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1. 发明申请

WO2018236901A1 MICROFLUIDIC DEVICE HAVING PARTIALLY ENCLOSED MICROFLUIDIC CHANNEL AND USE THEREOF 审中-公开
公开(公告)号：WO2018236901A1
公开(公告)日：2018-12-27
申请号：PCT/US2018/038325
申请日：2018-06-19
申请人： CURIOCHIPS , JEON, Noo Li
发明人： JEON, Noo Li , KO, Jihoon , LEE, Somin , AHN, Jungho , PARK, Dohyun , LEE, Seung-Ryeol , KIM, Suryong , LEE, Byungjun
IPC分类号： C12Q1/68
摘要： A microfluidic device in which microfluidic channels are embedded in a culture medium chamber and have open sides. The microfluidic device is patterned with a fluid moved along a hydrophilic surface due to capillary force, and the fluid may be rapidly and uniformly patterned along an inner corner path and a microfluidic channel. In the microfluidic device, the microfluidic channel is connected to facilitate fluid flow with a culture medium through open sides thereof and openings, and thus may provide a cell culture environment in which high gas saturation is maintained. In addition, several microfluidic devices formed on one common substrate are described. Such microfluidic devices may be manufactured of a hydrophilic engineering plastic by injection or molding.

2. 发明申请

WO2006037033A3 A MICROFLUIDIC DEVICE FOR ENABLING THE CONTROLLED GROWTH OF CELLS 审中-公开
标题翻译：用于实现细胞控制生长的微流体装置
公开(公告)号：WO2006037033A3
公开(公告)日：2006-06-15
申请号：PCT/US2005034792
申请日：2005-09-26
申请人： UNIV CALIFORNIA , JEON NOO LI , TAYLOR ANNE M , COTMAN CARL W , CRIBBS DAVID H
发明人： JEON NOO LI , TAYLOR ANNE M , COTMAN CARL W , CRIBBS DAVID H
IPC分类号： C12M1/34 , C12M3/00 , C12N5/08
CPC分类号： B01L3/50273 , B01L3/502707 , B01L3/502738 , B01L2200/0668 , B01L2300/0681 , B01L2400/0409 , B01L2400/086 , C12M23/16 , C12M23/34 , C12M41/36
摘要： One or more embodiments of the invention are directed towards a multi-compartment microfluidic device for enabling fluidic isolation among interconnected compartments and accomplishing centrifugal positioning and / or patterned substrate positioning of biological specimens within the device. One or more devices comprises a micropatterned substrate coupled with an optically transparent housing for purpose of imaging. The optically transparent housing comprises a first microfluidic region having a first entry reservoir for accepting a first volume of fluid and further comprises at least one additional second microfluidic region having a second entry reservoir for accepting a second volume of fluid that is less than the first volume of fluid to create hydrostatic pressure. In some cases additional microfluidic regions such as a center region are introduced. A barrier region that couples the first microfluidic region with the second microfluidic region to enables a biological specimen to extend across the first microfluidic region, the barrier region, the second microfluidic region, and optionally the center region. The barrier region comprises at least one embedded microgroove having a width and height that enables the second volume of fluid to be fluidically isolated from the first volume of fluid via hydrostatic pressure maintained via the at least one embedded microgroove. Cells are aligned to a chosen location through the use of certrifugual force or through patterned substrate techniques.
摘要翻译：本发明的一个或多个实施例涉及一种多室微流体装置，用于实现互连室之间的流体隔离，并实现生物样本在装置内的离心定位和/或图案化衬底定位。一个或多个装置包括与用于成像的光学透明壳体耦合的微图案化基底。光学透明壳体包括第一微流体区域，其具有用于接收第一体积流体的第一入口容器，并且还包括至少一个另外的第二微流体区域，其具有第二入口容器，用于接受小于第一容积的第二体积流体的液体以产生静水压力。在一些情况下，引入了诸如中心区域的额外的微流体区域。阻挡区域，其将第一微流体区域与第二微流体区域耦合，以使得生物样本能够延伸穿过第一微流体区域，阻挡区域，第二微流体区域以及可选的中心区域。阻挡区域包括至少一个具有宽度和高度的嵌入式微槽，该宽槽和高度使得能够经由至少一个嵌入的微槽维持的静水压力使第二体积的流体与第一体积的流体流体隔离。通过使用绝缘力或通过图案化底材技术将细胞对准所选择的位置。

3. 发明申请

WO2006037033A2 A MICROFLUIDIC DEVICE FOR ENABLING THE CONTROLLED GROWTH OF CELLS AND METHODS RELATING TO SAME 审中-公开
标题翻译：用于实现细胞控制生长的微流体装置和与其相关的方法
公开(公告)号：WO2006037033A2
公开(公告)日：2006-04-06
申请号：PCT/US2005/034792
申请日：2005-09-26
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , JEON, Noo, Li , TAYLOR, Anne, M. , COTMAN, Carl, W. , CRIBBS, David, H.
发明人： JEON, Noo, Li , TAYLOR, Anne, M. , COTMAN, Carl, W. , CRIBBS, David, H.
IPC分类号： C12M3/04
CPC分类号： B01L3/50273 , B01L3/502707 , B01L3/502738 , B01L2200/0668 , B01L2300/0681 , B01L2400/0409 , B01L2400/086 , C12M23/16 , C12M23/34 , C12M41/36
摘要： One or more embodiments of the invention are directed towards a multi-compartment microfluidic device for enabling fluidic isolation among interconnected compartments and accomplishing centrifugal positioning and / or patterned substrate positioning of biological specimens within the device. One or more devices comprises a micropatterned substrate coupled with an optically transparent housing for purpose of imaging. The optically transparent housing comprises a first microfluidic region having a first entry reservoir for accepting a first volume of fluid and further comprises at least one additional second microfluidic region having a second entry reservoir for accepting a second volume of fluid that is less than the first volume of fluid to create hydrostatic pressure. In some cases additional microfluidic regions such as a center region are introduced. A barrier region that couples the first microfluidic region with the second microfluidic region to enables a biological specimen to extend across the first microfluidic region, the barrier region, the second microfluidic region, and optionally the center region. The barrier region comprises at least one embedded microgroove having a width and height that enables the second volume of fluid to be fluidically isolated from the first volume of fluid via hydrostatic pressure maintained via the at least one embedded microgroove. Cells are aligned to a chosen location through the use of certrifugual force or through patterned substrate techniques.
摘要翻译：本发明的一个或多个实施例涉及一种多室微流体装置，用于实现互连室之间的流体隔离，并实现生物样本在装置内的离心定位和/或图案化衬底定位。一个或多个装置包括与用于成像的光学透明壳体耦合的微图案化基底。光学透明壳体包括第一微流体区域，其具有用于接收第一体积流体的第一入口容器，并且还包括至少一个另外的第二微流体区域，其具有第二入口容器，用于接受小于第一容积的第二体积流体的液体以产生静水压力。在一些情况下，引入了诸如中心区域的额外的微流体区域。阻挡区域，其将第一微流体区域与第二微流体区域耦合，以使得生物样本能够延伸穿过第一微流体区域，阻挡区域，第二微流体区域以及可选的中心区域。阻挡区域包括至少一个具有宽度和高度的嵌入式微槽，该宽槽和高度使得能够经由至少一个嵌入的微槽维持的静水压力使第二体积的流体与第一体积的流体流体隔离。通过使用绝缘力或通过图案化底材技术将细胞对准所选择的位置。

4. 发明申请

WO2021127538A1 MICROFLUIDIC DEVICE HAVING PARTIALLY ENCLOSED MICROFLUIDIC CHANEL AND USE THEREOF 审中-公开
公开(公告)号：WO2021127538A1
公开(公告)日：2021-06-24
申请号：PCT/US2020/066174
申请日：2020-12-18
申请人： CURIOCHIPS , JEON, Noo Li
发明人： LEE, Byungiun , YU, James , KO, Jihoon
IPC分类号： C12Q1/68 , B01L2200/0647 , B01L2300/0858 , B01L2300/0861 , B01L2300/088 , B01L2300/12 , B01L2400/0406 , B01L3/50273 , B01L3/502761 , C12M23/12 , C12M23/16 , C12M23/20 , C12M23/58 , C12M35/08 , C12N2513/00 , C12N2521/00 , C12N5/0068
摘要： A microfluidic device in which microfluidic channels are embedded in a culture medium chamber and have open sides. The microfluidic device is patterned with a fluid moved along a hydrophilic surface due to capillary force, and the fluid may be rapidly and uniformly patterned along an inner corner path and a microfluidic channel. In the microfluidic device, the microfluidic channel is connected to facilitate fluid flow with a culture medium through open sides thereof and openings, and thus may provide a cell culture environment in which high gas saturation is maintained. In addition, several microfluidic devices formed on one common substrate are described. Such microfluidic devices may be manufactured of a hydrophilic engineering plastic by injection molding.

5. 发明申请

WO0222264A8 METHOD AND APPARATUS FOR GRADIENT GENERATION 审中-公开
标题翻译：梯度产生的方法和装置
公开(公告)号：WO0222264A8
公开(公告)日：2002-07-18
申请号：PCT/US0142195
申请日：2001-09-18
申请人： HARVARD COLLEGE , JEON NOO LI , DERTINGER STEPHAN K W , CHIU DANIEL T , CHOI INSUNG S , WHITESIDES GEORGE M
发明人： JEON NOO LI , DERTINGER STEPHAN K W , CHIU DANIEL T , CHOI INSUNG S , WHITESIDES GEORGE M
IPC分类号： G01N33/53 , B01D3/00 , B01F5/06 , B01F13/00 , B01F15/04 , B01J4/00 , B01J19/00 , B01J19/24 , B01L20060101 , B01L1/00 , B01L3/00 , B65B3/00 , B65B3/04 , C12M1/34 , C23G1/00 , G01F11/28 , G01N1/28 , G01N1/38 , G01N33/543 , G01N37/00 , B01F4
CPC分类号： B01F5/0601 , B01F5/064 , B01F13/0059 , B01F15/0404 , B01J4/001 , B01J19/0093 , B01J2219/0086 , B01J2219/00889 , B01L3/5027 , G01N1/2813 , G01N1/38

6. 发明申请

WO1997007429A1 SELF-ASSEMBLED MONOLAYER DIRECTED PATTERNING OF SURFACES 审中-公开
标题翻译：自组装单面指向表面图案
公开(公告)号：WO1997007429A1
公开(公告)日：1997-02-27
申请号：PCT/US1996013223
申请日：1996-08-16
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , CLEM, Paul, G. , JEON, Noo-Li , MRKSICH, Milan , NUZZO, Ralph, G. , PAYNE, David, A. , WHITESIDES, George, M. , XIA, Younan
发明人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE
IPC分类号： G03F07/00
CPC分类号： B82Y30/00 , B01J2219/00317 , B01J2219/00382 , B01J2219/00659 , B05D1/283 , B41M3/003 , B82Y10/00 , B82Y40/00 , C23C16/01 , C23C16/04 , C23C16/042 , C40B60/14 , G03F7/0002 , H01L21/28562 , H01L21/76879 , H01L21/76898
摘要： A technique for creating patterns of material deposited on a surface involves forming a self-assembled monolayer in a pattern on the surface and depositing, via chemical vapor deposition or via sol-gel processing, a material on the surface in a pattern complementary to the self-assembled monolayer pattern. The material can be a metal, metal oxide, or the like. The surface can be contoured, including trenches or holes, the trenches or holes remaining free of self-assembled monolayer while the remainder of the surface is coated. When exposed to deposition conditions, metal or metal oxide is deposited in the trenches or holes, and remaining portions of the article surface remain free of deposition. The technique finds particular use in creation of conductive metal pathways selectively within holes passing from one side of a substrate to another.
摘要翻译：用于产生沉积在表面上的材料图案的技术包括以表面上的图案形成自组装单层，并通过化学气相沉积或经由溶胶 - 凝胶加工，以与自身互补的图案沉积在表面上的材料组装的单层图案。该材料可以是金属，金属氧化物等。表面可以是轮廓，包括沟槽或孔，沟槽或孔保持没有自组装单层，而表面的其余部分被涂覆。当暴露于沉积条件时，金属或金属氧化物沉积在沟槽或孔中，并且制品表面的剩余部分保持不沉积。该技术特别用于在从衬底的一侧通过到另一侧的孔内选择性地形成导电金属通路。

7. 发明申请

WO2003078586A3 VASCULARIZED TISSUE FOR TRANSPLANTATION 审中-公开
公开(公告)号：WO2003078586A3
公开(公告)日：2003-09-25
申请号：PCT/US2003/007720
申请日：2003-03-12
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , GEORGE, Steven, C , JEON, Noo, Li , HUGHES, Chris, C., W.
发明人： GEORGE, Steven, C , JEON, Noo, Li , HUGHES, Chris, C., W.
IPC分类号： A01N1/00
摘要： Tissue engineering holds enormous potential to replace or restore function to a wide range of tissues. However, the most successful applications have been limited to thin avascular tissues in which delivery of essential nutrients occurs primarily by diffusion. Pursuant to the present invention, a prevascularized, thick tissue construct is created having a network of capillaries with lumens capable of nutrient and origin delivery and forming anastamoses to host vasculature. A tissue transplantation strategy is comprised of (1) in vitro vascularization of a tisue construct, (2) transplantation of prevascularized tissue to wound bed of host where vessels of implantable tissue and host rapidly anastomose, and (3) host-directed remodeling and reorganization of the tissue and vascular network.

8. 发明申请

WO0189788A9 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：WO0189788A9
公开(公告)日：2002-12-12
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 , B01J4/00 , B29C39/02
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提供拓扑复杂和改进的微流体系统的方便的途径。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。

9. 发明申请

WO2001089788A3 PATTERNING OF SURFACES UTILIZING MICROFLUIDIC STAMPS INCLUDING THREE-DIMENSIONALLY ARRAYED CHANNEL NETWORKS 审中-公开
公开(公告)号：WO2001089788A3
公开(公告)日：2001-11-29
申请号：PCT/US2001/017246
申请日：2001-05-25
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , CHILDREN'S MEDICAL CENTER CORPORATION , 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： B01L3/00
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.

10. 发明申请

WO2004034016A3 MICROFLUIDIC MULTI-COMPARTMENT DEVICE FOR NEUROSCIENCE RESEARCH 审中-公开
标题翻译：用于神经病学研究的微流体多室装置
公开(公告)号：WO2004034016A3
公开(公告)日：2004-10-07
申请号：PCT/US0331503
申请日：2003-10-06
申请人： JEON NOO LI , COTMAN CARL
发明人： JEON NOO LI , COTMAN CARL
IPC分类号： B01F5/06 , B01F13/00 , B01L3/00 , C12M3/00 , C12M1/34 , C02F1/40 , C02F11/00 , C12M1/12 , C12M1/22 , C25B11/00 , C25B13/00 , G01N15/06 , G01N33/00 , G01N33/48
CPC分类号： B01F5/0641 , B01F5/0646 , B01F5/0647 , B01F13/0059 , B01F13/0093 , B01F2215/0431 , B01F2215/045 , B01L3/502707 , B01L2200/0636 , B01L2300/0816 , B01L2300/10 , B01L2400/0487 , C12M23/16 , C12M23/34 , C12M29/10
摘要： Embodiments of the invention are directed to a device that combines microfabrication, microfluidic, and surface micropatterning techniques to create a multi-compartment neuronal culturing device that has application across a number of different neuroscience uses. Devices configured in accordance with the invention allow directed growth of neurites and isolation of neurites from their cell bodies. The device can use hydrostatic pressure to isolate insults to one compartment and, thus, expose localized areas of neurons to insults. Due to the high resistance of the microgrooves for fluid transport, insults are contained in the neuritic compartment without appreciable leakage into the somal compartment for a certain period of time (e.g., over 15 h).
摘要翻译：本发明的实施方案涉及一种结合微细加工，微流体和表面微图案技术以创建跨多个不同神经科学用途的多室神经元培养装置的装置。根据本发明配置的装置允许神经突的指向生长和神经突从其细胞体分离。该装置可以使用静水压力将侮辱隔离成一个隔室，从而将神经元的局部区域暴露于侮辱。由于用于流体输送的微槽的高电阻，侮辱包含在神经细胞室中，而没有明显的泄漏进入体腔室一段时间（例如超过15小时）。

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