Perfusion loop assembly for an ex-vivo liver perfusion and a liver chamber assembly

{
  "publication_number": "US11785938B2",
  "country": "US",
  "kind": "B2",
  "title": "Perfusion loop assembly for an ex-vivo liver perfusion and a liver chamber assembly",
  "abstract": "The present invention relates to a perfusion loop assembly for an ex vivo liver perfusion including: a pump for providing a fluid flow of a perfusion fluid through a first branch line and a second branch line; the first branch line being configured to provide a first portion of the perfusion fluid to the hepatic artery of the liver; the first branch line being coupled with a first gas exchanger, the second branch line being configured to provide a second portion of the perfusion fluid to the portal vein of the liver; the second branch line further including a first valve for controlling the flow of the perfusion fluid into the portal vein of the liver, a liver chamber assembly configured to hold the liver ex vivo, a liver outlet line attached to the vena cava of the ex vivo liver, at least one reservoir connected to the liver outlet and upstream from the pump.",
  "claims": [
    "1. A perfusion loop assembly for an ex vivo liver perfusion comprising: only one pump for providing a flow of a perfusion liquid through a first branch line and a second branch line, wherein the perfusion flow is split downstream of the one pump into the first branch line and the second branch line at a branching point; the first branch line being configured to provide a first portion of the perfusion liquid to the hepatic artery of the liver, wherein at least one gas exchanger is arranged in the first branch line downstream of the branching point; the second branch line being configured to provide a second portion of the perfusion liquid to the portal vein of the liver, the second branch line further comprising at least one first valve for controlling the flow of the perfusion liquid into the portal vein of the liver; a liver chamber assembly configured to hold the liver ex vivo; a liver outlet line attached to the vena cava of the ex vivo liver, wherein the liver outlet line comprises at least one valve; and at least one reservoir connected to the liver outlet line and upstream from the one pump, wherein the first branch line, the second branch line and/or the liver outlet line comprise an interface configured to be inserted into the hepatic artery of the liver, the portal vein and/or the vena cava respectively; wherein the first branch line, the second branch line and/or liver outlet line comprise at least one flow rate sensor and/or at least one pressure sensor; wherein a bypass with a valve is established between the first branch line and the second branch line, wherein the valve of said bypass is operative for controlling a flow of the perfusion liquid between the first branch line and the second branch line; and wherein a flow throttling in the at least one first valve of the second branch line, in the valve in the bypass, and in the valve in the liver outlet line is accomplished over one or multiple stages, wherein each of the one or multiple stages includes a manually adjustable constriction, an automatically adjustable constriction, or both a manually and an automatically adjustable constriction.",
    "2. The perfusion loop assembly according to claim 1, further comprising: at least one third gas exchanger downstream of the one pump; and downstream from the at least one third gas exchanger the perfusion liquid flow being split into the first branch line and the second branch line.",
    "3. The perfusion loop assembly according to claim 1, wherein data from each sensor is transmitted to a control system for monitoring and/or controlling the perfusion loop assembly and/or manipulating devices depending on the measured sensor data.",
    "4. The perfusion loop assembly according to claim 1, wherein the second branch line comprises at least one second gas exchanger.",
    "5. The perfusion loop assembly according to claim 1, wherein the at least one first valve in the second branch line is a proportional pinch valve.",
    "6. The perfusion loop assembly according to claim 1, wherein the at least one reservoir is a hard shell or soft shell reservoir close to a liver outlet.",
    "7. The perfusion loop assembly according to claim 1, wherein a height of the at least one reservoir relative to the ex vivo liver is controlled by a linear motor for adjusting a liquid head.",
    "8. The perfusion loop assembly according to claim 1, wherein a control system effects a desired pressure variation in the vena cava liver outlet branch, wherein the control system comprises at least one pinch valve in the vena cava line and/or an alternatingly adjusting of a height of the reservoir.",
    "9. The perfusion loop assembly according to claim 1, wherein the perfusion loop assembly comprises at least one port for medication and/or liquid retrieval for analysis.",
    "10. The perfusion loop assembly according to claim 1, comprising a dialysis machine to remove toxins and desired substances from the perfusion media.",
    "11. The perfusion loop assembly according to claim 10, wherein the dialysis machine is connected to the liver chamber and the liver outlet line.",
    "12. The perfusion loop assembly according to claim 1, comprising at least one monitoring, controlling, and/or processing device for bile produced by the ex vivo liver.",
    "13. The perfusion loop assembly according to claim 12, wherein the monitoring, controlling and/or processing device uses measurements of the produced mass of the bile, optical parameters of the bile and/or the flow rate of the bile.",
    "14. The perfusion loop assembly according to claim 1, wherein the temperature in the loop is in the range of 2° C. and normothermic conditions.",
    "15. The perfusion loop assembly according to claim 1, comprising the second branch line including at least one second gas exchanger.",
    "16. The perfusion loop assembly according to claim 1, comprising at least one monitoring, controlling, and/or processing device for ascites produced by the ex vivo liver.",
    "17. The perfusion loop assembly according claim 16, wherein the monitoring, controlling and/or processing device uses measurements of the produced mass of the ascites, optical parameters of the ascites and/or the flow rate of the ascites.",
    "18. The perfusion loop assembly according to claim 16, comprising at least one dialysis machine for removing toxins and urea from the ascites."
  ],
  "description_excerpt": "The disclosure relates to a perfusion loop assembly for an ex vivo liver perfusion and a liver chamber assembly.\n\nWorldwide over half a million new patients are diagnosed with primary cancer in the liver each year. Furthermore, the liver is the primary site of metastases for most cancers. The majority of those patients are incurable.\n\nThe concept that the liver has the ability to regenerate has been known for centuries. Liver resection (surgical removal of the diseased part of the liver) for the treatment of liver cancer has been carried out for a few decades.\n\nHowever, many patients still cannot benefit from liver surgery because the removal of a too large piece of the liver leads to death.\n\nThe organ donor pool shortage is increasing in western countries. New strategies are required to alleviate current donor organ shortage. The ability of the liver to regenerate could also be used in liver transplantation to increase the donor pool, where a healthy donor liver will be split into a couple of parts that will be grown in the perfusion machine and transplanted into more than one patient.\n\nPerfusion systems are known from Ravikumar et. al. “ Normothermic liver preservation: a new paradigm?”, Steunstichting ESOT 28 (2015), 690-699, U.S. Pat. No. 7,410,474 B1, WO 2013/032319 A1 and WO 2015/187737 A1.\n\nSystems and methods are needed to extend the viability of liver tissue outside of the body and allow its growth (e.g. enabling liver regeneration systems and methods)\n\nIt is an issue to provide a system and a method to extend the viability of the liver, outside of the body, ex vivo.",
  "cpc": [
    "A01N 1/143",
    "A01N 1/0247"
  ],
  "ipc": [
    "A01N 1/02"
  ],
  "assignees": [
    "Eidgenoessische Technische Hochschule Zurich ETHZ",
    "Zurich Universitaet Institut fuer Medizinische Virologie"
  ],
  "inventors": [
    "Pierre-Alain Clavien",
    "Philipp Rudolf Von Rohr",
    "Philipp Dutkowski",
    "Rolf Graf",
    "Martin Schuler",
    "Dilmurodjon Eshmuminov",
    "Brian Burg"
  ],
  "filing_date": "2017-07-21",
  "publication_date": "2023-10-17",
  "grant_date": "2023-10-17",
  "priority_date": "2016-07-22",
  "application_number": "US-201716319608-A",
  "family_id": "56511407",
  "cited_by_count": 39,
  "citations": [
    "US3515370A",
    "DE2603139A1",
    "US4192308A",
    "US5141847A",
    "US5856081A",
    "EP0702515B1",
    "US5786136A",
    "US5890518A",
    "US20050147958A1",
    "US7410474B1",
    "US7572622B2",
    "US7811808B2",
    "US20070009881A1",
    "WO2005022995A1",
    "CN1543785A",
    "US20060148062A1",
    "WO2007014380A2",
    "US7977042B2",
    "US20070048725A1",
    "EP2009986B1",
    "US8287580B2",
    "US20080017194A1",
    "WO2008108996A1",
    "US8986978B2",
    "US9457179B2",
    "US20100117011A1",
    "EP2133610A1",
    "EP2203046B1",
    "US8927257B2",
    "US20090197240A1",
    "WO2009138446A2",
    "US20110065170A1",
    "WO2011050459A1",
    "US20120213798A1",
    "WO2011062621A2",
    "US20130177972A1",
    "US20130011823A1",
    "US20150173348A1",
    "WO2013029044A1",
    "US9756848B2",
    "WO2013032319A1",
    "US10362780B2",
    "WO2013068753A1",
    "US20140308654A1",
    "US20140377849A1",
    "US20150004677A1",
    "EP2633755A1",
    "WO2014001592A1",
    "US20140011182A1",
    "US20140017662A1",
    "US20140017658A1",
    "US10433538B2",
    "WO2014059316A1",
    "US10634686B2",
    "WO2015042602A1",
    "US20160262634A1",
    "CN103719075A",
    "WO2015187737A1",
    "US20150342177A1",
    "US10076112B2",
    "WO2016090498A1",
    "US20170339945A1",
    "CN205124849U",
    "CN105379707A",
    "CN105660604A",
    "WO2017200089A1",
    "EP3459351A1",
    "US20190141988A1",
    "WO2018015548A2",
    "CN206403020U",
    "WO2019141809A1",
    "US20200375178A1"
  ]
}