during filling or during operation of
the system in the preparation mode, so that air bubbles trapped in
the pump are released. When the system is ready for connection of
the organ, the pump 123 can be mounted on a pump support housing
509.
[0065] Referring to FIG. 13, when the system is in operation for
perfusing a liver, the surrogate organ 126 is removed, and the
liver 250 to be perfused is placed in the sling 10. The portal
vein, hepatic artery, inferior vena cava (IVC), and bile duct of
the liver are cannulated, and the cannulae connected to the portal
vein connector 108, the hepatic artery connector 116, the vena cava
connector 120, and the bile outlet port 60 respectively.
[0066] While the surrogate organ is present, and in particular
while the controller 18 detects that the surrogate organ is
present, the controller 18 operates in a preparation mode it which
it is preparing the system for connection of the real organ. In
this mode, the controller 18 is arranged to control the pump 123 so
that it pumps fluid through the oxygenator at a constant flow rate,
and monitor and adjust the various parameters of the fluid, as
described above, so as to bring them within target ranges suitable
for perfusion of a real organ.
[0067] To enable connection of the real organ, the pump 123 is
stopped. The GUI 17 allows a user demand to be input to the
controller 18 to stop the pump 123. When this demand is received by
the controller, the controller is arranged to stop the pump 123 so
that circulation of the perfusate stops. The surrogate organ 126 is
then disconnected from the circuit, and the organ 250 connected
into the circuit as shown in FIG. 3. The controller is arranged,
when it receives a "start" demand from a user, input via the GUI
17, to start the pump 123 at a constant rate again, and again to
monitor the pressures in the hepatic artery duct 102 and the IVC
duct 104 and compare them. Now, as the real organ 250 provides a
significant resistance to perfusate flow, a pressure differential
will quickly build up across the organ 250. Specifically, the
pressure in the hepatic artery duct 102 increases as perfusate is
pumped into it, and the pressure in the IVC duct 104 decreases as
perfusate is pumped away from it. When the controller detects that
the difference between the pressures in those two ducts reaches a
predetermined level, this provides an indication that the real
organ 250 is connected into the circuit and the controller switches
to a perfusion mode. In the perfusion mode the controller 18 is
arranged to control the pressure in the hepatic artery duct 102 and
the IVC duct 104, by controlling the speed of the pump 123 and the
degree of opening of the pressure control valve 146 as described
above, to maintain them at approximately constant pressures.
[0068] With the real organ 250 present, the controller 18 is
arranged to start to measure the volume of bile using the bile
measurement system 62 as described above. It is also arranged to
start draining ascites from the sump 26, and measuring the volume
of that ascites, as described above. The controller is also
arranged to record the total number times that the bile measurement
system valve 76 is opened and the total number of times that the
ascites pump 84 is activated to measure the total volume of bile
and the total volume of ascites that are produced by the liver
during perfusion. It is also arranged to measure the time between
each pair of subsequent operations of the valve 76, and each pair
of subsequent operations of the pump 84, and to calculate for each
pair of operations, an associated flow rate of bile, and an
associated flow rate of ascites, from the liver.
[0069] It will be appreciated that, if an organ other than the
liver is connected into the system, the bile measurement system and
the ascites measurement system can each be used to measure
different fluids as produced by that organ. For example they can be
used to measure urine from a kidney. Also in another embodiment of
the system, a measurement system which is the same as the bile
measurement system 62 described above is included in the ascites
duct 80 upstream of the pump 84 to give a more accurate measurement
of ascites.
[0070] In a still further embodiment, the bile measurement system
62 is provided without the rest of the perfusion system described
above, and can then be connected to an organ, such as a liver,
during surgery, to measure the volume or flow rate of fluid
produced by the organ during surgery.
[0071] To set the system up for use, the disposable set is first
unfolded and mounted on the support stand 500. The surrogate organ
126 is already connected into the circuit as part of the disposable
set, as is the oxygenator 14, and the pump 123. The perfusion
circuit is then filled with perfusate. To achieve this, the flow
control valves 112, 146 in the portal duct 100 and pressure control
duct are opened A perfusion bag 194 containing perfusate is
connected to the upper end of the priming duct 196. The priming bag
194 is then raised to a level that is higher than top of the fluid
reservoir 12. This causes perfusate fluid from the priming bag to
flow into the perfusion circuit at the priming point 104a in the
vena cava duct 104, and flow upwards through the whole perfusion
circuit from that point. As the fluid level in the perfusion
circuit rises, this fills the vena cava duct 104, the surrogate
organ 126, the hepatic artery duct 102 and the portal duct 100, the
through duct 150 of the oxygenator, and the pressure control duct
142, and the reservoir 12, with the ports 82, 178 in the top of the
reservoir being used to vent air out of the system as it fills. The
pump head can be independently moved and tapped relative to is
driving motor to enable removal of any gas trapped within the pump
head during filling. After filling, the ascites duct 80 is
connected to the ascites return port 82 and the nutrient feed duct
174 is connected to the nutrient feed port 178, and the system is
then complete and ready for use.
[0072] When the perfusion circuit 16 has been filled, the system is
switched on, for example by a user inputting a start command using
the GUI 17 and starts to run and the controller 18 is arranged to
control the system as follows. When the system starts to run, the
pressure control valve 146 in the pressure control duct is closed,
so that pumping fluid through the oxygenator will tend to increase
the pressure in the hepatic artery duct 102, and the flow control
valve 112 in the portal vein duct is opened. Initially, therefore,
the pump 123 pumps fluid through the hepatic artery duct 102,
through the surrogate organ 126, and through the IVC duct 104. As
the flow rate through the IVC duct 104 is the same as that through
the hepatic artery duct 102 (as they are connected together through
the oxygenator and there is no flow through the pressure control
duct 142) there will be substantially no flow through the portal
vein duct 100. The controller 18 is arranged initially to control
the pump 123 to operate at a constant speed and to monitor the
pressures in the hepatic artery duct 102 and the IVC duct 104 and
compare them. Since the surrogate organ 126 is present, the
pressure drop across it is low, in particular significantly lower
than what it would be if a real organ were connected into the
circuit, and this enables the controller 18 to detect the presence
of the surrogate organ from the outputs from the difference between
the pressures measured by the pressure sensors 136, 138.
[0073] While the surrogate organ is present, and in particular
while the controller 18 detects that the surrogate organ is
present, the controller 18 operates in a preparation mode it which
it is preparing the system for connection of the real organ. In
this mode, the controller 18 is arranged to control the pump 123 so
that it pumps fluid through the oxygenator at a constant flow rate,
and monitor and adjust various parameters of the fluid, so as to
bring them within target ranges suitable for perfusion of a real
organ.
[0074] To enable connection of the real organ, the pump 123 is
stopped. The GUI 17 allows a user demand to be input to the
controller 18 to stop the pump 123. When this demand is received by
the controller, the controller is arranged to stop the pump 123 so
that circulation of the perfusate stops. All ratchet clamps are
closed so as to avoid leakage of fluid from either the perfusion
circuit or the surrogate organ. The surrogate organ 126 is then
disconnected from the circuit, and the organ 250 connected into the
circuit as shown in FIG. 5. Following successfully connection, all
ratchet clamps are re-opened. The controller is arranged, when it
receives a "start" demand from a user, input via the GUI 17, to
start the pump 123 at a constant rate again, and again to monitor
the pressures in the hepatic artery duct 102 and the IVC duct 104
and compare them. Now, as the real organ 250 provides a significant
resistance to perfusate flow, a pressure differential will quickly
build up across the organ 250. Specifically the pressure in the
hepatic artery duct 102 increases as perfusate is pumped into it,
and the pressure in the IVC duct 104 decreases as perfusate is
pumped away from it. When the controller detects that the
difference between the pressures in those two ducts reaches a
predetermined level, this provides an indication that the real
organ 250 is connected into the circuit and the controller switches
to a perfusion mode. In the perfusion mode the controller 18 is
arranged to control the pressure in the hepatic artery duct 102 and
the IVC duct 104, by controlling the speed of the pump 123 and the
degree of opening of the pressure control valve 146 as described
above, to maintain them at approximately constant pressures. As
mentioned above, the presence of the real organ can be detected by
detecting simply when the pressure in the hepatic artery duct 102
reaches a predetermined level.
[0075] Referring to FIG. 14, the system of FIG. 1 can be modified
for perfusion of a pancreas, or other organ with only one vein and
one artery that need connection to the perfusion circuit. The only
significant modification is that the downstream end of the first
fluid supply duct 100 is not connected to the organ, but instead is
connected to the fluid removal duct 104 just upstream of the pump
123. The other two ducts are connected to the organ in the same way
as for the liver: the second fluid supply duct 102 is connected to
the organ to supply perfusion fluid to the organ, and the fluid
removal duct 104 is connected to the organ to carry perfusion fluid
from the organ. When the organ is not present, the circuit can be
completed using a surrogate organ 126' which in this case is a
simple length of conduit having an inlet end and an outlet end,
each of which has a connector on it so that they can be connected
to the second connector 116 and the third connector 120
respectively. Operation of the system in this configuration is the
same as that described above with reference to FIG. 1, and will not
be described again in detail, except that fluid flow from the
reservoir 12 through the first duct 100 simply replaces fluid that
flows through the pressure relief duct 142 back to the reservoir.
For an organ such as the kidney the bile sump and measurement
system is not used, and the fluid sump 24 collects urine rather
than ascites.
* * * * *