公开(公告)号：US07278278B2

公开(公告)日：2007-10-09

申请号：US10864921

申请日：2004-06-09

申请人： Brian Wowk ,  Michael Iarocci

发明人： Brian Wowk ,  Michael Iarocci

IPC分类号： F25D3/08

CPC分类号： A01N1/0263 ,  A01N1/02 ,  A01N1/0257 ,  A01N1/0268 ,  F17C2203/0304 ,  F17C2203/0617 ,  F17C2203/0629 ,  F17C2203/0636 ,  F17C2203/0646 ,  F17C2203/0648 ,  F17C2205/0149 ,  F17C2227/0337 ,  F17C2250/0439

摘要： The present invention provides devices and methods for the cryogenic storage of biological material. Devices of the invention are useful for storing material at a cryogenic temperature. The devices include a temperature chamber defined by a thermally-conductive container and at least one layer of thermal insulation surrounding the thermally-conductive container. Some embodiments utilize one or more heat sources thermally connected to the thermally conductive container. Other embodiments are arranged so that no net flow of heat occurs from the temperature chamber when the temperature chamber is at a set target temperature. Also provided are methods of using the devices.

摘要翻译： 本发明提供用于生物材料的低温储存的装置和方法。 本发明的装置可用于在低温下储存材料。 这些装置包括由导热容器限定的温度室和围绕导热容器的至少一层隔热层。 一些实施例利用热连接到导热容器的一个或多个热源。 布置其它实施例，使得当温度室处于设定的目标温度时，不会从温度室发生净热流。 还提供了使用这些装置的方法。

公开(公告)号：US06988370B2

公开(公告)日：2006-01-24

申请号：US10867987

申请日：2004-06-14

申请人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

发明人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

IPC分类号： F17C11/00

CPC分类号： A01N1/02 ,  A01N1/0257 ,  F17C2270/0509 ,  G01N1/42

摘要： A cryogenic storage system for cryogenic storage using liquid refrigerant is provided. The cryogenic storage system includes first and second vacuum vessels, a vacuum source, a quantity of a liquid refrigerant, and at least one temperature control assembly. An insulating wall may be provided on an interior surface of one of the vessels. A common vacuum condition is provided in voids that are present in the wall of the first and second vessels as well as in the insulating wall. The at least one temperature control assembly includes a power supply, a temperature sensor, a heater, and a conductive element. The at least one conductive element provides a link or thermal coupling between a space defined in the first vessel and the liquid refrigerant stored in the second vessel.

公开(公告)号：US20050016198A1

公开(公告)日：2005-01-27

申请号：US10864921

申请日：2004-06-09

申请人： Brian Wowk ,  Michael Iarocci

发明人： Brian Wowk ,  Michael Iarocci

IPC分类号： A01N1/02 ,  F17C5/00 ,  F17C13/00 ,  F25B21/00 ,  F25D3/08

CPC分类号： A01N1/0263 ,  A01N1/02 ,  A01N1/0257 ,  A01N1/0268 ,  F17C2203/0304 ,  F17C2203/0617 ,  F17C2203/0629 ,  F17C2203/0636 ,  F17C2203/0646 ,  F17C2203/0648 ,  F17C2205/0149 ,  F17C2227/0337 ,  F17C2250/0439

摘要： The present invention provides devices and methods for the cryogenic storage of biological material. Devices of the invention are useful for storing material at a cryogenic temperature. The devices include a temperature chamber defined by a thermally-conductive container and at least one layer of thermal insulation surrounding the thermally-conductive container. Some embodiments utilize one or more heat sources thermally connected to the thermally conductive container. Other embodiments are arranged so that no net flow of heat occurs from the temperature chamber when the temperature chamber is at a set target temperature. Also provided are methods of using the devices.

摘要翻译： 本发明提供用于生物材料的低温储存的装置和方法。 本发明的装置可用于在低温下储存材料。 这些装置包括由导热容器限定的温度室和围绕导热容器的至少一层隔热层。 一些实施例利用热连接到导热容器的一个或多个热源。 布置其它实施例，使得当温度室处于设定的目标温度时，不会从温度室发生净热流。 还提供了使用这些装置的方法。

公开(公告)号：US20050005614A1

公开(公告)日：2005-01-13

申请号：US10867987

申请日：2004-06-14

申请人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

发明人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

IPC分类号： F17C1/00 ,  F17C3/08 ,  F17C13/02

CPC分类号： A01N1/02 ,  A01N1/0257 ,  F17C2270/0509 ,  G01N1/42

摘要： A cryogenic storage system for cryogenic storage using liquid refrigerant is provided. The cryogenic storage system includes first and second vacuum vessels, a vacuum source, a quantity of a liquid refrigerant, and at least one temperature control assembly. An insulating wall may be provided on an interior surface of one of the vessels. A common vacuum condition is provided in voids that are present in the wall of the first and second vessels as well as in the insulating wall. The at least one temperature control assembly includes a power supply, a temperature sensor, a heater, and a conductive element. The at least one conductive element provides a link or thermal coupling between a space defined in the first vessel and the liquid refrigerant stored in the second vessel.

摘要翻译： 提供了一种使用液体制冷剂的低温储存系统。 低温存储系统包括第一和第二真空容器，真空源，一定数量的液体制冷剂和至少一个温度控制组件。 绝缘壁可以设置在其中一个容器的内表面上。 在存在于第一和第二容器的壁以及绝缘壁中的空隙中提供常见的真空条件。 所述至少一个温度控制组件包括电源，温度传感器，加热器和导电元件。 所述至少一个导电元件提供在第一容器中限定的空间和存储在第二容器中的液体制冷剂之间的连接或热耦合。

公开(公告)号：US07299641B2

公开(公告)日：2007-11-27

申请号：US11299578

申请日：2005-12-12

申请人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

发明人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

IPC分类号： F17C3/08 ,  F17C7/02

CPC分类号： A01N1/02 ,  A01N1/0257 ,  F17C2270/0509 ,  G01N1/42

摘要： A cryogenic storage system for cryogenic storage using liquid refrigerant is provided. The cryogenic storage system includes first and second vacuum vessels, a vacuum source, a quantity of a liquid refrigerant, and at least one temperature control assembly. An insulating wall may be provided on an interior surface of one of the vessels. A common vacuum condition is provided in voids that are present in the wall of the first and second vessels as well as in the insulating wall. The at least one temperature control assembly includes a power supply, a temperature sensor, a heater, and a conductive element. The at least one conductive element provides a link or thermal coupling between a space defined in the first vessel and the liquid refrigerant stored in the second vessel.

摘要翻译： 提供了一种使用液体制冷剂的低温储存系统。 低温存储系统包括第一和第二真空容器，真空源，一定数量的液体制冷剂和至少一个温度控制组件。 绝缘壁可以设置在其中一个容器的内表面上。 在存在于第一和第二容器的壁以及绝缘壁中的空隙中提供常见的真空条件。 所述至少一个温度控制组件包括电源，温度传感器，加热器和导电元件。 所述至少一个导电元件提供在第一容器中限定的空间和存储在第二容器中的液体制冷剂之间的连接或热耦合。

公开(公告)号：US20060090479A1

公开(公告)日：2006-05-04

申请号：US11299578

申请日：2005-12-12

申请人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

发明人： Michael Iarocci ,  Stephen Valentine ,  Brian Wowk

IPC分类号： F17C3/08 ,  F17C13/02

CPC分类号： A01N1/02 ,  A01N1/0257 ,  F17C2270/0509 ,  G01N1/42

摘要： A cryogenic storage system for cryogenic storage using liquid refrigerant is provided. The cryogenic storage system includes first and second vacuum vessels, a vacuum source, a quantity of a liquid refrigerant, and at least one temperature control assembly. An insulating wall may be provided on an interior surface of one of the vessels. A common vacuum condition is provided in voids that are present in the wall of the first and second vessels as well as in the insulating wall. The at least one temperature control assembly includes a power supply, a temperature sensor, a heater, and a conductive element. The at least one conductive element provides a link or thermal coupling between a space defined in the first vessel and the liquid refrigerant stored in the second vessel.

摘要翻译： 提供了一种使用液体制冷剂的低温储存系统。 低温存储系统包括第一和第二真空容器，真空源，一定数量的液体制冷剂和至少一个温度控制组件。 绝缘壁可以设置在其中一个容器的内表面上。 在存在于第一和第二容器的壁以及绝缘壁中的空隙中提供常见的真空条件。 所述至少一个温度控制组件包括电源，温度传感器，加热器和导电元件。 所述至少一个导电元件提供在第一容器中限定的空间和存储在第二容器中的液体制冷剂之间的连接或热耦合。

公开(公告)号：US06391224B1

公开(公告)日：2002-05-21

申请号：US09400791

申请日：1999-09-21

申请人： Brian Wowk

发明人： Brian Wowk

IPC分类号： C09K318

CPC分类号： A01N37/02 ,  A01N1/02 ,  A01N1/0221 ,  A01N31/02 ,  C09K3/18 ,  C09K3/185 ,  C09K5/20

摘要： Polyvinyl alcohol and related compounds are provided that inhibit the freezing of water and water solutions. These synthetic compounds preferentially bind and inhibit ice nucleating surfaces in a manner similar to natural antifreeze proteins. The resulting inhibition allows water and water solutions to supercool without ice formation to temperatures below the thermodynamic freezing point. The freezing inhibition occurs at concentrations as small as one part per million, although concentrations up to one part per hundred are preferred. These polyvinyl alcohol additives are very useful for enhancing the performance of antifreeze formulations, biological cryopreservation solutions, and for preventing frost damage to plants and other industrial products and processes.

摘要翻译： 提供了聚乙烯醇和相关化合物，其抑制水和水溶液的冻结。 这些合成化合物优选以与天然防冻蛋白相似的方式优先结合并抑制冰成核表面。 所得到的抑制使得水和水溶液在没有冰形成的情况下过冷却到低于热力学冰点的温度。 冷冻抑制发生在浓度小至百万分之一的浓度，尽管优选浓度高达一百分之一。 这些聚乙烯醇添加剂对于提高防冻配方，生物冷冻保存溶液的性能以及防止对植物和其他工业产品和工艺的霜冻伤害非常有用。

公开(公告)号：US06616858B2

公开(公告)日：2003-09-09

申请号：US09726857

申请日：2000-11-30

申请人： Greg Fahy ,  Brian Wowk

发明人： Greg Fahy ,  Brian Wowk

IPC分类号： C09K318

CPC分类号： A01N1/0221 ,  A01N1/02 ,  C09K3/18 ,  C09K5/20

摘要： Linear polymers of glycerol can prevent or delay ice nucleation in a variety of contexts. Polyglycerol can also be employed in combination with other ice control agents, such as polyvinyl alcohol/polyvinyl acetate copolymers and antifreeze proteins, to provide antinucleation effects that are superior to those of either polyglycerol or the co-antinucleator alone. Polyglycerol has a number of advantageous physical and toxicological properties, such as extreme water solubility, non-toxicity to human beings, non-toxicity to animal tissues and organs in vitro even at extreme concentrations, minimal foaming tendency, minimal retention on hydrophobic surfaces, and stability in solution without the need for periodic heating to reactivate its antinucleation properties.

摘要翻译： 甘油的线性聚合物可以防止或延迟各种情况下的冰核化。 聚甘油也可以与其它冰控制剂（例如聚乙烯醇/聚乙酸乙烯酯共聚物和防冻蛋白）组合使用，以提供优于单独的聚甘油或共聚单核苷酸的抗核苷酸化作用。 聚甘油具有许多有利的物理和毒理学性质，例如极端的水溶性，对人体无毒性，甚至在极端浓度下体内对动物组织和器官无毒性，最小发泡倾向，疏水性表面上的最小保留性，以及 溶液的稳定性，不需要定期加热来重新激活其反核化性能。

公开(公告)号：US08679735B2

公开(公告)日：2014-03-25

申请号：US10571968

申请日：2004-09-16

申请人： Gregory M. Fahy ,  Brian Wowk

发明人： Gregory M. Fahy ,  Brian Wowk

IPC分类号： A01N1/00

CPC分类号： A01N1/02 ,  A01N1/0221 ,  A01N1/0284

摘要： Methods and compositions are provided for the cryopreservation of human organs and tissues. In certain embodiments, Step 1 comprises perfusion with a vitrifiable cryoprotectant solution at a temperature above −10° C. for a time insufficient for the approximate osmotic equilibration of the organ with the solution, followed by cooling the organ to below −10° C. by perfusion with said solution at a reduced temperature. In certain embodiments, Step 2 comprises increasing the concentration of cryoprotectant further at a temperature from −10 to −40° C. In certain embodiments, Step 3 comprises cooling and vitrifying the organ, rewarming it, and perfusing the organ with a vitrifiable concentration of cryoprotectant whose temperature is either raised gradually or is held at ≧−15° C. Compositions are provided that allow safe organ perfusion with vitrifiable media at >−10° C. and almost complete avoidance of chilling injury at −20 to −25° C. and that allow slow warming after vitrification without freezing.

摘要翻译： 为人体器官和组织的低温保存提供了方法和组合物。 在某些实施方案中，步骤1包括在高于-10℃的温度下用可玻璃化的冷冻保护剂溶液灌注不足以使器官与溶液的近似渗透平衡的时间，然后将器官冷却至低于-10℃。 通过在降低的温度下用所述溶液灌注。 在某些实施方案中，步骤2还包括在-10至-40℃的温度下进一步增加冷冻保护剂的浓度。在某些实施方案中，步骤3包括将器官冷却和玻璃化，对其进行再温热，并以可玻璃化浓度 其温度缓慢升高或保持在-15℃以下的冷冻保护剂。提供的组合物允许在-20℃至-25℃几乎完全避免在-20℃至-25℃的冷冻损伤下安全的器官灌注玻璃培养基 并且允许玻璃化后缓慢升温而不冻结。

公开(公告)号：US20070190517A1

公开(公告)日：2007-08-16

申请号：US10571968

申请日：2004-09-16

申请人： Gregory Fahy ,  Brian Wowk

发明人： Gregory Fahy ,  Brian Wowk

IPC分类号： A01N1/00

CPC分类号： A01N1/02 ,  A01N1/0221 ,  A01N1/0284

摘要： Methods and compositions are provided for the introduction and washout of vitrifiable concentrations of cryoprotectant in organs and tissues. The methods comprise cooling the organ to below −10° C. by perfusion with a solution having a freezing point below −10° C., a temperature from −10 to −40° C., and a tonicity from 1.1 to 2.0 times isotonic, after previous perfusion with said solution for a time insufficient for approximate osmotic equilibration of the organ with the solution. The methods further comprise increasing the concentration of cryoprotectant further at a temperature from −10 to −40° C. to prepare the organ or tissue for vitrification. The methods further comprise cooling and vitrifying the organ, rewarming it, and perfusing the organ with a vitrifiable concentration of cryoprotectant that is the same as or less than the concentration used for vitrification, without the addition of an osmotic buffering agent. Rewarming is accomplished either by rapid (>1°C./min, and preferably −0.2-20° C./min) elevation of arterial perfusate temperature from below −20° C. to above −15° C. during continuous perfusion of the organ or by perfusing the organ with pre-warmed arterial perfusate at >−15° C. Extraordinarily effective multicomponent compositions are also provided for the process, particularly involving a vitrification solution whose warming rate after vitrification can be

摘要翻译： 提供了方法和组合物，用于在器官和组织中引入和冲洗可冷冻浓度的冷冻保护剂。 所述方法包括通过用冰点低于-10℃，-10至-40℃的温度和1.1至2.0倍的渗透压等渗进行灌注来冷却器官至低于-10℃ 之前用所述溶液灌注一段时间不足以使器官与溶液的近似渗透平衡。 所述方法还包括进一步在-10至-40℃的温度下增加冷冻保护剂的浓度，以制备用于玻璃化的器官或组织。 所述方法还包括冷却和玻璃化器官，对其进行再温热，并且在不添加渗透缓冲剂的情况下，以可玻璃化浓度的冷冻保护剂浓度与用于玻璃化的浓度相同或低于玻璃化的灌注器官。 在连续灌注期间，通过快速（> 1℃/ min，优选-0.2-20℃/ min）将动脉灌注液温度从低于-20℃升高至-15℃以上来实现重组 器官或通过在> -15℃下预热的动脉灌注液灌注器官。还提供了特别有效的多组分组合物，特别涉及玻璃化后的升温速率可以<1℃/分钟的玻璃化溶液 在暖和期间不冻结，并且在0℃下对全身器官具有零毒性的寒冷伤害保护溶液，并允许几乎完全避免-20至-25℃的寒冷伤害。