Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberCN1985170 A
Publication typeApplication
Application numberCN 200580008622
PCT numberPCT/US2005/003008
Publication date20 Jun 2007
Filing date27 Jan 2005
Priority date2 Feb 2004
Also published asCA2554872A1, DE602005009322D1, EP1711816A2, EP1711816B1, US7749693, US20040224298, WO2005074681A2, WO2005074681A3
Publication number200580008622.8, CN 1985170 A, CN 1985170A, CN 200580008622, CN-A-1985170, CN1985170 A, CN1985170A, CN200580008622, CN200580008622.8, PCT/2005/3008, PCT/US/2005/003008, PCT/US/2005/03008, PCT/US/5/003008, PCT/US/5/03008, PCT/US2005/003008, PCT/US2005/03008, PCT/US2005003008, PCT/US200503008, PCT/US5/003008, PCT/US5/03008, PCT/US5003008, PCT/US503008
Inventors约翰布拉塞尔, 道格拉斯沙因, 克里斯托夫G.柯蒂斯
Applicant器官恢复系统公司
Export CitationBiBTeX, EndNote, RefMan
External Links: SIPO, Espacenet
Apparatus and method for determining effects of a substance on an organ
CN 1985170 A
Abstract
An organ perfusion apparatus and method monitor, sustain and/or restore viability of organs and preserve organs for storage and/or transport. Other apparatus include an organ transporter, an organ cassette and an organ diagnostic device. The method includes perfusing the organ at hypothermic and/or normothermic temperatures, preferably after hypothermic organ flushing for organ transport and/or storage. The method can be practiced with prior or subsequent static or perfusion hypothermic exposure of the organ. Organ viability is restored by restoring high energy nucleotide (e.g., ATP) levels by perfusing the organ with a medical fluid, such as an oxygenated cross-linked hemoglobin-based bicarbonate medical fluid, at normothermic temperatures. During the period in which the organ is preserved and/or maintained, various drug research and development may be performed on and/or with the organ. The organ may be perfused with a fluid containing a substance such as a test substance to obtain data regarding the organ, the substance and an interaction of the substance and the organ. The data may then be used to ultimately provide information regarding the drugs efficacy in support of regulatory filings for new drugs.
Claims(18)  translated from Chinese
1.一种确定物质对器官的影响的方法,包括:使用第一医用流体灌注至少一个器官以保存所述至少一个器官;使所述至少一个器官接受至少一种测试物质的作用;以及收集有关所述至少一个器官、所述至少一种测试物质、以及所述至少一个器官和所述至少一种测试物质之间相互作用这三者中的至少其中之一的数据。 1. A method for determining the influence of substances on organ, comprising: using a first medical fluid perfused organ to hold at least one of said at least one organ; receiving said at least one organ of the role of at least one test substance; and collect said at least one organ, the at least one test substance, and the at least one organ and the at least one of these three test interaction data of at least one of between the substance.
2.如权利要求1所述的方法,其中使所述至少一个器官接受至少一种测试物质的作用的步骤是通过使用包含所述测试物质的第二医用流体灌注所述器官来执行。 2. The method of claim 1, wherein said at least one step of at least one organ acceptance test is performed by the effect of substance containing the test substance the second medical fluid perfused organ to perform.
3.如权利要求2所述的方法,其中所述第一医用流体和所述第二医用流体相同。 The method as claimed in claim 2, wherein said first medical fluid and the same second medical fluid.
4.如权利要求2所述的方法,其中所述第一医用流体和所述第二医用流体不同。 4. The method of claim 2, wherein said first and said second medical fluid different medical fluid.
5.如权利要求1所述的方法,其中所述至少一个器官和来自所述器官的流出物这两者中的至少其中之一由传感器进行监视,所述传感器检测所述流出物和所述至少一个器官这两者中的至少其中之一的特性。 5. The method of claim 1, wherein said at least one organ and the organ effluent from at least one of these two is monitored by a sensor, said sensor detecting the effluent and the at least one characteristic of both organ of at least one of.
6.如权利要求5所述的方法,其中该方法还包括产生由被检测的特性组成的数据。 6. The method according to claim 5, wherein the method further comprises generating data to be detected by the characteristic thereof.
7.如权利要求6所述的方法,其中所述数据可以实时地产生和显示、存储、传送到远程位置、传输到记录介质、或者传递给用于评估的微处理器。 7. The method of claim 6, wherein the data may be generated and displayed in real time, stored, transmitted to a remote location, is transferred to the recording medium, or transmitted to the microprocessor for evaluation.
8.如权利要求2所述的方法,其中该方法还包括:收集已经经过所述至少一个器官的、从器官浴槽流出的所述第二医用流体,并且检测所收集医用流体的能表明所述至少一个器官与所述测试物质之间相互作用的特性。 8. The method of claim 2, wherein the method further comprises: collecting has passed said at least one organ from the second organ bath effluent medical fluid, and detecting the collected medical fluid can indicate the the at least one characteristic of the interaction between the organ and the test substance.
9.如权利要求2所述的方法,其中所述测试物质为化学化合物。 9. The method of claim 2, wherein the test substance is a chemical compound.
10.如权利要求2所述的方法,其中所述测试物质为天然抗体和改良抗体中的至少一种。 10. The method of claim 2, wherein the test substance is at least one natural antibodies and modified antibodies.
11.如权利要求2所述的方法,其中所述测试物质为免疫毒素。 11. The method of claim 2, wherein the test substance is an immunotoxin.
12.如权利要求2所述的方法,其中所述第二医用流体为血液。 12. The method of claim 2, wherein the second medical fluid is blood.
13.如权利要求5所述的方法,其中被检测的特性涉及吸收、分布、新陈代谢和排泄中的至少一种。 13. The method of claim 5, wherein the detected characteristic involves absorption, distribution, metabolism and excretion of at least one of.
14.如权利要求5所述的方法,其中被检测的特性涉及药物代谢动力学、药效学和毒性中的至少一种。 14. The method of claim 5, wherein the sensed characteristics relate pharmacokinetic, pharmacodynamic and toxicity of at least one of.
15.如权利要求5所述的方法,其中被检测的特性涉及确定所述物质对所述至少一个器官的作用和所述至少一个器官对所述物质的作用这两种作用中的至少一种。 15. The method of at least one of claim 5, wherein the detected characteristic involves determining the effect of the substance on the at least one organ and the at least one organ of the effect of the substance on the role of these two .
16.一种使用生物活性剂筛选至少一个器官的方法,包括:确定所述至少一个器官将不会被移植;使用第一医用流体灌注所述少一个器官以保存所述器官;使所述至少一个器官接受至少一种测试物质的作用;以及收集有关所述至少一个器官、所述至少一种测试物质、以及所述至少一个器官和所述至少一种测试物质之间相互作用这三者中的至少其中之一的数据。 16. A biologically active agent screening using at least one organ, comprising: determining at least one organ will not be transplanted; using a first medical fluid perfused organ to hold the at least one of said organ; causing the at least receiving at least one effect of an organ of a test substance; and gather information about the at least one organ, the at least one test substance, and at least one between said at least one organ and the test substance in the three interactions at least one of the data.
17.如权利要求16所述的方法,其中所述器官不适合移植。 17. The method of claim 16, wherein the organ is not suitable for transplantation.
18.如权利要求16所述的方法,其中该方法还包括步骤:使用第一医用流体灌注所述至少一个器官;以及检测能表明器官活性的流体特性。 18. The method of claim 16, wherein the method further comprises the step of: using a first of said at least one medical fluid perfused organ; and detecting fluid characteristics can indicate organ activity.
Description  translated from Chinese
用于确定物质对器官的影响的设备和方法 It used to determine the effects of substances on the organs of the apparatus and method

本申请是2003年7月11日提交的美国专利申请No.10/617130的部分继续申请,美国专利申请No.10/617130是2000年8月25提交的No.09/645525的分案申请,No.09/645525是2000年3月29日提交的美国专利申请No.09/537180的部分继续申请,No.09/537180是1998年9月29日提交的美国专利申请No.09/162128的部分继续申请,这些专利申请的全部内容通过参考并入本文。 This application is a US patent July 11, 2003, filed part No.10 / 617130 continuation application, US Patent Application No.10 / 617130 is a divisional application 25 August 2000 filed No.09 / 645525, the No.09 / 645525 US patent March 29, 2000, filed part No.09 / 537180 continuation application, No.09 / 537180 US Patent September 29, 1998 filed No.09 / 162128 of section continue to apply, the entire contents of these patent applications are incorporated herein by reference.

技术领域 Technical Field

本发明涉及用于灌注一个或多个器官以监视、维持与/或恢复所述器官的活性(viability),以及/或者用于运输与/或贮存所述器官的设备和方法。 The present invention relates to infusion for one or more organs to monitor, transport and / or storage of the apparatus and method maintain organ / organ or restore the activity (viability), and / or used. 本发明还涉及确定所述器官是否为用于移植的可存活候选。 The present invention also relates to a viable candidate for use in determining whether the organ transplant. 具体地,如果所述器官不是可存活的移植候选,则本发明进一步涉及使用流体灌注所述器官以采集与所述器官及/或流体有关的数据。 In particular, if the organ is not a viable candidate for transplantation, the present invention further relates to the use of perfusion fluid to an organ or organs and collecting the data associated with / fluid.

背景技术 Background

无论是否使用计算机控制,已经利用晶胶灌注液并且无需供氧地实现了在低于体温温度下的借助机器灌注的器官保存。 Whether or not the use of computer-controlled, has used perfusion liquid crystal plastic and does not need oxygen to achieve a temperature below the temperature by means of machine perfusion of organ preservation. 例如参见申请人为Klatz等的美国专利No.5149321、5395314、5584804、5709654及5752929以及美国专利申请No.08/484601,这些专利或专利申请在此通过参考并入本文。 See, for example such as the applicant is Klatz No.5149321,5395314,5584804,5709654 and U.S. Patent 5,752,929 and U.S. Patent Application No.08 / 484601, these patents or patent applications are hereby incorporated herein by reference. 低于体温的温度能减小器官新陈代谢,降低能量需求,延缓高能磷酸化合物储备的耗尽以及乳酸的积聚,并能阻止与供血中断相关的形态和功能上的退化。 Below body temperature can be reduced organ metabolism, reduce energy demand and slow the depletion of high-energy phosphate compounds accumulate lactic reserves, and to prevent the degradation associated with the blood supply interruption on the morphology and function. 在低于约20℃下线粒体无法有效地利用氧来产生能量,并且在低温下生成的接触酶/超氧化物岐化酶减少,同时抗坏血酸和谷胱甘肽再生的减少可允许形成高度游离的自由基。 Mitochondria can not effectively use less than about 20 ℃ under oxygen to produce energy, and at low temperatures produced catalase / superoxide dismutase reduced while the reduction of ascorbic acid and glutathione regeneration may allow the formation of highly free free radicals. 在低温机器灌注过程中除去灌注液中的氧已经被一些研究者证明有助于改善器官移植结果。 In the process of removing the low temperature machine perfusion perfusate oxygen has been shown to help improve some investigators transplant outcome.

通过向灌注液添加抗氧化剂,也减小了潜在的氧损伤。 By adding antioxidants to the perfusate, also reduces the potential oxygen damage. 具体地,已经证实这有助于减小长时间热缺血状态后的器官损伤。 Specifically, it has been confirmed that this will help reduce organ damage after prolonged ischemia state. 已经报导有许多其它灌注液添加剂以改善机器灌注的结果。 The results have been reported there are many other perfusate additives to improve the machine perfusion.

理想情况下,应该以这样的方式获得器官,即,将热缺血的时间限制到基本上为零。 Ideally, you should obtain organs in such a way that the warm ischemia time limit to substantially zero. 然而实际情况中,许多器官——尤其是从无心跳的供体中获得的器官——是在经历了比较长的热缺血时间段(即45分钟或以上)之后获得的。 However, in reality, many organs - especially the organ donor heart never obtained - is experiencing a longer warm ischemia time (ie 45 minutes or more) obtained after. 在低温下对这些器官的机器灌注已经显示了显著的改进(Transpl Int1996 Daemen)。 At a low temperature machine perfusion of these organs it has shown significant improvement (Transpl Int1996 Daemen). 另外,现有技术教导,优选地在低压下(Transpl.Int 1996Yland)使用利用受控压力输送灌注液的滚筒或隔膜泵进行器官的低温机器灌注。 Further, the prior art teaches, preferably at low pressures (Transpl.Int 1996Yland) utilizing controlled using a pressure roller or transporting the perfusate diaphragm low temperature machine perfusion of organs. 已经利用许多控制电路和泵送抽吸装置以获得该目标并进行机器灌注器官。 Has been using a number of control circuits and pumping suction means to achieve this objective and machine perfused organs. 例如参见申请人为Sadri的美国专利5338662和5494822、申请人为Bauer等的美国专利No.4745759、申请人为Fahy等的美国专利No.5217860和5472876、申请人为Martindale等的美国专利No.5051352、申请人为Clark等的美国专利No.3995444、申请人为Gruenberg的美国专利No.4629686、申请人为Thorne等的美国专利No.3738914和3892628、申请人为Bacchi等的美国专利No.5285657和5476763、申请人为McGhee等的美国专利No.5157930、以及申请人为Sugimachi等的美国专利No.5141847。 See, for example applicant Sadri U.S. Patent 5,338,662 and 5,494,822, the applicant of Bauer et al U.S. Patent No.4745759, the applicant is Fahy et al U.S. Patent No.5217860 and 5472876, the applicant for the Martindale et al U.S. Patent No.5051352, the applicant is Clark et al U.S. Patent No.3995444, the applicant is Gruenberg U.S. Patent No.4629686, the applicant is Thorne et al U.S. Patent No.3738914 and 3892628, the applicant for the Bacchi et al U.S. Patent No.5285657 and 5476763, the applicant for the McGhee et al U.S. Patent No.5157930, and the applicant is Sugimachi et al U.S. Patent No.5141847. 然而,在一些情形中,在使用这些泵装置进行器官的机器灌注时,一旦器官灌注设备功能异常则可能会增大该器官过压的风险。 However, in some cases, when using these machines pump device organ perfusion, organ perfusion device once dysfunction may increase the risk of the organ overpressure. 高压灌注(例如高于约60mmHg)会冲走该器官的脉管内皮层并通常会损伤器官组织,特别是在低于体温的温度下更是如此,因为此时器官并没有神经或内分泌连接能在高压下通过扩大其脉管系统而自我保护。 Perfusion pressure (eg greater than about 60mmHg) will be washed away in the vascular endothelial lining of the organ and often damaged organs and tissues, especially in the below body temperature is especially true, because at this time and no neurological or endocrine organ capable connection Under high pressure by expanding its vascular system and self-protection.

另外,用于评估这些机器灌注的器官的活性的技术已经成为限制这些器官得到更广应用的关键因素。 In addition, the technology used to evaluate the activity of these machine perfusion of organs has become the key factor limiting these organs get wider applications. 尽管在机器灌注期间增加的器官阻力(即,压力/流量)测量为一种有用的指标,但这些测量仅演示了最槽糕的情况。 Despite the increase during machine perfusion organ resistance (ie, pressure / flow) is measured as a useful indicator, but these measurements will show only the most disastrous situations groove.

在对由于热缺血时间或者机器灌注本身而已经受损的器官进行低温机器灌注的过程中,该器官将洗提细胞内成分和内皮成分以及膜成分。 In warm ischemia time or due to machine perfusion itself already damaged organs during low temperature machine perfusion, the organs will elute intracellular and endothelial component composition and film composition. 在过去许多年里,已经将在灌注液中出现各种普遍存在的细胞内酶——例如乳酸脱氢酶(LDH)和碱性磷酸酶——作为器官受损的生物标记。 Such as lactate dehydrogenase (LDH) and alkaline phosphatase - - organ damage as a biomarker for the past many years, various ubiquitous intracellular enzymes have appeared in the perfusate. 最近,确定低温机器灌注的灌注液中存在阿尔法谷胱甘肽-S-转移酶(a-GST)和Pi谷胱甘肽-S-转移酶(p-GST)已经证实为用于在移植之前预测无心跳供体肾脏移植的功能结果的一个令人满意的指标(Transpl 1997 Daemen)。 Recently, to determine the presence of alpha glutathione -S- transferase (a-GST) and Pi glutathione -S- transferase (p-GST) in low temperature machine perfusion has been demonstrated for the perfusate prior to transplantation a satisfactory predictor of non-heart beating donor kidney transplants Results of (Transpl 1997 Daemen).

现有技术还致力于解决在低于体温的温度下长时间保存之后恢复或维持器官的生理学功能的需要。 The prior art also committed to addressing the need to restore or maintain the organ after long-term storage at a temperature below body temperature physiological functions. 具体地,申请人为Wikman-Coffelt的美国专利No.5066578公开了一种器官保存溶液,其包含大量的丙酮酸盐。 In particular, the applicant is Wikman-Coffelt U.S. Patent No.5066578 discloses an organ preservation solution, which contains a large amount of pyruvate. Wikman-Coffelt教导,使用丙酮酸盐冲洗该器官使解糖旁路——利用三磷酸腺苷(adenosine triphosphate、ATP)产生丙酮酸盐的细胞能量循环步骤,随后线粒体可利用丙酮酸盐以进行产生ATP的氧化磷酸化作用。 Wikman-Coffelt teachings, using pyruvate flushing the organ so that the sugar solution bypass - use ATP (adenosine triphosphate, ATP) to produce cell energy cycle steps pyruvate, then pyruvate mitochondria can be used for oxidation of ATP phosphorylation. Wikman-Coffelt教导使用包含丙酮酸盐的第一保存溶液在热温度下灌注或清洗器官,从而从该器官的血管中清除血液或其它碎片,并舒张血管、增大流量并且以清洁的培养基(即,丙酮酸盐)的形式向细胞供应能量。 Wikman-Coffelt teaches the use of a first preservation solution containing pyruvate organ perfusion or cleaning under hot temperature to remove blood or other debris from the organ's blood vessels and relaxing blood vessels, increasing the flow and to clean the media ( i.e., pyruvate) in the form of supply of energy to the cells. Wikman-Coffelt教导,丙酮酸盐防止水肿、局部缺血、钙过载以及酸中毒,并有助于维持细胞膜两侧的动作电位。 Wikman-Coffelt teachings, pyruvate prevents edema, ischemia, calcium overload and acidosis, and helps to maintain the action potential on both sides of the cell membrane. 随后使用包含丙酮酸盐和小百分比的乙醇的第二灌注溶液灌注该器官,从而中止该器官的工作,使血管舒张以允许完全的脉管流通,继续向细胞供应丙酮酸盐,并维持该器官的能量状态。 Then containing pyruvate and a small percentage of ethanol in the second perfusion solution was perfused organs, thereby suspend the organ work, vasodilation vessel to allow full circulation, to continue to cell supply pyruvate, and maintain the organ energy state. 最后将该器官存储在大量的第一溶液中,在4℃至10℃的温度下保存24个小时或更长。 Finally, the large number of the first solution, stored 24 hours or more organs stored at temperatures of 4 ℃ to 10 ℃.

然而,线粒体为细胞中的能量来源,需要大量的氧以发挥其功能。 However, the mitochondria of the cell energy source, requires large amounts of oxygen in order to fulfill its function. 器官天然具有非常高的丙酮酸盐水平,但是如果不为线粒体提供足够的氧以发挥其功能,则为器官提供附加的丙酮酸盐也不会有助于恢复与/或维持器官的完全生理功能。 Natural organ has a very high level of pyruvate, but if you do not provide enough oxygen for the mitochondria to fulfill its function, for the organ to provide additional pyruvate will not help restore and / or maintain complete physiological function of organs . 另外,简单地使用丙酮酸盐冲洗器官实际上可能容易扯掉该器官的脉管内皮层。 In addition, simply using pyruvate may actually be easily torn off flush organ within the vascular endothelial lining of the organ.

申请人为Brasile等的美国专利No.5599659也公开了用于热保存组织、外植体和内皮细胞的保存溶液。 Applicants for the Brasile et al U.S. Patent No.5599659 also discloses a preservation solution for heat preservation organization, explant and endothelial cells. Brasile等教导了冷器官存储的缺点,并建议采用热保存技术作为替换方案。 Brasile et al. Teach the shortcomings of the cold storage of organs, and suggested as an alternative heat preservation technology. Brasile等教导了该溶液具有增强的能力以用作组织脉管内皮培养基的介质,并且能用作使用热保存技术来保存移植器官的溶液,这是因为该溶液加入有:血清清蛋白,作为蛋白质和胶体的来源;微量元素,加强活性和细胞功能;丙酮酸盐和腺苷,用作氧化性磷酸化载体;铁传递蛋白,作为附着因子;胰岛素和糖,作为新陈代谢载体;谷胱甘肽,清除有毒自由基及非透膜体(impermeant)源;环式糊精,作为非透膜体源、清除剂以及细胞附着和生长因子的增效剂;高的Mg++浓度,用作微脉管新陈代谢载体;主要包含硫酸软骨素和硫酸肝素的粘多糖以用作生长因子增效剂和止血;以及ENDO GROTM作为胶体、非透膜体以及特定脉管生长促进剂的来源。 Brasile et teaches that the solution has an enhanced ability to serve as a vascular endothelial tissue culture media, and can be used as heat preservation techniques used to transplant organ preservation solution, because the solution is added are: serum albumin, as source of protein and colloid; trace elements, strengthening activity and cell function; pyruvate and adenosine, used as oxidative phosphorylation carrier; transferrin as attachment factor; insulin and sugar metabolism as a carrier; glutathione , removal of toxic free radicals and non-permeable membrane (impermeant) source; cyclodextrin, as a non-permeable membrane source, scavengers and cell adhesion and growth factors synergist; a high Mg ++ concentration, used as microvascular metabolism vector; mainly containing chondroitin sulfate and heparin sulfate glycosaminoglycans for use as growth factors synergist and hemostasis; and ENDO GROTM as colloid, a non-permeable membrane and specific vascular growth promoters sources. Brasile等还教导了在30℃下热灌注器官12小时,或者只是将该器官在25℃的温度下储存在该保存溶液中。 Brasile et al. Also teaches at 30 ℃ perfusion of organs 12 hours, or just the organ at a temperature 25 ℃ stored in the preservation solution.

然而,当未向线粒体提供足够的氧使其起作用而产生能量时,使用这种化学制剂的冲洗不足以停止或修复缺血性损伤。 However, does not provide enough oxygen to the mitochondria it to work and produce energy, the use of such chemicals is not enough rinse stop or repair ischemic injury. 高于20℃时器官对氧的需求非常大,通过合理流量的简单晶胶无法满足。 When higher than 20 ℃ organ oxygen demand is very large, with a simple crystal plastic flow can not be reasonably met. 另外,在确定使用任何类型的溶液是富有成效之前,必需评估器官的活性。 Further, in determining the use of any type of solution is effective before the organ is necessary to assess the activity.

申请人为Owen的WO 88/05261公开了一种包含器官用容器的器官灌注系统,其中向该器官用容器提供通过灌注系统进行输运的乳化流体或生理电解液。 Owen applicant's WO 88/05261 discloses an organ perfusion system comprising a container for organs, which were provided to the transport of the organ perfusion system through emulsification or physiological electrolyte fluid container. 该容器包含合成液囊用于支持该器官。 The container comprises a synthetic sac to support the organ. 灌注液通过插入到动脉的导管进入该器官。 Perfusion fluid is inserted into the artery through a catheter into the organ. 由两个独立的流体源提供灌注液,各个流体源包含两个贮存器。 Perfusate provided by two independent fluid sources, each source comprises two fluid reservoirs.

发明内容 DISCLOSURE

本发明关注于避免在灌注时对器官的损伤,同时监视、维持与/或恢复该器官的活性,并保存该器官以用于储存、运输、移植或其它用处。 The present invention is concerned to avoid damage to the organ perfusion while monitoring, maintaining and / or restoring the activity of the organ, and the organ preservation for storage, transport, transplantation or other uses. 本发明旨在提供用于灌注器官从而监视、维持与/或恢复该器官的活性与/或运输与/或恢复与/或使用该器官的设备和方法。 The present invention seeks to provide for organ perfusion and thus monitor, maintain and / or restore the organ's activity and / or transport and / or restoration and / or using the devices and methods of the organ. 更为具体地,根据本发明的器官灌注设备和方法,通过在低于体温的温度下(低于体温灌注模式)与/或正常体温的温度下(正常体温灌注模式)灌注该器官以监视、维持与/或恢复该器官活性,所述灌注操作优选地在冲洗该器官(例如通过低于体温的冲洗)后进行,然后将器官静态地存放与/或在低于体温的温度下进行器官灌注而输运与/或存储该器官。 More specifically, the organ perfusion apparatus and method according to the present invention, by at hypothermic temperature (hypothermic perfusion mode) and / or normothermic temperatures (normothermic perfusion mode) of the perfused organ to monitor, maintain and / or restore the activity of the organ, the perfusion is preferably in the flushing operation of the organ (e.g. by hypothermic flushing) was performed, and then the organ statically stored, and / or at a temperature below body organ perfusion The transport and / or storage of the organ.

通过使用氧合的医用流体(例如氧合的交联血红蛋白基重碳酸盐医用流体)在正常体温或接近正常体温的温度下灌注该器官,恢复该器官中的高能量核苷酸(例如三磷酸腺苷(ATP))水平以及酶水平(其由于热缺血时间以及/或者组织缺氧而降低),可以恢复器官的活性。 By using the oxygenated medical fluid (e.g., cross-linked hemoglobin-based bicarbonate medical fluid oxygenation) at normal body temperature to normal body temperature or near the organ perfusion, the organ recovery of high energy nucleotide (e.g., adenosine triphosphate (ATP)) levels and enzyme levels (which is due to the warm ischemia time and / or reduced hypoxia), to restore the activity of the organ. 在使用该氧合医用流体灌注之前,可以用医用流体冲洗该器官。 Before using the oxygenation medical fluid infusion, medical fluid can rinse the organ. 这种灌注可以在正常体温或低于体温的温度下进行,优选地在低于体温的温度下执行。 This can be in the normothermic perfusion or hypothermic temperatures, preferably performed at a temperature below body temperature. 对于低于体温的冲洗、静止存储和低于体温的灌注,该医用流体优选地包含很少或不包含氧,优选地包含抗氧化剂,既可以有分子抗氧化剂(例如2-抗坏血酸生育酚)也可以有酶抗氧化剂(例如接触酶和超氧化物岐化酶(SOD))。 For hypothermic flush, static storage and hypothermic perfusion, the medical fluid preferably contains little or does not contain oxygen, preferably containing antioxidants, there can be either an antioxidant molecule (e.g., 2-ascorbic acid tocopherol) also It may have antioxidant enzymes (such as catalase and superoxide dismutase (SOD)). 既可以在体内也可以在体外执行正常体温与/或低于体温的灌注,优选地执行低于体温的灌注。 You can also perform both in vitro and in vivo normothermic and / or hypothermic perfusion is preferably performed hypothermic perfusion. 这种灌注能限制缺血性伤害以准备用于该器官的运输、存储与/或移植。 This can limit the ischemic reperfusion injury in preparation for the organ transportation, storage and / or transplant.

在器官已经经受低于体温的温度之后、静止与/或正在灌注时,优选地采用正常体温的处理。 After the organ has been subjected to hypothermic temperatures, static and / or perfusion is preferable to adopt normal body temperature processing. 例如在摘除器官之后,在器官的运输和/或存放过程中可能发生这种低于体温的情况。 After the removal of organs such as the case of this lower than body temperature may occur during transport and / or storage of the organ. 该处理也适用于最终将在低于体温的条件下存储与/或输运的器官。 This process is also applicable to eventually store the organ, and / or transport at a temperature below the temperature conditions. 换而言之,可以在冷存储与/或输运之前对器官进行该处理。 In other words, you can before cold storage and / or transport of organs in the process.

在正常体温的灌注模式中,优选地通过由传感器控制的气动加压的医用流体贮存器来提供总的器官灌注压力,其中该传感器安置在置于该器官内的导管的端部且其可以与步进马达/凸轮阀或节流阀组合使用,所述步进马达/凸轮阀或节流阀提供灌注压力的精细调节,防止过压与/或提供紧急情况下的流量截断。 In the normothermic perfusion mode, preferably by the sensor-controlled pneumatic pressurized medical fluid reservoir to provide a total of organ perfusion pressure, wherein the sensor is disposed in the end portions of the organ disposed within the catheter and which can be stepping motor / cam valve or a combination of throttle use, said stepping motor / cam valve or throttle provides perfusion pressure fine-tuning, to prevent over-voltage and / or to provide emergency flow cut off. 可选地,可以由例如滚子泵或蠕动泵的泵直接灌注该器官,其中所述泵具有适当的泵控制装置以及/或者充足的故障保护控制器,以防止特别是由于系统故障而导致的器官的过压。 Alternatively, for example, by a roller pump or a peristaltic pump pumps the perfusion of the organ directly, wherein the pump has an appropriate pump control device and / or a sufficient fault protection controllers, in particular in order to prevent system failure due to a result of Organ overpressure. 将过压基本消除可以防止与/或减小对脉管内皮层的损伤以及对普通器官组织的损伤。 The overvoltage can be prevented substantially eliminated, and / or reduce damage to the vascular endothelial lining of the inner and the general organ tissue damage. 优选地通过监视器官阻力(压力/流量)与/或已经被灌注穿过该器官并被收集的该医用流体的pH、pO2、pCO2、LDH、T/GST、T蛋白质、乳酸、葡萄糖、碱过剩与/或电离钙水平,在正常体温灌注模式中优选地自动地监视该器官的活性。 Preferably by monitoring organ resistance (pressure / flow rate) and / or has been perfused through the organ and medical fluid that collected pH, pO2, pCO2, LDH, T / GST, T protein, lactic acid, glucose, base excess and / or ionized calcium levels in the normothermic perfusion mode, preferably automatically monitors the activity of the organ.

可在低于体温的灌注之前与/或之后进行正常体温的灌注。 It may precede hypothermic perfusion and / or after normothermic perfusion. 在低于体温的灌注模式中,使用基本上不含氧的、优选使用抗氧化剂增强的医用流体——优选地为简单的晶体液——间歇地或以低的连续流速灌注该器官。 In the hypothermic perfusion mode, using substantially free of oxygen, it is preferable to use an antioxidant enhanced medical fluid - preferably a simple crystalloid solution - intermittently or continuously at a low flow rate of the perfused organ. 在从供体摘除该器官之前,也可在体内及体外执行低于体温的灌注。 Prior to removal of the organ from a donor, but also lower than the temperature of perfusion in vivo and in vitro execution. 低于体温的灌注能减小器官的新陈代谢速率,允许器官保存更长的时间。 Hypothermic perfusion organ metabolic rate can be reduced, allowing longer organ preservation. 医用流体优选地在压力作用下从中间液罐注入该器官,其中该中间液罐具有低压头以避免该器官的过压。 Preferably medical fluid under pressure from the tank is injected into the middle of the organ, wherein the intermediate tank has a low pressure head of the organ to avoid overpressure. 可选地,在实施例中,如果合适,可利用重力将该医用流体从该中间液罐注入该器官。 Alternatively, in an embodiment, if appropriate, can take advantage of gravity the medical fluid from the intermediate tank is injected into the organ. 可选地,可以由例如滚子泵或蠕动泵的泵直接灌注该器官,所述泵具有适当的泵控制装置与/或充足的故障保护控制器以防止特别是由于系统故障而导致的器官的过压。 Alternatively, for example, by a roller pump or a peristaltic pump pumps the perfusion of the organ directly, the pump having a suitable pump control means, and / or adequate protection controller to prevent organ failure in particular due to the system failure caused by the overpressure. 将过压基本上消除可防止或减小对该器官的脉管内皮层的损伤以及对普通器官组织的损伤,特别是在低于体温的温度下时,此时该器官通过脉管收缩而自我保护的能力较低。 The overvoltage substantially eliminate damage and prevent or reduce damage to the internal organs of the vascular endothelial lining of organs and tissues of the ordinary, especially in lower than body temperature, at which time the organ through the vasculature contraction of self-protection The lower capacity. 在恢复过程中,还可以监视且优选自动地监视该器官的活性,优选地通过监视器官阻力(压力/流量)与/或已经被灌注穿过该器官并被收集的该医用流体的pH、pO2、pCO2、LDH、T/GST、T蛋白质、乳酸、葡萄糖、碱过剩与/或电离钙水平。 During the recovery process, and it can also monitor preferably automatically monitors the activity of the organ, preferably by monitoring organ resistance (pressure / flow) and / or the pH has been perfused through the organ and collected medical fluid, pO2 , pCO2, LDH, T / GST, T protein, lactic acid, glucose, base excess and / or ionized calcium levels.

还可提供一种器官诊断设备以产生诸如器官活性指标的诊断数据。 An organ diagnostic apparatus may also be provided to produce diagnostic data such as organ viability index. 该器官诊断设备包含器官灌注设备的特征,例如传感器和温度控制器,还包含盒等特征,并且提供对该器官的分析以及灌注系统中的输入流体和输出流体。 The organ diagnostic apparatus characterized by comprising organ perfusion apparatus, such as sensors and temperature controllers, further comprising boxes and other features, and provides analysis of the organ and perfusion fluid system input and output fluid. 典型地,该器官诊断设备为一种简化的灌注设备,其在单程串联灌注中提供诊断数据。 Typically, the organ diagnostic equipment for a simplified perfusion apparatus, which provides a series of diagnostic data in a single pass perfusion.

通过综合考虑前述各种测量因子例如脉管阻力、pH等,可以提供一个器官活性指标。 By considering the factors such as the aforementioned various measurements vascular resistance, pH, etc., an organ viability index may be provided. 该指标可以是针对各个器官而有所不同,或者是可适用于各种器官。 This indicator may be vary for each organ, or be applied to a variety of organs. 该指标将所监视的参数汇编成诊断概括参数,用于进行器官治疗决定并决定是否移植该器官。 The index will be compiled into a diagnostic parameter monitored parameters are summarized for an organ transplant treatment decisions and decide whether the organ. 该指标可以自动生成并被提供给医生。 This indicator can be automatically generated and provided to the physician.

本发明的实施例中包含一种控制系统,该系统通过在灌注模式和控制参数之间选择而可以自动地控制一个或多个器官的灌注。 Embodiments of the present invention comprises a control system which by between perfusion modes and control parameters can automatically select and control one or more organ perfusion. 可以基于该系统中检测到的条件或者手动输入的参数而自动地进行灌注。 The system can be parameterized condition is detected or manually entered automatically based perfusion. 该系统可预先进行编程或者在使用期间编程。 The system can be programmed in advance or during the use of programming. 可以利用默认数值和活性校核值。 You can use the default values and active checking values.

该灌注设备可用于各种器官,例如肾脏、心脏和肺,且可适用于具有多脉管结构的更为复杂的器官,例如具有肝动脉及门静脉的肝脏。 The infusion device can be used for various organs, such as kidney, heart and lungs, and is applicable to more complex organs having multiple vasculature structures, for example, a hepatic artery and portal vein of the liver.

本发明还提供了一种器官盒,允许器官容易且安全地在用于灌注、存储、分析与/或输运该器官的设备之间移动。 The present invention also provides an organ cassette, allowing the organ easily and safely used for the perfusion, storage, analysis and / or transport device to move between the organ. 该器官盒可配置成在运输、恢复、分析与存储(包括在运输设备、灌注设备以及器官诊断设备之间的转换)期间提供不间断的无菌条件以及有效的热传递。 The organ cassette may be configured to transport, recovery, analysis and storage (including the transition between the transport devices, as well as organ perfusion apparatus diagnostic equipment) to provide uninterrupted sterile conditions during and efficient heat transfer.

本发明还提供了一种器官运输设备,允许长距离地输运器官。 The present invention also provides an organ transport device, allows long distance transport of organs. 该器官运输设备可用于各种器官,例如肾脏,且可适用于具有多脉管结构的更为复杂的器官,例如具有肝动脉及门静脉的肝脏。 The device can be used for organ transport various organs, such as kidneys, and applicable to more complex organs having multiple vasculature structures, for example, a hepatic artery and portal vein of the liver. 该器官运输设备包含器官灌注设备的特征,例如传感器和温度控制,以及盒等特征。 The organ transport device containing organ perfusion device features, such as other sensors and temperature control, as well as box feature.

本发明关注于在灌注时对器官的损伤,同时监视、维持与/或恢复该器官的活性并保存该器官以用于存储与/或输运与/或移植与/或其它用处。 The present invention is concerned with damage to organ perfusion while monitoring, maintaining and / or restoring the activity of the organ and the organ preservation for storage and / or transport and / or graft and / or other use. 出于各种原因,可能会决定该器官不应用于移植。 For various reasons, it may be decided that the organ transplant should not be used. 考虑到从供体获得器官以及恢复器活性的困难性,优选地任何器官都不应完全遗弃。 Taking into account the activity of obtaining organs and restorer from donor difficulties, it is preferable to any organ should not be completely abandoned. 因此根据本发明的另外的示范性实施例,即使器官不适合进行移植,该器官仍可以用于其它目的,例如使用生物活性剂筛选该器官,以用于药品研究等。 Thus according to a further exemplary embodiment of the present invention, even if the organ is not suitable for transplant, the organ can still be used for other purposes, e.g., screening of bioactive agents using the organ, for pharmaceutical research.

根据本发明的示范性实施例,本发明的灌注、诊断及运输设备可以与上述技术和方法结合使用,并且/或者与另外的技术及方法结合使用,从而执行对器官或组织的研究。 According to an exemplary embodiment of the present invention, perfusion, diagnostic and transport apparatus of the present invention can be used in combination with the above techniques and methods, and / or in combination with other techniques and methods to study the implementation of an organ or tissue. 除非另外特别指明,本申请中的器官包含组织。 Unless otherwise specifically indicated, the present application contains the organ tissue. 在保存与/或维持该器官期间,可在该器官上与/或利用器官进行各种药品研究和改进活动。 The preservation and / or maintained during the organ, can be a variety of pharmaceutical research and improvement activities and / or use of the organ on the organ. 可使用包含诸如药品或其它生物活性剂或其它测试物质的医用流体灌注该器官,从而获得有关该医用流体与/或该物质与该器官相互作用的数据。 It may contain information such as the use of drugs or other biologically active agents or other medical fluid to the organ perfusion test substance, to obtain about the medical fluid and / or the data substance interacting with the organ. 该数据随后可用于提供有关该物质的功效、毒性或其它性能,例如用于支持新药品或其新用途的规范文档。 This data can then be used to provide information about the efficacy of the substance, toxicity or other properties, for example to support new drugs or new uses of specification document.

该灌注、诊断与/或运输设备可用于将医用流体灌注穿过一器官,同时监视该器官以及该器官流出物以分析该器官的状况,与/或确定引入医用流体与/或诸如药品或其它生物活性剂的物质对该器官的影响。 The perfusion, diagnostic and / or devices may be used to transport medical fluid perfused through an organ while monitoring the organ and the organ effluent to analyze the condition of the organ, and / or determining the introduction of medical fluid and / or such other drugs or Substance of the biologically active agent organ affected.

关于该器官、医用流体及其之间相互作用的数据可以进行汇编。 On the organ, medical fluid interaction between their data can be compiled. 另外,可以提供器官数据指标,以用于存储灌注该器官所产生的数据。 In addition, data can provide organs indicators to be used to store the organ perfusion data generated. 该数据便于研究器官和医用流体,且还可以从该灌注、诊断或运输设备中直接获取信息以监视该器官的状态。 The data is easy to study organ and medical fluid, and can also obtain information directly from the perfusion, diagnostic or transport equipment to monitor the status of the organ. 各种类型的数据和信息可被分组成子记录或子目录,以辅助数据管理和传递。 Various types of data and information can be grouped into sub-records or subdirectory to aid data management and transfer. 所有子记录可被组合以形成整体器官筛选记录,该记录可提供给医生、科学家或其它机构以用于研究目的。 All the sub-records may be combined to form an overall organ screening record, doctors, scientists or other agencies that may be provided to record for research purposes.

该灌注设备、运输设备、盒以及器官诊断设备可被联网以允许远程管理、跟踪和监视正被存储或输运的一个或多个器官的位置以及治疗和诊断参数。 The perfusion equipment, transportation equipment, boxes and organ diagnostic apparatus may be networked to allow remote management, tracking and monitoring the position of being a storage or transport of one or more organs, as well as therapeutic and diagnostic parameters. 该信息系统可用于将器官输运和存储的历史数据汇编,并提供与医院与器官共享联合网络(United Network for Organ Sharing、UNOS)关于供体和受体的数据的交叉参考。 The information system may be used to transport and store historical data compilation of organ and provides hospital and United Network for Organ Sharing (United Network for Organ Sharing, UNOS) on the donor and recipient of a cross-reference data. 该系统还可以提供结果数据以便于研究灌注参数以及移植结果。 The system can also provide data in order to study the results of perfusion parameters and transplant results.

附图说明 Brief Description

从下述结合附图对实施例的详细描述,本发明的这些和其它方面及优点将变得显而易见,附图中:图1为根据本发明的器官灌注设备;图2为图1的设备的示意图;图3为图1的设备的电路部分的简图;图4为根据本发明的组合式的抽吸、过滤、氧合与/或去泡设备的第一抽吸模块的分解图;图5为根据本发明的组合式的抽吸、过滤、氧合与/或去泡设备的过滤模块的分解图;图6为根据本发明的组合式的抽吸、过滤、氧合与/或去泡设备的氧合模块的分解图;图7为根据本发明的组合式的抽吸、过滤、氧合与/或去泡设备的去泡器模块的分解图;图8为根据本发明的组合式的抽吸、过滤、氧合与/或去泡设备的第二抽吸模块的分解图;图9为示出了图4-图8的模块组装在一起时的分解透视图;图10为根据本发明的组装完毕的组合式的抽吸、过滤、氧合与/或去泡器设备的正面透视图;图11A-图11D示出了根据本发明的器官盒(cassette)的各种实施例的侧面透视图;图12为配置成同时灌注多个器官的器官灌注设备的示意图;图13A和13B示出了根据本发明的步进马达/凸轮阀;图14A-图14F示出了根据本发明的另一种步进马达/凸轮阀;图15示出了示意性示出根据本发明的控制系统的方框图;图16示出了根据本发明的可能处理步骤的示例性的简图;图17和图17A示出本发明的器官盒的实施例;图18和图18A示出了根据本发明的器官座的实施例;图19示出了根据本发明的器官运输设备的外部透视图;图20示出了图19的器官运输设备的剖面图;图21示出了图19的器官运输设备的方框图;图22示出了图19的器官运输设备的工作状态; Conjunction with the drawings from the following detailed description of embodiments, these and other aspects and advantages of the invention will become apparent from the drawings: Figure 1 is an organ perfusion apparatus according to the present invention; Figure 2 is the device of FIG. 1 schematic view; FIG. 3 is a schematic circuit portion of the device of FIG. 1; FIG. 4 is a composite of the present invention, suction, filtration, oxygenation and exploded view / or defoaming device first suction module; FIG. 5 is a composite of the present invention, suction, filtration, exploded view of oxygenation, and / or to soak device filtering module; Figure 6 is a composite of the present invention, suction, filtration, oxygenation and / or to bubble exploded view of the oxygenation module device; Figure 7 is based on modular suction present invention, an exploded view of filtration, oxygenation and / or equipment to bubble to bubble module; Figure 8 is based on a combination of the present invention. an exploded view of a second pump module type suction filtration, oxygenation and / or defoaming device; FIG. 9 is an exploded perspective view of Figure 4 - Figure 8 of the module assembly together; and FIG. 10 is According to the present invention is completed assembling modular suction, filtration, oxygenation and / or de-foaming device front perspective view; Fig. 11A- FIG. 11D illustrates an organ cassette of the invention (cassette) in various embodiments side perspective view; Figure 12 is configured to simultaneously schematic organ perfusion multiple organ perfusion device; 13A and 13B show a stepping motor of the present invention / cam valve; Fig. 14A- 14F shows a diagram Another stepping motor of the present invention / cam valve; Figure 15 shows a schematic block diagram showing the control system of the present invention; Figure 16 illustrates a possible process steps of the invention according to an exemplary diagram; 17 and FIG. 17A shows an embodiment of the present invention, an organ cassette; Figs. 18 and 18A shows an embodiment of the present invention according to the organ seat; Figure 19 shows a perspective view of an external organ transport device according to the invention ; FIG. 20 shows a cross-sectional view of organ transport device 19; FIG. 21 shows a block diagram of an organ transport device 19; FIG. 22 shows an operation state of organ transport device of FIG. 19;

图23示出了图19的器官运输设备的另一个剖面图;图24示出了本发明的灌注及器官移植系统的数据结构和信息传递方案;图25和图25A示出了根据本发明的灌注泵的马达控制;图26示出了根据本发明的肝脏灌注设备;图27示出了用于图26的灌注设备的蠕动泵的近距视图;图28示出了根据本发明的器官诊断系统的整体视图;图29示出了用于图28的器官诊断系统的器官评估仪器的透视图;图30示出了用于图28的器官诊断系统的串联(in-line)灌注系统;以及图31示出了图28的器官诊断系统的逻辑电路。 Figure 23 shows a cross-sectional view of another organ transport device 19; Figure 24 shows a data structure and information transfer program perfusion and organ transplant system of the present invention; Fig. 25 and 25A shows according to the present invention. infusion pump motor control; Fig. 26 shows a liver perfusion apparatus of the present invention; Figure 27 shows a close-up view of a peristaltic pump for the infusion device of FIG. 26; Figure 28 shows the present invention according to the organ diagnosis Overall view of the system; Figure 29 shows a perspective view of FIG. 28 for organ diagnostic system organ assessment instrument; Fig. 30 shows a series 28 for the organ diagnostic system (in-line) perfusion system; and Figure 31 shows a diagram organ diagnostic system logic circuit 28.

具体实施方式 DETAILED DESCRIPTION

为了全面地了解本发明的特征,现参考附图。 In order to fully understand the features of the present invention, reference is now made to the drawings. 在附图中,使用类似的附图标记指代类似的元件。 In the figures, like reference numerals refer to similar elements.

图1示出了根据本发明的器官灌注设备1。 Figure 1 illustrates the organ perfusion apparatus according to the present invention. 图2为图1的设备的示意性说明。 Figure 2 is a schematic illustration of the device of FIG. 1. 设备1优选地至少部分由微处理器控制,并且是靠气压致动。 Device 1 is preferably at least partially controlled by a microprocessor, and is pneumatically actuated. 在图3中示意性示出了微处理器150与设备1的传感器、阀、热电装置和泵的连接情况。 In Figure 3 schematically illustrates a microprocessor 150 and device sensors, valves, and pumps thermoelectric device connections 1. 微处理器150和设备1可配置成且优选地能够进一步被连接到计算机网络以提供局域网或者因特网上的数据共享。 Microprocessor 150 and apparatus may be configured and preferably can be further connected to a computer network to provide local area network or data sharing on the Internet.

器官灌注设备1能够同时在正常体温以及低于体温的温度下(下文中称为正常体温模式和低于体温模式)同时灌注一个或多个器官。 Organ perfusion apparatus 1 can simultaneously at normal body temperature and below body temperature (hereinafter referred to as normal temperature mode and under temperature mode) while one or more organ perfusion. 所有医用流体接触表面优选地由与所使用的医用流体兼容的材料制成或者涂敷该材料,更优选地由非凝血酶原材料制成或涂敷该材料。 All medical fluid contact surfaces are preferably compatible with the medical fluid by the use of the material or coating material, more preferably made of a non-thrombin material or coating the material. 如图1所示,设备1包含壳体2和贮存器进出门3,其中壳体2包含优选地为半透明的前盖4。 1, the apparatus 1 comprises a housing 2 and out into the reservoir 3, wherein the housing 2 preferably comprises a front translucent cover 4. 该设备优选地具有一个或多个控制及显示区域5a、5b、5c和5d,以用于监视和控制灌注。 The apparatus preferably has one or more control and display areas 5a, 5b, 5c and 5d, in order to monitor and control perfusion.

如图2示意性所示,在壳体2内放置有贮存器10,贮存器10优选地包含三个贮罐15a、15b和17。 2 schematically shown in FIG. 2 is placed in the housing reservoir 10, the reservoir 10 preferably comprises three tanks 15a, 15b and 17. 两个贮罐15a和15b优选地为标准一升输液袋,每个输液袋分别具有压力气囊(pressure cuff)16a和16b。 Two tanks 15a and 15b are preferably standard one liter infusion bag, infusion bag, respectively, each having a pressure balloon (pressure cuff) 16a and 16b. 压力源20优选地是气动的,并可以是如图2所示的通过导气管26、26a和26b至少提供10LPM的外部气囊致动气体的板上压缩机装置21。 Pressure source 20 is preferably pneumatic and may be as shown in airway 26,26a and 26b by providing at least the outer air bag gas 10LPM actuating plate 21 shown in compressor means. 然而,本发明不限于使用板上压缩机装置,因为可以采用任何足够的压力源,例如,优选地具有1.5升的体积且内部压力不小于100psi的压缩气体(例如空气、CO2、氧气、氮气等)罐(未示出)。 However, the present invention is not limited to the use of plate compressor means, it may be used as any adequate pressure source, e.g., preferably having a volume of 1.5 liters of compressed gas and the internal pressure not less than 100psi (e.g. air, CO2, oxygen, nitrogen, etc. ) tank (not shown). 可选地,可以使用内部加压的贮罐(未示出)。 Alternatively, you can use the internal pressure of the storage tank (not shown). 贮罐15a、15b和17在各实施例中可以为能通过重力供应灌注液或者通过压缩气体加压来供应灌注液的瓶子或其它适当的刚性贮存器。 Tanks 15a, 15b and 17 in various embodiments may supply perfusate by gravity or pressurized by a compressed gas supplied perfusate bottle or other suitable rigid reservoir.

在导气管26上设置有气阀22和23以允许对板上压缩机装置21提供的压力进行控制。 On the airway 26 is provided with a valve 22 and a pressure plate 23 to allow the compressor 21 to provide a control apparatus. 在导气管26a和26b上可分别设置止回阀24a和24b。 On the airway 26a and 26b respectively check valve 24a and 24b. 在导气管26a和26b上可分别设置压力传感器P5和P6,以将这些传感器中的状态传递给微处理器150,如图3所示。 May be provided on airway pressure sensors 26a and 26b, respectively, P5 and P6, to the status of these sensors is passed to the microprocessor 150, shown in Figure 3. 灌注、诊断与/或运输设备可设置传感器,以监视具体设备中的灌注流体压力和流量以检测具体设备中的故障,例如压力高于维护该器官的适当水平。 Perfusion, diagnostic and / or transport equipment may be provided sensors to monitor specific device perfusion fluid pressure and flow in order to detect specific equipment failures, such as a higher pressure than maintaining an appropriate level of the organs. 可设置气阀GV1和GV2来释放气囊16a和16b的压力。 GV1 and GV2 valve can be set to release the pressure of the air bag 16a and 16b. 气阀GV1和GV2中的一个或两个可排放到大气中。 Valves GV1 and GV2, one or two may be vented to the atmosphere. 可以设置通过导管18a和18b与贮罐15a和15b连通的气阀GV4,以通过导管18排放贮罐15a和15b的气体。 It may be provided through conduits 18a and 18b and the tank valves 15a and 15b in communication GV4, through conduit 18 to tank 15a and 15b of the discharge gas. 导管18、18a、18b、26、26a与/或26b可配置有过滤器与/或单向阀,以阻止生物材料进入这些导管或者进一步沿流体路径前进。 Ducts 18,18a, 18b, 26,26a and / or 26b may be configured with filters and / or check valves to prevent biological material into the further advancement of the catheter or along the fluid pathway. 这些单向阀与/或过滤器可用于在多器官灌注配置中防止生物材料离开某一器官灌注导管组而传至下一个器官的导管组中。 The one-way valve and / or filter may be used to prevent the biological material leaves an organ perfusion catheter group and transmitted to the next group of organ pipe organ perfusion in multiple configurations. 对于诸如细菌或病毒的生物材料残留于使用之后的灌注设备的情况,这些单向阀与/或过滤器还可用于防止这些物料在该灌注设备的后续使用中从一个器官传递到另一个器官。 In the case of biological material such as bacteria or viruses remaining in use after the infusion device, these one-way valve and / or filter can also be used to prevent subsequent use of these materials in the perfusion apparatus from one organ to another organ. 这些单向阀与/或过滤器防止由于气体与/或排气线路中的回流而产生的污染问题。 The one-way valve and / or filter to prevent pollution problems due to gas and / or exhaust lines generated reflux. 例如,这些阀可以配置成止回阀以防止回流。 For example, the valve may be a check valve configured to prevent backflow. 第三贮罐17优选地被从一个压力气囊通过气阀GV2释放的压力进行加压。 The third tank 17 is preferably pressurized from pressure through a pressure valve GV2 balloon release.

该医用流体可以是血液或合成流体,并且可以是例如简单的晶体液,或者可以使用适当的氧载体来增强该医用流体。 The medical fluid may be blood or a synthetic fluid and may be for example a simple crystalloid solution, or may use an appropriate oxygen carrier to enhance the medical fluid. 该氧载体例如可以是清洗过的、稳定的红血细胞;交联血红蛋白;聚乙二醇化血红蛋白或碳氟化合物基乳液。 The oxygen carrier may be cleaned, for example, stabilized red blood cells; crosslinked hemoglobin; pegylated hemoglobin or fluorocarbon based emulsions. 该医用流体还可包含已知可减小生理环境中的过氧反应或自由基损伤的抗氧化剂,以及已知辅助保护组织的特别制剂。 The medical fluid may also contain known physiological environment can reduce peroxide reaction or free radical damage antioxidants, as well as known formulations subsidiary protection organizations in particular. 在下文中将详细讨论,对于正常体温模式而言优选使用氧合(例如交联血红蛋白基重碳酸盐)溶液,而对于低于体温的模式而言优选使用非氧合溶液(例如优选使用抗氧化剂增强的简单的晶体液)。 Discussed in greater detail hereinafter, the normal temperature mode is preferably used in terms of oxygenation (e.g., cross-linked hemoglobin-based bicarbonate) solution, and for the hypothermic mode is preferably used in terms of non-oxygenation solution (e.g., anti-oxidants are preferably used Enhanced Simple liquid crystal). 在正常体温模式和低于体温模式中都能用的特殊医用流体被设计成减少或防止冲洗掉或伤害该器官的脉管内皮层。 Special medical fluid in normothermic and hypothermic modes mode can be designed to be used to reduce or prevent damage or washed off the vascular endothelial lining of the organ. 对于低于体温的灌注模式,以及对于冲洗与/或静止贮存,一种优选的溶液为2000年7月28日提交的美国专利申请No.09/628311中所公开的溶液,该申请的全部内容通过参考并入本文。 For hypothermic perfusion mode, and for washing and / or static storage, a preferred solution for the United States Patent July 28, 2000 filed No.09 / 628311 disclosed the solution, the entire contents of the application incorporated by reference herein. 在申请人为Hassanein的美国专利No.6046046中还公开有可用于本发明的灌注溶液的添加剂的示例,该专利的全部内容也通过参考并入本文。 In applicant's U.S. Patent No.6046046 Hassanein also discloses an example of additives that can be used according to the present invention, the perfusion solution, the entire disclosure of which is also incorporated herein by reference. 当然可以使用本领域中公知的其它适合的溶液和材料。 Of course, you can use well-known in the art solution and other suitable materials.

该灌注溶液可置于灌注溶液工具包内,例如一种适于销售的封装装置中,其中该封装装置优选地包含至少一个第一容器和至少一个第二容器,该第一容器容置用于正常体温灌注的第一灌注溶液,该第二容器容置用于低于体温灌注的不同的第二灌注溶液;可选地,该封装装置为图2中所示的箱子10。 The perfusion solution may be placed in a perfusion solution kit, for example, a salable packaging apparatus in which the packaging means preferably comprises at least one first container and at least one second container for accommodating the first container normothermic perfusion first perfusion solution, the second container for accommodating different hypothermic perfusion second perfusion solution; alternatively, the packaging unit is shown in Figure 2 the box 10. 该第一灌注溶液可包含至少一种氧载体,可以是氧合的与/或可以选自由交联血红蛋白和稳定红血细胞组成的群组。 The first perfusion solution may contain at least one oxygen carrier, may be oxygenated and / or may be selected from cross-linked hemoglobin and stabilized red blood cells thereof. 该第二灌注溶液可以是非氧合的,可包含至少一种抗氧化剂,并且/或者包含至少一种血管扩张剂。 The second perfusion solution may be non-oxygenated, may contain at least one antioxidant, and / or contain at least one vasodilator. 另外,该溶液优选地包含不高于5mM的溶解的丙酮酸盐。 In addition, the solution preferably contains not more than the dissolution of 5mM pyruvate. 此外,由于灌注流体贮存器与灌注机器的灌注液管道流体连通,因此该第一容器和第二容器可配置成与所述灌注机器可操作地连接。 Further, since the perfusion fluid communication with the reservoir of the perfusion machine perfusate fluid conduit, so that the first and second containers may be configured to be operably connected to the perfusion machine. 另外,该第一容器和第二容器中之一可被压缩从而对其内的灌注溶液施加压力。 In addition, the second one container and the first container can be compressed to exert pressure on its inside perfusion solution. 另外,该第一容器和第二容器中的至少一个可包含用于使所包含的灌注溶液流出该容器的第一开口以及压缩气体进入该容器的第二开口。 Further, the first and second containers may comprise at least one second opening for containing perfusion solution outflow opening of the first container and the compressed gas into the container. 该封装装置可以是配置成可操作地连接到灌注机器的盒,以将该盒内的第一容器和第二容器与灌注机器的灌注管道或导管流体连通。 The packaging unit may be configured to be operably connected to a perfusion machine cassette, a first container and a second fluid infusion conduit or conduits of the container box and filling machine communication.

在其它实施例中,该灌注溶液工具包可包含:至少一个第一容器,容置用于在第一温度下进行低于体温灌注时要用的第一灌注溶液;以及至少一个第二容器,容置用于在低于第一温度的第二温度下进行低于体温灌注时要用到的不同的第二灌注溶液。 In other embodiments, the perfusion solution kit may comprise: at least one first container accommodating when used for hypothermic perfusion to use a first perfusion solution at a first temperature; and at least one second container, for receiving a first temperature lower than a second temperature lower than the temperature of the infusion time to use a second, different perfusion solution. 在该工具包内,第一灌注溶液可至少包含晶胶并可包含至少一种血管扩张剂。 Within this toolkit, the first perfusion solution may contain at least crystal plastic and contains at least one vasodilator. 该第二灌注溶液可以是增强的氧载体,其中该氧载体选自由血红蛋白和稳定红血细胞组成的群组。 The second perfusion solution may be enhanced oxygen carrier, wherein the carrier is selected from the hemoglobin and oxygen stable group consisting of red blood cells. 此外,如果需要,该第二灌注溶液可包含至少一种抗氧化剂或自由基清除剂。 In addition, if desired, the second perfusion solution may contain at least one antioxidant or free radical scavenger. 优选地,第二溶液包含有不多于5mM的溶解丙酮酸盐。 Preferably, the second solution contains no more than the dissolution of 5mM pyruvate. 如前所述,第一容器和第二容器可配置成可操作地连接到灌注机器,以用作与所述灌注机器的灌注管道流体连通的灌注流体贮存器。 As described above, the first and second containers may be configured to be operatively connected to the perfusion machines, to be used as the perfusion with perfusion machine perfusion fluid conduit in fluid communication with the reservoir. 另外,第一容器和第二容器中之一可被压缩以对其内的灌注溶液施加压力。 Further, the first and second containers may be compressed to one of them within the infusion solution pressure. 此外,第一容器和第二容器中的至少一个可包含用于使所包含的灌注溶液流出该容器的第一开口和允许压缩气体进入该容器的第二开口。 In addition, the first container and the second container may comprise at least one of the perfusion solution used to contain the outflow opening of the first container and allowing compressed gas into the second opening of the container. 该封装装置可以是配置成可操作地连接到灌注机器的盒,以将该盒内的第一及第二容器与灌注机器的灌注管道或导管流体连通。 The packaging unit may be configured to be operably connected to a perfusion machine cassette to the fluid infusion conduit or catheter cartridge container and filling the first and second machine communication.

贮存器10内的该医用流体优选地通过与贮存器10可传热地连通的第一热电装置30a加热至预定的温度。 The medical fluid within reservoir 10 is preferably heated by means of the first thermoelectric heat reservoir 10 may be in communication 30a to a predetermined temperature. 温度传感器T3将贮存器10内的温度传递给微处理器150,该微处理器150调节热电装置30a以维持贮存器10内的期望温度,并且/或者显示于控制和显示区域5a上供手动调节。 Temperature sensor temperature T3 inside the reservoir 10 is passed to the microprocessor 150, the microprocessor 150 of the thermoelectric device 30a regulating the reservoir 10 to maintain the desired temperature, and / or displayed on the control and display areas 5a for reference manual adjustment . 可选地或附加地,在将要运输该器官灌注装置时,优选地,可以使用低温流体热交换器对该低于体温的灌注流体贮存器进行冷却,所述低温流体热交换器例如可以是同时待决的专利申请09/039443所公开的类型,该专利申请通过参考并入本文。 Alternatively or additionally, the organ to be transported in the perfusion apparatus, preferably, the heat exchanger of the cryogenic fluid may be used hypothermic perfusion fluid reservoir is cooled, for example, the cryogenic fluid heat exchanger can be simultaneously pending patent application 09/039443 of the type disclosed, the patent application is incorporated herein by reference.

还设置有器官腔40,其如图2所示支撑一个容置待灌注器官的盒65;或者如图12所示支撑多个盒65,所述多个盒65优选地彼此相邻设置。 40 is also provided with an organ chamber, which supports one shown in Figure 2 to be perfused organ accommodating cassette 65; 12 or 65 supports a plurality of cartridges, the plurality of cartridges 65 are preferably disposed adjacent to each other. 盒65的各种实施例如图11A至图11D所示。 Various embodiments of the cartridge 65, for example as shown in Figs. 11A to 11D. 盒65优选地由轻质耐用的材料制成,从而使得盒65极为便携。 Box 65 is preferably made of a lightweight, durable material, so that the cartridge 65 is extremely portable. 该材料还可是透明的以允许对器官进行视觉检查。 The material may also be transparent to permit visual inspection of the organ.

优选地,盒65包含侧壁67a、底壁67b和器官支撑表面66,该器官支撑表面优选地由多孔或网状材料制成以允许流体流过该表面。 Preferably, the cartridge 65 comprises side walls 67a, bottom wall 67b and an organ supporting surface 66, the organ supporting surface is preferably made of a porous or mesh material to allow fluid flow through the surface. 盒65还可包含顶部67d,并设置供导管穿过的一个或多个开口63(例如见图11D)。 Cartridge 65 may also include top 67d, and a supply conduit provided through one or more openings 63 (e.g. see FIG. 11D). 所述开口63可包含密封件63a(例如膜片密封件或环形密封圈),且可选地可以设置插塞(未示出)以防止器官污染并维持无菌环境。 The opening 63 may comprise a seal member 63a (e.g., a diaphragm seal or ring seals) and optionally be provided a plug (not shown) to prevent contamination of the organ and maintain a sterile environment. 另外,盒65可设有可关闭的通风孔61(例如见图11D)。 In addition, the box 65 may be provided with a closable vent hole 61 (for example, see FIG. 11D). 此外,盒65可设有用于连接到该器官或者从器官浴槽中移走医用流体的导管,并可设有用于将该导管连接到例如导管50c、81、82、91与/或132的一个或多个连接装置64(例如见图11D)。 In addition, the cartridge 65 may be provided with duct for connection to the organ or medical fluid is removed from the organ bath, and can be provided with means for connection to the catheter, for example catheter 50c, a 81,82,91 and / or 132 or a plurality of connection means 64 (e.g., see FIG. 11D). 盒65——更具体地是指该器官支撑部分、开口、导管与/或连接装置——可根据待灌注的器官的类型与/或器官的尺寸而具体设计。 Box 65-- more specifically refers to the organ support portion, openings, ducts and / or connecting means - according to the type and / or size of organ to be perfused organs and specific design. 侧支撑壁67a的外部边缘67c可以用于将盒65支撑设置于器官腔40内。 Lateral support wall 67a of the outer edge 67c can be used to support the cartridge 65 is set at 40 in the lumen. 盒65还可以例如如图11C和图11D所示包含手柄部分68,以便于抓握盒65。 Box 65 may be, for example as shown in FIG. 11C and FIG. 11D comprises a handle portion 68, so as to grip the cartridge 65. 各个盒65还可设有自己的步进马达/凸轮阀75(例如如图11C所示设置在手柄部分68内),用于精细调节被灌注到置于盒65中的器官60内的医用流体的压力,这将在下文中得到更详细的描述。 Each box 65 also has its own stepping motor / cam valve 75 (such as shown in Figure 11C disposed within the handle portion 68) for fine adjustment of medical fluid to be infused into the box 65 placed in the organ (60) The pressure, which will be described in more detail below. 可选地,在所述实施例中,可通过气动腔——例如每个器官设置单独的气动腔(未示出)——来控制压力;或者也可以通过任意适当的可变阀——例如旋转式螺旋阀或螺旋型螺旋阀——来控制压力。 Alternatively, in the embodiment, by pneumatic chamber - for example, every organ set up a separate pneumatic chamber (not shown) - to control the pressure; or it can be by any suitable variable valve - for example, a rotary valve or helical screw spiral valve - to control the pressure.

图17示出了盒65的另一实施例。 Figure 17 shows another case of Example 65. 在图17中,盒65图示为具有导管组400。 In Figure 17, the cartridge 65 is illustrated as having a conduit 400 group. 导管组400可连接到灌注设备1或连接到器官运输设备或器官诊断设备,并允许盒65在不破坏盒65内部的无菌状态下在各种设备之间移动。 Catheter infusion set 400 may be connected to the device 1 or connected to an organ or organ transport equipment diagnostic devices and allows the cartridge 65 without damaging the interior of the cartridge 65 under sterile conditions to move between various devices. 优选地,盒65由可以防止穿透并能承受剧烈冲击的足够耐用材料制成。 Preferably, the cartridge 65 is able to prevent penetration and can withstand severe shocks sufficiently durable material. 盒65设有盖,优选为两个盖——内盖410和外盖420。 Box 65 is provided with lid, preferably two cover - inner cover 410 and outer cover 420. 盖410及420可以是可移动的或者通过铰接或者其他方式连接到盒65的本体。 410 and the cover 420 may be movable or attached to the cartridge body 65 by a hinge or other means. 扣钩405提供了将盖410及420固定到盒65的顶部的机构。 Clasp 405 provides the ability to cover 410 and 420 fixed to the case 65 of the top institutions. 扣钩405还可附加配置有锁,以提供进一步的安全性及稳定性。 Clasps 405 may additionally equipped with a lock, to provide further security and stability. 在内盖410中或者同时在内盖410及外盖420中还可以包括有活体检查端口430。 The inner cover 410 or 410 while the inner cover and the outer cover 420 may also include a biopsy port 430. 活体检查端口430提供了对器官的访问通路,从而允许在最低程度地干扰器官的情况下对器官进行附加诊断。 Biopsy port 430 provides access to the organ passages, allowing in the case of minimum interference organ to organ additional diagnosis. 盒65还可具有溢流槽440(在图17A中示出)。 Cartridge 65 may also have an overflow trough 440 (shown in FIG. 17A). 溢流槽440为位于盒65顶部的沟道。 Overflow tank 440 is located in the channel 65 at the top of the box. 当盖410及420固定到盒65上时,溢流槽440提供了一个容易检查确定内部密密封件是否泄漏的区域。 65 410 and 420 when the cover is secured to the box, the overflow tank 440 provides an easy check to determine whether internal leak tight seal area. 灌注液可以被倾倒入及倾倒出盒65,并可通过龙头或可拆卸的插塞从盒65排尽。 Perfusion liquid can be poured and poured out of the box 65, and the best by a leader from the cassette row 65 or removable plugs.

盒65与/或盖410及420可由光学透明材料构成,以允许查看盒65内部及监测该器官,并允许对该器官采集视频图像或照片。 Cartridge 65, and / or the cover 410 and 420 may be formed of optically transparent material to allow viewing inside the cartridge 65 and the monitoring of the organ, and allows the organ to capture video images or photographs. 灌注设备1或盒65可以配备摄像机或照相机、数码的或其他类型的设备,以记录器官的进展和状态。 Perfusion apparatus 1 or cassette 65 can be equipped with a video camera or a camera, or other type of digital equipment to record the progress and status of the organ. 获取的图像可以设计成能在诸如局域网或因特网的计算机网络上使用,以提供附加的数据分析及远程监视。 Image acquisition may be designed to be used on a local area network or the Internet, such as a computer network, to provide additional data analysis and remote monitoring. 盒65还可设置标签,该标签通过例如条形码、磁性装置、射频装置或其它装置将盒在设备中的位置以及/或者器官的确认等信号发送给灌注设备或运输设备。 Box 65 may also be provided a label for example bar codes, magnetic devices, RF devices or other means to send the cartridge position in the apparatus and / or organ confirmation signal to the infusion device or transport equipment. 盒65可以是无菌封装,并且/或者可以作为一次性使用盒——例如撕扯打开的袋状结构——封装或出售。 Box 65 may be sterile packaged and / or may be used as a disposable cartridge - tearing open the bag-like structure, for example - or sell the package. 包含盒65的一次性使用封装结构还可包含导管组400。 Disposable cartridge 65 containing a package structure may further comprise a catheter 400 group.

盒65还可另外地设置器官座1800,如图18及图18A所示。 Box 65 may additionally be provided organ chair 1800 shown in FIG. 18 and FIG. 18A. 器官座1800是可拆卸的,其为盒65内的器官提供支撑表面。 Organ chair 1800 is removable, which provides a support surface for the organ within cassette 65. 利用可拆卸的器官座1800允许在从供体收回器官且将该器官放置到盒65内之前,向该器官插入导管并将器官保存在寒冷条件下。 Use removable organs seat before 1800 to allow recovery of organs from a donor and the organ is placed into the cassette 65, a catheter is inserted to the organs and organ preservation in cold conditions. 器官座1800可以是可再用的或者是一次性使用的。 Organ chair 1800 may be reusable or disposable. 器官座1800可被特别地构造以对应于各种类型的器官,例如肾脏、心脏或肝脏。 Organ chair 1800 may be constructed specifically to correspond to various types of organs such as kidney, heart or liver. 器官座1800优选地设计成与该器官相称,但会考虑到器官尺寸的完整人体测量范围。 Organ chair 1800 is preferably designed to be commensurate with the organ, but will consider the full range of human organ size measurement.

优选地,器官座1800至少部分被穿孔以允许流体流过器官座1800。 Preferably, organ chair 1800 is at least partially perforated to allow fluid to flow through organ chair 1800. 器官座1800中穿孔的大小被设计成捕获器官碎片,或者设置有优选地由布、织物、尼龙、塑料等构造成的附加过滤层以捕捉直径至少15微米的器官碎片。 Organ chair 1800 perforation size is designed to capture fragments of organs, or is provided with preferably made of cloth, fabric, nylon, plastic and other additional filter layer configured to capture the organ debris diameter of at least 15 microns. 此外,可以在从灌注浴槽直接摄入流体的导管上使用单独的过滤器,从而防止预定尺寸的器官碎片——例如直径至少10至15微米的器官碎片进入灌注导管。 In addition, you can use a separate filter on the direct intake of fluid from the infusion catheter bath to prevent organ debris of a predetermined size - such as the diameter of organ pieces at least 10-15 microns into the perfusion catheter.

器官座1800还可配置有静脉流出物取样器1810。 Organ chair 1800 may also be configured with a venous outflow sampler 1810. 器官座1800将静脉流出物集中到静脉流出物取样器1810。 Organ chair 1800 will concentrate venous outflow venous outflow sampler 1810. 静脉流出物取样器1810提供了容易获得的用于采集器官静脉流出物的的来源。 Venous outflow sampler 1810 provides a source of organs for the collection of venous outflow readily available. 以这种方式获取静脉流出物,允许在不经过对静脉插入导管的情况下对离开器官的灌注液进行分析,且可以通过比较分析流入及流出器官的灌注液而高度灵敏地测量器官的活性。 In this manner obtain venous outflow, without allowing in the case of the intravenous catheter insertion perfusate leaving the organ analyzed, and may be measured with high sensitivity by comparative analysis of the activity of the organ into and out of the organ perfusate. 可选地,可通过将导管插入静脉而直接地获取静脉流出物,但这种方法会增大损伤静脉或器官的风险。 Alternatively, the catheter is inserted into the vein by direct access to venous outflow, but this method increases the risk of damaging the vein or the organ. 器官座1800还可以在盒65内升高或降低以便于从静脉流出物取样器1810中取样。 Organ chair 1800 may also be raised or lowered to facilitate sampling from venous outflow sampler 1810 in the cartridge 65. 可选地,可以从盒65排出足够多的器官浴液,从而在静脉流出物与器官浴槽中的剩余灌注液混合之前能够接触到静脉流出物取样器1810或者获取该静脉流出物。 Alternatively, a sufficient number of organ bath is discharged from the cartridge 65, thereby venous outflow of the organ bath and the residual perfusate prior to mixing with access to venous outflow sampler 1810 or to obtain the venous outflow.

器官座1800优选地另外配置有套管1820,该套管连接至被灌注的动脉例如肾脏动脉。 Organ chair 1800 is preferably configured with additional casing 1820, the casing is connected to the perfused artery such as kidney artery. 套管1820可以是可再用的或者可以是一次性使用的,优选地设于具有盒65、器官座1800及导管组400的无菌封装内。 Sleeve 1820 may be reusable or may be single-use, preferably provided in the cartridge 65 having inner organ chair 1800 and sterile packaging pack 400 of the catheter. 套管1820设有套管夹1830,以将套管1820绕灌注动脉固定并优选地提供密封灌注。 Casing has a casing clamp 1820 1830 to 1820 around the perfused artery cannula fixed and preferably provide a seal perfusion. 也可以使用直进凸缘的套管(straight-in flanged cannula),不过优选地绕着动脉夹紧,以防止与容易受损的动脉内表面接触。 You can also use straight into the flange sleeve (straight-in flanged cannula), but preferably clamped around the artery to prevent contact with the inner surface of the likely damage to the artery. 套管1820还可配置有另外的与辅助动脉的分支连接。 1820 can also be configured with additional casing of the auxiliary artery branch connections. 可以使用多种套管及套管夹尺寸,以适应各种尺寸的动脉;或者可以使用可调节的套管及套管夹以适应各种尺寸的动脉。 You can use a variety of casing and casing clip size to accommodate various sizes of arteries; or you can use an adjustable clamp casing and casing to accommodate various sizes of arteries. 套管夹1830可以是蛤壳式结构或者可以是两部分的设计。 Sleeve clamp 1830 may be a clamshell structure or may be a two-part design. 套管夹1830可配置成有一体的或分离的装置,以对套管夹1830施加恰当的压力以提供密封灌注。 Sleeve clamp 1830 can be configured with an integral or separate means to apply the proper casing pressure of 1830 to provide a seal perfusion folder. 此外,套管1820可设置搭钩1840以保持套管1820闭合。 In addition, you can set the hook sleeve 1820 1840 1820 in order to maintain the sleeve closed. 套管1820还可设有通风孔1850以除去套管1820中的气泡。 Sleeve 1820 may also be provided with ventilation holes 1820 in the sleeve 1850 to remove air bubbles.

器官座1800优选地具有与套管1820上的凸起1870相对应的凹陷区域1860。 Organ chair 1800 1870 preferably has a projection on the sleeve 1820 corresponding recessed area 1860. 器官座1800上的这些凹陷区域、轨道或沟槽允许套管1820定位于多个位置以提供被灌注的动脉上的各种张力。 These recessed areas on organ chair 1800, 1820 tracks or grooves allow the sleeve positioned in a plurality of positions to provide a variety of tension on the perfused artery. 这样就允许为各动脉设置理想的最小张力。 This allows you to set the ideal for the smallest arterial tension. 套管夹1830将灌注导管固定到要被灌注的动脉。 Infusion catheter tube clip 1830 will be fixed to the arterial perfusion. 套管1820可以进行调节地固定到器官座1800上,以适应被灌注的动脉从而适应器官尺寸及动脉长度的变化,防止动脉的拉伸、扭曲、松弛或扭结。 Sleeve 1820 can be adjustably secured to organ chair 1800 to accommodate the perfused artery to accommodate variations in organ size and artery length to prevent stretching of the artery, twisted, loose or kinked. 器官座1800、套管1820及附加的条带或宽绑带的组合为运输器官以及在盒与手术场地之间转移该器官提供了可靠的平台。 Organ chair 1800, 1820 and additional casing strip or a wide array of straps for the transportation of organs and between the cartridge and the surgical site to transfer the organ provides a reliable platform.

器官座1800、套管1820与/或套管夹1830可由光学透明材料构成,以便于监测该器官以及灌注状态。 Organ chair 1800, cannula 1820 and / or cannula clamp 1830 may be formed of optically transparent material to facilitate monitoring of the organ and perfusion status.

盒65配置成其能从器官灌注设备1中移除,并通过便携式运输设备将该盒运输到另一个器官灌注设备,该便携式运输设备例如为传统冷却器,或者如申请人为Fahy的同时提交的美国同时待决申请No.09/161919或美国专利No.5586438中所公开的便携式容器,这些文献通过参考并入本文。 Box 65 are arranged so that from organ perfusion apparatus 1 is removed, and transport the cartridge transport device to another through a portable organ perfusion device, the portable device, such as a traditional cooler transport, or if the applicant submitted at the same time as Fahy -pending U.S. Application No.09 / 161919, or a portable container disclosed in U.S. Patent No.5586438, which are incorporated by reference herein.

在所述实施例中,器官在被运输时置于器官支撑表面66上,且盒65优选地封装在优选无菌的袋子69内,例如如图11A所示。 In the illustrated embodiment, the organ is placed in the organ while being transported on a support surface 66, and the cartridge 65 is preferably packaged in a sterile bag 69 is preferably, for example, shown in Figure 11A. 当使用医用流体灌注器官时,流出的医用流体收集在袋69内以形成器官浴液。 When using a medical fluid perfused organs, medical fluid outflow is collected in the bag 69 to form organs within the bath. 可选地,盒65可形成具有流体密封性的下部,流出的医用流体可以收集在该下部中,或者流出的医用流体可收集在器官腔40中以形成器官浴液。 Alternatively, the lower portion of the box 65 may be formed with a fluid-tight, medical fluid outflow can be collected in the lower, or medical fluid outflow can be collected in the organ chamber 40 to form an organ bath. 在任一可选情形中,优选地在将盒插入器官腔40之前移除袋69。 In either alternative case, preferably the cartridge is inserted into the organ chamber 40 before the bag 69 is removed. 此外,当有多个器官待灌注时,可以为每个器官提供器官腔。 In addition, when there are multiple organ to be perfused, it can provide the organ chamber for each organ. 可选地,盒65可在图17的两个盖的盒中运输,且另外可在便携式器官运输设备内被运送。 Alternatively, the cartridge 65 of FIG. 17 in two box cover transport, and in addition may be transported within the portable organ transport device.

图19示出了本发明运输设备1900的一实施例的外部视图。 Figure 19 shows an external view of an embodiment of the present invention transportation equipment 1900. 图19的运输设备1900具有便于获得直立姿势的稳定的基底,以及用于运送运输设备1900的手柄1910。 1900 19 Figure transport equipment having an upright posture facilitate access to stable base, and transport equipment for carrying handle 1900 1910. 运输设备1900还可安装有肩带与/或轮子以辅助运送运输设备1900。 Transporter 1900 may also be equipped with a shoulder strap and / or wheels to assist in the delivery of transport equipment 1900. 优选地还提供有控制面板1920。 Preferably also provided with a control panel 1920. 控制面板1920可显示如下的多个特征——例如但不限于——灌注压力、电源是开还是关、错误或故障条件、流速、流阻、灌注温度、浴液温度、抽吸时间(pumping time)、电池充电、温度曲线(最大值及最小值)、顶盖是敞开还是闭合、历史日志或历史曲线图以及其他状态细节及消息,这些特征优选地被进一步传送到远程位置用于数据存储与/或分析。 Control panel 1920 may display the following multiple features - such as, but not limited to - perfusion pressure, the power is on or off, an error or fault condition, flow, flow resistance, infusion temperature, bath temperature, suction time (pumping time ), battery charge, temperature profile (maximum and minimum), the cover is open or closed, history log or history graphs, and other status details and messages, these features are preferably further transmitted to a remote location for data storage and / or analysis. 在运输设备1900中可以使用流量及压力传感器来计算各种器官特征——包括器官的泵压力及脉管阻力,这些特征可以存储在计算机存储器中,从而允许例如分析脉管阻力历史并检测设备中的故障例如压力增大。 In the transport device 1900 in the flow and the pressure sensor can be used to calculate various organ characteristics - including the organ pump pressure and vascular resistance, these features may be stored in a computer memory, for example, allowing analysis of the historical and vascular resistance detecting apparatus failures such as pressure increases.

运输设备1900具有闩锁1930,该闩锁1930需要用户主动动作来开启,从而可以避免在运输过程中运输设备1900非有意开启的可能性。 Transporter 1900 has latches 1930, 1930 latch the active actions require the user to open, thus avoiding the possibility of 1900 opened unintentionally during transport carriage. 闩锁1930将顶部1940固定在运输设备1900上的适当位置。 Latch 1930 will top 1940 fixed in place on the transport equipment 1900. 顶部1940或其一部分可由光学透明材料构成,以便于查看盒及器官灌注状态。 Top 1940 or a portion thereof may be optically transparent material for viewing boxes and organ perfusion. 运输设备1900可配置有顶盖敞开探测器,该探测器监视并显示顶盖是敞开还是闭合。 Transporter 1900 may be configured with the cap open detector that monitors and displays the top cover is open or closed. 运输设备1900可配置成具有各种厚度的绝缘外部构件,以允许用户将运输设备1900配置用于不同的运输范围及距离。 Transporter 1900 may be configured to insulating outer member having various thicknesses to allow the user to configure transporter 1900 for different modes of transport, and the distance range. 在这些实施例中,可提供隔室1950以容放诸如图表的患者及器官数据、测试补给、附加电池、手持计算装置与/或用于运输设备1900的其它附件。 In these embodiments, the compartment 1950 may be provided to patients and organ accommodating data such as charts, testing supplies, additional battery, handheld computing devices and / or other accessories used for transport equipment 1900. 运输设备1900还可配置有用于显示UNOS标签及/或标识并返回运送信息的装置。 Transporter 1900 may also be configured for displaying a UNOS label and / or logo and return means delivery information.

图20示出了运输设备1900的剖视图。 Figure 20 shows a cross-sectional view of the transport device 1900. 运输设备1900包含盒65及泵2010。 Transporter 1900 contains 65 boxes and pump 2010. 盒65可以在不需要将导管组400与盒65断开的情况下放入运输设备1900以及取出,由此维持器官的无菌状态。 Box 65 may be placed in transport equipment 1900 and removing the catheter without the need to set off 400 and the cartridge case 65, thereby maintaining a sterile state organs. 运输设备1900中的传感器可探测运输设备1900中是否存在盒65,并根据该传感器,可从与盒65集成的条形码或射频或者其它智能标签读取器官标识。 Transporter 1900 sensors can detect the presence or absence of transport equipment 1900 cassette 65, and based on the sensor can be read from the integrated organ identifies the cartridge 65 bar codes or radio frequency or other smart tag. 这允许对器官的自动识别和跟踪,并辅助监视并控制保管链。 This allows automatic identification and tracking of organs, and secondary surveillance and control of the chain of custody. 运输设备1900与/或盒65中可加入全球定位系统以便于跟踪该器官。 Transport Equipment 1900 and / or cassette 65 can be added to the global positioning system in order to track the organs. 运输设备1900可借助网线连接到局域网络或者无线通信而在输运时与计算机网络交互。 Transporter 1900 can take advantage of the network cable to the LAN or wireless communications while in transport to interact with the computer network. 这种交互使得灌注参数、脉管阻力、和器官识别以及运输设备及盒位置被跟踪并被实时显示或者被获取以用于将来的分析。 This interaction makes perfusion parameters, vascular resistance, and organ recognition and transport equipment and box location to be tracked and displayed in real time or be captured for future analysis.

运输设备1900优选地包含过滤器2020,以除去灌注液中的沉淀物及其它颗粒物——优选地直径范围为0.05微米至15微米或者直径更大,以防止堵塞设备或器官。 Transport device 1900 preferably comprises a filter 2020 to remove sediment perfusate and other particles - preferably a diameter in the range of 0.05 microns to 15 microns in diameter or larger, in order to prevent clogging device or organs. 运输设备1900还包含电池2030,电池2030可置于运输设备1900的底部或者泵2010的下方,或者位于便于更换电池2030的任何其它位置。 Transport 1900 also includes a battery 2030, the battery 2030 can be placed at the bottom or below the transport device 1900 2010 pump, or in 2030 to facilitate the replacement battery anywhere else. 电池2030可在运输设备1900外部充电或者可就在运输设备1900内充电,并且/或者优选地可以热插拔。 Rechargeable battery 2030 1900 external transport or transport equipment may be charged in 1900, and / or, preferably, hot-pluggable. 电池2030优选能快速地且不需要彻底放电地进行充电。 Preferably the battery 2030 can be quickly and do not need to be charged completely discharged. 运输设备1900还可在其底部提供附加的存储空间2040以存储电源线、电池及其它附件。 Transporter 1900 may also provide additional storage space at its bottom 2040 to store the power cord, batteries and other accessories. 运输设备1900还可包含用于直流连接到诸如汽车或飞机的交通工具与/或用于交流连接的电源端口。 Transporter 1900 may also include a direct connection to be used as a car or airplane transportation and / or for the ac power port.

图21示出了运输设备1900的框图。 Figure 21 shows a block diagram of a transport device 1900. 图21的运输设备1900旨在主要提供低于低温的灌注,但其可工作于任何温度,例如-25℃至60℃的区间,大约0至8℃,优选地约4℃。 1900 21 Figure transport equipment designed to provide less than the main cryogenic perfusion, but it can work in any temperature range of -25 ℃ to 60 ℃ for example, and about 0 to 8 ℃, preferably about 4 ℃. 所述温度可基于所使用的具体流体进行调节,并且可以调节适于具体的运输细节例如运输时间的长短。 The temperature can be adjusted based on the particular fluid used, and can be adapted to adjust the specific details such as the length of the transport transit time. 运输设备1900由冷却剂2110进行冷却,冷却剂2110可以是冰与水浴或低温材料。 Transport equipment 1900 2110 cooled by the coolant, the coolant 2110 can be ice and water bath or cold material. 在使用低温材料的实施例中,应该避免器官冷冻。 In embodiments using cryogenic materials should be avoided organs freeze. 包围器官的灌注液的温度由温度传感器2115监视。 Surrounded organ perfusion fluid temperature by a temperature sensor 2115 monitoring. 运输设备1900还包含过滤器2020,以除去灌注液中的直径范围为0.05微米至15微米或者直径更大的沉淀物及其它微粒,以防止堵塞设备或器官。 Transporter 1900 also contains filters 2020 to remove the perfusate diameter ranging from 0.05 microns to 15 microns or greater in diameter, and other particulate precipitate, the device to prevent clogging or organs. 在泵2010下游使用过滤器2020允许截获意外的泵碎片并抑制泵2010的压力尖峰。 Use filter downstream of the pump 2010 2020 pumps allow intercepted accident debris and suppress pressure spikes pump 2010.

运输设备1900内灌注液的流量由泵2010控制,泵2010优选地为蠕动泵或滚子泵。 Perfusion fluid flow within the transport equipment 1900 2010 controlled by the pump, the pump 2010 is preferably a peristaltic pump or roller pump. 泵2010优选地不接触灌注液以帮助维持无菌性。 Pump 2010 preferably does not contact the perfusate to help maintain sterility. 此外,导管组400可不断开导管回路地连接至泵2010。 In addition, the catheter group constantly open conduit loop 400 may be connected to the pump 2010. 泵2010由计算机或微控制器控制。 Pump 2010 is controlled by a computer or microcontroller. 该计算机可以主动调制泵2010的角速度,以将泵2010的固有脉冲动作减小到低水平,从而形成基本上无脉动的流动。 The computer can actively modulate the angular velocity of the pump 2010, to the natural pulse actions of pump 2010 is reduced to a low level, so as to form a substantially pulseless flow. 进一步的计算机控制可施加合成的压力脉冲曲线,该合成的压力脉冲曲线可以为正弦曲线或生理学曲线或其它曲线。 Pressure pulse curve further computer-controlled synthesis of the pressure pulse curve can be applied, the composite may be sinusoidal or physiological curves or other curves. 通过对该合成的压力脉冲进行脉宽调制或幅值调制,不管脉冲重复频率为多少,均可以得到平均流速及压力。 Synthesis of pressure pulses through the pulse-width modulation or amplitude modulation, regardless of the number of pulse repetition frequency, can be obtained average flow rate and pressure. 用户可以通过控制面板1920或网络对部分或所有脉冲参数进行控制。 You can use the control panel or a network of 1920 some or all of the pulse parameters are controlled. 可以针对具体器官进行脉冲控制。 Pulse control can be organ-specific. 对于肝脏的情形,单个泵可向门静脉提供例如1至3升每分钟的连续流量,同时向肝动脉提供例如100至300毫升每分钟的脉动流量。 For the case of the liver, a single pump can provide, for example 1-3 liters per minute continuous flow into the portal vein, while providing, for example 100-300 ml per minute flow pulsation to the hepatic artery. 使这些分流阀与泵控制器同步,可以独立地对这两种流动进行压力调制。 These diverter valve and pump controller synchronization, it can independently modulate these two flow pressure.

灌注液进入器官的流动由流量传感器2125监视。 Organ perfusion fluid into the flow by the flow sensor 2125 monitoring. 可设置压力传感器2120以监视灌注液对导管施加的压力。 2120 pressure sensor can be set to monitor perfusion pressure was exerted on the catheter. 压力传感器2120可用于监视泵压力与/或灌输压力。 Pressure sensor 2120 can be used to monitor pump pressure and / or infusion pressure. 压力传感器2120可以只设置于器官的上游以监视器官灌输压力。 Pressure sensor 2120 may be provided only in the upper reaches of the organ to monitor organ instill pressure. 运输设备1900可配置气泡探测器2125,以在灌注液进入气泡截留装置2130之前探测气泡。 Transport equipment 1900 2125 bubble detector can be configured to bubble trapped in the perfusion fluid into the device before the 2130 probe bubbles. 这些气泡探测器例如气泡探测器2125可用于探测例如灌输管线与/或泵输出管线中的气泡。 These bubbles detectors such as bubble detector 2125 can be used to detect, for example infusion pipeline and / or pump output line of bubbles. 气泡截留装置2130除去灌注液中的气泡,并将这些气泡排放到清洗管。 2130 to remove air bubbles trapped device perfusion liquid bubbles and these bubbles to clean the discharge pipe. 气泡截留装置2130可以是一次性的,也可以构造成与导管组400一体。 2130 bubble trapping device may be disposable, it may also be configured with one catheter group 400. 从气泡截留装置2130出来的灌注液可以继续经过灌输阀2140或清洗阀2150。 2130 from the bubble trapping device out of the perfusion fluid infusion valve 2140 may continue after 2150 or purge valves. 清洗阀2150是常开的,灌输阀2140是常闭的。 2150 purge valve is normally open, instilling valve 2140 is normally closed. 优选地,清洗阀2150及灌输阀2140的开/关方式相互联系,使得当一个阀开启时,另一个阀闭合。 Preferably, the purge valve 2150 and instill valve open / close contact with each other the way 2140, so that when a valve is open, the other valve is closed. 尽管灌输阀2140是常闭的,但是如果传感器及监视器都报告运输设备1900中的灌输参数恰当,则阀2140可以开启以允许器官灌注。 Despite the infusion valve 2140 is normally closed, but if the sensor and monitor transportation equipment reported in 1900 to instill the proper parameters, the valve 2140 can be opened to allow organ perfusion. 在出现故障例如灌输压力高于器官的适当水平时,灌输阀2140切换回闭合状态且清洗阀2150开启以将液流转移到包围器官的灌注液中。 For example in the event of failure to instill a higher pressure than the appropriate level of the organ, the infusion valve 2140 switches back to the closed state and the purge valve 2150 is opened to divert the flow to surround the organ perfusion solution. 这提供了故障保护机制,即,在电源故障或计算机或电子器件出错时自动地分流灌注液流并阻止器官灌注。 This provides a fail-safe mechanism, namely, during a power failure or a computer or electronic device to automatically shunt perfusion flow error and prevent organ perfusion. 对于计算机及软件控制而言是冗余的压力传感器2120——例如由P2表示——可以硬接线到清洗阀2150和灌输阀2140,以在压力故障的情况下迅速将出错信息传递给这些阀。 For computer and software control in terms of redundant pressure sensors 2120-- example, a P2 represents - could be hard-wired to the purge valve 2150 and instill valve 2140 to quickly error message in case pressure is transmitted to the valve fault. 在这些实施例中,被转移的流体可以被分别收集在另一个容器或隔室中。 In these embodiments, the fluid may be transferred is collected in another container or compartment, respectively.

图22示出了运输设备1900的各种工作状态。 Figure 22 shows a variety of working conditions of transport equipment 1900. 例如,使用设于控制面板1920上的控制,用户可以选择诸如灌注、待机、清洗及填装的操作。 For example, using 1920 provided in the control panel on the control, the user can select, such as perfusion, standby, cleaning and filling operations. 图22示出了根据运输设备1900当前状态的各种选项。 Figure 22 shows a current state of transport equipment 1900 various options. 待机、填装、灌注及故障处理的标志表示运输设备1900的状态,其在相应操作期间优选地显示在控制面板1920上。 Standby, filling, filling and flag troubleshooting transport condition 1900 indicates, which is displayed on the control panel in the corresponding 1920 preferably during operation. 例如,当运输设备1900处于清洗操作时,控制面板1920显示清洗操作指示器,例如LED显示。 For example, in 1900, when transportation equipment cleaning operations, the control panel displays the cleaning operation indicator 1920, such as an LED display. 与运输设备1900各个操作连接的这些箭头显示了运输设备1900在不同操作状态之间过渡时可能出现的手动或自动的动作。 These arrows and transportation equipment 1900 various operations connected display device 1900 transport may occur during the transition between the different operating states manual or automatic operation. 手动动作需要用户动作,例如通过按按钮或旋转旋钮或转盘。 Manual operation requires a user action, such as by pressing a button or turn the knob or dial. 图22示范性示出了按按钮或其它指示器,例如,通过按停止按钮(按停止)从灌注操作转移到待机操作。 Figure 22 illustrates an exemplary press the button or other indicator, for example, by pressing the stop button (press stop) from the filling operation to standby operation. 为了从待机操作直接转移到灌注操作,用户可按灌注按钮(按灌注)。 In order to transfer directly from standby operation to filling operation, the user can perfusion button (press perfusion).

自动操作可以通过时间的流逝与/或运输设备1900内的内部监视器进行控制。 Automatic operation can be controlled by the passage of time and / or internal monitor within transporter 1900. 图22示出了例如将填装操作连接到待机操作这样的自动操作。 Figure 22 shows a example of such a filling operation automatically operatively connected to a standby operation. 如果在按下清洗按钮之前已经根据内部的运输设备程序参数完成了填装操作,则运输设备1900返回到待机操作。 If the cleaning button before pressing the filling operation has been completed according to the program parameters internal transport equipment, the transport device 1900 to return to standby operation. 另一个自动操作发生于出现错误或故障——例如器官的过压——的灌注操作期间。 Another automatic operation occurred in error or malfunction - such as organ overpressure - during the filling operation. 当故障或错误发生时,运输设备1900可以转移到故障处理操作以确定故障或错误的程度。 When a fault or error occurs, transporter 1900 can be transferred to troubleshooting operations to determine the degree of fault or error. 如果该故障或错误被确定为轻微或可校正的错误,运输设备1900则转变到清洗操作。 If the fault or error is determined to be minor or correctable mistakes, transport equipment 1900 transition to the cleaning operation. 如果运输设备1900可以随后调节系统参数以处理该故障或错误,则运输设备1900返回到灌注操作(错误恢复)。 If the transport device 1900 may then adjust the system parameters to handle the fault or error, transporter 1900 return to the filling operation (error recovery). 如果运输设备1900不能调节系统参数以处理该故障或错误,则运输设备1900转移到待机操作。 If transporter 1900 can not adjust the system parameters to handle the fault or error, transporter 1900 transferred to the standby operation. 如果该错误或故障被确定为是严重的,则运输设备1900可直接转移到待机操作。 If the error or fault is determined to be serious, the transport device 1900 may be directly transferred to the standby operation.

图23示出了运输设备1900的另一个剖面图。 Figure 23 shows another sectional view of the transport device 1900. 运输设备1900可具有外部壳体2310,壳体2310由金属构成,或者优选地由足够坚固以承受穿透及冲击的塑料或合成树脂构成。 Transporter 1900 may have an outer housing 2310, a housing 2310 made of a metal, or preferably by a strong enough to withstand penetration and impact plastic or synthetic resin. 运输设备1900包含隔层2320,隔层2320优选地为例如由玻璃棉或发泡聚苯乙烯制成的隔热层。 Transport equipment 1900 2320 contains compartments, spacers 2320 preferably for example glass wool or polystyrene foam insulation made. 隔层2320可以是从0.5英寸到5英寸或更厚的各种厚度,优选地为1至3英寸,例如约为2英寸厚。 Barrier 2320 may be from 0.5 inches to 5 inches thick or more of various thicknesses, preferably from 1 to 3 inches, e.g., about two inches thick. 运输设备1900被冷却剂2110冷却,冷却剂2110可以为例如冰水混合液或低温材料。 Transportation Equipment 1900 2110 cooling by coolant, coolant 2110 can, for example, a mixture of ice or cold material. 在使用低温材料的实施例中,应该设计防止器官冷冻。 In embodiments using cryogenic materials, the design should prevent organ freezing. 冰水混合物优选地最初以约1比1的比例混合,然而在实施例中该冰水混合液可以是冷冻的固体。 Ice-water mixture preferably in a ratio of about 1 initially mixing ratio 1, but in this embodiment may be a mixture of ice frozen solid. 运输设备1900可配置成能容放各种数量的冷却剂,优选地多达10至12升。 Transporter 1900 may be configured to accommodating various numbers of a coolant, preferably up to 10 to 12 liters. 冰水混合液是优选的,因为这种混合液不昂贵且不会太冷而使器官冷冻。 Ice-water mixture is preferred, because it is not expensive and not too cold mixture leaving the frozen organ. 冷却剂2110优选地在不改变的情况下持续最少6至12小时,更优选地持续至少30至50小时。 Coolant 2110 preferably without changing the minimum duration 6-12 hours, more preferably for at least 30-50 hours. 冷却剂2110的液位可以通过运输设备1900的透明区域进行察看,或者可由传感器自动探测和监视。 Coolant level in 2110. Transportation can look through the transparent area 1900, or by automatic sensor detection and monitoring. 可以在不停止灌注且不从运输设备1900除去盒65的情况下更换冷却剂2110。 The coolant can be replaced without stopping the infusion and not to remove the cartridge from transport equipment 1900 2110 65 situation. 冷却剂2110保持在运输设备1900的水密性隔室2115中。 Coolant 2110 held in transport equipment 1900 2115 in watertight compartments. 隔室2115防止冷却剂2110在运输设备1900倾斜或颠倒时发生损失。 Prevent coolant compartment 2115 2110 1900 in the transportation equipment is tilted or upside down when the loss occurred. 热量从灌注存储器及盒65的壁传导到冷却剂2110,这样能够将温度控制在预期温度范围内。 Heat from the perfusion and wall storage box 65 to the coolant 2110, so the temperature can be controlled within the desired temperature range. 冷却剂2110为一种故障保护(failsafe)机制,因为运输设备1900在掉电或电路故障或计算机故障的情况下自动地返回到冷储存。 Coolant 2110 as a fail-safe (failsafe) mechanism because transporter 1900 automatically returned to cold storage at power failure or circuit failure or malfunction of the computer case. 运输设备1900还可以配置有加热器以提高灌注液的温度。 Transporter 1900 may also be configured with a heater to raise the temperature of the perfusate.

运输设备1900可由电池或者通过插头2330提供的电源供电。 Transport equipment 1900 2330 by batteries or by a plug supplied power supply. 在运输设备1900内还设置有电子模块2335。 Within a transport device 1900 is also provided with an electronic module 2335. 电子模块2335被通风空气对流2370冷却,且还可由风扇冷却。 Electronic Modules 2335 2370 ventilated air convection cooling, and may also be cooled by a fan. 优选地,电子模块2335与灌注管分离地安放,从而防止灌注液弄湿电子模块2335并避免来自电子模块2335的外来热量添加到该灌注液。 Preferably, the electronic module 2335 and perfusion tube placed separately, thereby preventing contamination of the electronic module 2335 perfusate and avoid external heat from the electronic module to add 2335 to the perfusate. 运输设备1900具有泵2010,泵2010向灌注液导管2360提供压力以将灌注液2340发送到器官2350。 Transport equipment 1900 2010 having a pump, the pump 2010 2360 to provide pressure to the perfusion fluid conduit to send perfusate 2340 to organ 2350. 运输设备1900可用于灌注各种器官,例如肾、心、肝、小肠与肺。 Transporter 1900 can be used for perfusion of various organs such as kidney, heart, liver, small intestine and lung. 运输设备1900和盒65可容纳不同数量的灌注液2340,例如多达3至5升。 Transporter 1900 and cassette 65 can accommodate different number of perfusate 2340, for example up to 3-5 liters. 优选地,使用约1升的低于体温的灌注液2340灌注器官2350。 Preferably, about 1 liter of a hypothermic perfusate 2340 2350 perfused organ. 器官2350可以是各种器官,包括但不限于肾、心、肺、肝或小肠。 Organ 2350 may be various organs, including but not limited to kidney, heart, lung, liver or small intestine.

盒65和运输设备1900优选地构造成相互适合或匹配,使得可实现高效的热传递。 Cassette 65 and transporter 1900 is preferably configured to fit or match with each other, making it possible to achieve efficient heat transfer. 盒65与运输设备1900的几何元件优选地构造成使得当盒65置于运输设备1900内时,这些元件在运输时是安全的。 Box 65 and the geometric element transporter 1900 is preferably configured such that when the cartridge 65 is placed within a transport device 1900, these elements during transport is safe.

图24示出了可以促进辅助整体通信和数据传输的各种数据结构和信息连接,这对于器官处理之前、期间及之后都是有益的。 Figure 24 shows the auxiliary can facilitate overall communication and data transfer various data structures and connections, which for organ treatment before, during and after are beneficial. 灌注设备、运输设备、盒和器官诊断设备可连接到网络,从而实现远程管理、跟踪和监视正在储存或运输的一个或多个器官的位置和治疗及诊断参数。 Perfusion equipment, transportation equipment, boxes and organ diagnostic devices can be connected to a network, enabling remote management, tracking and monitoring are being stored or transported or multiple locations and therapeutic and diagnostic parameters organs. 这些信息系统可用于将器官运输和储存的历史数据进行汇编,并提供关于供体和任何受体的医院和UNOS数据以及/或者有关移植不合适的原因的信息之间的交叉参照。 The information system can be used to organ transport and storage of historical data compilation, and the provision of hospital and UNOS data on the donor and recipient of any cross-reference / or information on the causes of migration between inappropriate. 这些系统还可提供结果数据,以便于研究灌注参数和移植结果。 The system also provides the results of the data in order to study perfusion parameters and transplant results. 例如,可以在从供体取得器官的位置输入关于该供体的信息。 For example, you can enter information about the donor in obtaining organs from a donor location. 还可以直接从该灌注、诊断或运输设备中获取信息以监视器官状态和位置。 You can also obtain information directly from the perfusion, diagnostic or transporting equipment to monitor the status and location of organs. 各种类型的信息可以被分组成子记录或子目录以助于数据管理和传输。 Various types of information can be grouped into sub-records or subdirectory to facilitate data management and transmission. 所有这些子记录可以被组合以形成整体的移植记录,该整体移植记录可以提供给医生、科学家或其它机构以用于跟踪和监测的目的。 All of these sub-records may be combined to form an overall transplant record, the overall transplant records can provide to physicians, scientists or other organizations for purposes of tracking and monitoring.

运输设备1900的优选实施例可以自动地将许多或所有灌注过程数据以及运输设备1900的事件记录到内部数据库。 Transport equipment preferred embodiment 1900 can automatically process data in many or all of perfusion and transport equipment 1900 events are logged to an internal database. 每个盒65的射频标签或贴有条形码的标签等允许运输设备1900将数据与各个器官一一对应。 Each cartridge 65 RFID tags or barcode labels affixed to allow transportation equipment 1900 data with the various organs of the correspondence. 当运输设备1900到达对接端口时,运输设备1900可以通过LAN将数据上载到主数据库计算机。 When 1900 arrives docking port transport equipment, transport equipment by 1900 LAN computer to upload data to the master database. 无论运输设备1900在任何时候连接到LAN,运输设备1900还可提供实时状态。 Whether transport equipment 1900 connected at any time over the LAN, transport equipment 1900 also provides real-time status. 运输设备1900还可配置无线通信装备,以在运输期间提供实时数据传输。 Transporter 1900 can also be configured wireless communications equipment, to provide real-time data transmission during transport. 灌注设备1还可被连接到LAN,且由于灌注设备通常是静止的,可以连续且实时地上载数据。 Perfusion apparatus 1 can also be connected to the LAN, and since perfusion apparatus is generally stationary, continuous and real-time data contained in the ground. 这些数据可以与UNOS数据交叉引用,以利用有关器官识别、供体条件、供体补给(logistics)、受体补给以及受体结果。 These data can be cross-referenced with UNOS data to utilize on organ identification, donor condition, donor supply (logistics), receptors and receptor results supply. 数据可以显示在因特网上或能在因特网上进行访问,从而有利于在任何位置进行监视。 Data can be displayed on the Internet or can be accessed on the Internet, which will help to monitor in any position.

在该灌注、诊断与/或运输设备内,器官浴液优选地被与器官腔40热传递连通的第二热电装置30b冷却到预定温度,如图2所示。 In the perfusion, diagnostic and / or transport equipment, organ bath is preferably passed in thermal communication with the organ chamber 40 a second thermoelectric device 30b is cooled to a predetermined temperature, as shown in Fig. 可选地且优选地,当器官灌注装置将被输运时,可以利用热传递装置冷却贮存器10内的医用流体,所述热传递装置为例如冰水混合液,或者例如同时待决申请09/039443号(在此通过参考并入本文)中公开的低温流体热交换器设备。 Alternatively and preferably, when the organ perfusion device is transported, the heat transfer means can be used to cool medical fluid reservoir 10 within the heat transfer means, for example, a mixture of ice, or pending application 09 while e.g. / No. 039 443 (incorporated herein by reference) cryogenic fluid heat exchanger device disclosed. 器官腔40内的温度传感器T2将器官60的温度传送给微处理器150,微处理器150调节热电装置30b以维持期望的器官温度并且/或者将温度显示在控制和显示区域5c上供手动调节。 Temperature sensor T2 within the organ chamber 40 and the temperature of the transmission organ 60 to the microprocessor 150, the microprocessor 150 regulating the thermoelectric device 30b to maintain a desired organ temperature and / or temperature display in the control and display areas 5c for reference manual adjustment .

通过分别打开阀LV4或LV3,可将医用流体从袋15a经导管50a、50b、50c或者从袋15b经导管50d、50e、50c直接输入到置于器官腔40内的器官60。 Respectively, or by opening the valve LV4 LV3, may be a medical fluid from the bag 15a through the conduit 50a, 50b, 50c or 15b from the bag through the catheter 50d, 50e, 50c is placed directly into the organ 60 within the lumen 40. 可以利用传统的医用流体袋和导管连接。 You can use the traditional medical fluid bags and tubing connections. 所有导管优选是一次性的、容易被替换且可互换。 All catheter is preferably disposable, easily replaced and interchangeable. 此外,所有导管优选地由与所使用的医用流体兼容的材料形成或涂敷这种材料,更为优选地由非凝血酶原材料形成或涂敷这种材料。 In addition, all conduits are preferably compatible with the medical fluid by the use of such a material or coating material, more preferably formed from or coated with such a non-thrombin raw materials. 导管50c的一端插入到器官60内。 One end 50c of the catheter 60 is inserted into the organ. 可以使用传统方法例如通过缝合将该导管连接到器官。 Using conventional methods, for example by stitching organs connected to the catheter. 导管可包含凸缘(lip)以便于连接到器官。 Catheter may include a flange (lip) in order to connect to the organs. 可选地,前述套管1820可连接至器官座1800或并不与其连接。 Alternatively, the aforementioned sleeve 1820 can be connected to an organ chair 1800 or not connected thereto. 然而,具体的方法和连接方案取决于待灌注的器官类型。 However, the specific methods and connectivity solutions depending on the type of organ to be perfused.

微处理器150优选地根据来自压力传感器P1的信号控制压力源20,从而控制输入器官60的医用流体的压力。 The microprocessor 150 is preferably based on a signal from the pressure sensor P1 to control the pressure source 20, thereby controlling the pressure of the medical fluid input 60 of the organ. 微处理器150可以将该压力显示于控制与显示区域5a,可选地能用于手动调节。 The microprocessor 150 can control the pressure and displayed on the display area 5a, optionally can be used for manual adjustment. 还可以在导管50c上设置流体流量监视器F1以监视进入器官60的医用流体的流量,从而指示例如器官内是否存在任何泄漏。 You can also set the fluid flow monitor F1 on the conduit 50c to monitor the flow of medical fluid into the organ 60, which indicate, for example if there are any leaks in the inner organs.

可选地,医用流体可经导管51从贮罐17输入到中间罐70,中间罐70优选地具有约5至40mmHg的压力头(pressure head)。 Alternatively, the medical fluid may enter through the conduit 51 from the tank 17 to the intermediate tank 70, the intermediate tank 70 is preferably about 5 to 40mmHg pressure head (pressure head). 随后利用重力,优选地利用压力,通过致动阀LV6将医用流体从中间罐70沿导管50c输入到器官60。 Subsequently gravity, preferably by pressure, by actuating a valve LV6 will enter medical fluid 70 from the intermediate tank to the organ 60 along the conduit 50c. 在中间罐70内可以设置液位传感器71以维持该压力头。 70 in the intermediate tank level sensor 71 may be provided to maintain the pressure head. 当设置有多个器官腔40和器官60时,使用和图2中所示导管相同的适当导管,将这些器官60并联地连接到贮存器10,见例如图12。 When a plurality of organ chambers 40 and organs 60, using the same view of the catheter and a catheter suitable in Figure 2, these organs 60 are connected in parallel to the reservoir 10, see FIG. 12 for example. 使用配置成即使系统出现故障也能避免过压的气动加压及重力馈送的流体泵,能够减小或阻止对器官组织的一般损伤以及冲掉或损伤器官的脉管内皮层。 Even using the configured system failure could prevent overpressure pneumatic pressure and gravity feed fluid pump, can reduce or prevent damage to organs and tissues in general and within the vascular endothelial lining washed away or damaged organs. 这样,通过将液流从蠕动(滚筒)泵引入器官,可以使用例如流体静压灌注(重力或压力输入液流)或蠕动灌注执行该系统中的器官灌注。 Thus, by the flow from peristaltic (roller) pump is introduced organs can be used for example perfusion hydrostatic pressure (gravity or pressure input stream) or peristaltic perfusion implement the system in organ perfusion.

可以安装气泡探测系统以检测灌注液中的气泡。 Bubble detection system can be installed to detect bubbles in the perfusate. 优选地可以使用气体传感器和传感器板。 Preferably, you can use the gas sensors and sensor board. 传感器的输出致动去泡系统,例如打开的电磁阀,从而在灌注液流进入器官之前从灌注液流中除去气泡。 The output of the sensor to soak actuation systems, such as opening the solenoid valve, resulting in organ perfusion flow before entering remove air bubbles from the perfusion stream. 与该系统中的所有传感器和探测器一样,气泡探测器可以基于系统参数或设计特性安置于系统中任何有效的位置。 And the system of all sensors and detectors, as the bubble detector can be based on the system parameters or design features placed in the system any valid position. 例如,气泡探测器和去泡系统BD可置于凸轮阀205和压力传感器P1之间,如图1中所示。 For example, the bubble detector and to soak system BD valve can be placed between the cam 205 and a pressure sensor P1, as shown in FIG.

在导管50c上可以设置步进马达/凸轮阀205或诸如旋转螺旋阀的其它合适的可变阀,向器官60提供脉动传送的医用流体,从而降低输入器官60的医用流体的压力,并且/或者在灌注压力超过预定大小时停止医用流体流入器官60。 50c may be provided on the catheter stepping motor / cam valve 205 or other suitable variable valve such as a rotary screw valve, provide medical fluid pulsation transmitted to the organ 60, thereby reducing the pressure of medical fluid input organ 60, and / or stop medical fluid flow into the organ 60 in perfusion pressure exceeds a predetermined size. 可选地,可在该灌注设备中提供分流器或分流线路,当出现故障例如过压时,例如通过开启和闭合一个或一系列阀而将液态流量分流到这些分流器或分流线路。 Alternatively, it can provide a shunt or shunt line in the perfusion apparatus, when, for example overvoltage failure, for example by opening and closing a valve or a series of liquid flow will be diverted to the shunt or shunt line. 在图3A-图13B和图14A-图14F中示出了步进马达/凸轮阀的具体实施例。 In FIG. 13B and 14A- 3A- Figure 14F shows a stepping motor / cam valve specific examples. 图13A和图13B示出了步进马达/旋转式凸轮阀。 13A and 13B show a stepper motor / rotary cam valve.

图13A为该设备的俯视图。 Figure 13A for a plan view of the device. 导管例如导管50c介于支座(support)203和凸轮200之间。 Catheter such as catheter 50c between the holder (support) 203 and the cam 200. 凸轮200通过杆201连接到步进马达202。 Cam 200 is connected to the stepping motor 202 via rod 201. 图13B为该设备的侧视图。 FIG. 13B a side view for the device. 虚线示出了凸轮200的旋转范围。 The dotted line shows the rotation range of the cam 200. 在图13B中,凸轮200位于它的未阻塞位置。 In FIG. 13B, the cam 200 is in its non-occluding position. 旋转180度之后,凸轮200使导管彻底阻塞,其间存在不同的阻塞程度。 After 180 degrees of rotation, the cam 200 thorough catheter obstruction, there are different degrees therebetween blocked. 例如相对于图14A-图14F中所示的实施例,这种步进马达/凸轮阀相对较快,但需要强力的步进马达。 For example with respect to FIG. 14A- FIG. 14F shown embodiment, this stepping motor / cam valve is relatively fast, but requires a strong stepping motor.

图14A至图14F公开了根据本发明的另一种步进马达/凸轮阀210。 14A to 14F 210 discloses a valve according to another stepping motor / cam of the present invention. 图14A为该设备的侧视图,而图14C为俯视图。 Figure 14A a side view of the device for, and Figure 14C is a top view. 导管例如导管50c介于凸轮220与支座223之间。 Catheter such as catheter 50c between the cam 220 and seat 223. 凸轮220通过支撑件221a至221d与螺纹件225而连接到步进马达222,螺纹件225经板222a连接到步进马达222。 Cam 220 through the support member 221a to 221d and the threaded member 225 is connected to the stepping motor 222, the threaded member 225 through plate 222a is connected to the stepping motor 222. 图14B示出了支撑件221a与板222a的前视图。 14B shows a plate 221a and 222a of the front view of the support member. 如图14D所示,当支撑件221d位于螺纹件225中心的左侧时,导管50c未被阻塞。 As shown in FIG. 14D, when the support member 221d in the left center of the threaded member 225, the conduit 50c is not blocked. 然而,当螺纹件225被步进马达222转动,支撑件221d向左(相对于图14D至14F)朝凸轮220部分或完全阻塞导管50c的位置移动。 However, when the threaded member 225 is a stepping motor 222 is rotated, the support member 221d to the left (with respect to FIG. 14D to 14F) to move toward the cam 220 partially or completely blocked conduit 50c location. 这种设备比图13A和图13B的设备慢,但能量效率更高。 This equipment but more slowly than 13A and FIG. 13B equipment energy efficiency.

从器官60排出并且被收集在袋69的底部(盒65或器官腔40)内的医用流体或者经导管81被泵80抽出用于过滤、穿过过滤器装置82并返回到器官浴液,或者经导管91被泵90抽出进行循环。 Discharged from the organ 60 and is collected at the bottom of the bag 69 (box 65 or the organ chamber 40) or medical fluid is pumped through the conduit 80 out of 81 for filtering through the filter device 82 and returned to the organ bath, or Catheter 91 is a pump 90 out of cycle. 泵80、90优选地为传统的滚子泵或蠕动泵,然而还可以使用其它类型的适当的泵。 Pumps 80,90 preferably a conventional roller pump or a peristaltic pump, but you can also use other types of appropriate pumps.

图25示出了泵及脉冲控制器2500以及该泵及脉冲控制器与例如图1中所示的灌注设备的相互作用的简化示意图。 Figure 25 shows a pump and pulse controller 2500 as well as the pump and pulse controller such as simplifying the interaction between perfusion apparatus shown in Figure 1. Fig. 泵及脉冲控制器2500接收来自压力传感器P的压力传感器数据输入2510以及转速计数据输入2520。 Pump and pulse controller 2500 to receive pressure data from the pressure sensor P sensor inputs 2510 and 2520 tachometer data input. 转速计可用于设定主动波(active wave)的相位角。 Tachometer can be used to set the active wave (active wave) phase angle. 泵及脉冲控制器2500将该信息转换成马达驱动输出2530,马达驱动输出2530激励泵2540。 Pump and pulse controller 2500 converts the information into a motor drive output 2530, motor-driven pump output 2530 Incentive 2540. 图25A示出了泵及脉冲控制器2500可以提供的各种工作模式,以及泵及脉冲控制器2500是怎样消除来自灌注液流量的压力脉冲波,还示出了该泵及脉冲控制器2500如何调制灌注液流速且同时维持恒定的压力脉冲速率。 FIG. 25A shows various operating modes pump and pulse controller 2500 may provide, as well as pump and pulse controller 2500 is how to eliminate the pressure pulse wave from the perfusion fluid flow, but also shows the pump and pulse controller 2500 how Modulation perfusate flow rate while maintaining a constant pressure and pulse rate.

以恒定速度驱动的蠕动泵在相关的导管内提供恒定的压力波。 Constant speed drive peristaltic pump provides a constant pressure wave in the associated conduit. 图25A在第一工作模式中示出了对蠕动泵施加恒定驱动速度时的波形。 In the first mode of FIG. 25A shows a waveform of the peristaltic pump applying a constant driving speed. 第二工作模式,称为主动连续工作模式,示出了如何通过施加和泵的压力波相反的马达驱动波来消除或抵消该压力脉冲波。 The second mode of operation, called active continuous mode, shows how and by applying pump pressure waves opposite to the motor drive wave to eliminate or counteract the pressure pulse wave. 在第三工作模式中,称为主动波形幅值调制工作模式,泵压力脉冲波被马达驱动波抵消,并添加了选定的波,该选定波和原始压力脉冲波幅值相比具有新的幅值。 In a third mode of operation, called active waveform amplitude modulation mode, the pump pressure pulse wave is offset motor driven waves, and add the selected wave, which is selected and the original pressure pulse wave amplitude value compared with the new The amplitude. 在第四工作模式中,称为主动波形脉冲宽度调制工作模式,泵压力脉冲波被马达驱动波抵消,并添加了选定的波,该选定波和原始压力脉冲波宽度相比具有新的脉冲宽度。 In a fourth mode of operation, called active waveform pulse width modulation mode, the pump pressure pulse wave offset by a motor drive, and add the selected wave, wave and pulse width original pressure compared to the selected new pulse width. 在可选的工作模式中,可以向被抵消的波添加新频率波进行频率调制。 In an alternative mode of operation, you can add a new frequency waves to be offset by the wave frequency modulation.

与微处理器150(见图3)连通的液位传感器L2确保器官腔40内维持预定水平的流出医用流体。 And microprocessor 150 (see FIG. 3) to ensure that the level sensor L2 in communication within the organ to maintain a predetermined level of effluent medical fluid chamber 40. 如图2所示,置于导管91内的温度传感器T1将沿导管91从器官浴槽抽出的医用流体的温度传送给微处理器150并由微处理器150监视该医用流体的温度。 As shown in Figure 2, at a temperature sensor T1 conduit 91 will be transmitted along the catheter 91 withdrawn from the organ bath temperature of medical fluid to the microprocessor 150 by the microprocessor 150 to monitor the temperature of the medical fluid. 沿导管91设置的压力传感器P2将导管91内的压力传送给微处理器150,如果导管91内的流体压力超过预定极限,则微处理器150关闭该系统,或者致动警报以通知操作人员系统应该被关闭,例如进行过滤器的清洁等。 A pressure sensor P2 disposed along the conduit 91 and the pressure transmitted to the microprocessor 91 within the conduit 150, if the fluid pressure in conduit 91 exceeds a predetermined limit, the microprocessor 150 of the system shut down, or alert actuated to notify the operator system should be closed, for example, the filter cleaning.

当医用流体沿导管91被抽吸时,该医用流体优选地穿过过滤器装置95(例如25μ,8μ,2μ,0.8μt,0.2μ与/或0.1μ过滤器)、CO2洗涤器/O2隔膜100以及氧合器110,例如JOSTRATM氧合器。 When the medical fluid is pumped along the conduit 91, the medical fluid is preferably passed through the filter device 95 (e.g. 25μ, 8μ, 2μ, 0.8μt, 0.2μ and / or 0.1μ filter), CO2 scrubber / O2 membrane oxygenator 100 and 110, for example JOSTRATM oxygenator. CO2洗涤器/O2隔膜100优选地为壳体上具有亲水(例如Hypol)涂层的亲水大孔膜。 CO2 scrubber / O2 membrane 100 is preferably a housing having a hydrophilic (eg Hypol) hydrophilic coating microporous film. 通过致动阀VV1,利用真空源(未示出)在与该亲水涂层相对的一侧上施加负压。 By actuating valve VV1, with a vacuum source (not shown) is applied to the negative pressure on the side opposite the hydrophilic coating. 对于水溶液流过该隔膜的流体净压优选地为约100mmHg。 For the solution of fluid flow through the membrane net pressure it is preferably about 100mmHg. 机械式的泄放阀(未示出)防止压力差到达上述水平。 Mechanical relief valve (not shown) to prevent the pressure differential reaches the level. 在该亲水涂层内可以包含固定化的碳水化酶。 Within the hydrophilic coating may contain immobilized carbonic anhydrase enzyme. 这允许将重碳酸盐转换成CO2,且随后通过真空通风去除。 This allows the bicarbonate is converted into CO2, and then removed by vacuum ventilation. 然而,对于有能力消除重碳酸盐的器官例如肾,除非在特定的情况下,否则无需这样做。 However, the ability to eliminate bicarbonate of organs such as the kidney, except under certain circumstances, it is not recommended to do so.

氧合器110优选地为两段式氧合器,优选地包含亲水涂敷的低孔隙度的透氧隔膜。 Oxygenator 110 is preferably a two-stage oxygenator, preferably comprises a hydrophilic coating low porosity oxygen permeable membrane. 该医用流体的一部分沿导管111绕过该氧合器而进行分流,该导管111中放置有活性传感器V1,该活性传感器111检测流体特性,例如表明器官活性的器官阻力(压力/流量)、pH、pO2、pCO2、LDH、T/GST、T蛋白质、乳酸、葡萄糖、碱过剩与/或电离钙水平。 The portion of medical fluid conduit 111 along bypass the oxygenator and triage, the conduit 111 active sensors placed V1, 111 detect the fluid nature of the activity sensor, such as organ resistance showed organ viability (pressure / flow rate), pH , pO2, pCO2, LDH, T / GST, T protein, lactic acid, glucose, base excess and / or ionized calcium levels. 活性传感器V1与微处理器150连通,并可实现自动或手动地评估器官的活性。 V1 activity sensor 150 in communication with the microprocessor, and can be automatically or manually assess the activity of the organ. 根据被分流的医用流体的pH水平,在隔膜的对立侧上设置以下两种气体中之一——优选地为100%氧气,以及95%氧气和5%二氧化碳的混合物。 Depending on the pH level of the diverted medical fluid, provided one of the following two gases in the opposite side of the membrane - preferably 100% oxygen and mixtures of 95% oxygen and 5% carbon dioxide. 可选地,可以提供另一个泵(未示出),该泵将从器官腔40流出的医用流体抽出并在将该医用流体送回到浴槽之前使其流过活性传感器;或者,该活性传感器可以置于使用泵80的导管81上。 Alternatively, another pump may be provided (not shown), the pump medical fluid from flowing out of the organ chamber 40 and the flow of medical fluid before sending it back to the bath over the active sensors; Alternatively, the active sensor pump 80 may be placed on the use of the catheter 81. 在所述实施例中,流体特性可以在如图28-31所示的单独的诊断设备与/或分析器中进行分析。 In the illustrated embodiment, a separate diagnostic apparatus and / or fluid properties in the analyzer shown in FIG. 28-31 were analyzed.

检测到的流体特性,例如器官阻力(压力/流量)、pH、pO2、pCO2、LDH、T/GST、T蛋白质、乳酸、葡萄糖、碱过剩与电离钙水平,可以用于分析和确定器官的生产能力与/或所施加的生物活性物质或其它测试物质对该器官的影响。 Detected fluid properties, such as organ resistance (pressure / flow), pH, pO2, pCO2, LDH, T / GST, T protein, lactate, glucose, base excess and ionized calcium levels, may be used to analyze and determine an organ's production Capacity and / or the biologically active substance applied to the test substance or other organs affected. 可以单独地分析这些特性或者分析多个特性,以确定各种因素的影响。 Analysis of these characteristics may be used alone or more characteristics of the analysis, to determine the effect of various factors. 通过获取器官的静脉流出物并将流出物的化学性质与灌注液流入物比较,可以测量这些特性。 Comparison was by taking venous outflow of the organ and the effluent perfusate inflow and chemical properties, these properties can be measured. 可以直接获取静脉流出物并进行测量,或者,可以测量器官浴液一段时间以提供粗略近似的流体特性供比较。 You can directly access and the venous outflow was measured or the organ bath may be measured over time to provide a rough approximation of the fluid characteristics for comparisons.

在这些实施例中,将前述各种测量因素例如脉管阻力、pH等综合考虑而提供一个器官活性指标。 In these embodiments, the aforementioned various factors such as vascular resistance measurements, pH and other factors considered to provide an organ viability index. 该指标可以是针对具体器官定制,或者也可以适用于各种器官。 This indicator can be customized for a specific organ, or may be applied to a variety of organs. 该指标将监视的参数汇编成诊断概括参数,该诊断概括参数可用于做出器官治疗决定并可用于决定是否移植该器官或其它方面的用途。 The parameters of the indicators will be compiled into a diagnostic summarize monitored parameters, the diagnostic parameters can be used to make organ summarizes treatment decisions can be used to determine whether the organ transplant or other aspects of the application. 该指标可以自动产生并被提供给医生。 This indicator can be automatically generated and provided to the physician. 该指标优选地是经过与灌注设备、运输设备、盒与/或器官诊断设备的连接由计算机产生。 The index is preferably connected to the perfusion through equipment, transportation equipment, boxes and / or organ diagnostic equipment produced by a computer. 附加信息——例如供体的具体信息——可以被输入到位于灌注设备、运输设备、盒与/或器官诊断设备所在位置处的单个计算机,或者可以被输入到远程计算机并链接到该灌注设备等。 Additional information - such as specific donor information - may be input to located perfusion equipment, transportation equipment, boxes and / or a single computer at the location of the organ diagnostic device, or may be input to the remote computer and linked to the infusion device and so on. 在所述实施例中,该指标可以设计成能在计算机网络例如局域网或因特网上使用,从而用于快速比较、远程分析和数据存储。 In the described embodiment, the indicator can be designed to use on a local area network or the Internet, for example in a computer network, so for quick comparison, remote analysis and data storage.

器官活性指标提供了各个特性的测量结果以及正常范围,所述特性为例如脉管阻力以及基于pH、pO2、pCO2、LDH、T/GST、T蛋白质、乳酸、葡萄糖、碱过剩与电离钙水平的灌注液化学特性。 Organ viability index provides measurements and normal ranges for each characteristic, the characteristic, for example, vascular resistance, and based on pH, pO2, pCO2, LDH, T / GST, T protein, lactate, glucose, base excess and ionized calcium levels perfusion liquid chemical characteristics. 例如,在约5℃时,正常pH可以为7.00至8.00,优选地为7.25至7.75,更优选地为7.50至7.60,而碱过剩范围为-10至-40,优选地从-15至-30,更优选地为-20至-25。 For example, at about 5 ℃, normal pH may be from 7.00 to 8.00, preferably 7.25 to 7.75, more preferably 7.50 to 7.60, while the excess base in the range of -10 to -40, preferably from -15 to -30 , more preferably -20 to -25. 位于正常范围之外的测量结果以视觉可见的形式——例如通过使用星号或其它恰当的符号,或者以可听见的形式,或者用机器可识别的信号来指示。 Measurement results are outside the normal range of visual visible form - for example by using asterisks or other appropriate symbols, or in audible form, or by machine-readable signal indication. 这些特性使医生能够了解诸如器官新陈代谢情况,例如新陈代谢的稳定性、葡萄糖的消耗、乳酸的产生和氧气消耗。 These features enable doctors to understand the situation, such as organ metabolism, metabolic stability, for example, glucose consumption, lactate production and oxygen consumption.

该指标还可以提供:识别信息,例如年龄、性别、供体血型和任何扩展的标准;器官信息,例如器官收集日期和时间、热缺血时间、冷缺血时间和脉管阻力;设备信息,例如流速、泵工作的时间和压力;以及其它标识符,例如UNOS编号和主管的医生。 The index can also provide: identifying information, such as age, sex, blood donor, and any extension of the standard; organ information, such as organ collection date and time, warm ischemia time, cold ischemia time and vascular resistance; device information, such as time and pressure flow rates, pump; and other identifiers, such as doctors UNOS number and supervisor. 如果需要,该指标还可以另外提供温度校准。 If desired, the indicator may additionally provide temperature calibration.

返回到图2以及灌注设备1中的医用流体或灌注液的流量与/或处理,可以采用例如同时提交的同时待决的美国专利申请No.09/039318号(该专利申请通过参考并入本文)中详细描述的模块化的组合式抽吸、过滤、氧合与/或去泡的设备,来作为泵90、过滤器装置95、CO2洗涤器/O2隔膜100与/或氧合器110的替换装置。 2 and the flow returns to FIG. 1, a medical infusion device or perfusate fluid and / or process, for example, may be used while concurrently filed U.S. Patent pending Application No.09 / No. (Patent Application 039,318 which is incorporated herein by reference ) modular composite described in detail in suction, filtration, oxygenation and / or to soak the device, as the pump 90, a filter unit 95, CO2 scrubber / O2 membrane 100 and / or 110 of the oxygenator Replace device. 如图4-图10所示,该设备5001由可堆叠的模块形成。 4- shown in FIG. 10, the apparatus 5001 is formed of stackable modules. 设备5001能够将流体抽吸穿过系统并且对该流体进行氧合、过滤与/或除去气泡。 Device 5001 can draw fluid through the system and the fluid oxygenation, filtration and / or remove air bubbles. 这些模块中的每一个均分别由多个可堆叠的支撑构件形成,并易于组合形成包含所需元件的紧凑设备。 Each of these modules are each formed of a plurality of stackable support member, and readily combined to form a compact apparatus containing desired components. 过滤、氧合与/或除气隔膜放置于这些支撑构件之间。 Filtration, oxygenation and / or degassing membrane is positioned between the support member.

图4-图8示出了各种模块,这些模块可以堆叠形成组合式的抽吸、过滤、氧合与/或去泡设备,例如如图9和图10中所示的组合式的抽吸、过滤、氧合和去泡设备5001。 Figure 4 - Figure 8 shows various modules can be stacked to form a combined suction, filtration, oxygenation and / or defoaming device, such as modular as shown in FIG. 9 and 10 suction , filtration, oxygenation and to soak equipment 5001. 如这些图中所描述,该组合式的抽吸、过滤、氧合和去泡设备5001优选地由多个可堆叠支撑构件形成,这些支撑构件可分组形成一个或多个模块。 As depicted in these figures, the modular suction, filtration, oxygenation and to soak device 5001 is preferably formed from a plurality of stackable support members, the support member may be grouped to form one or more modules.

位于所述多个可堆叠支撑构件之间的是符合用户具体需要的过滤、氧合与/或除气隔膜。 Located between the plurality of stackable support members is in line with the specific needs of the user filter, oxygenation and / or degassing membrane. 这些过滤、氧合与/或除气隔膜优选地为通过商业手段能获得的大孔的憎水聚合物膜,所述聚合物膜通过商业上已知的方式例如乙氧基化进行结合,从而阻止蛋白质脱离,增强与例如血的生物兼容性,并减小堵塞趋势。 These filters, oxygenation and / or degassing membrane preferably by hydrophobic macroporous polymer film can be obtained by means of a commercial, the polymer film is formed by commercially known manner such as ethoxylated binding, thereby prevent protein from, for example, to enhance the biocompatibility of blood, and reduce clogging trend. 所述过滤隔膜优选地以亲水的方式依次结合,并优选地孔径(孔尺寸)为15至35μ,更优选地为20至30μ,从而过滤流体中的碎片且优选地不过滤掉流体的细胞或分子成分。 The filter membrane is preferably hydrophilic sequentially combined manner, and preferably pore (pore size) of 15 to 35μ, more preferably 20 to 30μ, to filter debris in a fluid and filtered fluid, but preferably the cells or molecular components. 所述除气隔膜和氧合隔膜进行表面亲水处理以维持液-气边界。 The degassing membrane oxygenation membrane surface hydrophilic treatment to maintain the liquid - gas boundary. 这些除气隔膜和氧合隔膜的孔径优选地为15μ以下,更优选地为10μ以下。 The degassing membrane oxygenation membrane pore size is preferably 15μ or less, more preferably 10μ or less.

这些模块可包含如图4中分解图所示的第一抽吸模块5010、如图5中分解图所示的过滤模块5020、如图6中分解图所示的氧合模块5030、如图7中分解图所示的去泡器模块5040和如图8中分解图所示的第二抽吸模块5050。 These modules filter module 5020 may comprise an exploded view shown in FIG. 4 in a first suction module 5010, as shown in FIG. 5 in an exploded, exploded view shown in FIG. 6 oxygenation module 5030, as shown in Figure 7 shown in exploded view to soak module 5040 and 8 shown in an exploded view of a second pump module 5050. 所述抽吸模块被分别连接到待抽吸流体源,并被手动地或由微处理器致动。 The suction module are respectively connected to a fluid source to be pumped, and by a microprocessor or manually actuated. 这些支撑构件优选地具有相似形状。 The support member preferably has a similar shape. 例如,这些支撑构件可以分别是板状的,然而其它形状可能也是合适的。 For example, the support member may be plate-like, respectively, although other shapes may also be suitable. 如图10所示,这些支撑构件优选地通过螺丝或螺栓5066进行可拆卸地连接,然而也可以是用于组装该设备的其它适当紧固件。 As shown in Figure 10, the support member preferably by screws or bolts 5066 be removably attached, but may also be used for other suitable fastener assembly of the apparatus.

第一抽吸模块5010优选包含第一(端部)支撑构件5011、具有中心切除区域5012c的第二支撑构件、横膈膜5013和第三支撑构件5014。 The first pump module 5010 preferably includes a first (end) support member 5011, having a central cutout area 5012c of the second support member, the diaphragm 5013 and a third support member 5014. 这个模块以及各个其它模块的支撑构件优选地薄且基本上平坦(呈板状),并可以由具有足够刚性且优选地还具有生物兼容性的任何适当材料形成。 The support member of each module and other modules are preferably thin and substantially flat (plate-shaped), and may be formed having a sufficient rigidity and preferably also have any suitable biocompatible material formed. 例如,可以是各种树脂和金属。 For example, various resins and metals. 优选的材料为丙烯酸/聚碳酸酯树脂。 A preferred material is an acrylic / polycarbonate resin.

第一(端部)支撑构件5011优选地是实心的,用于支撑抽吸模块5010。 The first (end) support member 5011 is preferably solid, for supporting the suction module 5010. 第一(端部)支撑构件5011优选地包含向外隆起的腔,用于接收诸如空气的抽吸流体。 The first (end) of the support member 5011 preferably comprises outward bulge chamber for receiving a fluid, such as air suction. 设置有导管5011t,以允许抽吸流体进入抽吸模块5010。 It is provided with a duct 5011t, to allow fluid to enter the suction pump module 5010. 横膈膜5013可由任何合适的弹性材料且优选地为生物兼容性的材料制成,所述材料优选地为聚氨酯。 Diaphragm 5013 may be formed of any suitable elastomeric material and preferably biocompatible material, said material is preferably a polyurethane. 第三支撑构件5014包含向外隆起的流体腔5014d和导管5014t,例如用于接收诸如血液或人造灌注液的流体进入抽吸模块5010的腔5014d。 Third support member 5014 outward bulge contains a fluid chamber 5014d and tubing 5014t, for example, for receiving a fluid such as blood or artificial perfusion fluid into the pumping chamber module 5010 5014d. 第一抽吸模块或任何其它模块还可包含用于传感器等装置的端口5014p。 First suction module or any other module may also include a port 5014p for sensors and other devices for. 优选地,与血液相容的止回阀可用于允许单向流动穿过抽吸模块5010。 Preferably, the blood compatibility of the check valve can be used to allow unidirectional flow through the pump module 5010.

过滤模块5020优选地包含形成腔5014d边界的过滤隔膜5021m、具有中心切除区域5022c的第一支撑构件5022、除气隔膜5022m和第二及第三支撑构件5023与5024。 Filter membrane filtration module 5020 preferably comprises a formed cavity 5014d boundary 5021m, 5022c cutout area having a first central support member 5022, the degassing membrane 5022m and second and third support members 5023 and 5024. 过滤隔膜5021m优选地为25μ的大孔过滤隔膜,并且该隔膜被改性以增强与例如血液的生物兼容性并减小堵塞趋势(与该装置中的其它支撑构件、过滤构件及隔膜相同)。 5021m filter membrane filter membrane is preferably 25μ big hole, and the membrane is modified to enhance biocompatibility with, for example blood and reduce clogging trend (with the device other support member, the same components and membrane filtration). 除气隔膜5022m优选地为0.2-3μ大孔除气隔膜,其表面被改性以增强生物兼容性,且其逆流水压差至少为100mmHg以用于除去CO2。 Degassing membrane 5022m is preferably a macroporous 0.2-3μ degassing membrane, the surface thereof is modified to enhance biocompatibility, and which at least 100mmHg countercurrent water pressure for removing CO2.

第一支撑构件5022包含导管5022t,在流体经过过滤隔膜5021m并沿除气隔膜5022m流过之后,用于将流体输送到氧合模块5030或另一个相邻模块(如果应用需要)。 The first support member 5022 comprising a catheter 5022t, after fluid flow through the filtration membrane 5021m and along the degassing membrane 5022m over for the fluid to the oxygenation module 5030 or another adjacent module (if the application requires). 过滤模块5020的第二支撑构件5023包含向外隆起的腔5023d和导管5023t,可通过导管5023t对腔5023d施加负压以从经过除气隔膜5022m的流体中抽出气体。 The second support member 5023 filter module 5020 contains a cavity bulge outward 5023d and tubing 5023t, it can be a negative pressure chamber through conduit 5023t 5023d to 5022m from degassed membrane fluid extracted gas. 第四支撑构件5024优选地是实心的,并为过滤模块5020提供支撑。 The fourth support member 5024 is preferably solid and provides support for the filtration module 5020. 第三支撑构件还可包含导管5024t,通过导管5024t可以施加负压以从经过氧合模块5030的除气隔膜5031m的流体中抽出气体,这一点将在下面描述。 The support member may further comprise a third conduit 5024t, 5024t may negative pressure is applied through the catheter to withdraw gas from the degassing module 5030 through the oxygenation membrane 5031m fluid, as will be described below. 过滤模块5020或任何其它模块还可包含用于传感器等装置的端口5023p。 Filtration module 5020, or any other module may also include sensor means for port 5023p.

该氧合模块5030包含除气隔膜5031m、第一支撑构件5032、过滤隔膜5033m、氧合隔膜5034m、具有中心切除区域5034c的第二支撑构件5034、以及第三和第四支撑构件5035和5036。 The oxygenation module 5030 contains the degassing membrane 5031m, the first support member 5032, filtration membrane 5033m, oxygenation membrane 5034m, 5034c has a central cut-out area of the second support member 5034, and the third and fourth support members 5035 and 5036. 除气隔膜5031m优选地为0.2-3μ的大孔除气隔膜,其表面被改性以增强生物兼容性,且其逆流水压差至少为100mmHg。 Degassing membrane 5031m is preferably a macroporous 0.2-3μ degassing membrane, the surface thereof is modified to enhance biocompatibility, and its counter current water pressure of at least 100mmHg.

第一支撑构件5032包含向外隆起的流体腔5032d。 The first support member 5032 outward bulge contains a fluid cavity 5032d. 该向外隆起的流体腔5032d的表面优选地形成曲折的流体路径,以增强流体的氧合和除气效果。 The bulge outward surface of the fluid cavity 5032d preferably forms a tortuous fluid path to enhance oxygenation and degassing effect of the fluid. 过滤隔膜5033m优选地为25μ的大孔过滤隔膜,其被改性以增强生物兼容性。 5033m filter membrane filter membrane is preferably 25μ large hole, which is modified to enhance biocompatibility. 氧合隔膜5034m优选地为0.2-1μ的大孔除气隔膜,其表面被改性以增强生物兼容性,且其逆流水压差至少为100mmHg。 Oxygenation membrane 5034m is preferably a macroporous 0.2-1μ degassing membrane, the surface thereof is modified to enhance biocompatibility, and its counter current water pressure of at least 100mmHg.

第二支撑构件5034包含导管5034t,用于将从氧合模块5030流出的流体输送到去泡器模块5040或另一个相邻模块(如果应用需要)。 The second support member 5034 comprising a catheter 5034t, for the fluid from flowing out of the oxygenation module 5030 module to soak transported to 5040 or another adjacent module (if the application requires). 第三支撑构件5035包含向外隆起的腔5035d和导管5035t,用于接收来自外部源的氧气。 Third support member 5035 contains a cavity bulge outward 5035d and tubing 5035t, for receiving oxygen from an external source. 第四支撑构件5036优选地是实心的,并为氧合模块5030提供支撑。 The fourth support member 5036 is preferably solid and provides support for the oxygenation module 5030.

去泡器模块5040包含第一支撑构件5041、过滤隔膜5042m、除气隔膜5043m、具有中心切除区域5043c的第二支撑构件、以及第三支撑构件5044。 To soak module 5040 includes a first support member 5041, filtration membrane 5042m, degassing membrane 5043m, 5043c has a central cut-out area of the second support member, and a third support member 5044. 第一支撑构件5041具有向外隆起的流体腔5041d。 5041 first support member having a fluid cavity bulge outward 5041d.

过滤隔膜5042m优选地为25μ的大孔过滤隔膜,其被改性以增强生物兼容性。 5042m filter membrane filter membrane is preferably 25μ large hole, which is modified to enhance biocompatibility. 除气隔膜5043m优选地为0.2-3μ的大孔除气隔膜,其表面被改性以增强生物兼容性,且其逆流水压差至少为100mmHg。 Degassing membrane 5043m is preferably a macroporous 0.2-3μ degassing membrane, the surface thereof is modified to enhance biocompatibility, and its counter current water pressure of at least 100mmHg. 第二支撑构件5043包含导管5043t,用于将从去泡器模块5040流出的流体输送到抽吸模块5050或另一个相邻模块(如果应用需要)。 The second support member 5043 comprising a catheter 5043t, from 5040 to bubble out of the fluid module for delivery to the suction module 5050 or another adjacent module (if the application requires). 第三支撑构件5044包含向外隆起的腔5044d和导管5044t,通过导管5044t可以施加真空以从经过除气模块5043m的流体中抽出气体。 Third support member 5044 contains a cavity bulge outward 5044d and tubing 5044t, 5044t vacuum may be applied through the catheter to extract gas from the fluid through the degassing module in the 5043m.

第二抽吸模块5050可对应于第一抽吸模块5010。 The second pump module 5050 may correspond to the first pump module 5010. 第二抽吸模块5050优选地包含第一支撑构件、横膈膜5052、具有中心切除区域5053c的第二支撑构件5053、以及第三(端部)支撑构件5054。 The second pump module 5050 preferably comprises a first support member, the diaphragm 5052, having a central cutout area 5053c of the second support member 5053, and a third (end) support member 5054. 第一支撑构件5051包含向外隆起的流体腔5051d和导管5051t,导管5051t允许流体离开该抽吸模块。 The first support member 5051 outward bulge contains a fluid chamber 5051d and tubing 5051t, 5051t catheters allow fluid to leave the pump module. 横膈膜5052优选地为聚氨酯囊。 Diaphragm 5052 is preferably a polyurethane bladder.

第三(端部)支撑构件5054优选地是实心的,为抽吸模块5050提供支撑。 The third (end) support member 5054 is preferably solid and provides support for the pump module 5050. 支撑构件5054优选地包含向外隆起的腔(未示出),用于接收抽吸的流体。 5054 support member preferably comprises outwardly bulging cavities (not shown) for receiving the pumping fluid. 设置有导管5054a,以允许诸如空气的抽吸流体进入抽吸模块5050。 It is provided with a duct 5054a, allowing fluid such as air sucked into the pump module 5050. 优选地,与血液相容的止回阀可用于允许单向流动穿过抽吸模块5050。 Preferably, the blood compatibility of the check valve can be used to allow unidirectional flow through the pump module 5050.

工作中,血液与/或其它医用流体经导管5014t进入第一抽吸模块5010,穿过过滤隔膜5021m并沿除气隔膜5022m流动。 Work, blood and / or other medical fluid through the catheter into the first suction module 5014t 5010, passes through the filter membrane 5021m and along the degassing membrane 5022m flows. 经导管5023t施加少量负压,从而经过除气隔膜5022m抽取气体。 A small amount of negative pressure is applied through a catheter 5023t, thereby extracting gas through the degassing membrane 5022m. 接着,该血液与/或医用流体经内部的导管5022t进入氧合模块5030,沿除气隔膜5031m、经过过滤隔膜5033m并沿氧合隔膜5034m流动。 Then, the blood and / or medical fluid inside the catheter through 5022t into the oxygenation module 5030, along the degassing membrane 5031m, 5033m and 5034m through the filter membrane oxygenation flow along the membrane. 氧气经导管5035t输入到氧合模块5030的第三支撑构件的向外隆起的腔5035d,然后经过氧合隔膜5034m并在血液与/或其它医用流体沿该氧合隔膜表面移动时进入所述血液与/或其它医用流体。 Transcatheter 5035t oxygen input into the oxygenation module 5030 third support member outward bulge cavity 5035d, and then after the oxygenation membrane 5034m and along in the blood and / or other medical fluid at the surface membrane oxygenation moving into the blood / or other medical fluid.

在通过氧合模块5030进行氧合之后,血液与/或其它医用流体随后经过内部导管5034t进入去泡器模块5040。 After oxygenation through the oxygenation module 5030, blood and / or other medical fluid then passes through the inner catheter 5034t to soak into the module 5040. 血液与/或其它医用流体穿过过滤隔膜5042m并沿除气隔膜5043m流动。 Blood and / or other medical fluid passes through the filter membrane 5042m and along the degassing membrane 5043m flows. 经导管5044t施加少量负压,以将经过除气隔膜5043m的血液与/或其它医用流体中的气体抽出。 Transcatheter 5044t small amount of negative pressure applied to the degassing membrane 5043m after blood extraction and / or other medical fluid gas. 血液与/或其它医用流体经过除气模块5040之后,经导管5041t行进到第二抽吸模块5050内,并经导管5051t从第二抽吸模块5050排出。 Blood and / or other medical fluid after degassing module 5040, 5041t travels through conduit into the second suction module 5050, and discharged from the second pump module 5050 Transcatheter 5051t.

在穿过氧合器110之后,或者可选地经过组合式的抽吸、氧合、过滤与/或除气设备5001之后,循环的医用流体可以选择通过致动导管92a或92b上的相应阀LV2和LV5而分别沿导管92a或92b被导引向未使用的贮罐15a或15b;或者,通过致动阀LV1被导引向进入器官腔40以补给器官浴液。 After passing through the oxygenator 110, or alternatively through modular pumping, oxygenation, filtration and / or after degassing device 5001, the medical fluid circulation can be selected by actuating the respective valves on the pipe 92a or 92b LV2 and LV5 respectively 92a or 92b along the catheter is guided to the tank unused 15a or 15b; or, to be guided by actuating the valve LV1 to enter the organ chamber 40 to supply the organ bath. 压力传感器P3和P4监视返回到未使用的贮罐15a或15b的医用流体的压力。 Pressure sensor P3 and P4 monitor the return to pressure the unused medical fluid reservoir 15a or 15b is. 在导管91上设置有机械式的安全阀MV2,以允许紧急手动截断通过导管91的流动。 The catheter 91 is provided with a mechanical valve MV2, to allow emergency manual cut off the flow through the conduit 91. 同样,设置有导管96和手动阀MV1,以允许该设备在使用之后被排干并且允许工作于单程模式之下,其中在单程模式中,从器官流出的灌注液作为废料排放而不是用来循环(循环模式)。 Similarly, the conduit 96 and is provided with a manual valve MV1, to allow the apparatus to be drained after use and allows the work under way in the mode in which the one-way mode, the discharge of waste from the organ effluent perfusate are not intended as a loop (loop mode).

靠近器官腔40并且与器官腔40连通地设置有重碳酸盐贮存器130、注射泵131、导管132、经真空阀VV2与真空(未示出)连通的排泄物收回装置120,以及导管121a和122a。 Close to the organ chamber 40 and is in communication with the organ chamber 40 provided with a bicarbonate reservoir 130, syringe pump 131, the conduit 132, vacuum valve VV2 vacuum (not shown) communicating fecal recovery means 120, and the conduit 121a and 122a.

本发明还提供了适用于具有复杂脉管结构的器官例如肝的灌注设备。 The present invention further provides a vessel suitable for organs with complex structures such as the liver perfusion apparatus. 以肝作为示例,图26示出了灌注设备2600。 Liver As an example, Figure 26 shows the infusion device 2600. 灌注设备2600具有单个泵2610,泵2610优选地为滚子泵或蠕动泵。 Perfusion apparatus 2600 has a single pump 2610, the pump 2610 is preferably a roller pump or a peristaltic pump. 导管将分成两个或以上的方向,例如三个导管朝向肝的门静脉侧(门静脉导管2625),一个导管朝向肝的肝动脉侧(肝动脉导管2626)。 The conduit is divided into two or more directions, for example, three conduit toward the portal vein side of the liver (portal vein catheter 2625), a conduit toward the hepatic artery side of the liver (hepatic artery catheter 2626). 灌注设备2600的门静脉侧具有较多的导管是因为肝的门静脉侧使用的流量为肝动脉侧的三至十倍。 Perfusion apparatus 2600 side portal with more traffic portal vein catheter is because liver side used three to ten times the hepatic artery side. 图27示出了泵2610以及分成门静脉导管2625和肝动脉导管2626的导管的透视图。 Figure 27 shows a pump 2610 and a perspective view of a catheter into the portal vein and the hepatic artery catheter 2625 catheter 2626.

灌注设备2600的门静脉侧和肝动脉侧优选地都具有过滤器2630、气泡截留装置2640、压力传感器2650、温度传感器2660和流量传感器2670。 Perfusion device portal and hepatic arterial side 2600 preferably have a filter 2630, the bubble trapping device 2640, pressure sensor 2650, a temperature sensor and a flow sensor 2670 2660. 流体返回导管2620中可设置附加的温度传感器2660。 Fluid return conduit 2620 can set additional temperature sensor 2660. 该器官可以如前所述地例如通过冰水混合液2680或利用低温流体冷却。 The organ can be a mixture of ice as previously described for example by 2680 or at low temperature fluid cooling. 在使用低温流体的实施例中,应该设计避免器官冷冻。 In embodiments using cryogenic fluids, the design should avoid freezing the organ.

可以使用多个泵,然而利用多个泵通常会增大设备的尺寸和成本。 You can use multiple pumps, but the use of multiple pumps generally increases the size and cost of the device. 两个脉管系统使用单个泵2610提供了可以用于灌注肝的多种模式。 Two vasculature using a single pump 2610 offers a variety of models that can be used perfusion liver. 在各个气泡截留装置2640之后,导管分成两个方向。 After each bubble trapping device 2640, a catheter into two directions. 在肝动脉侧,肝动脉灌输阀2685控制流到肝的肝动脉侧的流量,肝动脉清洗阀2686控制流入器官浴槽的流量。 Hepatic arterial side, hepatic artery infusion valve 2685 to control the flow of hepatic artery flow side of the liver, hepatic artery purge valve 2686 controls the flow of traffic organ bath. 在门静脉侧,门静脉灌输阀2695控制流到肝的门静脉侧的流量,门静脉清洗阀2696控制流入器官浴槽的流量。 In the portal side, portal vein infusion valve 2695 controlling the flow flowing hepatic portal vein side portal purge valve 2696 controls the flow of traffic organ bath. 优选地,各对灌输阀和清洗阀工作于一开一关或二者择一的方式。 Preferably, each of the valve and purge valve indoctrination work in opening and closing, or alternatively a way. 换而言之,例如当门静脉侧设为灌输时,门静脉清洗阀2696闭合。 In other words, for example, when the portal side to instill portal wash valve 2696 is closed. 下表示出了灌注设备2600的各种工作模式。 The following table shows the various modes of infusion device 2600.

在上表中列出的工作模式示出了灌输肝脏的可选项。 Mode listed in the above table shows instill the liver options. 在第一模式“仅门静脉”中,肝的门静脉侧被灌输。 In the first mode, "only portal", the portal side of the liver is implanted. 因此门静脉阀设置为灌输,这意味着门静脉灌输阀2695开启,门静脉清洗阀2696闭合。 Therefore, portal vein valve to instill, which means that portal infusion valve 2695 open portal purge valve 2696 is closed. 并且,在“仅门静脉”模式中,肝动脉灌输阀2685闭合,门静脉清洗阀2686开启。 And, in the "only portal" mode, hepatic artery infusion valve 2685 is closed, the portal wash valve 2686 to open. 在“仅门静脉”模式中,门静脉压力占主导,这意味着由门静脉侧上的压力传感器2650控制压力。 In the "only portal" mode, the dominant portal venous pressure, which means that by the pressure sensor on the side of the portal vein pressure control 2650. 在这个模式中,没有肝动脉灌输。 In this mode, there is no hepatic artery infusion.

在“门静脉优先”模式中,门静脉阀和肝动脉阀设置为灌输。 In the "portal priority" mode, the portal vein and hepatic artery valve valve set to indoctrination. 门静脉压力占主导,门静脉侧为主而肝动脉侧为辅。 Portal pressure is dominant side of the main portal vein and the hepatic artery side supplement. 在“交替”模式中,门静脉阀设置为灌输,肝动脉阀在灌输设置和清洗设置之间切换。 In the "alternate" mode, the portal valves set to instill, hepatic artery infusion set between the valve and purge setting is switched. 在“交替”模式中,当肝动脉阀设置为灌输时,肝动脉侧提供主导的压力。 In the "alternate" mode, when the hepatic artery valve is set to instill, the hepatic artery side provides the dominant pressure. 当肝动脉阀设置为清洗时,门静脉侧提供主导的压力。 When the valve is set to purge the hepatic artery, the portal side provides the dominant pressure. 这种交替的压力控制在门静脉侧提供了波动的流量,在肝动脉侧提供了脉冲的流量。 This alternating pressure control in the portal side provides a flow fluctuations in the hepatic artery side provides a flow pulse.

本发明还提供了器官诊断系统2800,如图28所示。 The present invention also provides an organ diagnostic system 2800, shown in Figure 28. 器官诊断系统2800具有计算机2810和分析器2820。 Organ diagnostic system 2800 having a computer and analyzer 2820 2810. 器官评估仪器2830同时连接到计算机2810和分析器2820,如图29所示。 Organ assessment instrument 2830 2810 simultaneously connected to the computer and analyzer 2820 shown in Figure 29. 器官诊断系统2800优选地设有适当的显示器,以显示系统和器官的状态。 Organ diagnostic system 2800 is preferably provided with a suitable display to show the status of the system and organs. 器官评估仪器2830具有灌注液腔2840和器官腔2850。 Assess organ perfusion apparatus 2830 has a liquid chamber 2840 and 2850 lumen. 传输管线2860连接分析器2820和器官评估仪器2830。 Transmission lines 2820 and 2860 to connect the analyzer to assess organ instrument 2830. 器官诊断系统2800提供了对无菌盒内的器官的分析,并且快速地产生器官活性指标,该无菌盒优选地可从灌注设备1与/或运输设备1900传递过来。 Organ diagnostic system 2800 provides an analysis of the sterile cartridge organs and organ viability index quickly produce the sterile cassette preferably from perfusion apparatus 1 and / or transport equipment 1900 passed over. 优选地由流量和温度编程的单程灌注和串联自动分析产生该器官活性指标。 Preferably by the one-way flow and temperature-programmed automatic analysis of perfusion and series produce the organ viability index. 这种分析也可以用于多程循环系统中。 This analysis can also be used for multi-pass loop system. 该多程循环系统将使流体循环,用于分析并同时维持和评估该器官。 The multi-pass loop fluid circulation system will allow for the analysis and assessment while maintaining the organ. 可由阀(未示出)控制流体,且该流体可以在到达分析器2820之前循环返回到系统的起点。 By a valve (not shown) to control the fluid, and the fluid before it reaches the analyzer 2820 may be recycled back to the beginning of the system.

单程系统的有利一面为,该系统可配置有有限数目的传感器且仅需要足够的灌注液以进行分析。 One-way system is advantageous aspect, the system may be configured with a limited number of sensors and requires only enough perfusate to perform the analysis. 单程灌注还允许利用具有已知和预定化学性质的灌注液灌注器官。 One way perfusion also allows the use of perfusion fluid having a known and predetermined chemical properties perfused organs. 这提高了可以输送的诸如血液或合成血液载体或其组合的灌注液的类型和成分的灵活度,可以根据具体分析过程定制与/或调节该灌注液。 This increases the flexibility of the type and composition can be delivered, such as blood or a synthetic blood perfusion liquid carrier or a combination thereof, and can process customization and / or adjusted according to the specific analysis of perfusion liquid.

图29示出了器官评估仪器2830的透视图。 Figure 29 shows a perspective view of the organ assessment instrument 2830. 器官评估仪器2830包含灌注液腔2840和器官腔2850。 Organ perfusion assessment instrument that contains liquid chamber 2830 lumen 2840 and 2850. 器官腔2850可以是绝缘的,优选地具有盖子2910,盖子2910是可拆卸的或者可以是铰接连接。 Organ chamber 2850 may be insulated, preferably with a cover 2910, 2910 is a removable lid or may be hingedly connected. 器官腔2850优选地配置成容置盒65,优选地不需要打开盒65或破坏盒65内部的无菌性。 Organ chamber 2850 is preferably configured to accommodating cassette 65, preferably without opening cassette 65 or destroy the sterility of the interior of the cartridge 65. 盒65与器官腔2850优选地构造成相互匹配,以便实现高效的热传递。 Cassette 65 and organ chamber 2850 are preferably configured to match each other, in order to achieve efficient heat transfer. 盒65与器官腔2850的几何构件优选地构造成使得当盒65置于器官腔2850内时,这些构件能可靠地用于分析。 Cassette 65 and organ chamber 2850 geometric member is preferably configured such that when the cartridge 65 is placed within organ chamber 2850, these components can be reliably used for the analysis. 还设置有端口2920以连接传输管线2860。 2920 is also provided with a port to connect the transmission line 2860.

图30示出了器官诊断系统2800的单程流体系统。 Figure 30 shows the organ diagnostic system 2800 one-way fluid system. 初始的灌注流体3000容置于腔3010内。 The initial perfusion fluid 3000 housed within the cavity 3010. 腔3010优选地由加热与冷却系统控制温度。 Lumen 3010 preferably by a heating and cooling system to control the temperature. 该系统内的流体流量由流量传感器3020监控,并且通过向节流阀3030与泵3040发送信号而控制流体流量。 Fluid flow within the system is monitored by the flow sensor 3020, and 3030 through the throttle valve and the pump to the transmission signal 3040 and control fluid flow. 流体系统还提供气泡截留装置3050、压力传感器3060和温度传感器3070。 Bubbles trapped fluid system also provides means 3050, a pressure sensor and a temperature sensor 3070 3060. 热交换器3080在器官灌注之前向系统内的流体提供温度控制,并且加热与冷却所述流体。 Heat exchanger 3080 before organ perfusion fluid to provide temperature control system, and the heating and cooling of the fluid. 器官在盒65内进行灌注。 (65) In the case of organ perfusion. 器官浴槽内的流体可以被收集,也就是说可以获取静脉流出物,以用于分析。 The fluid within the organ bath may be collected, i.e. venous effluent can be obtained, for analysis. 收集的流体经传输管线2860传至分析器2820。 Collection of fluid through the transmission line 2860 is transmitted to the analyzer 2820. 传输管线2860还可以设置单独的加热和冷却装置。 Transmission line 2860 can also set up a separate heating and cooling devices. 流体在被进行完分析之后可被收集在废物容器3090内。 After the completion fluid is subjected to analysis it can be collected in a waste container 3090.

图31示出了器官诊断系统2800的逻辑电路。 Figure 31 shows the organ diagnostic system 2800 of a logic circuit. 计算机提供控制参数并从分析器接收结果和数据。 Computer provides control parameters and receives the results and the data from the analyzer. 该逻辑电路示出了从传感器到微处理器的输入以及到硬件的输出,该硬件为例如灌注液冷却器、灌注液加热器、节流阀、泵、传输管线加热器/冷却器和显示器。 The logic circuit shows inputs from the sensors to the microprocessor and to the output of the hardware, the hardware such as perfusate coolers, perfusate heaters, throttle valve, pump, transfer line heater / cooler and displays.

根据本发明的方法优选地利用诸如前述的设备来灌注器官,从而维持、监视与/或恢复器官的活性与/或运输与/或存储该器官。 The method according to the present invention is preferably utilized such as the aforementioned organ perfusion device, in order to maintain, monitor and / or restore the activity of the organ, and / or transport and / or storage of the organ. 保护维持器官的活性对于成功的器官移植或器官的其它用途而言有着重要的意义。 Protection to maintain organ activity for other uses successful organ transplant or organ in terms of great significance. 在从供体身体摘除该器官与/或在存储与/或运输期间,这些器官经常由于供体身体的疾病或受伤而长时间缺氧(所谓的缺血)。 Removal from the donor body of the organ and / or / or during storage and transport, these organs are often due to the donor body of illness or injury prolonged hypoxia (called ischemia). 本发明的灌注、诊断与/或运输设备具有如下能力,即,探测待移植器官的细胞化学性质从而调节灌注液并控制细胞新陈代谢以修复器官缺血伤害并防止再灌注损伤。 Perfusion, diagnostic and / or transport apparatus of the present invention has the ability, that is, the chemical nature of the probe cells to be transplanted organs so as to adjust the perfusate and control the cellular metabolism to repair the damage and prevent organ ischemia-reperfusion injury. 缺血损伤的一个具体后果是细胞凋亡或程式化的细胞死亡。 A specific consequence of ischemic injury is stylized apoptosis or cell death. 在受灌注、诊断与/或运输设备控制的条件下,由该灌注、诊断与/或运输设备提供给器官的特殊试剂和添加剂可以中断、减小与/或反转细胞凋亡。 Under the conditions by perfusion, diagnostic and / or transportation device control, provided by the organ perfusion, diagnostic and / or transport equipment special reagents and additives can be interrupted, reduce and / or reverse apoptosis.

在本发明的优选方法中,通过机械的、物理的、化学的或者遗传的操纵与/或改性在体外对器官或组织进行处理,从而对该组织或器官进行疾病治疗与/或伤害处理与/或增强其性能。 In a preferred method of the present invention, by mechanical, physical, chemical or genetic manipulation and / or modified in vitro organ or tissue, whereby the tissue or organ in disease treatment and / or dealing with injuries / or enhance their performance. 可以从第一身体移除器官或组织样品,然后在第一身体之外进行改性、处理与/或分析,并将该样品返回到第一身体或者移植到第二身体或做它用。 May be removed from the first body organ or tissue sample, and then modified, processing and / or analysis in addition to the first body, and the sample was returned to the first body or the second body or transplanted to do with it. 该设备的优点是延伸了器官可用于体外处理的时间,例如可长达几个小时(例如2、4、6、8、10、12或更多个小时)或者甚至几天(例如2、4、6、8、10、12或更多天)或几周(例如1、2、3、4、5、6、7、8或更多周)。 The advantage of this device is an extension of the time organs can be used for in vitro treatment, for example, up to several hours (for example 2,4,6,8,10,12 or more hours), or even days (for example 2,4 , 6,8,10,12 or more days) or weeks (for example, 6, 7, or more weeks). 在优选实施例中,本发明的灌注、诊断与/或运输设备可用于向器官或组织提供具体的溶液或化学品或制剂,或者可以用于执行具体处理,包括使用具体溶液或化学品冲洗或清洗组织或器官。 In a preferred embodiment, the perfusion, diagnostic and / or transport apparatus of the present invention may be used to provide specific solutions or chemicals or agents to an organ or tissue, or may be used to perform a specific process, including the use of specific solutions or chemical wash or cleaning tissue or organ. 体外处理可以在待移植的组织或器官上进行,也可以对已经从病人身上移除并且在进行完预期处理后将要移回病人身上的组织或器官上进行,或者还可以在将要用于物质测试等的组织或器官上进行。 In vitro treatment can be transplanted in tissues or organs may be removed from a patient who has been carrying on and finish expected to move back after treatment on the patient's tissues or organs, or also can be used for material testing progressive and other tissues or organs. 体外处理包含但不限于对已经长时间缺血与/或缺氧的组织或器官进行处理。 In vitro process including but not limited to prolonged ischemia has been, and / or tissue or organ hypoxia processing. 体外处理可涉及对器官采取外科方面的技术,例如切除和缝合器官,例如切除坏死组织。 In vitro treatment may involve surgical aspects of technology to take organs, such as suture removal and organs, such as removal of necrotic tissue. 任何可以对体内的组织或器官进行的外科或其它处理技术都可以用于体外的组织或器官。 Any surgical or other treatment technologies can be the body's tissues or organs can be used for in vitro tissue or organ. 这种体外处理的优点是看得见的,例如,在施加辐射或化疗以治疗器官内/上的肿瘤时,可以防止病人其它部位在治疗过程中遭受外来辐射或化疗。 The advantage of this process is visible in vitro, for example, in the application of radiation or chemotherapy to treat the tumor organ / on other parts of the patient can be prevented from suffering from external radiation or chemotherapy treatment. 本发明的灌注和运输设备还为医生在对组织或器官进行具体技术之前、期间与/或之后维持该组织或器官提供了额外的时间。 Perfusion and transport apparatus of the present invention is also a medical doctor before the tissue or organ specific technology, during and / or after the maintenance of the tissue or organ to provide additional time.

留在器官脉管系统中的颗粒可能会在移植之前与/或之后妨碍器官恰当地灌输或者可能导致器官无法正当工作。 Particles remain in the organ vasculature may later before transplantation and / or interfere with the proper organ or may lead to organ unable to instill decent work. 本发明的灌注、诊断和运输设备提供了体外技术,这些体外技术包括使用适量的溶血栓剂例如溶栓酶来灌注、冲洗或清洗器官,从而溶解已经形成的凝块或者防止在器官中形成血凝块并导通器官的脉管系统。 Perfusion, diagnostic and transport apparatus of the present invention provide in vitro techniques, these techniques include the use of an appropriate amount of in vitro thrombolytic agent such as streptokinase to perfusion, rinse or cleaning organ, to dissolve clots already formed or to prevent the formation of blood clotting in organs block and turned the organ vasculature. 这些技术例如在2000年8月25日提交的代理机构案号为106996的美国专利申请第09/938597号中被公开,该专利申请的全部内容通过参考并入本文。 These techniques, such agency in Docket No. 25 August 2000 filed 106,996 U.S. Patent Application No. 09/938597 is disclosed, the entire contents of this patent application is incorporated herein by reference.

器官移植关心的另一个问题是对受体进行何种程度的药物治疗以防止器官排斥。 Another issue of concern is organ transplantation receptors extent to which medication to prevent organ rejection. 在器官移植中,进一步的体外技术涉及对器官改性以避免该器官致动受体的免疫系统,从而防止或减小器官排斥,并限制或防止在器官移植之前、期间与/或之后抑制受体免疫系统的必要性,从而提高受体对所移植器官的耐受度。 In organ transplantation, a further in vitro technique involves modifying the organ to avoid actuation of the organ recipient's immune system to prevent or reduce organ rejection and to limit or prevent organ transplant prior to, during and / or after the inhibition by Necessity body's immune system, thereby increasing tolerance of the transplant recipient organ. 器官改性例如可以是促使受体身体认为所移植的器官是自身的。 For example, can be modified to promote organ recipient body thinks the transplanted organ itself.

本发明的灌注、诊断与/或运输设备可向器官输送诸如化学化合物、天然的或改良的抗体、免疫毒素等物质,并可辅助器官吸收或代谢这些物质以提高器官不会被排斥的可能性。 Perfusion of the present invention, diagnosis and / or transport equipment can transport materials such as chemical compounds, natural or modified antibodies, immunotoxins, etc. to organs, and auxiliary organs absorb or metabolize these substances will not be to increase the likelihood of organ rejection . 这些物质还可通过阻拦、杀死、耗尽与/或防止同种免疫刺激细胞(allostimulatory cell)(例如树枝状细胞、过路白细胞、抗原呈递细胞等)的成熟而将器官“隐藏”,使得受体的免疫系统不会意识到该器官或者认为该器官是自身的。 These materials can also stop, killing, depletion and / or prevent the same kind of immune-stimulating cells (allostimulatory cell) (for example dendritic cells, crossing the white blood cells, antigen presenting cells, etc.) and will mature organ "hidden", so that by the the immune system does not recognize the body organ or that the organ is itself. 可以在就要移植之前处理器官,或者可在移植前几小时、几天或几周预处理该器官。 You can handle just prior to transplant organs, or may be a few hours before transplantation, a few days or weeks pretreatment of the organ. 这种技术在于2000年8月25日提交的代理机构案号为100034的美国临时专利申请第60/227841号中得到进一步描述,该专利申请的全部内容通过参考并入本文。 This technique consists Agency Docket No. 25 August 2000 filed provisional patent application No. 60/227841 100034 in the United States further described, the entire disclosure of which are incorporated herein by reference.

还可以向器官或组织提供诸如改良或未改良的免疫球蛋白、类固醇与/或包含聚乙烯乙二醇(PEG)以及诸如谷胱甘肽的抗氧化剂的溶液的物质,从而掩蔽该器官,或者用于对付在低温存储与/或器官或组织移植时内膜增生的发作。 May also be provided to an organ or tissue, such as modified or unmodified immunoglobulin, steroids and / or contain polyethylene glycol (PEG) and antioxidant substances such as glutathione solution, thereby masking the organ, or It used against the low temperature storage and / or organ or tissue transplant intimal hyperplasia attack. 这些溶液可通过本发明的灌注、诊断与/或运输设备提供给器官。 These solutions can be provided to the organs by perfusion, diagnostic and / or transport apparatus of the present invention. 示范性的这种溶液和方法在美国专利申请第09/499520号中被公开,该专利申请的全部内容通过参考并入本文。 Exemplary of such solutions and methods are disclosed in U.S. Patent Application No. 09/499520, the entire disclosure of which are incorporated herein by reference.

如前所述,本发明涉及避免在灌注过程中对器官的损伤,同时监视、维持与/或恢复器官的活性并保存该器官供存储与/或运输。 As mentioned above, the present invention relates to avoid damage to organs during perfusion while monitoring, maintaining and / or restoring the activity of organs and save the organ for storage and / or transportation. 然而,并非所有捐赠的并根据前述示范性实施例进行灌注的器官最终都会被移植到受体体内。 However, not all the donations and the preceding exemplary embodiments perfused organs will eventually be transplanted into a recipient body. 在经过仔细的分析之后可能做出该器官不适合移植的决定。 After careful analysis may make a decision that is not suitable organ transplant. 然而,该器官不一定要抛弃掉。 However, this need not be discarded organ. 即,这种被确定为不适合移植的器官可用于其它目的。 That is, this is determined to be unsuitable for an organ transplant can be used for other purposes.

根据本发明另外的示范性实施例,可以使用医用流体灌注器官,以筛选生物活性试剂或其它测试剂,并且可以为研究和改进提供数据。 According to the present invention, a further exemplary embodiment, the medical fluid perfused organs may be used to screen bioactive agent or other test agent, and may provide data for research and improvement. 由于可以在或接近生理参数的情况下维持并且/或者分析器官或组织,因此可以在体外对器官进行使用各种物质——诸如生物活性剂或药品——的处理对该器官或组织的影响的测试。 Because you can maintain and / or analysis in the case of organ or tissue at or near physiological parameters, it can be carried out in vitro using a variety of materials to organs - such as biologically active agents or drugs - treatment effect on the organ or tissue test. 这种体外处理可以实施于小型哺乳动物的器官、大型哺乳动物——包括例如牛、猪、绵羊和山羊——的器官、以及/或者人的器官。 This in vitro process may be implemented in small mammals organ, large mammals - including such as cattle, pigs, sheep and goats - organ, and / or human organs. 另外,器官的这种体外处理可以用于各种器官,例如肾、肠、胰腺、心和肺,且可适用于更复杂器官,例如具有肝动脉和门静脉的多脉管结构的肝。 In addition, in vitro treatment of organs that can be used for various organs, such as kidney, intestine, pancreas, heart and lungs, and is applicable to more complex organs, such as having a hepatic artery and portal vein of multiple vascular structure.

本发明的灌注、诊断与/或运输设备可以与上述技术和方法结合使用,并且/或者与另外的技术和方法结合使用,从而对器官或组织进行研究。 Perfusion of the present invention, diagnosis and / or transport device can be combined with the above techniques and methods, and / or in combination with other techniques and methods to the study of organ or tissue. 这些设备可保存与/或维持器官并允许该器官在体外使用。 These devices can be saved and / or maintenance of the organ and allow the use of the organ in the body.

在器官保存与/或维持阶段,可对该器官与/或使用该器官进行各种活动。 In organ preservation and / or the maintenance phase, the organ can be a variety of activities and / or use of the organ. 例如,可以使用包含诸如一种或多种生物活性剂或其它物质(例如,推定的惰性剂)的流体灌注该器官或多个器官,从而获得有关该物质与/或该器官的行为与/或该物质与该器官之间相互作用的数据。 For example, such fluid comprises one or more bioactive agents or other substances (e.g., inert putative agent) or multiple organ perfusion of the organ, to obtain about the substance, and / or behavior of the organ and / or data interaction between the substance and the organ.

本发明的灌注、诊断与/或运输设备通过将血液、合成的血液替代品或其组合,或者是混合了具有已知或未知化学性能的灌注液的血细胞灌注通过器官,同时监视该器官、器官脉管流出物或其它器官流出物,可用于收集数据,以进行研究并分析该器官的状态与/或通过筛选该物质而确定对该器官的影响。 Perfusion, diagnostic and / or transport apparatus of the present invention is by blood, synthetic blood substitutes, or combinations thereof, or a mixture having a known or unknown chemical properties perfusate perfused through the organ blood cells, while monitoring the organ, organ vessel effluent effluent or other organs, may be used to collect data, for research and analysis of the status of the organ and / or by screening to determine the effect of the substance of the organ.

例如,如参考本发明的图28-31所述的,器官诊断系统2800具有计算机2810和分析器2820。 For example, with reference to the present invention, and organ diagnostic system 28-31 of the 2810 and 2800 computers with the analyzer 2820. 器官评估仪器2830同时连接到计算机2810和分析器2820,以提供自动采样。 Organ assessment instrument 2830 2810 simultaneously connected to the computer and analyzer 2820 to provide automatic sampling. 本发明的系统和方法允许手动采样。 Systems and methods of the present invention allow for manual sampling. 器官诊断系统2800提供了对器官和灌注液的分析。 Organ diagnostic system 2800 provides for organ and perfusion fluid analysis. 根据本发明的这些实施例,允许具有已知和预定化学性质的灌注液流入器官进行器官的灌注。 According to these embodiments of the present invention, allows to have known and predetermined chemical properties organ perfusion fluid into the organ perfusion. 这提高了可以输送的诸如血液或合成血液载体或其组合的灌注液的类型和成分的灵活度,可以根据具体分析过程定制与/或调节该灌注液。 This increases the flexibility of the type and composition can be delivered, such as blood or a synthetic blood perfusion liquid carrier or a combination thereof, and can process customization and / or adjusted according to the specific analysis of perfusion liquid.

流量传感器3020监视该系统内的流体流量。 3020 flow sensor monitors the fluid flow within the system. 被收集的流体经传输管线2860传至分析器2820。 The collected fluid is transmitted via the transmission line 2860 2820 analyzer. 通过获取任意的可测量的器官流出物例如静脉流出物、胆汁、内管腔流出物和尿流出物,以及通过来自诸如肺的这种器官的呼吸通路的测量物,并将被检测的特性例如与流入物或其它实际或理想器官的特性进行比较,可以测量被检测的特性。 By obtaining any organ effluent measurable venous outflow e.g., bile, intraluminal, and urine effluent effluent, and from organs such as the lungs through the respiratory passage was measured, and the characteristics of the detected e.g. with the influent or other characteristics of the actual or desired organ by comparing the detected characteristics can be measured. 静脉流出物可以直接获取和测量,或者可以测量器官浴液以提供流体特性的粗略近似供比较。 Venous outflow can directly access and measurement, or an organ bath may be measured to provide a rough approximation of fluid properties for comparison.

如前所述,可选地,可以在例如如图28-图31所示的单独的诊断设备与/或分析器中分析该器官和医用流体特性。 As described above, alternatively, it may be for example a separate diagnostic apparatus shown in FIG 28- FIG 31 and / or the analyzer analyzes the organ and medical fluid characteristics. 被检测的特性使得研究人员可以确定流入器官的测试物质量以及流出器官的测试物质量。 Detected feature allows researchers to determine the mass flow into the test object organ out of the test substance and quality of organs. 另外,可以使用放射性同位素为测试物质作标记,以帮助跟踪该测试物质以及可能的该测试物质与器官的相互作用。 In addition, the use of radioisotopes for the test substance as markers to help track the substance and the test substance may interact with organs that test. 可以使用诸如质谱仪的仪器跟踪放射性同位素。 Such as a mass spectrometer instrument can be used to track a radioisotope. 这些被检测的特性的结果使研究人员可以分析器官筛选结果,例如吸收、分布、新陈代谢、排泄、药物代谢动力学、药效学和毒性,这些结果可用于提供例如改进药品的数据,这些数据最终将可帮助确定药品的功效与/或毒性。 The results of these detected characteristics enable researchers to analyze organ screening results, such as absorption, distribution, metabolism, excretion, pharmacokinetics, pharmacodynamics and toxicity, these results can be used to provide improved drugs such as data, these data will eventually It will help determine drug efficacy and / or toxicity. 可以单独地分析被检测的特性,或者可以分析多个特性,从而确定包含物质的该医用流体对器官的影响与/或该医用流体与器官的相互作用。 Analysis can be individually detected characteristics, or a plurality of characteristics can be analyzed to determine the interaction of the medical fluid containing a substance to affect the organs and / or the medical fluid and organ.

然而,如前所述,器官诊断系统2800分析器官与/或灌注液与/或器官和灌注液之间的相互作用,并可以产生有关分析结果的数据。 However, as described above, the organ diagnostic system 2800 analyzes the interaction of organs and / or the perfusate and / or between the organ and perfusion fluid, and may generate data related to analysis results. 如前所述,图31示出了器官诊断系统2800的逻辑电路。 As described above, FIG. 31 shows the organ diagnostic system 2800 of a logic circuit. 计算机提供控制参数并从分析器2820接收结果和数据。 Computer provides control parameters and 2820 results and data received from the analyzer. 计算机进一步控制本发明的如下特征,例如:自动采样、对采样保持的控制、以及其它进行质量保证的特征。 Computer control as further features of the invention, such as: automatic sampling, sample and hold control of, and other quality assurance features. 根据本发明实施例收集的数据为收集有关例如吸收、分布、新陈代谢和排泄(ADME)的数据提供了效率。 According to the data collected embodiment of the invention is to collect information about such as absorption, distribution, metabolism and excretion (ADME) data provide efficiency. 这些数据可以实时地产生和显示,并被存储、传送到远程位置、以及/或者传送到记录介质。 These data may be generated and displayed in real time, and stored, transmitted to a remote location, and / or transferred to the recording medium. 收集这种类型的数据可使科学家和研究人员确定物质对器官的作用以及反过来器官对物质的作用。 Collect this type of data allows scientists and researchers to determine the role of substance on organ and in turn the role of organ substances. 利用该数据,研究人员能够进行更为有效和更安全的研究过程,并且能够在对整个动物进行测试之前分析这些物质及其对器官的影响(如果存在的话)。 Using this data, researchers were able to be more effective and safer research process and prior to the whole animal can be tested and analyzed the impact of these substances on the organs (if any). 另外,根据前述各种示范性实施例可能得到的数据包含有关循环前消除、吸收和药物释放、药物代谢动力学和新陈代谢、药效学、毒性动力学、药品-药品互作用等的数据。 Further, before the relevant data of the preceding cycle according to various exemplary embodiments may contain obtained elimination, absorption and drug delivery, pharmacokinetics and metabolism, pharmacodynamics, toxicokinetics, drug - Drug interactions such data. 本发明的各种示范性实施例可收集涉及物质、器官、以及其间相互作用的任何数据,这些均落在本发明的精神和范围之内。 Various exemplary embodiments of the present invention can be collected material, organs, and any data related to the interaction therebetween, which are within the spirit and scope of the present invention.

各种数据结构和信息连接以及分析子记录有助于整体通信和数据传输,这对于器官处理之前、期间及之后都是有益的。 Various data structures and connections as well as contribute to the overall analysis of sub-record communications and data transmission, which for organ treatment before, during and after are beneficial. 该灌注设备、运输设备和器官诊断设备可连接到网络,从而实现远程管理和监视该器官、医用流体和测试物质。 The perfusion equipment, transportation equipment, and organ diagnostic devices can be connected to a network, enabling remote management and monitoring of the organ, medical fluid and test substance. 该信息系统可用于将该器官、医用流体、测试物质及其之间相互作用的数据汇编。 The information system can be used for the organ, medical fluid, the interaction between the test substance and data compilation. 这些系统还可用于将有关这些系统本身的化学清洁度和化学完整性的数据汇编,并提供有关该系统内化学药品的痕量的信息。 These systems can also be used data integrity of these systems to its chemical cleanliness and chemical compile and provide information about the chemicals within the system trace amounts. 这些系统还可提供结果数据,使得可以容易地研究器官和医用流体及物质,并且可以直接从该灌注、诊断或运输设备中获取信息以监视这些数据。 The system also provides the results of the data, making it easy to study organ and medical fluid and material, and can get information directly from the perfusion, diagnostic or transporting equipment to monitor these data. 各种类型的数据和信息可以被分组成子记录或子目录以助于数据管理和传输。 Various types of data and information can be grouped into sub-records or subdirectory to facilitate data management and transmission. 所有这些子记录可以被组合以形成一个整体记录,该整体记录可以传给或提供给医生、科学家或其它机构用于研究目的。 All of these sub-records may be combined to form an overall record, the overall record can be passed or provided to doctors, scientists or other organizations for research purposes.

该灌注、诊断和运输设备的优选实施例可以自动地将许多或所有数据记录到内部的数据库。 The perfusion, diagnostic and transport equipment preferred embodiments can automatically many or all of the data recorded to the internal database. 该设备还可以连接到LAN,且可以间歇地或连续且实时地进行数据上载。 The device can also be connected over the LAN, and can be intermittently or continuously and in real time, perform data upload. 数据可以被显示在因特网上或能够通过因特网上进行访问,从而有利于在任何位置进行监视。 Data can be displayed on the Internet or can be accessed via the Internet, thereby facilitating monitoring at any location.

根据示范性的实施例,将上面指出的各种测量和分析的因素考虑在内产生一个器官数据指标。 According to an exemplary embodiment, the organ will produce an indicator data of the various considerations noted above, including measurement and analysis. 该数据指标可以是针对具体器官定制,或者可以适用于各种器官。 The data indicator can be customized to specific organs, or can be applied to a variety of organs. 该数据指标将检测的特性和数据汇编成诊断概括参数,从而用于做出器官处理和研究的决定。 The index will detect the characteristic data and data compiled into diagnostic summarize parameters to make decisions for organ treatment and research. 该数据指标可以自动产生并被提供给研究人员或医生。 The index data can be automatically generated and provided to the researcher or doctor. 该指标优选地是经过与该灌注设备、运输设备与/或器官诊断设备连接的计算机产生的。 The index is preferably connected to the computer through the perfusion equipment, transportation equipment and / or organ diagnostic equipment produced. 在这些实施例中,可以在计算机网络例如局域网或因特网上获得该指标,以便于快速比较、远程分析和数据存储。 In these embodiments can be obtained over a computer network such as LAN or the Internet this indicator for quick comparison, remote analysis and data storage. 该器官数据指标可提供诸如吸收、分布、新陈代谢、排泄、药物代谢动力学、药效学和毒性的各种特性的测量结果和正常范围。 The organ data index may provide services such as absorption, distribution, metabolism, excretion, pharmacokinetics, measure the results of various characteristics of pharmacodynamic and toxicity and the normal range. 位于正常范围之外的测量结果可以通过可在视觉上察觉的方式例如使用星号或其它恰当的可见符号指示,或者可以通过可在听觉上察觉的方式指示,或者用计算机可识别的信号指示。 Measurement results are outside the normal range may be visually perceived by way of example using an asterisk or other appropriate symbol indicates visible, or can be perceived in the auditory mode indicator, or a computer can recognize the signal indicator. 这些特性使医生或研究人员能够理解诸如器官新陈代谢的这些效果,例如新陈代谢的稳定性、葡萄糖的消耗、乳酸的产生和氧气消耗。 These features enable doctors or researchers to understand these effects such as metabolic organs, such as the stability of the metabolism of glucose consumption, lactate production and oxygen consumption.

根据本发明的这些方法优选地利用诸如前述的设备灌注器官,从而维持、监视与/或恢复器官的活性与/或运输与/或存储该器官。 According to the methods of the present invention is preferably utilized perfused organs such as the aforementioned devices, so as to maintain, monitor and / or restore the activity of the organ and / or transport and / or storage of the organ. 在从供体身体摘除该器官与/或在存储与/或运输期间,这些器官经常由于供体身体的疾病或受伤而长时间缺氧(所谓的缺血)。 Removal from the donor body of the organ and / or / or during storage and transport, these organs are often due to the donor body of illness or injury prolonged hypoxia (called ischemia). 本发明的灌注、诊断与/或运输设备具有如下能力,即,探测待移植的器官的细胞化学性质从而调节灌注液并控制细胞新陈代谢以修复器官缺血伤害并防止再灌注损伤。 Perfusion, diagnostic and / or transport apparatus of the present invention has the ability, that is, to detect cells to be transplanted organ perfusion fluid and chemical properties which regulate and control cell metabolism to repair the damage and prevent organ ischemia-reperfusion injury. 缺血损伤的一个具体后果是细胞凋亡或程式化的细胞死亡。 A specific consequence of ischemic injury is stylized apoptosis or cell death. 在受灌注、诊断与/或运输设备控制的条件下,由该设备提供给器官的特殊的试剂和添加剂可以中断、减小与/或反转细胞凋亡。 Under the conditions by perfusion, diagnostic and / or transportation device control, provided by the device to organ specific reagents and additives can be interrupted, reduce and / or reverse apoptosis.

为了在将器官移植到受体体内之前,或者在将器官用于研究和发展之前保持器官的活性,根据本发明的优选的方法集中在三个概念:处理细胞线粒体以维持与/或恢复缺血之前的能量和酶水平;防止对器官普通组织的伤害;以及冲掉或伤害器官的脉管内皮层。 In order to the recipient prior to organ transplantation in vivo, or in organs for research and development will remain active until an organ, according to the preferred method of the present invention is focused on three concepts: process mitochondria to maintain and / or restore ischemia Before the energy and enzyme levels; to prevent tissue damage to organs common; and wash away within a vessel or organ injury cortex.

线粒体是细胞中的能量源。 Mitochondria are the energy source of the cell. 线粒体需要大量的氧以发挥其功能。 Mitochondria require a lot of oxygen to perform its functions. 当缺氧时,线粒体产生能量的能力降低或受抑制。 When hypoxia, the ability of mitochondria to produce energy reduced or inhibited. 另外,在低于20℃的温度下,线粒体无法利用氧产生能量。 Further, at a temperature below 20 ℃ mitochondrial oxygen can not be used to produce energy. 通过在正常体温的温度下使用富氧医用流体灌注器官,可为线粒体提供足够数量的氧,使得由于缺氧而减小的器官中备用高能量核苷酸的缺血前水平,即ATP水平,以及阻止器官细胞产生自由基清除剂的酶的水平一起得到维持与/或恢复。 By using oxygen-rich medical fluid perfused organs at normal body temperature, can provide a sufficient amount of oxygen for the mitochondria, so that pre-ischemia levels due to the decrease of oxygen in organs alternate high energy nucleotide, i.e. the level of ATP, and to prevent organ cells radical scavenger enzyme levels obtained along with maintaining / or recovery. 诸如美国专利第5066578号中公开的富丙酮酸盐溶液无法维持与/或恢复器官的缺血前能量水平,只能在短期内起到少量地增加ATP水平的作用。 Such as pyruvate solution rich in U.S. Patent No. 5,066,578 disclosed unable to maintain and / or restore the organ before ischemia energy levels, can only play a small amount of increase in ATP levels in the short term. 也就是说,器官天然地具有显著的丙酮酸盐水平。 That is, organs naturally have significant pyruvate levels. 如果不为线粒体提供足够的氧以产生能量,则为器官提供附加的丙酮酸盐将不会有助于恢复与/或维持器官的缺血前能量水平。 If it does not provide enough oxygen for the mitochondria to produce energy, for the organ to provide additional pyruvate will not help to restore and / or maintain energy levels before ischemia organs. 因此,正常体温的灌注流体可包含丙酮酸盐,但也可以包含少量的或不包含丙酮酸盐。 Thus, the normothermic perfusion fluid may contain pyruvate but may also contain minor amounts of or does not contain pyruvate. 例如,该灌注液可能包含小于6mM的丙酮酸盐、5mM、4mM或者甚至不包含丙酮酸盐。 For example, the perfusion solution may contain less than 6mM pyruvate, 5mM, 4mM or even does not contain pyruvate. 其它公知的保存溶液,例如美国专利第5599659号中所公开的,同样未能包含足够的氧以恢复与/或维持缺血前能量和酶水平。 Other well-known preservation solution, for example, US Patent No. 5,599,659 disclosed, also failed to contain enough oxygen to restore and / or maintain before ischemia energy and enzyme levels.

在通过使用富氧的第一医用流体在正常体温或接近正常体温的温度下(正常体温模式)灌注该器官而维持并且/或者恢复器官的缺血前能量水平之后,可以使用第二医用流体在低于体温的温度下(低于体温模式)灌注该器官。 After using oxygen rich first medical fluid at normothermic or near-normothermic temperatures (normothermic mode) the organ perfusion to maintain and / or restore pre-ischemia energy levels of the organ, can be used in a second medical fluid lower than body temperature (less than body temperature mode) perfused organs. 低于体温的温度减缓了器官在储存与/或运输过程中的新陈代谢并节约了能量。 Below body temperature slows the metabolism in an organ storage and / or transportation and energy savings. 在低于体温模式使用的医用流体中包含少量或不包含氧气,并且线粒体在低于约20℃下无法利用这些氧气产生能量。 Contained in the medical fluid used in the hypothermic mode contains little or no oxygen, and mitochondria can not less than about 20 ℃ using these oxygen to produce energy. 该医用流体例如包含抗氧化剂和其它组织保护剂,例如抗坏血酸、谷胱甘肽、水溶性维他命E、接触酶或超氧化物岐化酶,以阻止在低温下由于接触酶/超氧化物岐化酶生成减小导致的形成高度游离的自由基。 The medical fluid such as containing antioxidants and other tissue protective agent, such as ascorbic acid, glutathione, water soluble vitamin E, catalase or superoxide dismutase, to stop at a low temperature due to exposure to the enzyme / superoxide dismutase of enzymes generate reducing the formation of highly free radicals caused. 另外,可向任一种溶液中恰当地添加各种药品和制剂,例如荷尔蒙、维他命、营养成分、抗生素等。 In addition, you can add a variety of drugs and proper preparation to any one solution, such as hormones, vitamins, nutrients, antibiotics. 另外,例如可将诸如缩氨酸的血管舒张剂添加到医用流体以维持流量,即使在损伤的情况下。 In addition, for example, may be added, such as the vasodilator peptides to the medical fluid to maintain flow even in the case of injury.

在使用富氧的第一医用流体在正常体温下进行任何正常体温灌注之前,可以使用包含少量或不包含氧气且优选地包含抗氧化剂的医学溶液冲洗器官。 Before using oxygen rich first medical fluid any normothermic perfusion at normal body temperature, can be used contain little or no oxygen and preferably containing medical solution contains antioxidants flushing organs. 这种冲洗通常在低于体温的温度下进行,但是如果需要并且/或者必需的情况下,可以在正常体温或接近正常体温的温度下进行。 This flushing is usually performed at a temperature lower than body temperature, but if needed and / or when necessary, can be performed under normothermic or near normal body temperature. 冲洗之后可以进行低于体温灌注、正常体温灌注、与/或静止储存中的一种或多种操作,且可按任何需要与/或预期顺序进行上述操作。 After rinsing can be hypothermic perfusion, normothermic perfusion, and / or stationary store in one or more of operation, and may be any desired and / or expected order carry out such operations. 在一些情形中,可能无需进行正常体温灌注或低于体温灌注。 In some cases, it may be no need for normothermic perfusion or hypothermic perfusion.

对于处于静止或灌注条件下的、承受低于体温温度的器官,以及正常体温的器官,可以进行正常体温灌注——在此之前可以进行也可以不进行低于体温的冲洗。 For stationary or in perfusion conditions, to withstand a temperature lower than the temperature of the organ, as well as normal body organs, normothermic perfusion can be performed - before this can be performed without hypothermic flushing.

器官可以在正常体温或接近正常体温的温度下进行灌注,以在低于体温的温度下进行灌注方便储存之前与/或之后,维持、监视与/或恢复器官的活性,且随后无需或者优选地进行低于体温灌注之后输运该器官。 Organ perfusion can be performed at normothermic or near-normothermic temperatures, conveniently prior to perfusion at hypothermic temperatures after storage and / or maintenance, monitoring and / or restore the activity of the organ, and then without or preferably be lower than the temperature after transporting the organ perfusion. 此外,可以在将器官从供体身体内摘除之前在体内进行正常体温灌注。 In addition, prior to organ removal from the donor body in vivo normothermic perfusion. 另外,在对器官进行低于体温灌注从而准备储存与/或运输之前,可以在正常体温温度下灌注器官,以维持、监视与/或恢复器官活性。 Further, prior hypothermic perfusion of organs so as to prepare storage and / or transport, can be perfused organ at normothermic temperatures to sustain, monitor and / or restore organ viability. 然后,该器官可以被移植到受体身体内或者用于其它研究,同时保持在低于体温的温度下;或者,器官可以首先进行正常体温灌注以帮助其从储存与/或运输的影响中恢复。 Then, the organ can be transplanted into a recipient body or used for other research, while maintaining the temperature below body temperature; or organ can first be normothermic perfusion to help it recover from the storage and / or transportation of the impact . 在后一种情况下,器官可以在正常体温温度下被移植或使用,或者优选地再次进行低于体温温度的灌注以用于低于体温的温度下的移植。 In the latter case, the organ can be transplanted at normal body temperature or use, or, preferably, again lower than the body temperature to lower perfusion hypothermic temperatures for transplant. 移植之后,该器官可以可选地再次在体内在正常体温的温度下被灌注,或者允许通过供体的循环而温度上升。 After transplant, the organ may optionally again at normal body temperature in the body temperature is poured or allowed to pass through the cycle and the temperature rise of the donor. 优选地在正常体温的温度下进行物质研究。 Preferably at normothermic temperatures substances studied. 另外,优选地在接近标准生理条件的条件下进行物质测试。 Further, preferably under physiological conditions close to the standard conditions tested substances. 这些生理条件指例如温度、氧气水平等。 These refer to physiological conditions such as temperature, oxygen level and the like.

以一种示例性的而非限制性的方式,图16示出了根据本发明的可能的处理步骤的示范性图示。 In an illustrative rather than a restrictive manner, Figure 16 shows a possible processing step of the present invention, an exemplary illustration. 该图示出了从器官供体的摘除器官直到器官植入受体体内(或其它用途)的多器官恢复(MOR)的各个可能的处理步骤,包括可能的WIT(热缺血时间)和组织缺氧(hypoxia)伤害评估。 The figure shows the implanted organ recipient until the body (or other uses) recovery from multiple organ donor organ harvesting of organs (MOR) of each possible processing steps, including possible WIT (warm ischemia time) and organization hypoxia (hypoxia) damage assessment. 在下面列出多个示范性的情形。 An exemplary case of multiple listed below.

首先,在本发明的一个实施例中,可以在心脏跳动的条件下从供体中摘除器官。 First, in an embodiment of the present invention may be the removal of organs from a donor in the beating heart conditions. 在摘除之后,可以使用任何适当的溶液或材料来冲洗该器官,例如但不限于VIASPAN(可从DuPont获得的保存溶液)、其它晶体液、右旋糖酐、HES(羟乙胺淀粉)、以及2000年7月28日提交的美国专利申请第09/628311号(该申请的全文通过参考并入本文)中描述的溶液等。 After removal, you can use any suitable solution or material to wash the organ, such as, but not limited to VIASPAN (preservation solution available from DuPont), other liquid crystals, dextran, HES (hydroxyl amine starch), and 2000 7 May 28, U.S. Patent Application No. 09/628311 filed (the full text of this application is incorporated herein by reference) was like described. 然后该器官可以静止地存储,例如在冰温下(例如从约1℃到约10℃)。 Then the organ can still be stored, for example, ice temperature (for example, from about 1 ℃ to about 10 ℃).

在另一个实施例中,例如器官具有最小的WIT和最小的脉管阻塞的情况下,可以使用不同的处理。 In the case of another embodiment, such as organ has minimal WIT and minimal vascular occlusion, you can use a different process. 此时,同样可以在心脏跳动的条件下摘除该器官,然后优选地在低于体温的温度下进行冲洗。 In this case, the organ can also be removed under the conditions of the heart beat, and preferably at a temperature lower than body wash. 如果需要,该器官可以在例如冰温下储存在合适的运输设备中。 If desired, the organ can be stored in a suitable transport equipment such as ice temperature at. 通过设定压力最大值可以控制流到该器官的流量,其中预设的压力最小值和压力最大值控制该脉冲波的波形。 Pressure can be controlled by setting the maximum flow rate of the flow to the organ in which the preset pressure minimum and maximum pressure control waveform of the pulse wave. 如果需要长时间地储存该器官,例如24小时以上,则器官可以放置在MOR中。 If you take a long time to store the organ, e.g., more than 24 hours, the organ can be placed in the MOR. 在MOR中,优选地在低于体温的温度下,可以使用适当的灌注液,例如晶体液、右旋糖酐等。 In the MOR, preferably at a temperature below body temperature, you can use a suitable perfusion fluid, such as liquid crystal, dextran. 优选地,该低于体温的温度为约4℃到约10℃,但是如果需要与/或必需,也可以使用更高或更低的温度。 Preferably, the hypothermic temperatures of about 4 ℃ to about 10 ℃, but if you need to and / or necessary, higher or lower temperatures. 优选地,该灌注液溶液包含特殊的标记以允许进行伤害评估,不过也可以由其它公知的过程进行伤害评估。 Preferably, the perfusate solution contains specific markers to allow for damage assessment, although damage assessment can also be performed by other known processes. 在需要的时候,该器官可以返回到运输设备。 In time of need, the organ can be returned to the transport equipment.

作为上述过程的变形,具有最小WIT和最小脉管阻塞的器官可以在无心跳的条件下摘除。 As a modification of the above process with minimal WIT and minimal vascular occlusion of organs can be removed without heart conditions. 这里,该器官可以优选地在低于体温的温度下进行冲洗,且如果需要,可以在例如冰温下存放于适当的运输设备中进行输运。 Here, the organ can be preferably carried out at a temperature below body wash, and, if desired, can be stored in transport such as ice temperature is carried out in a suitable transportation equipment. 如前所述,可以通过设定压力最大值来控制流到该器官的流量,其中预设的压力最小值和压力最大值控制该脉冲波的波形。 As mentioned above, the maximum pressure can be controlled by setting the organ traffic flow, wherein the preset pressure minimum and maximum pressure control waveform of the pulse wave. 该器官可以放置在MOR中,以用于长时间储存与/或用于伤害评估与/或修复。 The organ can be placed in the MOR, for long-term storage and / or for damage assessment and / or repair. 在MOR中,可以使用适当的灌注液,例如晶体液、右旋糖酐等,且优选地在低于体温的温度下使用。 In the MOR, you can use a suitable perfusion fluid, such as liquid crystal, dextran, etc., and preferably used at a temperature lower than body temperature. 优选地,该低于体温的温度为约4℃到约10℃,但是如果需要与/或必需,可以使用更高或更低的温度。 Preferably, the hypothermic temperatures of about 4 ℃ to about 10 ℃, but if you need to and / or necessary, higher or lower temperatures. 优选地,该灌注液溶液包含特殊的标记以实现伤害评估,不过也可以由其它公知的过程进行伤害评估。 Preferably, the perfusate solution contains specific markers to achieve a damage assessment, although damage assessment can also be performed by other known processes. 在低于体温的灌注之后,可以进行第二灌注,优选地在正常体温的温度下进行。 Following hypothermic perfusion, a second perfusion can be carried out, preferably at normal body temperature. 该处理可以使用任何适当的灌注溶液,包括包含有所需要的氧合介质、营养成分与/或生长因子的溶液。 The process may use any suitable infusion solution, including oxygenation in need media containing nutrients and / or growth factors added. 优选地,正常体温的温度为约12℃到约24℃,但是如果需要与/或必需,可以使用更高或更低的温度,包括约37℃。 Preferably, the normal body temperature is about 12 ℃ to about 24 ℃, but if you need to and / or necessary, higher or lower temperatures, including about 37 ℃. 正常体温的灌注可以进行任何适当的时间长度,例如约1小时至约24小时。 Normothermic perfusion may be any suitable length of time, e.g., from about 1 hour to about 24 hours. 在从正常体温灌注恢复之后,该器官优选地重新进行低于体温的灌注,例如使用诸如晶体液、右旋糖酐等的恰当的溶液,且优选地在低于体温的温度下进行。 After recovery from the normothermic perfusion, the organ is preferably lower than the temperature of re-perfusion, such as using the appropriate solution such as liquid crystals, dextran, and preferably at a temperature lower than body temperature. 在需要的时候,该器官可返回到运输设备。 In time of need, the organ can be returned to the transport equipment.

在器官具有高WIT,并且/或者脉管很有可能阻塞或已经阻塞的实施例中,可以使用上述处理的变形。 Example organ with high WIT, and / or vascular occlusion or is likely to have been blocked, you can use variations of the above process. 例如,对于在无心跳条件下摘除器官的情形中,可以如前所述地冲洗该器官。 For example, for heart conditions in the absence of organ harvesting case, as explained above flushing of the organ. 不过,此时如果需要可在该冲洗溶液中加入自由基清除剂。 However, this time, if necessary, adding a free radical scavenger in the wash solution. 如前所述,该器官可在例如冰温下存放在适当运输设备中运输,其中可通过设定压力最大值控制流到该器官的流量,且其中预设的压力最小值和压力最大值控制脉冲波的结构。 Pressure minimum and pressure as previously described, for example, the organ can be stored under ice temperature in a suitable transportation equipment transport, which can be controlled by setting the maximum flow pressure flow of the organ, and wherein a predetermined maximum control Structure pulse waves. 该器官可以放置在MOR中,以用于长时间储存与/或用于伤害评估与/或修复。 The organ can be placed in the MOR, for long-term storage and / or for damage assessment and / or repair. 在MOR中,可以使用适当的灌注液,例如晶体液、右旋糖酐等,且优选地在低于体温的温度下使用。 In the MOR, you can use a suitable perfusion fluid, such as liquid crystal, dextran, etc., and preferably used at a temperature lower than body temperature. 优选地,该低于体温的温度为约4℃到约10℃,但是如果需要与/或必需,可以使用更高或更低的温度。 Preferably, the hypothermic temperatures of about 4 ℃ to about 10 ℃, but if you need to and / or necessary, higher or lower temperatures. 优选地,该灌注液溶液包含特殊的标记以实现伤害评估,不过也可以由其它公知的过程进行伤害评估。 Preferably, the perfusate solution contains specific markers to achieve a damage assessment, although damage assessment can also be performed by other known processes. 在低于体温的灌注之后,可以进行第二灌注,优选地在正常体温的温度下进行。 Following hypothermic perfusion, a second perfusion can be carried out, preferably at normal body temperature. 该处理可以使用任何适当的灌注溶液,包括包含所需要的氧合介质、营养成分与/或生长因子的溶液。 The process may use any suitable infusion solution, including the medium containing the desired oxygenation, nutrients and / or growth factors added. 优选地,正常体温的温度为约12℃到约24℃,但是如果需要与/或必需,可以使用更高或更低的温度。 Preferably, the normal body temperature is about 12 ℃ to about 24 ℃, but if you need to and / or necessary, higher or lower temperatures. 正常体温的灌注可以进行任何适当的时间长度,例如约1小时至约24小时。 Normothermic perfusion may be any suitable length of time, e.g., from about 1 hour to about 24 hours. 如果需要,具体而言如果确定或推定存在脉管阻塞,则可以在更高的正常体温温度下例如约24℃至约37℃下进行另外的灌注。 If needed, specifically if it is determined or estimated vascular obstructions exist, you can for example, an additional infusion at about 24 ℃ to about 37 ℃ at higher normal body temperature. 可以使用包含所需材料的合适溶液进行该另外的灌注以阻止脉管阻塞。 You can use a solution containing the desired material suitable to carry out the additional infusion to prevent vascular occlusion. 这些材料例如包含诸如溶栓酶。 The material includes, for example, such as streptokinase. 在从正常体温灌注恢复之后,该器官优选地重新进行低于体温的灌注,例如使用诸如晶体液、右旋糖酐等的恰当溶液,且优选地在低于体温的温度下进行。 After recovery from the normothermic perfusion, the organ is preferably lower than the temperature of re-perfusion, such as the proper use of liquid crystal solution, dextran or the like, and preferably at hypothermic temperatures. 在需要的时候,该器官可返回到运输设备。 In time of need, the organ can be returned to the transport equipment.

根据本发明的器官盒允许将一个或多个器官容易地输运到器官受体,并且/或者在器官灌注、诊断与/或便携运输设备之间输运,该运输设备例如为上述的运输设备1900,或者是传统冷却器,或者是例如如同时待决的美国专利申请第09/161919号中公开的便携容器。 According to the present invention allows the organ case one or more organs easily transported to the organ recipient, and / or organ perfusion, transport between the diagnosis and / or portable transport equipment, transport equipment, for example, the above-transport equipment 1900, or is the traditional cooler, or, for example, as a portable container-pending U.S. Patent Application No. 09/161919 disclosed. 因为该器官盒可设有开口以允许将器官灌注、运输设备或诊断设备的导管插入该盒以连接到置于盒内的器官,或者该器官盒也可设有自带的导管和连接装置以实现与器官灌注、运输设备或诊断设备的导管连接,并且/或者还设有自带的阀,因此该器官盒为器官的存储、分析与/或运输提供了保护环境,同时还便于将器官插入并且/或者将器官连接到器官灌注、运输设备或诊断装置的导管。 Because the organ cassette may be provided with openings to allow organ perfusion, diagnostic equipment, transportation equipment or catheter is inserted into the cartridge is put in a box to be connected to the organ, or the organ case also be provided with built-in conduit and connection means Implementation and organ perfusion, transport equipment or diagnostic devices conduit connections and / or valve also has a built-in, so the organ case for organ storage, analysis and / or transportation provided to protect the environment, while also facilitating the insertion of organs and / or organ connected to the organ perfusion catheter transport equipment or diagnostic devices. 另外,该器官盒还可包含手柄以有利于盒的运输,且该器官盒可由透明材料形成从而可以通过视觉监控该器官。 Further, the organ cassette may also include a handle to facilitate transport of the cartridge, and the organ cassette may be formed of a transparent material so the organ may be visually monitored.

可选地,运输设备1900与/或盒65可包含全球定位系统(GPS)(未示出)以允许跟踪器官的位置。 Optionally, transporter 1900 and / or cassette 65 may include a global positioning system (GPS) (not shown) to allow tracking of the location of the organ. 该设备还可包含数据记录器(logger)与/或发送器(未示出),以允许在该设备所在的位置或在其它位置监视器官。 The device may also include a data logger (logger) and / or transmitter (not shown) to allow the location of the device or monitor organ located in other locations.

下面将结合如图2所示的设备的操作论述本发明的方法。 Below in connection with FIG. 2 shows the method of operation of apparatus of the present invention is discussed. 然而,也可以使用其它设备来执行本发明方法。 However, other devices can also be used to perform the method of the present invention.

如前所述,上述设备可以工作于两种模式:正常体温灌注模式及低于体温灌注模式。 As previously mentioned, these devices can operate in two modes: normal body temperature perfusion and hypothermic perfusion mode mode. 接下来将先讨论正常体温灌注模式,然后讨论低于体温灌注模式。 Next will first discuss the normothermic perfusion mode, and then discuss the hypothermic perfusion mode. 重复性的描述将被尽可能地省略。 Repetitive description will be omitted as much as possible.

在正常体温或接近正常体温灌注模式中,器官被优选地灌注医用流体1/2至6小时,更优选地1/2至4小时,最优选地1/2至1小时,所使用的医用流体通过设置成与医用流体贮存器10可以热交换地连通的热电装置30a而将温度维持在优选地约10℃至38℃的范围内,更优选地12℃至35℃,最优选的12℃至24℃或18℃至24℃(例如,室温22-23℃)。 In the normothermic or near-normothermic perfusion mode, an organ perfusion medical fluid is preferably from 1/2 to 6 hours, more preferably from 1/2 to 4 hours, most preferably from 1/2 to 1 hour, the medical fluid used By setting a thermoelectric device 30a and medical fluid reservoir 10 can heat exchange to communicate and maintain the temperature within the range of preferably about 10 ℃ to 38 ℃, and more preferably from 12 ℃ to 35 ℃, 12 ℃ most preferred to 24 ℃ or 18 ℃ to 24 ℃ (for example, temperature 22-23 ℃).

如前所述,在这种模式下,医用流体优选地为氧合的交联血红蛋白基重碳酸盐溶液。 As described above, in this mode, the medical fluid is preferably crosslinked hemoglobin oxygenation yl bicarbonate solution. 与例如简单的威斯康星大学(UW)葡萄糖酸盐类型灌注液相比,交联血红蛋白基医用流体的每单位灌注体积向器官输送的氧气可以多出150倍以上。 Compared with the simple example of the University of Wisconsin (UW) gluconate type of infusion fluid per unit cross-linked hemoglobin-based oxygen volume of medical fluid to the organ perfusion can be delivered more than 150 times. 这允许正常体温灌注一至两个小时,以部分或完全恢复耗尽的ATP水平。 This allows normothermic perfusion one to two hours to partially or completely restore depleted ATP levels. 然而,本发明不限于这种保存溶液。 However, the present invention is not limited to such a preservation solution. 其它保存溶液可能也是合适的,例如在美国专利No.5149321、5234405和5395314以及同时待决的美国专利申请No.08/484601和2000年7月28日提交的代理机构案号为No.101311的美国专利申请09/628311所公开的保存溶液,这些专利文献的全部内容通过参考并入本文。 Other preservation solution may also be appropriate, for example, in U.S. Patent No.5149321,5234405 and 5,395,314 and US Patent-pending Application No.08 / 484601 Agency Docket No. July 28, 2000 and is filed No.101311 of as disclosed in U.S. Patent Application 09/628311 preservation solution, the entire contents of these patents are incorporated herein by reference documents.

在正常体温灌注模式中,医用流体从袋15a、15b中之一分别经导管50a、50b、50c或50d、50e、50c直接输入到置于器官腔40内的器官。 In the normothermic perfusion mode, the medical fluid from the bag 15a, 15b, respectively, through one of the conduit 50a, 50b, 50c or 50d, 50e, 50c is placed directly into the organ within the organ chamber 40. 该器官以低速进行灌注,流速优选为约3至5ml/gram/min的范围。 The organ perfusion at low speed, the flow rate preferably in the range from about 3 to 5ml / gram / min of. 压力传感器P1将灌注压力传送给微处理器150,微处理器150改变由压力源20提供的压力以控制灌注压力与/或将该压力显示在控制和显示区域5c上供手动调节。 Pressure sensors P1 perfusion pressure to the microprocessor 150, the microprocessor 150 by the pressure change in the pressure source 20 provided to control the perfusion pressure and / or the pressure display in the control and display areas 5c altar manual adjustment. 通过所使用的压力源20和压力气囊15a、15b以及步进马达/凸轮阀65,将该压力优选地控制在约10至100mmHg的范围内,优选地为50至90mmHg。 By using a pressure source 20 and pressure bladder 15a, 15b, and the stepping motor / cam valve 65, the pressure is preferably controlled in the range of from about 10 to 100mmHg, preferably 50 to 90mmHg. 压缩机和气囊提供大部分的压力控制。 Compressor and airbag provide the bulk of the pressure control. 步进马达/凸轮阀65(或者其它可变的阀或可变压力调节器)由操作人员进行控制,或者由微处理器150根据来自压力传感器P1的信号进行控制,其进一步减小并精细调节压力,并且/或者使进入器官60的流体产生脉冲波动。 Stepping motor / cam valve 65 (or other variable valve or variable pressure regulator) is controlled by the operator, or by the microprocessor 150 is controlled based on a signal from the pressure sensor P1, which is further reduced and the fine adjustment pressure and / or fluid entering the organ 60 generates a pulse fluctuations. 如果灌注压力超过预定的极限,则可以致动步进马达/凸轮阀65致动以截断流入器官60的流体。 If the perfusion pressure exceeds a predetermined limit, it can actuate the stepping motor / cam valve 65 is actuated to cut off the fluid flowing into the organ 60.

在特定温度下的特定压力、流速以及灌注时间的长短将根据要进行灌注的具体器官而改变。 Specific pressure at a specific temperature, flow rates and length of perfusion time will vary depending on the organ to be perfused specific changes. 例如,心脏和肾脏优选地在正常体温的温度下以约10至100mmHg的压力和约3至5ml/gram/min的流速灌注约2至4小时,通过恢复与/或维持器官缺血前的能量水平而维持与/或恢复器官的活性;随后优选地在低于体温的温度下以约10至30mmHg的压力和约1至2ml/gram/min的流速灌注约72小时至7天,以进行储存与/或运输。 For example, heart and kidneys preferably at normal body temperature of about 10 to 100mmHg pressure of about 3 to a flow rate of 5ml / gram / min infusion for about 2-4 hours, by restoring and / or maintaining energy levels before organ ischemia while maintaining / or restore the activity of the organ; then preferably at hypothermic temperature to a pressure of about 10 to 30mmHg flow rate of about 1 to 2ml / gram / min of perfusion from about 72 to 7 hours, for storage and / or transportation. 然而,这些标准将根据具体的器官、供体身体与/或受体身体、计划用途、与/或具体器官的尺寸而改变。 However, these standards will be based on specific organ donor body and / or receptor body, the intended use, with or size / specific organs change. 本领域普通技术人员根据这里所述的指导无需不当的实验就可以选择恰当的条件。 Those of ordinary skill in accordance with the teachings herein, without undue experimentation, you can choose the right conditions.

流出的医用流体收集在器官腔40的底部,并由第二热电装置30b将其维持在所陈述的温度范围内。 Effluent medical fluid collects in the bottom of the organ chamber 40, by a second thermoelectric device 30b to be maintained within the stated temperature range. 温度传感器T2将器官温度传送给微处理器150,微处理器150控制热电装置30a从而调节医用流体和器官浴液的温度以将器官60维持在预期温度,并且/或者将温度显示在控制和显示区域5c上供手动调节。 The temperature sensor T2 transmits organ temperature to the microprocessor 150, the microprocessor 150 controls the thermoelectric device 30a so as to adjust the medical fluid and organ to organ bath temperature was maintained at the desired temperature 60 and / or the temperature displayed on the control and display Regional 5c altar manual adjustment.

收集到的流出医用流体通过泵80经导管81抽出穿过过滤器装置82随后返回到器官浴液。 Collected medical fluid flowing through conduit 81 by pump 80 through the filter device 82 withdrawn subsequently returned to the organ bath. 这样将流出的医用流体中的手术与/或细胞碎片滤出,随后将过滤后的医用流体送回以用作器官60的浴液。 Thus the medical fluid flowing in the surgery and / or cell debris was filtered off, and then filtered medical fluid returned to bath 60 as an organ. 一旦液位传感器L2检测到在器官腔40中具有了一定水平的流出医用流体(优选地足以维持将器官60浸在流出医用流体中)时,由泵90经导管91将额外的流出医用流体抽出。 Once the level sensor detects L2 have a certain level of medical fluid flowing in the lumen 40 (preferably sufficient to maintain the organ 60 immersed in the effluent medical fluid), by a pump 90 through conduit 91 additional effluent medical fluid extraction . 温度传感器T1将器官浴液的温度传送给微处理器150,微处理器150控制热电装置30b从而调节医用流体的温度以将器官60维持在预期温度,并且/或者将温度显示在控制和显示区域5c上供手动调节和监视。 The temperature of the temperature sensors T1 transmission organ bath to the microprocessor 150, the microprocessor 150 controls the thermoelectric unit 30b so as to adjust the temperature of medical fluid to the organ 60 is maintained at the desired temperature, and / or the temperature displayed on the control and display areas 5c for reference manual tuning and monitoring.

如前所述,医用流体可以在单程模式下作为废物排放,或者最终循环返回器官与/或浴液(循环模式)。 As mentioned earlier, the medical fluid discharged as waste in one-way mode, or eventually recycled back organ and / or bath (circulation mode).

循环医用流体首先沿着导管91被抽吸通过过滤器装置95。 Circulating the medical fluid is first drawn through the filter means 95 along the conduit 91. 使用交联血红蛋白医用流体允许利用亚微米级的过滤以除去大的手术碎片和细胞碎片以及细菌。 Crosslinked hemoglobin medical fluid allows the use of submicron filtration to remove large surgical debris and cellular debris, and bacteria. 这允许使用最小量的抗生素,以辅助防止诸如肾损伤的器官损伤。 This allows the use of a minimum amount of an antibiotic to assist in preventing organ damage such as kidney damage.

接着,循环的医用流体被抽吸经过CO2洗涤器/O2隔膜100。 Then, the medical fluid is sucked through the circulating CO2 scrubber / O2 membrane 100. 该医用流体流过具有亲水涂层(例如Hypol)的亲水性大孔隔膜,并通过致动阀VV1而在另一侧上施加低真空,除去循环医用流体中的CO2。 The medical fluid flows through the hydrophilic macroporous membrane with a hydrophilic coating (e.g., Hypol) and a low vacuum is applied on the other side by the actuator valve VV1, removing circulating medical fluid CO2.

接着,一部分医用流体进入氧合器110(例如,JOSTRATM氧合器),还有一部分医用流体绕过氧合器110经导管111被分流而流过pH、pO2、pCO2、LDH、T/GST和T蛋白质传感器V1。 Then, part of the medical fluid into the oxygenator 110 (for example, JOSTRATM oxygenator), and part of the medical fluid to bypass oxygenator 110 through conduit 111 is split and flows pH, pO2, pCO2, LDH, T / GST and T protein sensor V1. 此时,根据被分流的医用流体的pH大小,,在隔膜的相对两侧上设置两种气体——优选地为100%氧气以及95%氧气与5%二氧化碳的混合气体。 At this time, the diverted medical fluid pH size ,, provided on opposite sides of the two gas membrane - preferably 100% oxygen and a mixed gas of 95% oxygen and 5% carbon dioxide. 优选地通过微米气阀GV3以高达200mmHg且优选地为50至100mmHg的压力来提供这些气体。 Preferably by valve GV3 microns and preferably up to 200mmHg to provide these gases 50 to 100mmHg pressure. 交联血红蛋白基重碳酸盐医用流体在优选7.25-7.45的pH范围的中点(7.35)处需要约40mmHg的pCO2。 Cross-linked hemoglobin-based bicarbonate medical fluid pH at the midpoint of the range of preferably 7.25-7.45 (7.35) takes about 40mmHg at the pCO2.

如果从氧合器流出的医用流体位于优选的pH范围内(例如7.25-7.45),向气体交换腔输送100%的氧气,关闭阀LV1,以允许灌注液返回到贮存器10进入不使用的袋15a或15b。 If it located within the preferred medical fluid from flowing out of the oxygenator pH range (e.g., 7.25-7.45), delivered to the gas exchange chamber 100% oxygen, closed valves LV1, allowing the perfusate to return to the reservoir 10 into the bag without the use of 15a or 15b. 如果返回的灌注液pH在该范围之外并位于酸性区域(例如,小于7.25),则向气体交换腔输送100%的氧气,且随后开启阀LV1,以允许灌注液返回到器官腔40。 If returning perfusate pH is outside this range and is located in an acidic region (e.g., less than 7.25), then the gas exchange chamber to the delivery of 100% oxygen, and then open the valves LV1, allowing the perfusate to return to the organ chamber 40. 然后致动注射泵131例如从重碳酸盐贮存器130抽取1cc重碳酸盐溶液,经导管132进入器官浴液。 Then actuating the syringe pump 131 such as heavier carbonate reservoir 130 extracts 1cc bicarbonate solution, the catheter 132 into the organ bath. 具有高血红蛋白含量的医用流体提供了重要的缓冲性能。 Medical fluid with high hemoglobin content provides an important buffer performance. 添加重碳酸盐有助于缓冲性能并提供一种可逆的pH控制机制。 Add bicarbonate helps buffer performance and provide a reversible pH control mechanism.

如果返回的灌注液pH在该范围之外并位于碱性区域(例如,大于7.25),则向气体交换腔输送95%氧气与5%二氧化碳的混合气体,且不致动阀LV1,允许灌注液返回到不使用的袋15a或15b。 If returning perfusate pH is outside this range and is located in an alkaline region (e.g., greater than 7.25), the delivery of 95% oxygen and 5% carbon dioxide gas mixture to the gas exchange chamber, and without valve LV1, allowing the perfusate to return to not use the bag 15a or 15b. 不使用的袋15a或15b允许经阀GV4除气(即除去多余的氧气)。 Bags 15a or 15b through the valve GV4 allow outgassing not used (ie remove excess oxygen). 当使用中的袋15a或15b中剩下的医用流体为约250ml或以下时,其相应的气囊16a、16b被允许通过相应的气阀GV1、GV2排气。 When using the bags 15a or 15b in the rest of the medical fluid is about 250ml or less, the corresponding airbag 16a, 16b are allowed to pass through the respective valve GV1, GV2 exhaust. 接着,压缩气源20为不使用的袋15a或15b的各个气囊16a、16b供应气体,从而将医用流体输送到器官以继续灌注该器官。 Subsequently, the compressed air source 20 is not used for each of the balloon bags 15a and 15b or 16a, 16b supply gas, so that the medical fluid to the organ to continue perfusion of the organ.

在低于体温模式下,使用冷却的医用流体灌注器官,医用流体的温度优选地在约1℃至15℃的温度范围内,更为优选地在4℃至10℃的温度范围内,最优选地约10℃进行该灌注。 In the hypothermic mode, using a cooled medical fluid perfused organs, medical fluid temperature is preferably at a temperature in the range of from about 1 ℃ to 15 ℃, more preferably at a temperature in the range of 4 ℃ to 10 ℃, and most preferably about 10 ℃ were the perfusion. 该医用流体优选地为未氧合的晶胶灌注液,且优选地补充有抗氧化剂和其它组织保护剂,例如抗坏血酸、谷胱甘肽、水溶性维他命E、接触酶或超氧化物岐化酶。 The medical fluid is preferably not oxygenated perfusion liquid crystal gum, and preferably supplemented with antioxidants and other tissue protective agent, such as ascorbic acid, glutathione, water soluble vitamin E, catalase or superoxide dismutase .

与将医用流体直接输入到器官不同的是,医用流体可以从贮罐17经导管51输入中间液罐70,该中间液罐压力头优选地为约5至40mmHg,更为优选地为10至30mmHg,最优选地为约20mmHg。 And the medical fluid directly into the organ is different, the medical fluid may enter from reservoir 17 through conduit 51 intermediate tank 70, the intermediate tank head pressure is preferably from about 5 to 40mmHg, more preferably 10 to 30mmHg , most preferably from about 20mmHg. 随后可以通过重力,优选地通过压力,通过致动阀LV6而将医用流体从中间液罐70沿导管50c输入到器官60。 Then by gravity, preferably by pressure, by actuating the valve and the medical fluids LV6 input from the intermediate tank 70 to the organ 60 along the conduit 50c. 中间液罐70中的液位传感器71用于控制来自贮罐17的供给量以维持预期的压力头。 Intermediate tank 70 is a level sensor 71 for controlling the amount of supply from the tank 17 to maintain a desired pressure head. 在低于体温模式中,通过重力或者优选地通过压力将医用流体输入该器官会使由于灌注压力引起的对器官的微脉管系统的伤害较少。 In the hypothermic mode, by gravity or, preferably, by the medical fluid pressure will enter the organ due to organ damage microvasculature perfusion pressure induced less. 实际上,灌注器官的压力由压力头限制在至多40mmHg。 In fact, the organ perfusion pressure limited by the pressure head up to 40mmHg.

在导管50c上可设置步进马达/凸轮阀205(或其它可变阀或压力调节器)以向器官60提供脉动的医用流体,从而减小输入到器官60的医用流体的压力,或者如前所述地阻断医用流体流入器官60。 50c may be provided on the conduit stepping motor / cam valve 205 (or other variable valve or pressure regulator) to provide medical fluid pulsation of the organ 60, thereby reducing the input into the organ 60 of medical fluid pressure, or as before The blocking medical fluid into the organ 60.

另外,在低于体温模式中,因为器官60对营养成分的需求较少,因此可以间歇地(例如,每两个小时以约100ml/min的流速)或者在长时间内缓慢的连续流速(例如约100ml/min)向器官60提供医用流体。 In addition, in the hypothermic mode, since the organ 60 less demand for nutrients, so you can intermittently (for example, every two hours to about 100ml / min flow rate) or over a long period of continuous slow flow rate (for example, about 100ml / min) to provide medical fluid to the organ 60. 间歇式灌注可以应用在单程模式或循环模式中。 Intermittent perfusion can be applied in a single pass mode or loop mode. 泵80、过滤器装置82和导管81可以和pH、pO2、pCO2、LDH、T/GST和T蛋白质传感器一起使用用于过滤器官浴液。 Pump 80, the filter device 82 and the conduit 81 can be an organ bath and pH, pO2, pCO2, LDH, T / GST and T protein sensor for use with the filter. 然而,由于器官在低于体温的温度无法利用氧气,因此不使用氧合器。 However, since the organ at hypothermic temperatures can not utilize oxygen, so do not use oxygenator. 如果需要与/或必需,可从经过滤的房间空气或其它适当的来源获得充足的氧气。 If you need to, and / or necessary, to obtain sufficient oxygen from room air or other suitable source filtered.

灌注液流量和温度调节都可以进行自动控制。 Perfusion fluid flow and temperature adjustment can be automatically controlled. 这种自动控制允许在工作期间对灌注条件作出快速且可靠的回应。 This automatic control during operation to allow fast and reliable response to the perfusion conditions. 自动流量控制可以基于从系统测量到的参数,包括灌注液流速、从器官流出的灌注液的pH值、器官入口压力、或者诸如预先选定的多个流速或多个灌注模式之间切换的定时顺序。 Automatic flow control can be measured from the system to the parameter based, including the perfusate flow rate, pH value of the effluent from the organ perfusate, switching between the organ inlet pressure or flow rate, such as a plurality of pre-selected timing modes or more perfusion order. 优选地,流量控制是基于对流入到器官的灌注液的压力监视。 Preferably, the flow control is based on the pressure of the fluid flow into the organ perfusion monitoring. 自动流量控制的优点包括,在工作于连续流量或受控间歇流量的同时,维持恰当的氧合和pH控制。 Advantages include automatic flow control, work in continuous flow or controlled intermittent flow while maintaining proper oxygenation and pH control. 热电装置(TED)的热控制可以调节器官盒或容器以及灌注液贮存器的温度。 Thermoelectric device (TED) thermal control can be adjusted boxes or containers and organ perfusion fluid reservoir temperature. 可以根据例如由灌注溶液内或器官内部的热敏探针或TEM内的传感器完成的热测量来进行该热控制。 The heat can be measured for example by a sensor inside the internal organ perfusion solution or a thermal probe or TEM to be completed within the thermal control.

优选地通过使用操作简单的菜单图标和显示器的交互控制程序实现自动控制。 Preferably automatically controlled by using a simple operation menu icon and display interactive control program. 参数可以被预先储存供用户在操作系统时进行选择或者编程。 Parameters can be pre-stored for the user to select the operating system or programming. 优选地在可编程的通用计算机中实施该控制程序。 Preferably the implementation of the control program in the programmable general purpose computer. 然而,该控制器也可以实施于专用计算机、可编程的微处理器或微控制器以及外围集成电路元件、ASIC或其它集成电路、数字信号处理器、硬接线电子或逻辑电路例如离散元件电路、可编程逻辑器件例如PLD、PLA、FPGA或PAL等。 However, the controller can also be implemented on special purpose computer, programmed microprocessor or microcontroller and peripheral integrated circuit element, ASIC or other integrated circuit, a digital signal processor, a hardwired electronic or logic circuits such as discrete element circuit, a programmable logic device such as PLD, PLA, FPGA, or PAL, etc. 通常,任何能够实施这里所述的控制过程的装置都可以使用。 In general, any device capable of implementing the control process described herein can be used. 优选地使用ROM实施该控制程序。 Preferably, the control program implemented using ROM. 然而,也可以使用PROM、EPROM、EEPROM、例如CD-ROM或DVD-ROM的光学ROM盘、以及磁盘驱动器等实施该控制程序。 However, you can also use PROM, EPROM, EEPROM, such as CD-ROM DVD-ROM optical ROM disk, and disk drive or the like to implement the control program. 然而,如果需要,可以使用静态或动态RAM实施该控制程序。 However, if desired, you can use static or dynamic RAM implementation of the control program. 还可以使用软盘和软盘驱动器、可写光盘和光盘驱动器、硬盘、闪存等实施该控制程序。 You can also use a floppy disk and floppy disk drives, writeable CDs and CD-ROM drives, hard drives, flash memory, etc. The implementation of the control program.

在工作时,可参见图15,控制对一个或多个器官进行灌注的操作的基本步骤首先包括输入器官数据。 At work, see Figure 15, controls the basic steps for one or more organ perfusion operation comprises first data input organ. 该器官数据至少包含器官类型和质量。 The organ data includes at least the type and quality of organs. 接着,程序将提示用户选择一种或多种灌注模式。 Subsequently, the program prompts the user to select one or more perfusion modes. 灌注模式的类型如前所述包含低于体温灌注、正常体温灌注、以及使用正常体温和低于体温灌注的顺序灌注。 As previously mentioned types of perfusion modes contain hypothermic perfusion, normothermic perfusion, and the use of normothermic and hypothermic perfusion of the order of less than perfusion. 当同时采用正常体温和低于体温灌注时,用户可以在不同温度下的医用流体之间进行选择。 When simultaneously using normothermic and hypothermic perfusion, the user can choose between a medical fluid at different temperatures. 当然,该系统包含基于预先储存的适于具体器官的默认值。 Of course, the system is adapted to contain default values based on the previously stored specific organ. 用户还可以选择间歇性的灌注、单程灌注和循环灌注。 Users can also select intermittent infusion, perfusion and perfusion way. 根据所选择的灌注类型,可以具体采用需氧或厌氧的医用流体。 According to the selected type of injury, you can use a medical fluid specific aerobic or anaerobic.

接着,为各个选定的灌注模式设定流量控制类型。 Next, set the flow control type for each selected perfusion mode. 流量控制选择器基于灌注液流速、灌注液pH值、器官入口压力以及定时顺序中的至少一种选择流量控制。 Flow control selection based on the flow rate of perfusate, perfusate pH, organ inlet pressure and timed sequence of at least one selected flow control. 在这些优选实施例中,流量控制是基于在器官的灌注入口探测到的压力。 In the preferred embodiment, the flow control is based on perfused organs detected inlet pressure. 该医用流体的流量随后是基于选定的灌注模式和流量控制。 The flow of the medical fluid is then selected based perfusion mode and flow control.

在操作过程中,该系统尤其是该器官和灌注液所经历的条件被探测和监视。 During operation, the system of the particular conditions experienced by the organ and the perfusion liquid to be detected and monitored. 将探测到的工作条件与预先储存的工作条件比较。 The detected operating conditions are compared with prestored operating conditions. 根据比较结果随后可以产生表明器官活性的信号。 According to the comparison result signal organ activity can then be produced show. 上文描述了各种探测器、传感器和监视装置,但是都至少包含压力传感器、pH值探测器、氧气传感器和流量计。 The foregoing describes the various detectors, sensors and monitoring devices, but contains at least a pressure sensor, pH value probe, oxygen sensor and flow meter.

该控制系统还可包含热控制器,用于控制灌注液及器官中的至少一个的温度。 The control system may also include a thermal controller for controlling organ perfusion solution and at least one temperature. 热控制器可以通过控制TED而控制医用流体贮存器及器官容器的温度。 Thermal Controller can be controlled by controlling the temperature of TED medical fluid reservoir and organ container. 如前所述,温度传感器被连接到该控制器以便有利于监视及控制。 As mentioned above, the temperature sensor is connected to the controller in order to facilitate monitoring and control.

可以在任何时刻手动调节该控制系统,或者将系统设置为遵从默认设置。 The control system can be adjusted manually at any time, or set the system to comply with the default settings. 该系统包含逻辑电路,以防止操作人员设置可能危害器官活性的参数。 The system includes logic circuitry to prevent possible harm to the operator to set parameters organ activity. 如前所述,该系统还可以工作于手动模式以依次进行低于体温与/或正常体温灌注,还可以工作于计算机控制模式以依次进行低于体温与/或正常体温灌注。 As mentioned above, the system can operate in manual mode to turn hypothermic and / or normothermic perfusion, may also work in computer control mode to turn hypothermic and / or normothermic perfusion.

上述设备和方法在对盒与/或压力及流速进行相应的必需调节后即可以用于小孩的或小的器官,也可以用于大的或成人的器官。 Or small organ above apparatus and methods of the cartridge and / or pressure and velocity necessary to adjust accordingly can be used after the child to be used for large or adult organs. 如前所述,这些器官盒可配置成具体的器官或器官尺寸的外形与尺寸。 As previously mentioned, these organs box can be configured to specific organs or organ size shape and size. 例如,该设备和方法还可以用于向诸如人造胎盘细胞培养基提供人造血源,用于生长/克隆器官。 For example, the apparatus and method can also be used to provide cell culture medium such as artificial placenta of human hematopoietic origin, for growing / cloning organs.

尽管已经结合本发明的具体实施例描述了本发明,但显然,许多可选、调节和变更对于本领域技术人员而言是显而易见的。 Although already in connection with specific embodiments of the invention are described in the present invention, it will be apparent that many options, adjust and change the skilled artisan is obvious. 因此,所述本发明优选实施例是说明性的,而非限制性的。 Accordingly, the present preferred embodiments of the invention are illustrative and not restrictive. 在不离开本发明的精神和范围的条件下可以进行许多改变。 Without departing from the spirit and scope of the present invention may be made many changes.

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
CN103519931A *30 Oct 201322 Jan 2014安徽英特电子有限公司Automatic water inflowing and draining structure of water bath
CN103519931B *30 Oct 201311 Mar 2015安徽英特电子有限公司Automatic water inflowing and draining structure of water bath
CN103747674A *7 Jun 201223 Apr 2014生命线科学有限公司Data record for organ transport and/or storage, comprising biomarker and events information
CN103747674B *7 Jun 201215 Jun 2016生命线科学有限公司器官/组织的活力的评价、维持和/或恢复
Classifications
International ClassificationA01N1/02, G01N33/50
Cooperative ClassificationA01N1/0247, A01N1/02, G01N33/5082
European ClassificationG01N33/50D2J, A01N1/02, A01N1/02M2P
Legal Events
DateCodeEventDescription
20 Jun 2007C06Publication
15 Aug 2007C10Request of examination as to substance
8 Jul 2015C12Rejection of an application for a patent