ORGAN PERFUSION PUMP RESERVOIR FILTER DEVICE

Abstract

An apparatus for cleaning transplant organs comprising an organ perfusion circuit and perfusion solution filtration circuit that removes virus and bacteria. The perfusion pump circuit has a cassette for containing perfusion fluid and an organ and a perfusion pump to circulate perfusion fluid in and out of the cassette. A perfusion solution filtering device has a filter and a pump coupled to the cassette to pump perfusion fluid out of the cassette, through the filter, and back into the cassette.

Claims

1. An organ preservation and virus filtration apparatus, said apparatus consisting essentially of: a) a perfusion pump circuit having: i) a cassette configured to contain an organ and a perfusion fluid for preservation of said organ; and ii) a first pump and a first tubing fluidly coupled to said pump and to said cassette to circulate said perfusion fluid through said organ and back to said first pump; b) a perfusion solution filtering device having: i) a filter configured to remove virus and bacteria from said perfusion fluid; and ii) a second pump and a second tubing fluidly coupled to said cassette and to said second pump to circulate said perfusion fluid out of said cassette, through said filter to remove virus and bacteria and send cleaned perfusion fluid back into said cassette.

2. The apparatus of claim 1, wherein said first pump is a peristaltic pump.

3. The apparatus of claim 1, further comprising a sampling port on said second tubing.

4. The apparatus of claim 1, wherein said second tubing comprises: a) input tubing connecting said perfusion pump circuit to said perfusion solution filtering device; and b) output tubing connecting said perfusion solution filtering device to said perfusion pump circuit.

5. The apparatus of claim 4, further comprising: a) a sampling port in said input tubing, and b) a sampling port in said output tubing.

6. The apparatus of claim 1, said perfusion solution filtering device further comprising a housing to contain said filter, said pump and a portion of said second tubing.

7. An organ preservation and filtration apparatus, said apparatus consisting essentially of: a) a perfusion pump circuit having: i) a cassette configured to contain an organ and a perfusion fluid for preservation of said organ; and ii) a first pump and a first tubing to circulate said perfusion fluid into and out of said cassette and said organ; b) a perfusion solution filtering device having: i) a filter configured to remove virus from said perfusion fluid; and ii) a second pump and a second tubing coupled to said cassette and said second pump to circulate said perfusion fluid out of said cassette, through said filter to remove virus, and circulate filtered perfusion fluid without said virus back into said cassette, thereby cleaning said organ for use in transplant surgery.

8. The apparatus of claim 7, said second tubing comprising: a) input tubing fluidly coupling said perfusion pump circuit to said perfusion solution filtering device; b) output tubing fluidly coupling said perfusion solution filtering device to said perfusion pump circuit; c) a sample port in said input tubing, and d) a sample port into said output tubing.

9. The apparatus of claim 7, said perfusion solution filtering device further comprising a housing to contain said filter, said pump and a portion of said second tubing.

10. An organ preservation and virus removal method, said method comprising: a) coupling a perfusion pump circuit to a perfusion solution filtering device; i) wherein the perfusion pump circuit has: (1) a cassette for containing an organ and a perfusion fluid to preserve said organ, and (2) a perfusion pump and a first tubing to circulate said perfusion fluid into said organ and said cassette and out of said cassette; ii) wherein the perfusion solution filtering device has: (1) a filter configured to remove virus and bacteria from said perfusion fluid; and (2) a pump and a second tubing to circulate perfusion fluid out of the cassette, through said filter to remove virus, and circulate filtered perfusion solution back into said cassette; b) placing an organ comprising a virus plus perfusion fluid into said cassette; c) operating said perfusion pump circuit to perfuse said organ; d) operating said perfusion solution filtering device to filter said perfusion fluid, thereby removing virus from said organ to produce a cleaned organ; and e) removing said cleaned organ from said cassette.

11. The method of claim 10, wherein said organ is a kidney.

12. The method of claim 10, wherein said virus is a hepatitis virus.

13. The method of claim 10, wherein said organ is a kidney and said virus is a hepatitis virus.

14. An organ transplant method, said method comprising: a) testing a donated organ for virus to identify a virus positive organ; b) filling said cassette of said apparatus of claim 1 with perfusion fluid; c) placing said virus positive organ into said cassette and connecting said first tubing to an artery of said organ; d) operating said perfusion pump circuit to perfuse said organ with said perfusion fluid; e) operating said perfusion solution filtering device to filter said perfusion fluid, thereby removing virus from said organ and providing a cleaned organ; f) removing said cleaned organ from said cassette; and g) transplanting said cleaned organ into a patient needing an organ transplant.

15. The method of claim 14, wherein said organ is a kidney.

16. The method of claim 14, wherein said virus is a hepatitis virus.

17. The method of claim 14, wherein said organ is a kidney and said virus is a hepatitis virus.

18. An organ transplant method, said method comprising: a) testing a donated organ for virus to identify a virus positive organ; b) filling said cassette of said apparatus of claim 7 with perfusion fluid; c) placing said virus positive organ into said cassette and connecting said first tubing to an artery of said organ; d) operating said perfusion pump circuit to perfuse said organ with said perfusion fluid; e) operating said perfusion solution filtering device to filter said perfusion fluid, thereby removing virus from said organ and providing a cleaned organ; f) removing said cleaned organ from said cassette; and g) transplanting said cleaned organ into a patient needing an organ transplant.

19. The method of claim 18, wherein said organ is a kidney.

20. The method of claim 18, wherein said organ is a kidney and said virus is a hepatitis virus.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG. 1A. is a block diagram of perfusion pump circuit and solution viral clearance pump.

[0022] FIG. 1B. is a variant of FIG. 1A where the cleaned fluid directly enters the perfusion circuit line.

[0023] FIG. 2 is a cross section of the filter arrangement. Only one filter is shown, but of course, multiple filters could be used, preferably in decreasing pore size along the direction of flow.

[0024] FIG. 3 shows a perspective view of the layout of FIG. 1A.

DETAILED DESCRIPTION

[0025] The following detailed description illustrates embodiments of the present disclosure. These embodiments are described in sufficient detail to enable a person of ordinary skill in the art to practice these embodiments without undue experimentation. It should be understood, however, that the embodiments and examples described herein are given by way of illustration only, and not by way of limitation. Various substitutions, modifications, additions, and rearrangements may be made that remain potential applications of the disclosed techniques. Therefore, the description that follows is not to be taken as limiting on the scope of the appended claims. In particular, an element associated with a particular embodiment should not be limited to association with that particular embodiment but should be assumed to be capable of association with any embodiment discussed herein.

[0026] The premise of the preservation pump reservoir filtering system is to filter deleterious viral (and potentially bacterial) particles from the organ effluent during the pulsatile preservation process in an attempt to lower the remaining inoculum in the organ below the threshold of clinical disease transmission. By diminishing the circulating viral and bacterial load in the organ perfusion circuit and replenishing fresh preservation solution, the transplanted viral/microbial inoculum will be diminished, rendering the recipient more likely to be immune to low-dose viral/microbial exposure, and more likely to be responsive to post-transplant antiviral/antibiotic therapy.

[0027] A device for this purpose is shown in a top down view of FIG. 1A wherein the perfusion solution filtering device 100 is typically an external device that connects to the sterile organ cassette 104 of the perfusion pump circuit 106 via a Luer lock port 108/109, or similar device, herein shown connecting on the organ cassette 104 wall. Alternatively, the sterile organ cassette 104 could be accessed through a different entry point, such as the lid.

[0028] Ideally, the perfusion pump is a peristaltic (pulsating) pump, such as the micro-perfusion pump by Thomas Scientific® or the FCS micro-perfusion pump by Bioptechs®. Unlike most peristaltic pumps that are driven by stepper motors, the micro-perfusion pump by Thomas Scientific® is driven by a tachometer regulated, multi-stage DC gear motor. This assures a smooth analog rotation of the roller spindle, free of instantaneous steps. Other similar pumps include the Quantum Roller Pump by Spectrum Medical®, the Organ Recovery Systems (ORS) and more recently ex-situ normothermic perfusion pumps.

[0029] Preferred first and second pumps roll over the tubing containing the perfusion fluid and thus never contact the fluid, eliminating the need to address pump sterility. The ideal pump can operate in push or pull mode, is small and does not require flow rate calibration.

[0030] The cassette can be stored on ice, or the one or more units fitted with temperature control units to keep the organ cool during perfusion. In addition, some perfusion circuits have an in-line oxygenator feature.

[0031] In an alternate embodiment (not shown), the perfusion pump circuit 106 and filter 114 could be combined into a single unit. In such a case, the filter may be installed in the perfusion fluid return line 105 before perfusion pump 101. It could also be placed on fluid input line 102. However, in FIG. 1A and FIG. 1B the filter circuit is separate from the perfusion circuit, allowing the addition of this unit to already existing perfusion pump circuits for any organ, and obviating the purchase of an entire new unit. This design also allows continuous and even flow through the filter 114, rather than the peristaltic flow of the perfusion pump 101, and is thus preferred.

[0032] Sterile silastic tubing 110 inserts through the wall port or other entry point, preferably down into the most gravity dependent portion of the organ reservoir 104 (e.g., the ports are low in the housing). Tubing 110 sterilely connects to the perfusion solution filtering device 100 containing a pump 112 that will draw fluid from the organ cassette 104 and push it through a filter 114 (herein tested an Aethlon Medical Filter). In FIG. 1 we show the pump 112 before the filter 114, but its placement can be before or after.

[0033] Preferred tubing for both units is silastic tubing—a silicon tubing. Ideally the tubing will be platinum-cured, nonpyrogenic, bacteria and fungus-resistant, extremely low extractables, and does not impart a taste or odor, such as that provided by VWR® or Bioseal®

[0034] The filtered effluent will then return to the sterile organ cassette 104 via return tubing 124 for continued pulsatile preservation of the organ 116, herein shown a kidney. At the inflow 118 and outflow 120 channels of the device 102 will be Luer lock specimen sampling ports, or similar devices, allowing the user to infuse therapy or fresh preservation solution to improve particle clearance or to sample the perfusion fluid and measure viral or bacterial load.

[0035] The perfusion solution filtering device 100 includes input tubing 110 and the output tubing 124, filter 114 and pump 112. Sample ports 118, 120 can be primed with 250-500 cc of fresh perfusion solution to promote fluid exchange without introduction of air into the system.

[0036] Once the organ perfusion and filtration is completed, the filtering pump lines 110, 124 can be removed, and the ports capped for removal of the organ from the cassette for transplantation. The filter cartridge 114 and tubing 102, 110, 124 are a disposable unit that can be removed from the filter pump housing 126 for hazardous waste discard at the completion of use. The pump 112 ideally does not require any calibration or additional maintenance. In addition, the housing is not strictly essential, but is included to contain and protect filter 114 and lines 110/124 in a neat manner.

[0037] The perfusion pump perfusion cassette is a single contained entity that contains in-line sensors that measure pressure, flow, and resistance. Thus, the filter pump does not need any inline sensors, and therefore does not require any additional calibration to achieve accuracy of these measurements.

[0038] FIG. 1B is very similar to 1A, but the return line 124 is directly connected to return line 105.

[0039] FIG. 2 shows a cross section of the filter 114 in filter cassette 160, and connectors 140 to tubing 110/124. Filter 114 is chosen to filter out viruses, and thus pore size is chosen to be small enough to catch the virus of concern. A virus may be as small as 20 nm (e.g., Parvovirus), thus, the pore size may be <20 nm or e.g., 15 nm. However, smaller pores restrict flow so it may be preferred to provide a variety of filters in different pore sizes to capture different viruses. Thus, an HCV specific filter would have pores <30-65 nm, e.g., 25 nm. It may also be desired to use an array of filters or decreasing pore size (e.g., 100 nm>60 nm>25 nm) so as to reduce the need to replace filters.

[0040] Generally, any filter with pores small enough to catch HCV will also filter out blood cells and bacteria, such as M. tuberculosis, E. coli, and S. Aureus. However, the organ is being maintained with perfusion fluid, and the blood cells need not be retained.

[0041] Suitable filters may include highly asymmetric Viresolve® Pro and Viresolve® NFP filters from MilliporeSigma®, or the relatively homogeneous Ultipor DV20 and Pegasus™ SV4 virus filters from Pall®.

[0042] FIG. 3 shows the system of FIG. 1A in perspective. All the same numerals are employed.

[0043] While the description and FIG. 1 herein illustrates the use of the inventive apparatus with a kidney, it will be understood that the system can be used with all potential perfused organs. Further, the system is designed to filter all transmissible virus and bacteria and is not limited to those specific virus and bacteria mentioned herein.

[0044] In one aspect, an apparatus includes a perfusion pump circuit having a cassette for containing perfusion fluid and a perfusion pump to circulate perfusion fluid in and out of the cassette and organ. The apparatus includes a perfusion solution filtering device having a filter or hemofilter and a pump coupled to the cassette to pump perfusion fluid out of the cassette, through the filtration unit, and back into the cassette.

[0045] The apparatus may include input tubing connecting the perfusion pump circuit to the perfusion solution filtering device by which fluid is drawn from the perfusion pump circuit and delivered to the pump and output tubing connecting the perfusion solution filtering device to the perfusion pump circuit by which fluid is pumped from the filter to the perfusion pump circuit.

[0046] The apparatus may include a port into the input tubing, and a port into the output tubing. The perfusion solution filtering device, the input tubing, and the output tubing may be disposable. The input tubing may be inserted into the most gravity dependent (lowest) portion of the perfusion pump circuit. The pump in the perfusion solution filtering device may not require calibration.

[0047] In one aspect, a method includes coupling a perfusion pump circuit to a perfusion solution filtering device, each of these as describe herein. The perfusion pump circuit may have a cassette for containing perfusion fluid and an organ to be perfused and a perfusion pump to circulate perfusion fluid in and out of the cassette. The perfusion solution filtering device may have a hemofilter or any filter configured to remove virus, and bacteria and a pump coupled to the cassette to pump perfusion fluid out of the cassette, through the filter, and back into the cassette.

[0048] Implementations may include one or more of the following.

[0049] The method may include running the perfusion solution filtering device until the organ perfusion is completed and disconnecting and discarding the perfusion solution filtering device. Coupling the perfusion pump circuit to the perfusion solution filtering device may include coupling the perfusion pump circuit to the perfusion solution filtering device with an input tubing by which fluid is drawn from the perfusion pump circuit and delivered to the pump and coupling the perfusion solution filtering device to the perfusion pump circuit with an output tubing by which fluid is pumped from the hemofilter to the perfusion pump circuit. The method may include running the perfusion solution filtering device until the organ perfusion is completed and disconnecting and discarding the input and output tubing and filter.

[0050] The word “coupled” herein means a direct connection or an indirect connection.

[0051] The following are each incorporated by reference in its entirety for all purposes.

[0052] US2014017666 Filtration in organ perfusion apparatus.

[0053] US2010092939 (U.S. Pat. No. 9,113,624) System and method for perfusing biological organs.

[0054] US2006129082 Selective plasma exchange therapy.

[0055] US20200080050 US2021139843 Systems and methods for growing cells in vitro.

[0056] U.S. Pat. Nos. 5,549,674, 5,686,289 Methods and compositions of a bioartificial kidney suitable for use in vivo or ex vivo.