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1. 发明授权

US06759245B1 Cell culture systems and methods for organ assist devices 失效
标题翻译：器官辅助装置的细胞培养系统和方法
公开(公告)号：US06759245B1
公开(公告)日：2004-07-06
申请号：US09599891
申请日：2000-06-21
申请人： Mehmet Toner , Arno W. Tilles , Ulysses J. Balis , Martin L. Yarmush , Maury D. Cosman , Paul A. Dimilla
发明人： Mehmet Toner , Arno W. Tilles , Ulysses J. Balis , Martin L. Yarmush , Maury D. Cosman , Paul A. Dimilla
IPC分类号： C12N500
CPC分类号： A61M1/3472 , A61F2/022 , A61M1/3482 , A61M1/3489 , A61M1/3633 , A61M2210/1071 , C12M23/24 , C12M29/04 , C12M29/10 , C12N5/0068 , C12N5/0671
摘要： The invention features modular cell culturing devices including one or more flat-plate modules, and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver, assist systems, for production of cells, for production of cell-derived products, such as, proteins or viruses, or for systems to treat biological liquids to remove toxins, such as, ammonia, or add cell-synthesized products, or both.
摘要翻译：本发明的特征在于包括一个或多个平板模块的模块化细胞培养装置，并且基于如下发现：如果液体介质和氧合流体的流动被透气的液体不可渗透膜分离，并且细胞生长附着于膜的液体侧，该装置可用于通过膜输送氧气（即，直接氧合）来培养细胞，而不考虑通过该装置的液体介质的流速。因此，新的流通细胞培养装置可用于培养细胞，例如肝细胞，在器官中具有高水平的细胞功能，例如肝，辅助系统，细胞产生，细胞衍生产品的生产，例如或蛋白质或病毒，或用于处理生物液体以除去毒素（例如氨）或添加细胞合成产物或两者的系统。

2. 发明授权

US06465252B1 Cell culture systems and methods for organ assist devices 有权
公开(公告)号：US06465252B1
公开(公告)日：2002-10-15
申请号：US09599891
申请日：2000-06-21
申请人： Mehmet Toner , Arno W. Tilles , Ulysses J. Balis , Martin L. Yarmush , Maury D. Cosman , Paul A. Dimilla
发明人： Mehmet Toner , Arno W. Tilles , Ulysses J. Balis , Martin L. Yarmush , Maury D. Cosman , Paul A. Dimilla
IPC分类号： C12N500
摘要： The invention features modular cell culturing devices including one or more flat-plate modules, and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver, assist systems, for production of cells, for production of cell-derived products, such as, proteins or viruses, or for systems to treat biological liquids to remove toxins, such as, ammonia, or add cell-synthesized products, or both.

3. 发明授权

US06562616B1 Methods and devices for cell culturing and organ assist systems 失效
标题翻译：细胞培养和器官辅助系统的方法和装置
公开(公告)号：US06562616B1
公开(公告)日：2003-05-13
申请号：US09599297
申请日：2000-06-21
申请人： Mehmet Toner , Martin L. Yarmush , Ulysses J. Balis , Arno W. Tilles
发明人： Mehmet Toner , Martin L. Yarmush , Ulysses J. Balis , Arno W. Tilles
IPC分类号： C12M304
CPC分类号： A61M1/3633 , A61F2/022 , A61M2210/1071 , C12M23/24 , C12M23/34 , C12M29/04 , C12M29/10 , C12M41/00
摘要： The invention relates to new flow-through cell culturing devices that include plates arranged in parallel and spaced to control the flow patterns and velocity of liquid medium flowing between the plates. The devices can also include gas-permeable, liquid impermeable membranes arranged between the plates. The devices can be used to culture cells, such as hepatocytes, at high levels of mass transport of nutrients, oxygen, and waste products, yet low levels of shear stress for extended periods of time and with high levels of cell function, e.g., in organ assist systems. The invention also includes new culturing plates for use in the devices, and methods of manufacturing these plates.
摘要翻译：本发明涉及新的流通细胞培养装置，其包括平行布置并间隔开的板，以控制在板之间流动的液体介质的流动模式和速度。装置还可以包括布置在板之间的透气的液体不可渗透膜。这些装置可以用于培养细胞，如肝细胞，在营养物质，氧气和废物产品的高质量运输水平下，延长的时间段和高水平的细胞功能的低水平的剪切应力，例如，器官辅助系统。本发明还包括用于装置的新培养板以及制造这些板的方法。

4. 发明申请

US20100273675A1 Methods for detecting fetal abnormality 审中-公开
标题翻译：检测胎儿异常的方法
公开(公告)号：US20100273675A1
公开(公告)日：2010-10-28
申请号：US12702614
申请日：2010-02-09
申请人： Ulysses J. Balis , Mehmet Toner , Ravi Kapur , John Walsh
发明人： Ulysses J. Balis , Mehmet Toner , Ravi Kapur , John Walsh
IPC分类号： C40B30/04 , C12Q1/68
CPC分类号： C12Q1/6881 , B01L3/502746 , B01L3/502753 , B01L3/502761 , B01L2200/0668 , B01L2300/0816 , B01L2400/0487 , B01L2400/086 , B82Y15/00 , B82Y30/00 , C12Q2600/156 , G01N2015/1486
摘要： The invention relates to a method of identifying fetal abnormality from a maternal blood sample by capturing an image of a fetal nucleated red blood cell obtained from the maternal blood sample; inputting probe intensities for a plurality of nucleic acid probes that bind fetal nucleic acids of interest; analyzing the probe intensities; and generating a diagnostic output according to results of the analysis. In some embodiments, the probes are specific to a chromosome.
摘要翻译：本发明涉及一种从母体血液样本中鉴别胎儿异常的方法，该方法是从母体血液样品中获取胎儿有核红细胞的图像，输入结合感兴趣的胎儿核酸的多个核酸探针的探针强度; 分析探针强度; 并根据分析结果生成诊断输出。在一些实施方案中，探针对染色体是特异性的。

5. 发明申请

US20140030231A1 METHODS AND COMPOSITIONS FOR PRESERVING TISSUES AND ORGANS 审中-公开
标题翻译：用于保存组织和器官的方法和组合物
公开(公告)号：US20140030231A1
公开(公告)日：2014-01-30
申请号：US13695459
申请日：2011-05-04
申请人： Martin L. Yarmush , Mehmet Toner , Maria-Louisa Izamis , Timothy Antonie Berendsen , Robert Marius Bieganski , Osman Berk Usta , Basak Elif Uygun , Mustafa Korkut Uygun , Sinem Perk
发明人： Martin L. Yarmush , Mehmet Toner , Maria-Louisa Izamis , Timothy Antonie Berendsen , Robert Marius Bieganski , Osman Berk Usta , Basak Elif Uygun , Mustafa Korkut Uygun , Sinem Perk
IPC分类号： A01N1/02
CPC分类号： A01N1/0226 , G01N1/42 , G01N33/5091
摘要： The present invention generally relates to methods and compositions to determine viability of an organ for transplantation and other medical purposes. One aspect of the invention relates to a method for assessing the viability of an organ by measuring the energy parameters to determine the energy level of the organ by determining the stored cellular energy (e.g., ATP levels), and/or energy consumption over a particular time period of viability. The energy parameters can be compared to reference energy parameters as a highly accurate and reliable prediction of viable cell yield, and organ viability. Another aspect of the invention relates methods to preserve or extend the time period of viability of an organ any combination of (i) preservation perfusion of the organ to prevent ischemic damage, (ii) chemical metabolic suppression of the organ e.g., using metabolic suppressants, (iii) metabolic suppression by physical or environmental conditions, e.g., sub-zero non-freezing storage.
摘要翻译：本发明一般涉及用于确定用于移植和其它医疗目的的器官的活力的方法和组合物。本发明的一个方面涉及一种通过测量能量参数来确定器官的能量水平来评估器官活力的方法，该方法是通过确定存储的细胞能量（例如，ATP水平）和/或特定的能量消耗生存时间段能量参数可以与参考能量参数进行比较，作为对活细胞产量和器官存活力的高度准确和可靠的预测。本发明的另一方面涉及保存或延长器官存活时间的方法，任何组合（i）器官的保留灌注以预防缺血性损伤，（ii）器官的化学代谢抑制，例如使用代谢抑制剂，（iii）物理或环境条件下的代谢抑制，例如零度非冻结储存。

6. 发明授权

US10575515B2 Methods and compositions for preserving tissues and organs 有权
公开(公告)号：US10575515B2
公开(公告)日：2020-03-03
申请号：US13695459
申请日：2011-05-04
申请人： Martin L. Yarmush , Mehmet Toner , Maria-Louisa Izamis , Timothy Antonie Berendsen , Robert Marius Bieganski , Osman Berk Usta , Basak Elif Uygun , Mustafa Korkut Uygun , Sinem Perk
发明人： Martin L. Yarmush , Mehmet Toner , Maria-Louisa Izamis , Timothy Antonie Berendsen , Robert Marius Bieganski , Osman Berk Usta , Basak Elif Uygun , Mustafa Korkut Uygun , Sinem Perk
IPC分类号： A01N1/02 , G01N33/50 , G01N1/42
摘要： The present invention generally relates to methods and compositions to determine viability of an organ for transplantation and other medical purposes. One aspect of the invention relates to a method for assessing the viability of an organ by measuring the energy parameters to determine the energy level of the organ by determining the stored cellular energy (e.g., ATP levels), and/or energy consumption over a particular time period of viability. The energy parameters can be compared to reference energy parameters as a highly accurate and reliable prediction of viable cell yield, and organ viability. Another aspect of the invention relates methods to preserve or extend the time period of viability of an organ any combination of (i) preservation perfusion of the organ to prevent ischemic damage, (ii) chemical metabolic suppression of the organ e.g., using metabolic suppressants, (iii) metabolic suppression by physical or environmental conditions, e.g., sub-zero non-freezing storage.

7. 发明授权

US09538745B2 Methods for the cryopreservation of cells 有权
标题翻译：细胞冷冻保存方法
公开(公告)号：US09538745B2
公开(公告)日：2017-01-10
申请号：US12226300
申请日：2007-04-12
申请人： Xiaoming He , Thomas L. Toth , Mehmet Toner , Jon Edd
发明人： Xiaoming He , Thomas L. Toth , Mehmet Toner , Jon Edd
IPC分类号： A01N1/02
CPC分类号： A01N1/02 , A01N1/0221 , A01N1/0268 , A01N1/0278
摘要： The present invention features novel methods for the cryopreservation of mammalian cell that combine the advantages of the slow-freezing and vitrification approaches while avoiding their shortcomings. Generally, the methods include the use of a capillary tube made of a thermally conductive wall material and a thin wall such that the ratio of the thermal conductivity of the wall material to the wall thickness is at least 1,000-500,000. The solution is then exposed to temperatures equal to or less than −80° C. and the vitrification solution containing the mammalian cells is cooled at a rate equal to or greater than 30,000-100,000,000° C./minute. The exposure of the capillary tube with a thermally conductive and thin wall allows for vitrification of the solution in the absence of ice formation. Cryoprotectants can also be added to the vitrification solution to further prevent ice formation.
摘要翻译：本发明的特征在于用于冷冻保存哺乳动物细胞的新方法，其结合了缓慢冷冻和玻璃化方法的优点，同时避免了它们的缺点。通常，这些方法包括使用由导热壁材料制成的毛细管和薄壁，使得壁材料的导热率与壁厚之比至少为1,000-500,000。然后将溶液暴露于等于或小于-80℃的温度，并将含有哺乳动物细胞的玻璃化溶液以等于或大于30,000-10000,000℃/分钟的速率冷却。毛细管与导热和薄壁的接触允许在没有冰层形成的情况下玻璃化溶液。也可以将冷冻保护剂加入到玻璃化溶液中以进一步防止冰层形成。

8. 发明授权

US09422517B2 Microscale and nanoscale structures for manipulating particles 有权
标题翻译：用于操纵颗粒的微尺度和纳米级结构
公开(公告)号：US09422517B2
公开(公告)日：2016-08-23
申请号：US13812934
申请日：2011-07-29
申请人： Grace Chen , Fabio Fachin , Mehmet Toner , Brian Wardle
发明人： Grace Chen , Fabio Fachin , Mehmet Toner , Brian Wardle
IPC分类号： B07B9/00 , C12M1/12 , B01L3/00 , G01N15/14
CPC分类号： C12M25/16 , B01L3/502707 , B01L3/502746 , B01L3/502761 , B01L2200/0652 , B01L2200/0668 , B01L2300/0896 , B01L2400/086 , G01N15/1404 , G01N2015/1413
摘要： The devices and systems described herein include one or more fluid paths, e.g., channels, and one or more selectively permeable obstacles arranged in the fluid path(s), each including a plurality of aligned nanostructures, e.g., nanotubes or nanorods, defining an outer surface of the obstacle and an internal network of voids. The obstacle(s) can further include binding moieties applied to the outer surface and/or to the surfaces of the individual nanostructures within the obstacle(s). The devices can be manufactured by forming the dense groupings of nanostructures to extend outwards and upwards from a substrate; forming a fluidic channel, bonding the fluidic channel to the substrate; and optionally applying binding moieties to the obstacles. The devices can be used to manipulate cells within fluid samples.
摘要翻译：本文描述的装置和系统包括一个或多个流体路径，例如通道和布置在流体路径中的一个或多个选择性渗透的障碍物，每个包括多个对准的纳米结构，例如纳米管或纳米棒，限定外部障碍物的表面和内部的空隙网络。障碍物还可包括施加到障碍物内的各个纳米结构的外表面和/或表面的结合部分。可以通过形成从衬底向外和向上延伸的纳米结构的致密分组来制造器件; 形成流体通道，将流体通道粘合到基底上; 并且任选地将结合部分施加到障碍物上。这些装置可用于操纵流体样品中的细胞。

9. 发明授权

US09128091B2 Capturing particles 有权
标题翻译：捕获颗粒
公开(公告)号：US09128091B2
公开(公告)日：2015-09-08
申请号：US13121130
申请日：2009-09-25
申请人： Mehmet Toner , Shannon Stott , Chia-Hsien Hsu
发明人： Mehmet Toner , Shannon Stott , Chia-Hsien Hsu
IPC分类号： B01L3/00 , G01N33/569 , G01N33/543 , G01N33/574
CPC分类号： G01N1/405 , B01L3/502761 , B01L2200/0647 , B01L2200/0668 , B01L2300/0816 , B01L2300/0858 , B01L2400/0487 , B01L2400/086 , G01N33/54366 , G01N33/56966 , G01N33/57434
摘要： Methods and systems capturing particles suspended in a fluid flowed through a micro-channel, can include flowing the fluid including the particles to be captured through a micro-channel and past a groove defined in a surface of a wall of the micro-channel such that flowing the fluid past the groove forms microvortices in the fluid; contacting at least some of the particles against an adherent disposed on one or more of walls of the microchannel after the microvortices form in the fluid; and capturing at least some of the particles contacting the adherent.
摘要翻译：捕获悬浮在流过微通道的流体中的颗粒的方法和系统可以包括使包含要捕获的颗粒的流体流过微通道并经过限定在微通道壁的表面中的凹槽，使得使流体流过凹槽，形成微流体; 在微流体在流体中形成之后，使至少一些颗粒抵靠设置在微通道的一个或多个壁上的粘附剂; 并捕获与粘附剂接触的至少一些颗粒。

10. 发明授权

US08807879B2 Systems and methods for particle focusing in microchannels 有权
公开(公告)号：US08807879B2
公开(公告)日：2014-08-19
申请号：US13619309
申请日：2012-09-14
申请人： Mehmet Toner , Dino Dicarlo , Jon F. Edd , Daniel Irimia
发明人： Mehmet Toner , Dino Dicarlo , Jon F. Edd , Daniel Irimia
IPC分类号： B65G53/00
CPC分类号： B01L3/502776 , B01D21/0087 , B01D21/265 , B01D45/04 , B01D45/12 , B01L3/502746 , B01L3/502761 , B01L2200/0652 , B01L2300/0883 , B01L2400/0409 , B01L2400/043 , B01L2400/0433 , B01L2400/0454 , B01L2400/0487 , B01L2400/0622 , B01L2400/084 , B33Y80/00 , C12M23/16 , C12M41/36 , C12M47/04 , F16L41/02 , F17D1/00 , G01N15/0255 , G01N15/10 , G01N2015/0288 , G01N2015/1006 , G01N2015/1081 , Y10T137/85938 , Y10T137/85978 , Y10T436/117497 , Y10T436/2575
摘要： Various systems, methods, and devices are provided for focusing particles suspended within a moving fluid into one or more localized stream lines. The system can include a substrate and at least one channel provided on the substrate having an inlet and an outlet. The system can further include a fluid moving along the channel in a laminar flow having suspended particles and a pumping element driving the laminar flow of the fluid. The fluid, the channel, and the pumping element can be configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.

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