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1. 发明申请

WO2011163312A3 IMPROVING EFFICACY OF CANCER THERAPY 审中-公开
标题翻译：改善癌症治疗效果
公开(公告)号：WO2011163312A3
公开(公告)日：2012-04-19
申请号：PCT/US2011041368
申请日：2011-06-22
申请人： CHILDRENS MEDICAL CENTER , NORTHEAST OHIO MEDICAL UNIVERSITY , THODETI CHARLES K , INGBER DONALD E
发明人： THODETI CHARLES K , INGBER DONALD E
IPC分类号： A61K38/17 , A61K38/16 , A61P35/00 , C12N15/12 , C12N15/63 , C12N15/83
CPC分类号： A61K38/1709 , A61K31/00 , A61K31/22 , A61K31/221 , A61K31/336 , A61K31/365 , A61K38/177 , A61K45/06 , A61N5/10
摘要： Embodiments of the invention provide a method of improving the efficacy of an anti-cancer therapy and a method of treatment of cancer by normalizing angiogenesis in cancer. By enhancing the cell signaling pathway via a TRPV4 receptor in tumor endothelial cells, either by a TRPV4 agonist or by increasing the expression of TRPV4 in the tumor endothelial cells, the tumor endothelial cells behave normally and form normal angiogenic network for better anti-cancer therapy to the tumors.
摘要翻译：本发明的实施方案提供了通过使癌症中的血管生成正常化来提高抗癌治疗的功效的方法和治疗癌症的方法。通过TRPV4激动剂或通过增加TRPV4在肿瘤内皮细胞中的表达，通过肿瘤内皮细胞中的TRPV4受体增强细胞信号传导途径，肿瘤内皮细胞表现正常并形成正常的血管生成网络以获得更好的抗癌治疗到肿瘤。

2. 发明申请

WO0189788A2 PATTERNING OF SURFACES UTILIZING MICROFLUIDIC STAMPS INCLUDING THREE-DIMENSIONALLY ARRAYED CHANNEL NETWORKS 审中-公开
标题翻译：使用包括三维阵列通道网络在内的微流感标记的表面图案
公开(公告)号：WO0189788A2
公开(公告)日：2001-11-29
申请号：PCT/US0117246
申请日：2001-05-25
申请人： HARVARD COLLEGE , CHILDRENS MEDICAL CENTER , CHIU DANIEL T , JEON NOO LI , HUANG SUI , KANE RAVI , CHOI INSUNG S , INGBER DONALD E , WHITESIDES GEORGE M , ANDERSON JANELLE R
发明人： CHIU DANIEL T , JEON NOO-LI , HUANG SUI , KANE RAVI , CHOI INSUNG S , INGBER DONALD E , WHITESIDES GEORGE M , ANDERSON JANELLE R
IPC分类号： B01F13/00 , B01L3/00 , B01L3/02 , B29C31/04 , B29C33/42 , B29C39/10 , B81B1/00 , B81C1/00 , C40B40/10 , C40B60/14 , G01N33/50 , B29C
CPC分类号： C12N11/00 , B01F13/0059 , B01J2219/00382 , B01J2219/00527 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/0063 , B01J2219/00637 , B01J2219/00659 , B01J2219/0072 , B01J2219/00725 , B01J2219/00743 , B01L3/0258 , B01L3/0262 , B01L3/502707 , B01L2200/12 , B01L2300/0816 , B01L2300/0861 , B01L2300/0874 , B01L2300/0887 , B29C31/04 , B29C33/424 , B29C39/10 , B33Y80/00 , B81B1/00 , B81C99/009 , B82Y5/00 , B82Y30/00 , C40B40/10 , C40B60/14 , G01N33/5005 , Y10S530/81 , Y10S530/811 , Y10S530/812 , Y10S530/815
摘要： The present invention describes improved microfluidic systems and procedures for fabricating improved microfluidic systems, which contain one or more levels of microfluidic channels. The methods for fabrication the systems disclosed can provide a convenient route to topologically complex and improved microfluidic systems. The microfluidic systems can include three-dimensionally arrayed networks of fluid flow paths therein including channels that cross over or under other channels of the network without physical intersection at the points of cross over. The microfluidic networks can be fabricated via replica molding processes utilizing mold masters including surfaces having topological features formed by photolithography. The present invention also involves microfluidic systems and methods for fabricating complex patterns of materials, such as biological materials and cells, on surfaces utilizing the microfluidic systems. Specifically, the invention provides microfluidic surface patterning systems and methods for fabricating complex, discontinuous patterns on surfaces that can incorporate or deposit multiple materials onto the surfaces. The present invention also provides improved microfluidic stamps or applicators for microcontact surface patterning, which are able to pattern onto a surface arbitrary two-dimensional patterns, and which are able to pattern multiple substances onto a surface without the need for multiple steps of registration or stamping during patterning and without the need to selectively "ink" different regions of the stamp with different materials.
摘要翻译：本发明描述了改进的微流体系统和用于制造改进的微流体系统的程序，其包含一个或多个水平的微流体通道。用于制造所公开的系统的方法可以为拓扑复杂和改进的微流体系统提供方便的途径。微流体系统可以包括其中的流体流动路径的三维排列的网络，其中包括在交叉点处交叉的网络上或下方的通道，而没有物理交叉点。微流体网络可以通过使用模具主体的复制模制工艺制造，其中包括具有通过光刻形成的拓扑特征的表面。本发明还涉及在利用微流体系统的表面上制造诸如生物材料和细胞的复杂图案的微流体系统和方法。具体地，本发明提供了微流体表面图案化系统和用于在表面上制造复杂的不连续图案的方法，所述图案可以将多种材料结合或沉积到表面上。本发明还提供了用于微接触表面图案化的改进的微流体标记或涂布器，其能够将图案图案化成任意的二维图案，并且能够将多种物质图案化到表面上，而不需要多个对准或冲压的步骤在图案化期间，并且不需要使用不同材料选择性地“印刷”印模的不同区域。

3. 发明申请

WO2012135834A2 DIALYSIS LIKE THERAPEUTIC (DLT) DEVICE 审中-公开
标题翻译： DIALYSIS LIKE THERAPEUTIC（DLT）DEVICE
公开(公告)号：WO2012135834A2
公开(公告)日：2012-10-04
申请号：PCT/US2012031864
申请日：2012-04-02
申请人： HARVARD COLLEGE , CHILDRENS MEDICAL CENTER , 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 , B81B1/00 , G01N35/08 , G01N35/10
CPC分类号： C12Q1/04 , A61M1/36 , A61M1/3618 , B01L3/502715 , B01L3/50273 , B01L3/502761 , B01L3/56 , B01L2200/0652 , B01L2300/0864 , B01L2300/0867 , B01L2300/0887 , B01L2400/043 , B01L2400/0487 , B03C1/002 , B03C1/01 , B03C1/0332 , B03C1/0335 , B03C1/288 , B03C2201/26
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.
摘要翻译：提供透析治疗（DLT）装置。 DLT设备包括通过一个或多个传输信道连接至少一个收集信道的至少一个源信道。通道的流体接触表面可以是防污表面，例如滑动的液体注入的多孔表面（SLIPS）。流体可以通过通道以高流速流动。源流体的目标组分可以是磁性的或使用亲和分子结合到磁性颗粒。含有磁结合的靶组分的源流体可以泵送通过微流体装置的源通道。磁场梯度可以施加到源通道中的源流体，使得磁结合的目标分量通过传输通道迁移到收集通道中。收集通道可以包括收集流体以将目标组分冲洗出收集通道。随后分析目标成分进行检测和诊断。微流体装置的源通道和收集通道分别类似于脾小动脉和小静脉; 转移通道模拟脾脏的血管窦状，其中保留调理颗粒。因此，该装置通过组合流体学和磁性作为透析像治疗装置。

4. 发明申请

WO2010123545A2 ANGIOGENESIS INHIBITORS 审中-公开
标题翻译：血管生成抑制剂
公开(公告)号：WO2010123545A2
公开(公告)日：2010-10-28
申请号：PCT/US2010001121
申请日：2010-04-16
申请人： HARVARD COLLEGE , CHILDRENS MEDICAL CENTER , COREY ELIAS JAMES , CZAKO BARBARA , KUERTI LASZLO , MAMMOTO AKIKO , INGBER DONALD E
发明人： COREY ELIAS JAMES , CZAKO BARBARA , KUERTI LASZLO , MAMMOTO AKIKO , INGBER DONALD E
IPC分类号： C07J41/00 , A61K31/56 , A61P35/00 , C07J43/00
CPC分类号： C07J43/003 , C07J41/0005
摘要： Compounds of Structural Formula I or pharmaceutically acceptable salts thereof, are effective inhibitors of angiogenesis:
摘要翻译：结构式I的化合物或其药学上可接受的盐是血管生成的有效抑制剂：

5. 发明申请

WO2008156904A3 SYSTEMS AND METHODS FOR NANOMAGNETIC ACTUATION OF MOLECULAR CELL SIGNALING 审中-公开
标题翻译：用于分子细胞信号的纳米分解的系统和方法
公开(公告)号：WO2008156904A3
公开(公告)日：2009-03-19
申请号：PCT/US2008059738
申请日：2008-04-09
申请人： CHILDRENS MEDICAL CENTER , INGBER DONALD E , MANNIX ROBERT J , KUMAR SANJAY
发明人： INGBER DONALD E , MANNIX ROBERT J , KUMAR SANJAY
IPC分类号： A61K47/48 , A61N2/02
CPC分类号： A61K41/0052 , A61K47/48507 , A61K47/6835 , A61N2/00 , Y10S977/904
摘要： The present invention relates to signaling mechanisms that transduce magnetic inputs into physiological cellular outputs. More particularly, the present invention relates to systems and methods for non-invasively controlling cellular signaling functions and behaviors by harnessing receptor-mediated and intracellular molecular-mediated signal transduction using nanomagnetic cellular switches.
摘要翻译：本发明涉及将磁输入转换成生理细胞输出的信号传导机制。更具体地，本发明涉及通过利用纳米磁性细胞开关利用受体介导的和细胞内分子介导的信号转导来非侵入性地控制细胞信号传导功能和行为的系统和方法。

6. 发明申请

WO2008127295A2 GUIDED SELF-ASSEMBLY OF MATRICES WITH ORDERD NANO-SCALE STRUCTURE FOR TISSUE ENGINEERING 审中-公开
标题翻译：指导用于组织工程的订单纳米尺度结构的矩阵自组装
公开(公告)号：WO2008127295A2
公开(公告)日：2008-10-23
申请号：PCT/US2007022397
申请日：2007-10-22
申请人： CHILDRENS MEDICAL CENTER , INGBER DONALD E
发明人： INGBER DONALD E
IPC分类号： H04Q7/22
CPC分类号： C12N5/0075 , C12N2533/56 , C12N2535/10
摘要： Described herein are methods for producing structures useful, for example, for tissue engineering. In their most general form, the methods described herein involve an enzyme activity immobilized on a surface, which is placed in contact with a solution comprising polypeptide monomers. The activity of the enzyme modifies the polypeptide monomers to promote polymerization of the monomers to form polymer structures associated with the surface. Thus, the methods described herein provide a guided self-assembly of polypeptide structures. In preferred embodiments, the self assembly is guided to form regular lattices or other specific structures by specifying the arrangement of the surfaces to which the enzyme, optionally with one or more co-factors, is attached.
摘要翻译：这里描述的是用于产生可用于例如组织工程的结构的方法。在其最一般的形式中，本文描述的方法涉及固定在表面上的酶活性，其被置于与包含多肽单体的溶液接触。酶的活性改变多肽单体以促进单体的聚合以形成与表面相关的聚合物结构。因此，本文所述的方法提供多肽结构的引导自组装。在优选的实施方案中，通过指定酶，任选地与一个或多个辅因子连接的表面的布置，引导自组装形成规则晶格或其它特定结构。

7. 发明申请

WO2006039675A3 APPARATUS AND METHOD FOR NANOMANIPULATION OF BIOMOLECULES AND LIVING CELLS 审中-公开
标题翻译：生物分子和生物细胞纳米生物的装置和方法
公开(公告)号：WO2006039675A3
公开(公告)日：2006-06-29
申请号：PCT/US2005035551
申请日：2005-10-03
申请人： CHILDRENS MEDICAL CENTER , INGBER DONALD E , MATTHEWS BENJAMIN D , LAVAN DAVID A , OVERBY DARRYL
发明人： INGBER DONALD E , MATTHEWS BENJAMIN D , LAVAN DAVID A , OVERBY DARRYL
IPC分类号： A61N2/00
CPC分类号： A61B18/08 , A61M2037/0046 , A61N2/002
摘要： The present invention relates to an electromagnetic needle for magnetically manipulating microscopic particles and a method of making the same, and more particularly, to a method for nanomanipulating biomolecules and/or living cells using the electromagnetic needle of the present invention. The temperature-controlled electromagnetic microneedle includes an electromagnetic core having a magnetic probe tip. A wire coil is wound around at least a portion of the core and electrically isolated from the core. A thermo-regulating water jacket having a first and second end and enveloping the electromagnetic core and wire coil allows the probe tip to extend from the first end. Magnetically responsive particles upon which a biologically active substance is absorbed are administered to a subject. A catheter having a magnet attached thereto is inserted into the body of the subject. The magnet guides the particles to a site to be treated with the biologically active substance.
摘要翻译：本发明涉及一种用于磁微操作微粒的电磁针及其制造方法，更具体地说，涉及使用本发明的电磁针对生物分子和/或活细胞进行纳米操作的方法。温度控制电磁微针包括具有磁性探头尖端的电磁铁心。线圈缠绕在芯的至少一部分上并与芯电隔离。具有第一端和第二端并包封电磁铁芯和线圈线圈的热调节水套允许探针尖端从第一端延伸。对受试者施用吸收了生物活性物质的磁性响应性颗粒。具有附着于其上的磁体的导管插入到受试者的身体中。磁体将颗粒引导到要用生物活性物质处理的部位。

8. 发明申请

WO2004081729A3 A METHOD AND APPARATUS FOR DISPLAYING INFORMATION 审中-公开
标题翻译：一种用于显示信息的方法和装置
公开(公告)号：WO2004081729A3
公开(公告)日：2005-06-02
申请号：PCT/US2004006901
申请日：2004-03-05
申请人： CHILDRENS MEDICAL CENTER , INGBER DONALD E , HUANG SUI , EICHLER GABRIEL
发明人： INGBER DONALD E , HUANG SUI , EICHLER GABRIEL
IPC分类号： G06T11/60 , G09G5/22
CPC分类号： G06T11/60
摘要： A method for displaying large amounts of information. The method includes the steps of forming a spatial layout of tiles (Fig. 2, tiles A-I) each corresponding to a representative reference element; mapping (Fig. 3) observed elements onto the spatial layout of tiles of representative reference elements; assigning (Fig. 1, Table 1) a respective value to each respective tile of the spatial layout of the representative elements; and display (Fig. 4) an image of the spatial layout of tiles of representative elements. Each tile includes atomic attributes of representative elements. Each tile includes atomic attributes of representative elements. The invention also relates to an apparatus for displaying large amounts of information. The apparatus includes a tiler (SOM) forming a spatial layout of tiles, each corresponding to a representative reference element; a comparator (Fig. 3) mapping observed elements onto said spatial layout of tiles of representative reference elements; an assigner (Fig. 1, Table 1) assigning a respective value to each respective tile of said spatial layout of representative reference elements; and a display (Fig. 4) displaying an image of the spatial layout of tiles of representative reference elements.
摘要翻译：一种显示大量信息的方法。该方法包括以下步骤：形成每个对应于代表性参考元素的瓦片（图2，瓦片A-I）的空间布局; 将图像（图3）观察到元素到代表参考元素的瓦片的空间布局上; 将代表元素的空间布局的每个相应瓦片分配（图1，表1）相应的值; 并显示（图4）代表元素的瓦片的空间布局的图像。每个瓦片包括代表元素的原子属性。每个瓦片包括代表元素的原子属性。本发明还涉及一种用于显示大量信息的装置。该装置包括形成瓦片的空间布局的分片器（SOM），每个对应于代表参考元件; 将观察到的元素映射到代表性参考元素的瓦片的所述空间布局上的比较器（图3）分配器（图1，表1）为代表参考元件的所述空间布局的每个相应瓦片分配相应的值; 以及显示代表参考元素的瓦片的空间布局的图像的显示器（图4）。

9. 发明申请

WO2010123594A2 DEVICE FOR FILTRATION OF FLUIDS THERE THROUGH AND ACCOMPANYING METHOD 审中-公开
标题翻译：用于通过并伴随方法过滤流体的装置
公开(公告)号：WO2010123594A2
公开(公告)日：2010-10-28
申请号：PCT/US2010021195
申请日：2010-01-15
申请人： CHILDRENS MEDICAL CENTER , YUNG CHONG WING , INGBER DONALD E
发明人： YUNG CHONG WING , INGBER DONALD E
IPC分类号： B03C5/02 , B01D17/032 , B03C1/02 , G01N1/34 , G01N33/48
CPC分类号： B03C1/01 , B03C1/288 , B03C2201/18 , G01N1/40 , G01N33/54326 , G01N33/54366
摘要： A microfluidic device for separating target components from a source fluid includes one or more source channels connected to one or more collection channels by one or more transfer channels. The target components of the source fluid can be magnetic or bound to magnetic particles using a know binding agent. 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 that is stagnant until a predefined volume of source fluid is processed or a predefined volume of target components accumulate in the collection channel, at which point collection fluid can be pumped into the collection channel to flush the target components out of the collection channel. The target components can be subsequently analyzed for detection and diagnosis.
摘要翻译：用于从源流体分离目标组分的微流体装置包括通过一个或多个传输通道连接到一个或多个收集通道的一个或多个源通道。源流体的目标组分可以是磁性的或使用已知粘合剂结合到磁性颗粒。含有磁性结合的目标组分的源流体可以通过微流体装置的源通道泵送。磁场梯度可以应用于源通道中的源流体，使得磁性结合的目标组分通过传输通道迁移到收集通道中。收集通道可包括静止的收集流体，直到预定量的源流体被处理或预定体积的目标组分积聚在收集通道中，在该点处收集流体可被泵送到收集通道中以冲洗目标组分脱离收集渠道。随后可以分析目标组分以进行检测和诊断。

10. 发明申请

WO2010009307A3 ORGAN MIMIC DEVICE WITH MICROCHANNELS AND METHODS OF USE AND MANUFACTURING THEREOF 审中-公开
标题翻译：具有微通道的器件MIMIC器件及其使用方法和制造方法
公开(公告)号：WO2010009307A3
公开(公告)日：2010-07-15
申请号：PCT/US2009050830
申请日：2009-07-16
申请人： CHILDRENS MEDICAL CENTER , INGBER DONALD E , HUH DONGEUN
发明人： INGBER DONALD E , HUH DONGEUN
IPC分类号： C12M3/06 , B01L3/00 , C12N5/07
CPC分类号： C12M23/16 , B01L3/5027 , B01L3/50273 , B01L2200/0663 , B01L2300/0854 , B01L2300/0877 , B01L2300/0887 , B01L2300/163 , B01L2400/0472 , B01L2400/0481 , B01L2400/0487 , C12M21/08 , C12M23/58 , C12M25/02 , C12M29/10 , C12N5/0606 , C12N5/061 , C12N5/0623 , C12N5/0647 , C12N5/0654 , C12N5/0662 , C12N5/0671 , C12N5/0688 , C12N5/0696 , C12N5/0697 , G01N33/5005 , G01N33/5088 , G01N33/5091
摘要： System and method includes a body having a central microchannel separated by one or more porous membranes. The membranes are configured to divide the central microchannel into a two or more parallel central microchannels, wherein one or more first fluids are applied through the first central microchannel and one or more second fluids are applied through the second or more central microchannels. The surfaces of each porous membrane can be coated with cell adhesive molecules to support the attachment of cells and promote their organization into tissues on the upper and lower surface of the membrane. The pores may be large enough to only permit exchange of gases and small chemicals, or to permit migration and transchannel passage of large proteins and whole living cells. Fluid pressure, flow and channel geometry also may be varied to apply a desired mechanical force to one or both tissue layers.
摘要翻译：系统和方法包括具有由一个或多个多孔膜隔开的中央微通道的主体。膜构造成将中央微通道分成两个或更多个平行的中央微通道，其中一个或多个第一流体通过第一中央微通道施加，一个或多个第二流体通过第二或更多中央微通道施加。每个多孔膜的表面可以涂覆有细胞粘附分子以支持细胞附着并促进其在膜的上表面和下表面上的组织。毛孔可能足够大，只允许交换气体和小化学物质，或者允许大蛋白质和整个活细胞的迁移和穿过通道。流体压力，流量和通道几何形状也可以变化，以向一个或两个组织层施加期望的机械力。

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