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1. 发明申请

WO2011022650A3 NANOFILTER DEVICES USING ELASTOMERIC MICRO TO NANOCHANNEL INTERFACES AND METHODS BASED THEREON 审中-公开
公开(公告)号：WO2011022650A3
公开(公告)日：2011-02-24
申请号：PCT/US2010/046170
申请日：2010-08-20
申请人： CORNELL UNIVERSITY , PARK, Seung-min , HUH, Yun Suk , ERICKSON, David , CRAIGHEAD, Harold G.
发明人： PARK, Seung-min , HUH, Yun Suk , ERICKSON, David , CRAIGHEAD, Harold G.
IPC分类号： G01N21/65
摘要： A method is provided for fabricating a nanochannel. The method comprises providing a microchannel and controlling collapse of the microchannel so that it collapses to form a nanochannel of desired dimensions. The method employs a collapsible, flexible material such as the elastomer polydimethylsiloxane (PDMS) to form the nanochannel. A master is provided that is configured to have geometric conditions that promote a desired frequency of microchannel collapse. A collapsible material having a stiffness that also promotes a desired frequency of microchannel collapse is molded on the master. The molded collapsible material is removed from the master and bonded to a base, thereby forming the microchannel, which then collapses (or is collapsed) to form the nanochannel of desired dimensions. Nanofluidic and microfluidic devices comprising complex nanochannel structures and micro to nanochannel transitions are also provided.

2. 发明申请

WO2011162847A3 STRESS-BASED SENSOR, METHOD AND APPLICATIONS 审中-公开
公开(公告)号：WO2011162847A3
公开(公告)日：2011-12-29
申请号：PCT/US2011/030673
申请日：2011-03-31
申请人： CORNELL UNIVERSITY , PARPIA, Jeevak M. , CRAIGHEAD, Harold G. , SOUTHWORTH, Darren R. , BELLAN, Leon M.
发明人： PARPIA, Jeevak M. , CRAIGHEAD, Harold G. , SOUTHWORTH, Darren R. , BELLAN, Leon M.
IPC分类号： B81B7/02 , G01N33/497
摘要： A composite, analyte sensor includes a substrate; a micro- or nano-electro-mechanical (MEMS; NEMS) resonator that is coupled to the substrate at at least two edge locations (i.e., it is at least doubly-clamped) of the resonator, wherein the resonator is in a statically-buckled state near a buckling transition point of the resonator; and a chemically-responsive substance covering at least a portion of the surface of the resonator that will undergo a conformational change upon exposure to a given analyte. The resonator may be a double-clamped, statically-buckled beam (or bridge), a multiply-clamped, statically-buckled dome (or crater), or other resonator geometry. The sensor may include two or more at least double-clamped, statically-buckled, composite MEMS or NEMS resonators each operating near a buckling transition point of the respective resonator, and each characterized by a different resonant frequency. A method for sensing an analyte in ambient air.

3. 发明申请

WO2010039307A2 CMOS INTEGRATED MICROMECHANICAL RESONATORS AND METHODS FOR FABRICATING THE SAME 审中-公开
标题翻译： CMOS集成微机电谐振器及其制造方法
公开(公告)号：WO2010039307A2
公开(公告)日：2010-04-08
申请号：PCT/US2009/048835
申请日：2009-06-26
申请人： CORNELL UNIVERSITY , THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE NAVY , PARPIA, Jeevak M. , CRAIGHEAD, Harold G. , CROSS, Joshua D. , ILIC, Bojan Robert , ZALALUTDINOV, Maxim K. , BALDWIN, Jeffrey W. , HOUSTON, Brian H.
发明人： PARPIA, Jeevak M. , CRAIGHEAD, Harold G. , CROSS, Joshua D. , ILIC, Bojan Robert , ZALALUTDINOV, Maxim K. , BALDWIN, Jeffrey W. , HOUSTON, Brian H.
CPC分类号： B81C1/00246 , B81B2201/0271 , Y10T29/49007
摘要： The present invention is directed to a CMOS integrated micromechanical device fabricated in accordance with a standard CMOS foundry fabrication process. The standard CMOS foundry fabrication process is characterized by a predetermined layer map and a predetermined set of fabrication rules. The device includes a semiconductor substrate formed or provided in accordance with the predetermined layer map and the predetermined set of fabrication rules. A MEMS resonator device is fabricated in accordance with the predetermined layer map and the predetermined set of fabrication rules. The MEMS resonator device includes a micromechanical resonator structure having a surface area greater than or equal to approximately 20 square microns. At least one CMOS circuit is coupled to the MEMS resonator member. The at least one CMOS circuit is also fabricated in accordance with the predetermined layer map and the predetermined set of fabrication rules.
摘要翻译：本发明涉及根据标准CMOS铸造制造工艺制造的CMOS集成微机械装置。标准CMOS铸造制造工艺的特征在于预定的层图和预定的制造规则集合。该器件包括根据预定层图形成或提供的半导体衬底以及预定的一组制造规则。根据预定层图和预定的制造规则集合制造MEMS谐振器装置。 MEMS谐振器装置包括具有大于或等于约20平方微米的表面积的微机械谐振器结构。至少一个CMOS电路耦合到MEMS谐振器构件。至少一个CMOS电路也是根据预定的层映射和预定的一组制造规则制造的。

4. 发明申请

WO2012170560A2 MICROFLUIDIC DEVICE FOR EXTRACTING, ISOLATING, AND ANALYZING DNA FROM CELLS 审中-公开
标题翻译：用于从细胞中提取，分离和分析DNA的微流体装置
公开(公告)号：WO2012170560A2
公开(公告)日：2012-12-13
申请号：PCT/US2012/041136
申请日：2012-06-06
申请人： CORNELL UNIVERSITY , CRAIGHEAD, Harold G. , TOPOLANCIK, Juraj , TIAN, Harvey , WALLIN, Christopher
发明人： CRAIGHEAD, Harold G. , TOPOLANCIK, Juraj , TIAN, Harvey , WALLIN, Christopher
IPC分类号： C12Q1/68 , C12M1/00 , C12N15/10
CPC分类号： C12N15/1017 , B01L3/502761 , B01L2200/0663 , B01L2400/0415 , B01L2400/0487 , B01L2400/086 , C12M47/10 , C12Q1/6806 , Y10T29/49826
摘要： The present invention relates to a microfluidic device for extracting and isolating DNA from cells. The device includes a support having an inlet port for receiving a sample containing a cell, an outlet port for dispensing DNA isolated from the cell, and a microfluidic channel disposed within the support and extending from the inlet port to the outlet port. The microfluidic channel includes a micropillar array, an inflow channel disposed between the inlet port and the micropillar array, and an outflow channel disposed between the micropillar array and the outlet port. The micropillar array includes micropillars spatially configured to entrap, by size exclusion, the cell, to immobilize DNA released from the cell, and to maintain the immobilized DNA in elongated or non-elongated form when hydrodynamic force is applied to the microfluidic channel. Systems and methods of making and using the device are also provided herein.
摘要翻译：本发明涉及从细胞中提取和分离DNA的微流体装置。该装置包括具有用于接收含有细胞的样品的入口端口，用于分配从该细胞分离出的DNA的出口端口和设置在该支架内并从该入口端口延伸到该出口端口的微流体通道的支架。微流体通道包括微柱阵列，设置在入口和微柱阵列之间的流入通道以及设置在微柱阵列和出口之间的流出通道。微柱阵列包括微空间，其空间配置为通过尺寸排除捕获细胞，以固定从细胞释放的DNA，并且当流体动力被施加到微流体通道时将固定的DNA保持在细长或非细长形式。本文还提供了制造和使用该装置的系统和方法。

5. 发明申请

WO2010096077A1 METHOD FOR MAKING A TRANSDUCER, TRANSDUCER MADE THEREFROM, AND APPLICATIONS THEREOF 审中-公开
标题翻译：制造传感器的方法，其制造的传感器及其应用
公开(公告)号：WO2010096077A1
公开(公告)日：2010-08-26
申请号：PCT/US2009/048750
申请日：2009-06-26
申请人： CORNELL UNIVERSITY , THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE NAVY , PARPIA, Jeevak M. , CRAIGHEAD, Harold G. , CROSS, Joshua D. , ILIC, Bojan Robert , ZALALUTDINOV, Maxim K. , BALDWIN, Jeffrey W. , HOUSTON, Brian H.
发明人： PARPIA, Jeevak M. , CRAIGHEAD, Harold G. , CROSS, Joshua D. , ILIC, Bojan Robert , ZALALUTDINOV, Maxim K. , BALDWIN, Jeffrey W. , HOUSTON, Brian H.
IPC分类号： H01L41/083
CPC分类号： B81C1/00246 , B81B2201/0271 , Y10T29/49007
摘要： A method for manufacturing or preparing thin-film stacks that exhibit moderate, finite, stress-dependent resistance and which can be incorporated into a transduction mechanism that enables simple, effective signal to be read out from a micro- or nano-mechanical structure. As the structure is driven, the resistance of the intermediate layers is modulated in tandem with the motion, and with suitable dc-bias, the motion is directly converted into detectable voltage. In general, detecting signal from MEMS or NEMS devices is difficult, especially using a method that is able to be integrated with standard electronics. The thin-film manufacturing or preparation technique described herein is therefore a technical advance in the field of MEMS/NEMS that could enable new applications as well as the ability to easily develop CMOS-MEMS integrated fabrication techniques. Also disclosed are: (i) transducers where current flows across a piezo layer from one major surface to the opposite major surface; and (ii) methods of making a transducer the resistivity of a piezoresistive layer is decreased and/or the gauge factor of a piezoresistive layer is increased.
摘要翻译：制造或制备薄膜叠层的方法，其显示中等的，有限的，受应力依赖的电阻，并且可以结合到转导机制中，使得能够从微机械结构或纳米机械结构读出简单有效的信号。当结构被驱动时，中间层的电阻与运动一起被调制，并且通过合适的直流偏置，运动被直接转换成可检测的电压。通常，来自MEMS或NEMS器件的检测信号是困难的，特别是使用能够与标准电子器件集成的方法。因此，本文所述的薄膜制造或制备技术是MEMS / NEMS领域的技术进步，其可以实现新应用以及容易地开发CMOS-MEMS集成制造技术的能力。还公开了：（i）电流从压电层从一个主表面流向相对的主表面的换能器; 和（ii）制造换能器的方法是减小压阻层的电阻率和/或压阻层的规格因子增加。

6. 发明申请

WO2017205267A1 MULTIFUNCTIONAL MICROFLUIDIC DEVICE FOR CAPTURING TARGET CELLS AND ANALYZING GENOMIC DNA ISOLATED FROM THE TARGET CELLS WHILE UNDER FLOW CONDITIONS 审中-公开
标题翻译：用于捕获靶细胞的多功能微流控装置和从靶细胞分离的流式条件下分离的基因组DNA
公开(公告)号：WO2017205267A1
公开(公告)日：2017-11-30
申请号：PCT/US2017/033789
申请日：2017-05-22
申请人： CORNELL UNIVERSITY
发明人： CRAIGHEAD, Harold G. , REINHOLT, Sarah J.
IPC分类号： G01N27/27 , A61B5/00 , G01N33/487
摘要： The present invention relates to, inter alia , a microfluidic device for capturing target cells and analyzing genomic DNA isolated from the target cells while under flow conditions. The microfluidic device includes a cell microchannel and a nucleic acid microchannel that intersect in an orthogonal manner, thereby forming a cell capture intersection region. The microfluidic device also includes a cell capture array and a nucleic acid entanglement array. The cell capture array includes a plurality of cell capturing micropillars and is located in the cell capture intersection region. The nucleic acid entanglement array includes a plurality of nucleic acid entanglement micropillars that function to physically entangle and maintain thereon genomic DNA isolated from the one or more target cell, and is located in a portion of the nucleic acid microchannel that is adjacent to and downstream of the cell capture intersection region. Methods of using the microfluidic device are also disclosed.
摘要翻译：本发明尤其涉及用于捕获靶细胞并在流动条件下分析从靶细胞分离的基因组DNA的微流体装置。微流体装置包括以正交方式相交的细胞微通道和核酸微通道，由此形成细胞捕获交叉区域。微流体装置还包括细胞捕获阵列和核酸纠缠阵列。细胞俘获阵列包括多个细胞俘获微细胞并且位于细胞俘获交叉区域中。核酸缠结阵列包括多个核酸缠结微柱，其起到物理缠结并保持在其上的基因组DNA的作用，所述基因组DNA分离自一个或多个靶细胞，并且位于核酸微通道的邻近于细胞捕获交叉区域。还公开了使用微流体装置的方法。

7. 发明申请

WO2014028781A1 RNA APTAMER ISOLATION VIA DUAL-CYCLE (RAPID) SELECTION 审中-公开
标题翻译：通过双周期（RAPID）选择的RNA APTAMER分离
公开(公告)号：WO2014028781A1
公开(公告)日：2014-02-20
申请号：PCT/US2013/055214
申请日：2013-08-15
申请人： CORNELL UNIVERSITY
发明人： CRAIGHEAD, Harold G. , LATULIPPE, David R. , LIS, John T. , OZER, Abdullah , SZETO, Kylan
IPC分类号： C12N15/115 , C12Q1/68
CPC分类号： C12N15/1058 , C12N15/1048 , C12N15/115 , C12N2310/16 , C12N2320/13 , C12N2330/31 , G06F19/28 , G06F19/702
摘要： The present invention relates to a method for selecting an aptamer for a target molecule. The method involves providing a random oligonucleotide library comprising a plurality of unique random sequence oligonucleotides; providing a target mixture comprising at least one target molecule; and subjecting the random oligonucleotide library and the target mixture to at least one round of an aptamer isolation protocol to yield at least one aptamer for the target molecule, wherein a round of the aptamer isolation protocol comprises at least one selection cycle followed by an amplification cycle. The present invention also relates to systems and devices for implementing or performing the method of the present invention. The present invention further relates to using the method to isolate aptamers for high-throughput sequencing analysis and other aptamer analysis protocols.
摘要翻译：本发明涉及用于选择靶分子适体的方法。该方法包括提供包含多个唯一随机序列寡核苷酸的随机寡核苷酸文库; 提供包含至少一种靶分子的目标混合物; 并将随机寡核苷酸文库和目标混合物进行至少一轮适体分离方案以产生用于靶分子的至少一种适体，其中一轮适体分离方案包括至少一个选择循环，随后是扩增循环。本发明还涉及用于实现或执行本发明方法的系统和装置。本发明还涉及使用该方法来分离用于高通量测序分析和其他适体分析方案的适体。

8. 发明申请

WO2013170256A1 MULTIPLEXED MICROCOLUMN DEVICES AND PROCESSES FOR SELECTION OF NUCLEIC ACID APTAMERS 审中-公开
标题翻译：用于选择核酸APTAMERS的多功能微型装置和方法
公开(公告)号：WO2013170256A1
公开(公告)日：2013-11-14
申请号：PCT/US2013/040762
申请日：2013-05-13
申请人： CORNELL UNIVERSITY
发明人： CRAIGHEAD, Harold G. , LATULIPPE, David R. , LIS, John T. , OZER, Abdullah , SZETO, Kylan
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/48 , G01N33/53
CPC分类号： G01N33/5308 , C12N15/115 , C12N2310/16 , C12N2330/00 , G01N33/48 , G01N33/5302
摘要： The present invention relates to a microcolumn device for selecting nucleic acid aptamers for single and multiple target molecules, as well as a method for making the microcolumn device. The present invention also relates to a system for selecting nucleic acid aptamers for single and multiple target molecules. The present invention further relates to methods of using the microcolumn device for selecting nucleic acid aptamers for multiple target molecules. Kits that include one or more microcolumn device and/or system of the present invention are also disclosed.
摘要翻译：本发明涉及用于选择单靶和多靶分子的核酸适体的微柱装置，以及制造微柱装置的方法。本发明还涉及用于选择单个和多个靶分子的核酸适配子的系统。本发明还涉及使用微柱装置选择多个靶分子的核酸适体的方法。还公开了包括本发明的一个或多个微柱装置和/或系统的试剂盒。

9. 发明申请

WO2020113173A1 MULTIOMIC ANALYSIS OF CELL ANALYTES USING MICROFLUIDIC SYSTEMS 审中-公开
公开(公告)号：WO2020113173A1
公开(公告)日：2020-06-04
申请号：PCT/US2019/063866
申请日：2019-11-29
申请人： CORNELL UNIVERSITY
发明人： CRAIGHEAD, Harold G. , TIAN, Harvey C. , LIN, David M. , BISOGNI, Adam J.
IPC分类号： B01L3/00 , C12M1/00 , C12N1/00
摘要： A method for isolating one or more distinct analyte component from a cell sample is disclosed, as well as processes for testing and analyzing the distinct analyte components. The distinct analyte components include: (i) a total protein fraction; (ii) a plasma membrane protein fraction; (iii) a total RNA fraction; (iv) a cytosolic RNA fraction; (v) a cytosolic protein fraction; (vi) a nuclear RNA fraction; (vii) a nuclear protein fraction; (viii) a chromatin fraction comprising genomic DNA (gDNA); (ix) a gDNA markers fraction. This method involves the use of microfluidic device having a cell capture component and a nucleic acid entanglement component, where the cell capture component includes a cell capture array having a plurality of cell capture micropillars, where the nucleic acid entanglement component includes a nucleic acid entanglement array having a plurality of nucleic acid entanglement micropillars, and where the microfluidic device operates under continuous flow conditions.

10. 发明申请

WO2017205304A1 SINGLE CELL WHOLE GENOME AMPLIFICATION VIA MICROPILLAR ARRAYS UNDER FLOW CONDITIONS 审中-公开
标题翻译：通过微流体阵列在流动条件下进行的单细胞整体基因组扩增
公开(公告)号：WO2017205304A1
公开(公告)日：2017-11-30
申请号：PCT/US2017/033885
申请日：2017-05-22
申请人： CORNELL UNIVERSITY
发明人： CRAIGHEAD, Harold G. , TIAN, Harvey C.
IPC分类号： C12M1/00 , C12N15/10 , C12Q1/68
CPC分类号： C12N15/10 , B01L3/502746 , B01L3/502761 , B01L2200/0647 , B01L2300/0803 , B01L2300/0864 , B01L2400/0487 , B01L2400/086 , C12Q1/6844 , C12Q2523/303 , C12Q2531/119 , C12Q2565/629
摘要： The present invention relates to, inter alia, a microfluidic device for performing single cell genomic DNA isolation and amplification under flow. The microfluidic device comprises a solid substrate having one or more microfluidic channel system formed therein. Each microfluidic channel system of the microfluidic device comprises: (a) an intake region comprising a single microchannel; (b) a plurality of cell segregation microchannels; (c) a cell capture site located downstream of each cell segregation microchannel; and (d) a DNA capture array positioned downstream of the cell capture site and comprising a plurality of micropillars. Also disclosed is a whole genome amplification system that includes the microfluidic device of the present disclosure, as well as a method for conducting single cell DNA analysis via on-chip whole genome amplification while under flow, and a method for multiple displacement amplification (MDA) reactions of one or more nucleic acid sequence isolated single cells.
摘要翻译：本发明尤其涉及用于在流动下进行单细胞基因组DNA分离和扩增的微流体装置。微流体装置包括具有在其中形成的一个或多个微流体通道系统的固体基底。微流体装置的每个微流体通道系统包括：（a）包括单个微通道的进入区域; （b）多个细胞分离微通道; （c）位于每个细胞分离微通道下游的细胞捕获位点; 和（d）位于细胞捕获位点下游并包含多个微柱的DNA捕获阵列。还公开了包括本公开的微流体装置的全基因组扩增系统，以及用于在流动下通过片上全基因组扩增进行单细胞DNA分析的方法，以及用于多位移扩增（MDA）的方法，一个或多个核酸序列分离的单个细胞的反应。

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