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1. 发明申请

WO2005123950A2 PERFUSED THREE-DIMENSIONAL CELL/TISSUE DISEASE MODELS 审中-公开
标题翻译：丰富的三维细胞/组织疾病模型
公开(公告)号：WO2005123950A2
公开(公告)日：2005-12-29
申请号：PCT/US2005/017594
申请日：2005-05-19
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , UNIVERSITY OF PITTSBURGH , DOMANSKY, Karel , GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , WELLS, Alan
发明人： DOMANSKY, Karel , GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , WELLS, Alan
IPC分类号： C12Q1/68
CPC分类号： B01L3/502715 , B01J2219/00315 , B01J2219/00743 , B01L3/50255 , B01L3/50273 , B01L3/502738 , B01L2300/0681 , B01L2300/0829 , B01L2300/0861 , B01L2400/0481 , B01L2400/0638 , B33Y80/00 , C12M23/12 , C12M23/40 , C12M25/14 , C12M29/10
摘要： A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a "multiwell plate" format amenable to highthroughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.
摘要翻译：已经构建了通过正常人体组织重现毛细血管床特征的系统。该系统有助于在毛细血管床的长度尺度上灌注三维（3D）细胞单一培养物和异型细胞共培养物。一个主要特征是该系统可以在“多孔板”格式中使用，适合与通常用于药物开发的机器人类型相容的高通量测定。该系统提供了进行毒理学和代谢测定的手段，并且作为人类疾病（如肝脏疾病，包括肝炎，暴露相关病理和癌症）的模型。癌症应用包括原发性肝癌以及转移瘤。该系统还可用作测试基因治疗方法的手段，用于治疗疾病和先天性遗传缺陷。

2. 发明公开

EP1773978A2 PERFUSED THREE-DIMENSIONAL CELL/TISSUE DISEASE MODELS 有权转让
标题翻译：丰富的梦幻精灵ZELLEN- / GEWEBEERKRANKUNGSMODELLE
公开(公告)号：EP1773978A2
公开(公告)日：2007-04-18
申请号：EP05779763.1
申请日：2005-05-19
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , University of Pittsburgh of the Commonwealth System of Higher Education
发明人： DOMANSKY, Karel , GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , WELLS, Alan
IPC分类号： C12M1/34 , C12M1/12 , C12M1/22
CPC分类号： B01L3/502715 , B01J2219/00315 , B01J2219/00743 , B01L3/50255 , B01L3/50273 , B01L3/502738 , B01L2300/0681 , B01L2300/0829 , B01L2300/0861 , B01L2400/0481 , B01L2400/0638 , B33Y80/00 , C12M23/12 , C12M23/40 , C12M25/14 , C12M29/10
摘要： A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a 'multiwell plate' format amenable to highthroughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.
摘要翻译：已经构建了通过正常人体组织重现毛细血管床特征的系统。该系统便于在毛细血管床的长度尺度上灌注三维（3D）细胞单一培养物和异型细胞共培养物。主要特征是该系统可以在适合于药物开发中通常使用的机器人类型的高通量测定的多孔板格式中使用。该系统提供了进行毒理学和代谢测定的手段，并且作为人类疾病（如肝脏疾病，包括肝炎，暴露相关病理和癌症）的模型。癌症应用包括原发性肝癌以及转移瘤。该系统也可用作检测基因治疗方法以治疗疾病和先天性遗传缺陷的手段。

4. 发明申请

WO2012135834A3 DIALYSIS LIKE THERAPEUTIC (DLT) DEVICE 审中-公开
公开(公告)号：WO2012135834A3
公开(公告)日：2012-10-04
申请号：PCT/US2012/031864
申请日：2012-04-02
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , CHILDREN'S MEDICAL CENTER CORPORATION , YUNG, Chong, Wing , DOMANSKY, Karel , TERRY, Richard , KALISH, David , SCHULTE, Alexa , KANG, Joo, Hun , INGBER, Donald, E. , SUPER, Mike , COOPER, Ryan, M.
发明人： YUNG, Chong, Wing , DOMANSKY, Karel , TERRY, Richard , KALISH, David , SCHULTE, Alexa , KANG, Joo, Hun , INGBER, Donald, E. , SUPER, Mike , COOPER, Ryan, M.
IPC分类号： G01N33/569 , G01N35/10 , G01N35/08 , B81B1/00
摘要： A dialysis like therapeutic (DLT) device is provided. The DLT device includes at least one source channel connected at least one collection channels by one or more transfer channels. Fluid contacting surface of the channels can be an anti-fouling surface such as slippery liquid-infused porous surface (SLIPS). Fluids can be flown at high flow rates through the channels. The target components of the source fluid can be magnetic or bound to magnetic particles using an affinity molecule. A source fluid containing magnetically bound target components can be pumped through the source channel of the microfluidic device. A magnetic field gradient can be applied to the source fluid in the source channel causing the magnetically bound target components to migrate through the transfer channel into the collection channel. The collection channel can include a collection fluid to flush the target components out of the collection channel. The target components can be subsequently analyzed for detection and diagnosis. The source channel and the collection channels of the microfluidic device are analogous to the splenic arterioles and venules, respectively; the transfer channels mimic the vascular sinusoids of the spleen where opsonized particles are retained. Thus, the device acts as a dialysis like therapeutic device by combining fluidics and magnetics.

5. 发明申请

WO2011091037A2 RAPID PATHOGEN DIAGNOSTIC DEVICE AND METHOD 审中-公开
标题翻译：快速病原体诊断装置和方法
公开(公告)号：WO2011091037A2
公开(公告)日：2011-07-28
申请号：PCT/US2011/021718
申请日：2011-01-19
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , YUNG, Chong Wing , INGBER, Donald E. , COOPER, Ryan Mcomber , VOLLMER, Frank , DOMANSKY, Karel , LESLIE, Daniel Christopher , SUPER, Michael
发明人： YUNG, Chong Wing , INGBER, Donald E. , COOPER, Ryan Mcomber , VOLLMER, Frank , DOMANSKY, Karel , LESLIE, Daniel Christopher , SUPER, Michael
IPC分类号： G01N35/08 , G01N33/48 , G01N33/52 , G01N33/58 , G01N1/38
CPC分类号： C12Q1/04 , B01L3/502761 , B01L2200/0668 , B01L2300/0816 , B01L2400/043 , G01N33/54306 , G01N33/54333 , G01N33/54366 , G01N35/0098
摘要： A microfluidic device of a diagnostic and detection system includes an inlet port connected by one or more microchannels to an outlet port and includes a capture and visualization chamber (CVC) connected to at least one microchannel. A fluid to be analyzed can be mixed with magnetic microbeads that have an affinity to become bound to target components, such as pathogens in the fluid. The fluid including the magnetically bound target components can be injected through the microfluidic device. Magnetic field gradient, such as provided by permanent or elecrto-magnets, can be applied to the fluid and the magnetically bound target components flowing through the microfluidic device to cause the magnetically bound target components to migrate into the (CVC) and become separated from the fluid. The magnetically bound target components can be analyzed and tested using various techniques to detect the presence of specific organic and inorganic materials, such as pathogens in bio-fluids and contamination in liquid food sources (e.g. water). The device and method provide a system for rapidly detecting pathogens and contamination in relatively small fluid samples.
摘要翻译：诊断和检测系统的微流体装置包括通过一个或多个微通道连接到出口端口的入口端口，并且包括连接到至少一个微通道的捕获和可视化腔室（CVC）。待分析的流体可以与具有亲和力的磁性微珠混合，以与目标组分（例如流体中的病原体）结合。包括磁性结合的目标组分的流体可以通过微流体装置注入。诸如由永久磁体或电磁体提供的磁场梯度可以施加到流体和流过微流体装置的磁性结合的目标组分，以使磁性结合的目标组分迁移到（CVC）中并与流体。可以使用各种技术来分析和测试磁性结合的目标组分，以检测特定有机和无机材料（例如生物流体中的病原体和液体食物源（例如水）中的污染）的存在。该装置和方法提供了用于快速检测相对较小的流体样品中的病原体和污染物的系统。

6. 发明申请

WO2012154834A1 AEROSOL DELIVERY TO A MICROFLUIDIC DEVICE 审中-公开
标题翻译： AEROSOL交付给微流控装置
公开(公告)号：WO2012154834A1
公开(公告)日：2012-11-15
申请号：PCT/US2012/037096
申请日：2012-05-09
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , LESLIE, Daniel Christopher , DOMANSKY, Karel , HAMILTON, Geraldine A. , BAHINSKI, Anthony , INGBER, Donald E.
发明人： LESLIE, Daniel Christopher , DOMANSKY, Karel , HAMILTON, Geraldine A. , BAHINSKI, Anthony , INGBER, Donald E.
IPC分类号： A61M15/00 , A61M11/00
CPC分类号： B05B15/00 , B01L3/502715 , B01L2300/0816 , B01L2300/0864 , C12M23/16 , C12M29/00 , C12M29/14 , G01N35/1002 , G01N2035/1046 , Y10T137/8593
摘要： The present invention is directed to systems and methods for delivering aerosolized micro-droplets into microfluidic devices. In some embodiments, the microfluidic devices are designed for the culture of living cells at an air interface. In some embodiments, the systems and methods described herein can be used to deliver aerosolized micro-droplet into detection systems and small animals, tissues, organs and organisms.
摘要翻译：本发明涉及用于将雾化的微滴输送到微流体装置中的系统和方法。在一些实施例中，微流体装置被设计用于在空气界面处培养活细胞。在一些实施方案中，本文所述的系统和方法可用于将雾化的微滴输送到检测系统和小动物，组织，器官和生物中。

7. 发明申请

WO2012154729A1 A MICROFLUIDIC MODULE AND USES THEREOF 审中-公开
标题翻译：微流控模块及其应用
公开(公告)号：WO2012154729A1
公开(公告)日：2012-11-15
申请号：PCT/US2012/036920
申请日：2012-05-08
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , DOMANSKY, Karel , LESLIE, Daniel C. , HAMILTON, Geraldine A. , BAHINSKI, Anthony , INGBER, Donald E.
发明人： DOMANSKY, Karel , LESLIE, Daniel C. , HAMILTON, Geraldine A. , BAHINSKI, Anthony , INGBER, Donald E.
IPC分类号： G01N33/48
CPC分类号： C12N5/0602 , B01J19/0093 , B01J2219/00783 , B01J2219/00833 , B01J2219/0084 , B01J2219/0086 , B01J2219/00907 , B01L3/502707 , B01L2300/161 , B32B37/18 , G01N33/54393
摘要： Described herein are microfluidic modules and methods for making the same, wherein the microfluidic modules include a substrate comprising at least one ether-based, aliphatic polyurethane, and at least one fluidic element disposed therein. The ether-based aliphatic polyurethane can be either the substrate of the microfluidic modules or a coating of another substrate material, such that at least a portion of the ether-based, aliphatic polyurethane is in fluid communication. In one embodiment, the ether-based, aliphatic polyurethane includes dicyclohexylmethane-4, 4'-diisocyanate. As the ether-based aliphatic polyurethane can decrease absorption of molecules, e.g., hydrophobic molecules, in such microfluidic modules, the microfluidic modules described herein can be used in various applications such as drug screening and fluorescent microscopy.
摘要翻译：本文描述的是微流体模块和用于制造其的方法，其中微流体模块包括包含至少一种醚基脂族聚氨酯和设置在其中的至少一个流体元件的基材。醚基脂肪族聚氨酯可以是微流体模块的基材或另一种基材的涂层，使得至少一部分醚基的脂族聚氨酯与流体连通。在一个实施方案中，醚基脂族聚氨酯包括二环己基甲烷-4,4'-二异氰酸酯。由于醚类脂族聚氨酯可以在这种微流体模块中减少分子（例如疏水性分子）的吸收，因此本文所述的微流体模块可用于各种应用，例如药物筛选和荧光显微镜。

8. 发明授权

EP1064353B1 VASCULARIZED PERFUSED MICROTISSUE/MICRO-ORGAN ARRAYS 无效
标题翻译：密克罗尼西亚的VASKULARISIERTE PERFUNDIERTE ANORDNUNGENFÜRMIKROGEWEBE
公开(公告)号：EP1064353B1
公开(公告)日：2002-11-06
申请号：EP99913967.8
申请日：1999-03-18
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , POWERS, Mark, J. , DOMANSKY, Karel , THOMPSON, Charles, D.
IPC分类号： C12M3/04 , C12M1/34
CPC分类号： G01N33/5038 , B01J19/0046 , B01J2219/00286 , B01J2219/00308 , B01J2219/00313 , B01J2219/00317 , B01J2219/00319 , B01J2219/00351 , B01J2219/00376 , B01J2219/00416 , B01J2219/00585 , B01J2219/00659 , B01J2219/0072 , B33Y10/00 , B33Y80/00 , B82Y30/00 , C12M21/08 , C12M23/12 , C12M41/46 , C40B60/14 , G01N33/5008 , G01N33/502 , G01N33/5058 , G01N33/5064 , G01N33/5073
摘要： Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form 'blood vessels', and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.
摘要翻译：系统包括（1）微阵列和灌注组件，其适用于将基质内的细胞接种和附着，并将种子细胞的形态发生转化为复杂的分层组织或器官结构，其中所述基质包括通道或血管，培养基，氧气或可以灌注其他营养液或体液，同时控制整个灌注路径中的营养物质和外源性代谢物的梯度，与灌注速率无关，和（2）用于检测基质内或细胞暴露的材料中任一细胞的变化的传感器装置，发达。制造微阵列的方法包括微加工，微胶印，压花，激光钻孔和电沉积加工。细胞可以是一种或多种，分化或未分化。在一个优选的实施方案中，用包含内皮细胞的细胞混合物接种基质，所述内皮细胞将通道形成“血管”，以及至少一种类型的实质细胞，例如肝细胞，胰腺细胞或其它器官细胞。该系统可用于筛选对细胞的影响的材料，用于细胞对材料的影响（例如，以等同于药物的组织代谢的方式），或用于测试必需的生物学上的材料首先感染细胞或组织，如病毒。该装置还可用于提供用于扩大干细胞的生理环境，或用于在体外实现基因治疗。

9. 发明公开

EP1064353A2 VASCULARIZED PERFUSED MICROTISSUE/MICRO-ORGAN ARRAYS 无效
标题翻译：血管灌注安排微结构和微器官
公开(公告)号：EP1064353A2
公开(公告)日：2001-01-03
申请号：EP99913967.8
申请日：1999-03-18
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： GRIFFITH, Linda, G. , TANNENBAUM, Steven, R. , POWERS, Mark, J. , DOMANSKY, Karel , THOMPSON, Charles, D.
IPC分类号： C12M3/04 , C12M1/34
CPC分类号： G01N33/5038 , B01J19/0046 , B01J2219/00286 , B01J2219/00308 , B01J2219/00313 , B01J2219/00317 , B01J2219/00319 , B01J2219/00351 , B01J2219/00376 , B01J2219/00416 , B01J2219/00585 , B01J2219/00659 , B01J2219/0072 , B33Y10/00 , B33Y80/00 , B82Y30/00 , C12M21/08 , C12M23/12 , C12M41/46 , C40B60/14 , G01N33/5008 , G01N33/502 , G01N33/5058 , G01N33/5064 , G01N33/5073
摘要： Systems including (1) a micromatrix and perfusion assembly suitable for seeding and attachment of cells within the matrix and for morphogenesis of seeded cells into complex, hierarchical tissue or organ structures, wherein the matrix includes channels or vessels through which culture medium, oxygen, or other nutrient or body fluids can be perfused while controlling gradients of nutrients and exogenous metabolites throughout the perfusion path independently of perfusion rate, and (2) sensor means for detecting changes in either cells within the matrix or in materials exposed to the cells, have been developed. Methods for making the micromatrices include micromachining, micromolding, embossing, laser drilling, and electro deposition machining. Cells can be of one or more types, either differentiated or undifferentiated. In a preferred embodiment, the matrix is seeded with a mixture of cells including endothelial cells which will line the channels to form 'blood vessels', and at least one type of parenchymal cells, such as hepatocytes, pancreatic cells, or other organ cells. The system can be used to screen materials for an effect on the cells, for an effect of the cells on the materials (for example, in a manner equivalent to tissue metabolism of a drug), or to test a material on a biological that must first infect cells or tissues, such as viruses. The apparatus also can be used to provide a physiological environment for expansion of stem cells, or for enabling gene therapy in vitro.

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