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1. 发明申请

WO2012016136A2 MICROSCALE AND NANOSCALE STRUCTURES FOR MANIPULATING PARTICLES 审中-公开
标题翻译：用于操纵颗粒的微观和纳米级结构
公开(公告)号：WO2012016136A2
公开(公告)日：2012-02-02
申请号：PCT/US2011045880
申请日：2011-07-29
申请人： GEN HOSPITAL CORP , MASSACHUSETTS INST TECHNOLOGY , CHEN GRACE , FACHIN FABIO , TONER MEHMET , WARDLE BRIAN
发明人： CHEN GRACE , FACHIN FABIO , TONER MEHMET , WARDLE BRIAN
IPC分类号： G01N33/48 , G01N35/08
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：这里描述的装置和系统包括布置在流体路径中的一个或多个流体路径（例如通道）和一个或多个选择性渗透障碍物，每个包括多个对准的纳米结构（例如纳米管或纳米棒）障碍物的表面和空隙的内部网络。障碍物还可以包括施加到障碍物内的外表面和/或各个纳米结构的表面的结合部分。这些器件可以通过形成密集的纳米结构组从衬底向外和向上延伸来制造; 形成流体通道，将所述流体通道结合到所述衬底; 并任选地将结合部分应用于障碍物。这些设备可以用来操纵流体样本中的细胞。

2. 发明申请

WO2012064878A3 COUNTING PARTICLES USING AN ELECTRICAL DIFFERENTIAL COUNTER 审中-公开
标题翻译：使用电动微分计数器计算粒子
公开(公告)号：WO2012064878A3
公开(公告)日：2012-08-16
申请号：PCT/US2011060041
申请日：2011-11-09
申请人： GEN HOSPITAL CORP , MASSACHUSETTS INST TECHNOLOGY , UNIV ILLINOIS , DAKTARI DIAGNOSTICS INC , WATKINS NICHOLAS , BASHIR RASHID , RODRIGUEZ WILLIAM , CHENG XUANHONG , TONER MEHMET , CHEN GRACE , OPPENHEIMER AARON
发明人： WATKINS NICHOLAS , BASHIR RASHID , RODRIGUEZ WILLIAM , CHENG XUANHONG , TONER MEHMET , CHEN GRACE , OPPENHEIMER AARON
IPC分类号： G01N33/53 , C12M1/34 , G01N21/17 , G01N33/52
CPC分类号： G01N27/02 , B01L2200/0652 , B01L2300/0877 , C12M41/36 , G01N15/12 , G01N15/1245 , G01N33/56972 , G01N2015/1006 , G01N2015/1486
摘要： This disclosure relates to methods and devices to count particles of interest, such as cells. The methods include obtaining a fluid sample that may contain particles of interest; counting all types of particles in a portion of the sample using a first electrical differential counter to generate a first total; removing any particles of interest from the portion of the fluid sample; counting any particles remaining in the portion of the fluid sample using a second electrical differential counter after the particles of interest are removed to generate a second total; and calculating a number of particles of interest originally in the fluid sample by subtracting the second total from the first total, wherein the difference is the number of particles of interest in the sample. These methods and related devices can be used, for example, to produce a robust, inexpensive diagnostic kit for CD4+ T cell counting in whole blood samples.
摘要翻译：本公开涉及用于对感兴趣的粒子（诸如细胞）进行计数的方法和设备。该方法包括获得可能含有感兴趣颗粒的流体样品; 使用第一电差分计数器对所述样本的一部分中的所有类型的粒子进行计数以生成第一总和; 从流体样品的该部分去除任何感兴趣的颗粒; 在移除感兴趣的颗粒以产生第二总数之后，使用第二电差分计数器对留在流体样本的该部分中的任何颗粒进行计数; 以及通过从所述第一总数中减去所述第二总数来计算原始在所述流体样本中的感兴趣粒子的数量，其中所述差值是所述样本中的所述感兴趣粒子的数量。例如，可以使用这些方法和相关装置来产生用于全血样品中CD4 + T细胞计数的稳健，便宜的诊断试剂盒。

3. 发明申请

WO2010132795A3 SYSTEMS, DEVICES, AND METHODS FOR SPECIFIC CAPTURE AND RELEASE OF BIOLOGICAL SAMPLE COMPONENTS 审中-公开
标题翻译：用于特定捕获和释放生物样品成分的系统，设备和方法
公开(公告)号：WO2010132795A3
公开(公告)日：2011-03-24
申请号：PCT/US2010034943
申请日：2010-05-14
申请人： GEN HOSPITAL CORP , MASSACHUSETTS INST TECHNOLOGY , SHAH AJAY , KOTZ KENNETH T , TONER MEHMET
发明人： SHAH AJAY , KOTZ KENNETH T , TONER MEHMET
IPC分类号： C12Q1/24 , C12N11/04 , C12Q1/68 , G01N33/53
CPC分类号： G01N33/54393 , C12N11/04 , G01N33/54353
摘要： Living cells can be selectively and reversibly bound to functionalized dissolvable material (e.g., cross-linked hydrogel compositions) and subsequently released from the composition as viable cells. In some examples, the cells are released by reducing the degree of cross-linking within a functionalized hydrogel composition and/or dissolving the functionalized hydrogel composition bound to the cells. The functionalized hydrogel compositions can be adhered to silicon- and silicon-oxide containing surfaces, such as glass and aminated silicon. The living cells can be isolated from biological samples, such as blood, by selectively binding certain cells from the sample to the functionalized hydrogel, removing unbound cells and later releasing viable bound cells from the functionalized hydrogel.
摘要翻译：活性细胞可以选择性地和可逆地结合到官能化的可溶解材料（例如，交联的水凝胶组合物）上，随后从组合物中释放为活细胞。在一些实例中，通过降低功能化水凝胶组合物内的交联度和/或溶解与细胞结合的官能化水凝胶组合物来释放细胞。官能化水凝胶组合物可以粘附到含硅和氧化硅的表面，例如玻璃和胺化硅。可以通过选择性地将样品中的某些细胞与功能化的水凝胶结合，去除未结合的细胞并随后从功能化的水凝胶中释放活的结合细胞，从而将活细胞与生物样品例如血液分离。

4. 发明申请

WO2006133208A3 HYDRODYNAMIC CAPTURE AND RELEASE MECHANISMS FOR PARTICLE MANIPULATION 审中-公开
标题翻译：用于粒子控制的水动力捕获和释放机制
公开(公告)号：WO2006133208A3
公开(公告)日：2007-11-22
申请号：PCT/US2006021953
申请日：2006-06-06
申请人： MASSACHUSETTS INST TECHNOLOGY , GEN HOSPITAL CORP , GERHARDT GWENDOLYN L , TONER MEHMET , GRAY MARTHA , SCHMIDT MARTIN
发明人： TONER MEHMET , GRAY MARTHA , SCHMIDT MARTIN , GERHARDT ANTIMONY L
IPC分类号： C12M1/34 , C12Q1/04 , G01N1/10
CPC分类号： G01N35/08 , B01L3/502707 , B01L3/502761 , B01L2200/0668 , B01L2200/12 , B01L2300/0816 , B01L2300/0819 , B01L2300/0877 , B01L2400/0415 , B01L2400/0442 , B01L2400/0487 , C12M47/04 , G01N15/1456 , G01N2035/00158 , G01N2035/00237 , G01N2035/00574
摘要： A cell analysis and sorting apparatus is capable of monitoring over time the behavior of each cell in a large population of cells. The cell analysis and sorting apparatus contains individually addressable cell locations. Each location is capable of capturing and holding a specified number of cells, and selectively releasing that specified number of cells from that particular location, hi one aspect of the invention, the cells are captured and held in wells, and released using vapor bubbles as a means of cell actuation. Disclosed are: a cell manipulation apparatus design; various resistive heater configurations for nucleating microbubbles; various well designs, each in communication with a nucleation chamber or channel, for capturing a specified number of cells; and methods of fabrication and cell population manipulation.
摘要翻译：细胞分析和分选装置能够随时间监视大量细胞群中每个细胞的行为。细胞分析和分选装置包含单独可寻址的细胞位置。每个位置能够捕获和保持指定数量的细胞，并且从该特定位置选择性地释放该特定数量的细胞。在本发明的一个方面，将细胞捕获并保持在孔中，并使用蒸汽气泡作为细胞致动装置。公开的是：细胞操纵装置设计; 用于成核微泡的各种电阻加热器配置; 各种井设计，各自与成核室或通道连通，用于捕获指定数量的细胞; 以及制造和细胞群体操作的方法。

5. 发明申请

WO2011119962A3 MICROFLUIDIC ENRICHMENT OF SELECTED CELL POPULATIONS 审中-公开
标题翻译：选择细胞群体的微流感增殖
公开(公告)号：WO2011119962A3
公开(公告)日：2012-01-12
申请号：PCT/US2011029999
申请日：2011-03-25
申请人： GEN HOSPITAL CORP , TONER MEHMET , FISHMAN ALAN , TOMPKINS RONALD G , KAPUR RAVI
发明人： TONER MEHMET , FISHMAN ALAN , TOMPKINS RONALD G , KAPUR RAVI
IPC分类号： G01N33/96 , G01N33/53 , G01N35/08
CPC分类号： B01L3/502753 , B01L2200/0652 , B01L2300/0816 , B01L2400/086 , G01N33/5094
摘要： Methods, devices, and systems for microfluidic enrichment of selected cell populations are described. Methods of labeling white blood cells include obtaining whole blood drawn from a patient, separating the white blood cells from the whole blood by flowing the whole blood through a microfluidic device that includes one or more arrays of obstacles configured to deflect the white blood cells in a direction away from a direction of remaining components of the whole blood, and collecting the separated white blood cells. A buffer containing a labeling agent with an affinity for white blood cells is mixed with the white blood cells either before or after separating the white blood cells from the whole blood resulting in labeled white blood cells.
摘要翻译：描述了所选细胞群体微流体富集的方法，装置和系统。标记白细胞的方法包括获得从患者抽取的全血，通过使全血流过包括一个或多个障碍物阵列的微流体装置将白细胞从全血中分离出来，所述微流体装置被配置为使白细胞偏转方向远离全血的剩余组分的方向，并收集分离的白细胞。在从全血分离白细胞之前或之后，将含有对白细胞亲和力的标记试剂的缓冲液与白细胞混合，得到标记的白细胞。

6. 发明申请

WO2011140241A3 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：WO2011140241A3
公开(公告)日：2012-04-05
申请号：PCT/US2011035223
申请日：2011-05-04
申请人： GEN HOSPITAL CORP , YARMUSH MARTIN L , TONER MEHMET , IZAMIS MARIA-LOUISA , BERENDSEN TIMOTHY ANTONIE , BIEGANSKI ROBERT MARIUS , USTA OSMAN BERK , UYGUN BASAK ELIF , UYGUN MUSTAFA KORKUT
发明人： YARMUSH MARTIN L , TONER MEHMET , IZAMIS MARIA-LOUISA , BERENDSEN TIMOTHY ANTONIE , BIEGANSKI ROBERT MARIUS , USTA OSMAN BERK , UYGUN BASAK ELIF , UYGUN MUSTAFA KORKUT
IPC分类号： G01N33/48 , A01N1/02 , A61B18/02 , G01N1/42
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。

7. 发明申请

WO2007035585A3 SYSTEMS AND METHODS FOR ENRICHMENT OF ANALYTES 审中-公开
标题翻译：用于分析分析的系统和方法
公开(公告)号：WO2007035585A3
公开(公告)日：2007-11-29
申请号：PCT/US2006036202
申请日：2006-09-15
申请人： LIVING MICROSYSTEMS INC , GEN HOSPITAL CORP , KAPUR RAVI , TONER MEHMET , HUANG LOTIEN RICHARD , BARBER TOM , CARVALHO BRUCE , GRAY DARREN , BALIS ULYSSES , WALSH JOHN , GRISHAM MICHAEL , TOMPKINS RON , SCHMIDT MARTIN
发明人： KAPUR RAVI , TONER MEHMET , HUANG LOTIEN RICHARD , BARBER TOM , CARVALHO BRUCE , GRAY DARREN , BALIS ULYSSES , WALSH JOHN , GRISHAM MICHAEL , TOMPKINS RON , SCHMIDT MARTIN
IPC分类号： C12Q1/68 , G06F19/18
CPC分类号： G01N33/80 , B01L3/502761 , B01L2200/0668 , B01L2300/0816 , B01L2300/0864 , B01L2400/043 , B01L2400/0487 , B01L2400/086 , B03C2201/18 , B03C2201/26 , B82Y15/00 , B82Y30/00 , G01N1/4077 , G01N33/54366 , G01N33/569 , G01N33/574 , G01N2001/4088 , G01N2333/805 , G01N2800/387 , G06F19/18
摘要： The invention relates to one or more size-based separation modules adapted to increase a concentration of a first analyte in a sample by at least 10,000 fold, wherein said first analyte has an initial concentration in said sample of less than 1 x 10 -3 analytes/µL, and an analyzer for analyzing said first analytes in an enriched medium. Methods of using the separation modules for identifying a characteristic associated with a condition in a patient e.g. a fetal abnormality are also provided.
摘要翻译：本发明涉及一种或多种基于尺寸的分离模块，其适于将样品中第一分析物的浓度增加至少10,000倍，其中所述第一分析物在所述样品中的初始浓度小于1×10 6 -3分析物/μL，以及用于分析富集介质中的所述第一分析物的分析器。使用分离模块来识别与患者的状况相关联的特征的方法，例如，还提供胎儿异常。

8. 发明申请

WO2007035498A3 DEVICES AND METHODS FOR MAGNETIC ENRICHMENT OF CELLS AND OTHER PARTICLES 审中-公开
标题翻译：用于细胞和其他颗粒的磁性增殖的装置和方法
公开(公告)号：WO2007035498A3
公开(公告)日：2007-11-29
申请号：PCT/US2006036061
申请日：2006-09-15
申请人： LIVING MICROSYSTEMS , GEN HOSPITAL CORP , KAPUR RAVI , HUANG LOTIEN RICHARD , BARBER TOM , CARVALHO BRUCE L , TONER MEHMET , SCHMIDT MARTIN
发明人： KAPUR RAVI , HUANG LOTIEN RICHARD , BARBER TOM , CARVALHO BRUCE L , TONER MEHMET , SCHMIDT MARTIN
IPC分类号： C12M1/34 , G01N33/53
CPC分类号： B01L3/502753 , B01L3/502746 , B01L3/502776 , B01L2200/0647 , B01L2300/0816 , B01L2300/0864 , B01L2400/0406 , B01L2400/0409 , B01L2400/0415 , B01L2400/043 , B01L2400/0487 , B01L2400/086 , B03C1/30 , B03C1/32 , B03C2201/18 , C12M35/06 , G01N33/5044
摘要： The invention features devices and methods for the enrichment of cells and other desired analytes by employing a magnetic field, alone or in conjunction with size-based separation. The devices and methods may be advantageously employed to enrich for rare cells, e.g., fetal cells or epithelial cells, present in a sample, e.g., maternal blood.
摘要翻译：本发明的特征在于通过单独使用磁场或结合基于尺寸的分离来富集细胞和其它所需分析物的装置和方法。可以有利地使用装置和方法来富集样品中存在的罕见细胞，例如胎儿细胞或上皮细胞，例如母体血液。

9. 发明申请

WO2004029221A3 MICROFLUIDIC DEVICE FOR CELL SEPARATION AND USES THEREOF 审中-公开
标题翻译：用于细胞分离的MICROFLUIDIC装置及其用途
公开(公告)号：WO2004029221A3
公开(公告)日：2004-05-13
申请号：PCT/US0330965
申请日：2003-09-29
申请人： GEN HOSPITAL CORP , GPB SCIENTIFIC LLC , TONER MEHMET , TRUSKEY GEORGE , KAPUR RAVI
发明人： TONER MEHMET , TRUSKEY GEORGE , KAPUR RAVI
IPC分类号： B01L3/00 , B01L11/00 , C12N5/00 , C12N5/02 , C12N5/06 , G01N33/543 , G01N33/569 , A01N1/02 , C12M1/00 , C12M1/34 , C12M3/00 , C12N5/10
CPC分类号： B01L3/502753 , B01L3/502746 , B01L3/502761 , B01L9/54 , B01L2200/0647 , B01L2200/0652 , B01L2200/0668 , B01L2200/12 , B01L2300/0681 , B01L2300/0816 , B01L2300/0864 , B01L2300/0867 , B01L2300/0877 , B01L2300/0883 , B01L2300/12 , B01L2400/0487 , B01L2400/086 , B33Y70/00 , B33Y80/00 , B82Y30/00 , C12N5/0087 , G01N1/40 , G01N1/405 , G01N33/5091 , G01N33/54366 , G01N33/54386 , G01N33/56966 , G01N33/574 , G01N2015/1006 , G01N2015/1081 , G01N2333/70582 , G01N2333/70589 , G01N2333/70596 , Y10T29/49982 , Y10T428/24744
摘要： The invention features methods for separating cells from a sample (e.g., separating fetal red blood cells from maternal blood). The method begins with the introduction of a sample including cells into one or more microfluidic channels. In one embodiment, the device includes at least two processing steps. For example, a mixture of cells is introduced into a microfluidic channel that selectively allows the passage of a desired type of cell, and the population of cells enriched in the desired type is then introduced into a second microfluidic channel that allows the passage of the desired cell to produce a population of cells further enriched in the desired type. The selection of cells is based on a property of the cells in the mixture, for example, size, shape, deformability, surface characteristics (e.g., cell surface receptors or antigens and membrane permeability), or intracellular properties (e.g., expression of a particular enzyme).
摘要翻译：本发明的特征在于从样品中分离细胞的方法（例如，从母体血液中分离胎儿红细胞）。该方法开始于将包括细胞的样品引入一个或多个微流体通道。在一个实施例中，该设备包括至少两个处理步骤。例如，将细胞混合物引入选择性地允许所需类型的细胞通过的微流体通道中，然后将富集了所需类型的细胞群体引入第二微流体通道中，所述第二微流体通道允许期望的细胞产生进一步富集所需类型的细胞群体。细胞的选择基于混合物中细胞的性质，例如大小，形状，可变形性，表面特征（例如细胞表面受体或抗原和膜渗透性）或细胞内特性（例如特定表达酶）。

10. 发明申请

WO2004011616A2 SYSTEMS AND METHODS FOR CELL PRESERVATION 审中-公开
标题翻译：用于小区保存的系统和方法
公开(公告)号：WO2004011616A2
公开(公告)日：2004-02-05
申请号：PCT/US0323553
申请日：2003-07-28
申请人： GEN HOSPITAL CORP , TONER MEHMET , ACKER JASON , CHEN TANI , BHOWMICK SANKHA , BAUST JOHN , FOWLER ALEX
发明人： TONER MEHMET , ACKER JASON , CHEN TANI , BHOWMICK SANKHA , BAUST JOHN , FOWLER ALEX
IPC分类号： A01N1/02 , C12N
CPC分类号： A01N1/02 , A01N1/0221
摘要： The present invention generally relates to devices and methods for the preservation of cells using drying, freezing, and other related techniques. In one set of embodiments, the invention allows for the preservation of cells in a dried state. In another set of embodiments, the invention allows for the preservation of cells within a glass or other non-viscous, non-frozen media. In some embodiments, the invention allows for the preservation of cells at temperatures below the freezing point of water, and in some cases at cryogenic temperatures, without inducing ice formation. The cells, in certain embodiments, may be preserved in the presence of intracellular and/or extracellular carbohydrates (which may be the same or different), for example, trehalose and sucrose. Carbohydrates may be transported intracellularly by any suitable technique, for example, using microinjection, or through non-microinjected methods such as through pore-forming proteins, electroporation, heat shock, etc. In certain instances, the glass transition temperature of the cells may be raised, e.g., by transporting a carbohydrate intracellularly. In some cases, the cells may be dried and/or stored, for example, in a substantially moisture-saturated environment or a desiccating environment. The cells may also be stored in a vacuum or a partial vacuum. The cells may be protected from oxygen, moisture, and/or light during storage. In certain cases, an inhibitor, such as a cell death inhibitor, a protease inhibitor, an apoptosis inhibitor, and/or an oxidative stress inhibitor may be used during preservation of the cells. The cells may be stored for any length of time, then recovered to a viable state, e.g., through rehydration, for further use.
摘要翻译：本发明一般涉及使用干燥，冷冻和其他相关技术保存细胞的装置和方法。在一组实施方案中，本发明允许保存处于干燥状态的细胞。在另一组实施方式中，本发明允许保存玻璃或其他非粘性非冷冻介质内的细胞。在一些实施方案中，本发明允许在低于水的冰点的温度下保存细胞，并且在一些情况下允许在低温下保存细胞而不诱导结冰。在某些实施方案中，细胞可以在细胞内和/或细胞外碳水化合物（可以相同或不同）存在下保存，例如海藻糖和蔗糖。碳水化合物可通过任何合适的技术在细胞内转运，例如使用显微注射，或通过非显微注射的方法，如通过成孔蛋白，电穿孔，热休克等。在某些情况下，细胞的玻璃化转变温度可以是例如通过在细胞内转运碳水化合物来提高。在一些情况下，可以将细胞干燥和/或储存在例如基本上潮湿饱和的环境或干燥环境中。细胞也可以储存在真空或部分真空中。在储存过程中，细胞可能受到氧气，湿气和/或光线的保护。在某些情况下，可以在细胞保存期间使用抑制剂，例如细胞死亡抑制剂，蛋白酶抑制剂，细胞凋亡抑制剂和/或氧化应激抑制剂。细胞可以储存任何时间长度，然后恢复到活的状态，例如通过再水合作用，以供进一步使用。

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