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1. 发明授权

US10191060B2 Functionalized chromophoric polymer dots and bioconjugates thereof 有权
公开(公告)号：US10191060B2
公开(公告)日：2019-01-29
申请号：US13508981
申请日：2010-11-09
申请人： Daniel T. Chiu , Changfeng Wu , Jason McNeill , Jiangbo Yu
发明人： Daniel T. Chiu , Changfeng Wu , Jason McNeill , Jiangbo Yu
IPC分类号： G01N33/58 , C09K11/06
摘要： The present invention provides, among other aspects, functionalized chromophoric polymer dots comprising a hydrophobic core and a hydrophilic cap, and bioconjugates thereof. Also provided are improved methods for preparing functionalized chromophoric polymer dots. Methods for in vivo imaging and molecular labeling are also disclosed.

2. 发明授权

US09428793B2 Methods and systems for performing digital measurements 有权
标题翻译：用于执行数字测量的方法和系统
公开(公告)号：US09428793B2
公开(公告)日：2016-08-30
申请号：US13980457
申请日：2012-01-20
申请人： Daniel T. Chiu , Bryant S. Fujimoto , Alexander R. Gansen , Gloria S. Yen , Robert M. Lorenz
发明人： Daniel T. Chiu , Bryant S. Fujimoto , Alexander R. Gansen , Gloria S. Yen , Robert M. Lorenz
IPC分类号： C12Q1/68 , C12M1/00
CPC分类号： C12Q1/6851 , C12Q1/6806 , C12Q2527/146 , C12Q2531/113 , C12Q2545/114
摘要： Methods, devices and systems for performing digital measurements are provided.
摘要翻译：提供了用于执行数字测量的方法，设备和系统。

3. 发明授权

US09382473B2 Chromophoric polymer dots 有权
标题翻译：发色聚合物点
公开(公告)号：US09382473B2
公开(公告)日：2016-07-05
申请号：US13865924
申请日：2013-04-18
申请人： Daniel T. Chiu , Changfeng Wu , Xuanjun Zhang , Jiangbo Yu , Fangmao Ye
发明人： Daniel T. Chiu , Changfeng Wu , Xuanjun Zhang , Jiangbo Yu , Fangmao Ye
IPC分类号： C09K11/06 , C09K11/07 , H01L51/00 , B82Y30/00 , B82Y40/00 , G01N33/58 , B82Y15/00
CPC分类号： G01N33/588 , B82Y15/00 , B82Y30/00 , B82Y40/00 , C08G61/126 , C08G2261/12 , C08G2261/1426 , C08G2261/228 , C08G2261/3142 , C08G2261/3246 , C08G2261/522 , C08G2261/54 , C08G2261/72 , C08G2261/94 , C08J3/11 , C08J2327/22 , C09K11/025 , C09K11/06 , C09K2211/1425 , H01L51/0039
摘要： The present invention provides, among other aspects, stabilized chromophoric nanoparticles. In certain embodiments, the chromophoric nanoparticles provided herein are rationally functionalized with a pre-determined number of functional groups. In certain embodiments, the stable chromophoric nanoparticles provided herein are modified with a low density of functional groups. In yet other embodiments, the chromophoric nanoparticles provided herein are conjugated to one or more molecules. Also provided herein are methods for making rationally functionalized chromophoric nanoparticles.
摘要翻译：本发明尤其提供了稳定的发色纳米颗粒。在某些实施方案中，本文提供的发色纳米颗粒用预定数量的官能团合理地官能化。在某些实施方案中，本文提供的稳定发色纳米粒子用低密度官能团修饰。在其它实施方案中，本文提供的发色纳米颗粒与一个或多个分子缀合。本文还提供了用于制备合理官能化的发色纳米颗粒的方法。

4. 发明授权

US08669044B2 Methods and apparatus for the isolation and enrichment of circulating tumor cells 有权
标题翻译：用于分离和富集循环肿瘤细胞的方法和装置
公开(公告)号：US08669044B2
公开(公告)日：2014-03-11
申请号：US12665521
申请日：2008-06-12
申请人： Daniel T. Chiu , Jason S. Kuo
发明人： Daniel T. Chiu , Jason S. Kuo
IPC分类号： C12Q1/00
CPC分类号： G01N1/34 , B01L3/502746 , B01L3/502753 , B01L2200/0668 , B01L2300/0681 , B01L2400/0409 , B01L2400/0415 , B01L2400/0487 , C12N5/0693
摘要： Embodiments in accordance with the present invention relate to methods and apparatuses for concentrating and isolating Circulating Tumor Cells (CTCs) from body fluids. One embodiment of the present invention includes a micro-fabricated or nano-fabricated device having channels configured for separating and excluding. Embodiments in accordance with the present invention utilize features that reduce the hydrodynamic pressure experienced by the cells during the separation, isolation and concentration processes, and therefore reduce the likelihood of cell lysis or other damage to the cells.
摘要翻译：根据本发明的实施例涉及用于从体液浓缩和分离循环肿瘤细胞（CTC）的方法和装置。本发明的一个实施例包括具有被配置为分离和排除的通道的微制造或纳米制造装置。根据本发明的实施方案利用降低细胞在分离，分离和浓缩过程中所经历的流体动力学压力的特征，并因此降低细胞裂解或细胞的其它损伤的可能性。

5. 发明申请

US20130052737A1 METHOD FOR SELECTIVE ELECTROFUSION OF AT LEAST TWO FUSION PARTNERS HAVING CELL-LIKE MEMBRANES 失效
标题翻译：具有细胞膜的最小二次融合合作伙伴的选择性电解方法
公开(公告)号：US20130052737A1
公开(公告)日：2013-02-28
申请号：US13555946
申请日：2012-07-23
申请人： Peter Eriksson , Daniel T. Chiu , Alexander Moscho , Owe Orwar , Richard N. Zare
发明人： Peter Eriksson , Daniel T. Chiu , Alexander Moscho , Owe Orwar , Richard N. Zare
IPC分类号： C12N15/06 , C12N13/00
CPC分类号： C12N15/87 , C12N5/12 , C12N13/00
摘要： Disclosed is a method for selective electrofusion of at least two fusion partners having cell-like membranes and cellular or subcellular dimensions, comprising the following steps: A) the fusion partners are brought into contact with each other and B) an electrical field of a strength sufficient to obtain fusion and highly focused on the fusion partners is applied. The fusion partners are independently selected from the group consisting of a single cell, a liposome, a proteoliposome, a synthetic vesicle, an egg cell, an enucleated egg cell, a sperm cell at any development stage and a plant protoplast.
摘要翻译：公开了一种用于选择性电融合具有细胞样膜和细胞或亚细胞尺寸的至少两个融合伴侣的方法，包括以下步骤：A）使融合伴侣彼此接触并且B）强度的电场足以获得融合并高度集中在融合伙伴上。融合对象独立地选自单细胞，脂质体，蛋白脂质体，合成囊泡，卵细胞，去核卵细胞，任何发育阶段的精细胞和植物原生质体。

6. 发明申请

US20120282632A1 FUNCTIONALIZED CHROMOPHORIC POLYMER DOTS AND BIOCONJUGATES THEREOF 审中-公开
标题翻译：功能化的色谱聚合物及其生物活性剂
公开(公告)号：US20120282632A1
公开(公告)日：2012-11-08
申请号：US13508981
申请日：2010-11-09
申请人： Daniel T. Chiu , Changfeng Wu , Jason McNeill , Jiangbo Yu
发明人： Daniel T. Chiu , Changfeng Wu , Jason McNeill , Jiangbo Yu
IPC分类号： C08L25/18 , G01N33/566 , C08L89/00 , G01N33/53
CPC分类号： G01N33/587 , C09K11/06 , G01N33/582
摘要： The present invention provides, among other aspects, functionalized chromophoric polymer dots comprising a hydrophobic core and a hydrophilic cap, and bioconjugates thereof. Also provided are improved methods for preparing functionalized chromophoric polymer dots. Methods for in vivo imaging and molecular labeling are also disclosed.
摘要翻译：除其他方面之外，本发明提供了包含疏水性核心和亲水性帽子的官能化发色聚合物点及其生物缀合物。还提供了制备官能化发色聚合物点的改进方法。还公开了体内成像和分子标记的方法。

7. 发明申请

US20110269131A1 SUBSTRATE FOR MANUFACTURING DISPOSABLE MICROFLUIDIC DEVICES 审中-公开
标题翻译：用于制造可替代的微流体装置的基板
公开(公告)号：US20110269131A1
公开(公告)日：2011-11-03
申请号：US13127207
申请日：2009-10-28
申请人： Daniel T. Chiu , Jason S. Kuo
发明人： Daniel T. Chiu , Jason S. Kuo
IPC分类号： C12M1/00 , B01D15/08 , C12Q1/02 , G01N33/559 , B01L3/00 , C12Q1/68
CPC分类号： C12M1/00 , B01L3/502707 , B01L3/502715 , B01L3/502723 , B01L3/502753 , B01L2200/027 , B01L2200/0689 , B01L2300/0681 , B01L2300/12 , B01L2400/0418 , B01L2400/0421 , B01L2400/0487 , B01L2400/086 , B29C33/44 , B29C65/08 , B29C65/14 , B29C65/1403 , B29C65/1406 , B29C65/1409 , B29C65/1412 , B29C66/028 , B29C66/1122 , B29C66/5346 , B29C66/71 , B29C66/73151 , B29C66/73365 , B29C66/73751 , B29C66/7392 , B29C66/73921 , B29C66/7394 , B29C66/81267 , B29C66/82661 , B29C2791/006 , B29K2075/00 , B29K2995/0025 , B29K2995/0027 , B29K2995/007 , B29L2031/756 , B81B2201/051 , B81C1/00119 , B81C2201/019 , B81C2201/034 , B29K2033/12
摘要： Embodiments of the present invention relate to a UV-curable polyurethane-methacrylate (PUMA) substrate for manufacturing microfluidic devices. PUMA is optically transparent, biocompatible, and has stable surface properties. Embodiments include two production processes that are compatible with the existing methods of rapid prototyping, and characterizations of the resultant PUMA microfluidic devices are presented. Embodiments of the present invention also relate to strategies to improve the production yield of chips manufactured from PUMA resin, especially for microfluidic systems that contain dense and high-aspect-ratio features. Described is a mold-releasing procedure that minimizes motion in the shear plane of the microstructures. Also presented are simple yet scalable able methods for forming seals between PUMA substrates, which avoids excessive compressive force that may crush delicate structures. Two methods for forming interconnects with PUMA microfluidic devices are detailed. These improvements produce a microfiltration device containing closely spaced and high-aspect-ratio fins, suitable for retaining and concentrating cells or beads from a highly diluted suspension.
摘要翻译：本发明的实施方案涉及用于制造微流体装置的可UV固化的聚氨酯 - 甲基丙烯酸酯（PUMA）基材。 PUMA是光学透明的，生物相容的，并且具有稳定的表面性质。实施例包括与现有快速成型方法兼容的两个生产方法，并且显示所得PUMA微流体装置的特性。本发明的实施方案还涉及提高由PUMA树脂制造的芯片的生产成本的策略，特别是对于含有密集和高纵横比特征的微流体系统。描述了使微结构的剪切平面中的运动最小化的脱模程序。还提出了用于在PUMA基材之间形成密封的简单且可扩展的方法，其避免了可能破坏微细结构的过大的压缩力。详细说明了与PUMA微流体装置形成互连的两种方法。这些改进产生了包含紧密间隔和高纵横比的翅片的微滤装置，适用于从高度稀释的悬浮液中保留和浓缩细胞或珠粒。

8. 发明申请

US20100323388A1 BIOCHIP FOR HIGH-THROUGHPUT SCREENING OF CIRCULATING TUMOR CELLS 审中-公开
标题翻译：用于循环肿瘤细胞高通量筛选的BIOCHIP
公开(公告)号：US20100323388A1
公开(公告)日：2010-12-23
申请号：US12665575
申请日：2008-06-12
申请人： Daniel T. Chiu , Jason S. Kuo , J. Patrick Shelby , David S. Lim
发明人： Daniel T. Chiu , Jason S. Kuo , J. Patrick Shelby , David S. Lim
IPC分类号： C12Q1/02 , C12N5/02 , C12M1/00
CPC分类号： B01D63/00 , B01D67/0062 , B01D2313/086 , B01D2315/10 , B01L3/502753 , B01L2300/0681 , B01L2400/0487 , Y10T436/25375
摘要： Embodiments in accordance with the present invention relate to the use of effusive filtration to segregate tumor cells from a sample of bodily fluid. In one embodiment, fluid containing a cell is flowed down a channel having a filtration medium present along at least one side wall. The tumor cell is captured when the fluid passes through the filtration medium. Accumulated pressure on the captured tumor cell is reduced by allowing the fluid that has passed through the filtration medium to re-enter the channel. In a particular embodiment, the filtration medium may comprise side wall apertures having a width smaller than that of the cell, with downstream apertures allowing re-entry of the fluid into the channel.
摘要翻译：根据本发明的实施方案涉及使用渗出过滤从体液样品中分离肿瘤细胞。在一个实施例中，含有电池的流体沿具有沿着至少一个侧壁存在的过滤介质的通道向下流动。当流体通过过滤介质时，捕获肿瘤细胞。通过允许已经通过过滤介质的流体重新进入通道来减少捕获的肿瘤细胞上的累积压力。在特定实施例中，过滤介质可以包括宽度小于电池的宽度的侧壁孔，下游孔允许流体重新进入通道。

9. 发明申请

US20100041046A1 METHOD AND APPARATUS FOR THE DISCRETIZATION AND MANIPULATION OF SAMPLE VOLUMES 有权
标题翻译：方法和装置的样品量的分离和操作
公开(公告)号：US20100041046A1
公开(公告)日：2010-02-18
申请号：US12510110
申请日：2009-07-27
申请人： Daniel T. Chiu , Dawn W. Cohen , Gavin D.M. Jeffries
发明人： Daniel T. Chiu , Dawn W. Cohen , Gavin D.M. Jeffries
IPC分类号： C12Q1/68 , C12M1/00 , C12M1/34
CPC分类号： B01L3/502 , B01L3/502784 , B01L7/52 , B01L2200/0642 , B01L2200/0673 , B01L2300/0877 , B01L2300/0883 , B01L2300/165 , B01L2300/1827 , B01L2300/1861 , B01L2400/0439 , B01L2400/0633 , G01N35/08 , G01N35/10 , G01N2035/00356 , G01N2035/1032 , G01N2035/1034
摘要： Embodiments of the present invention relate to methods and apparatuses for the discretization and manipulation of sample volumes that is simple, robust, and versatile. It is a fluidic device that partitions a sample by exploiting the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the formed droplet and/or discretized volume. These compartmentalized volumes allow for isolation of samples and partitioning into a localized array that can subsequently be manipulated and analyzed. The isolation of the discretized volumes along with the device's inherent portability render our invention versatile for use in many areas, including but not limited to PCR, digital PCR, biological assays for diagnostics and prognostics, cancer diagnosis and prognosis, high throughput screening, single molecule and single cell reactions or assays, the study crystallization and other statistical processes, protein crystallization, drug screening, environmental testing, and the coupling to a wide range of analytical detection techniques for biomedical assays and measurements. The minimal fluid interconnects and simple flow geometry makes the device easy to use and implement, economical to fabricate and operate, and robust in its operations.
摘要翻译：本发明的实施例涉及用于简单，稳健和多用途的样品体积的离散化和操作的方法和装置。它是通过利用流体力，界面张力，通道几何形状和形成的液滴和/或离散体积的最终稳定性之间的相互作用分隔样品的流体装置。这些分隔的容积允许将样品和分离分离成可随后被操纵和分析的局部阵列。离散体积的分离以及设备的固有可移植性使我们的发明具有多功能性，可用于许多领域，包括但不限于PCR，数字PCR，用于诊断和预后的生物测定，癌症诊断和预后，高通量筛选，单分子和单细胞反应或测定，研究结晶和其他统计过程，蛋白质结晶，药物筛选，环境测试以及与广泛的用于生物医学测定和测量的分析检测技术的耦合。最小的流体互连和简单的流动几何形状使得设备易于使用和实施，经济地制造和操作，并且在其操作中稳固。

10. 发明授权

US07267938B2 Patterning of surfaces utilizing microfluidic stamps including three-dimensionally arrayed channel networks 有权
标题翻译：使用包括三维排列的通道网络的微流体标记的表面图案化
公开(公告)号：US07267938B2
公开(公告)日：2007-09-11
申请号：US10654587
申请日：2003-09-02
申请人： Janelle R. Anderson , Daniel T. Chiu , Noo Li Jeon , Sui Huang , Ravindra Kane , Insung S. Choi , Donald E. Ingber , George M. Whitesides
发明人： Janelle R. Anderson , Daniel T. Chiu , Noo Li Jeon , Sui Huang , Ravindra Kane , Insung S. Choi , Donald E. Ingber , George M. Whitesides
IPC分类号： C12Q1/00 , C12N11/00 , C12N11/02 , C12M1/00 , C07K17/00 , C07K17/02
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流体流动路径的三维排列的网络，其中包括在交叉点处的交叉点处的交叉或不在其他通道上的通道，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，该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。

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