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1. 发明授权

US10035104B2 Biochip for high-throughput screening of circulating tumor cells 有权
公开(公告)号：US10035104B2
公开(公告)日：2018-07-31
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： B01L3/00 , B01L3/02 , B01D63/00 , B01D67/00
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.

2. 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。

3. 发明授权

US08841135B2 Biochip for high-throughput screening of circulating tumor cells 有权
标题翻译：生物芯片用于高通量筛选循环肿瘤细胞
公开(公告)号：US08841135B2
公开(公告)日：2014-09-23
申请号：US11766053
申请日：2007-06-20
申请人： Daniel T. Chiu , Jason S. Kuo , J. Patrick Shelby , David S. W. Lim
发明人： Daniel T. Chiu , Jason S. Kuo , J. Patrick Shelby , David S. W. Lim
IPC分类号： C12Q1/02 , C12Q1/00 , 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。

4. 发明申请

US20080318324A1 Biochip for High-Throughput Screening of Circulating Tumor Cells 有权
标题翻译：用于循环肿瘤细胞高通量筛选的生物芯片
公开(公告)号：US20080318324A1
公开(公告)日：2008-12-25
申请号：US11766053
申请日：2007-06-20
申请人： Daniel T. Chiu , Jason S. Kuo , J. Patrick Shelby , David S.W. Lim
发明人： Daniel T. Chiu , Jason S. Kuo , J. Patrick Shelby , David S.W. Lim
IPC分类号： G01N33/49 , B01D29/05 , B01D37/00
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。

5. 发明申请

US20120129190A1 ENSEMBLE-DECISION ALIQUOT RANKING 审中-公开
标题翻译： ENSEMBLE-DECISION ALIQUOT排名
公开(公告)号：US20120129190A1
公开(公告)日：2012-05-24
申请号：US13257571
申请日：2010-04-13
申请人： Daniel T. Chiu , Perry G. Schiro , Jason S. Kuo
发明人： Daniel T. Chiu , Perry G. Schiro , Jason S. Kuo
IPC分类号： G01N21/64 , C12M1/34 , G01N21/76 , C12Q1/04
CPC分类号： G01N33/6893 , G01N33/5302 , G01N33/5308 , G01N33/57407 , Y02A50/58
摘要： Provided herein, among other aspects, are methods and apparatuses for ranking aliquots from a suspension containing bioparticles. In certain embodiments, the bioparticles may be cells, organelles, proteins, DNAs, debris of biological origin, microbeads coated with biological compounds, or viral particles. As such, the methods and apparatuses provided herein may be used to quantify rare cells such as circulating cancer cells, fetal cells and other rare cells present in bodily fluids for disease diagnosis, prognosis, or treatment.
摘要翻译：除了其它方面之外，本文提供了用于从含有生物颗粒的悬浮液排列等分试样的方法和装置。在某些实施方案中，生物颗粒可以是细胞，细胞器，蛋白质，DNA，生物来源的碎片，用生物化合物涂覆的微珠或病毒颗粒。因此，本文提供的方法和装置可以用于定量罕见细胞，例如循环癌细胞，胎儿细胞和存在于体液中的其它稀有细胞用于疾病诊断，预后或治疗。

6. 发明授权

US07524409B2 Method and system for electrokinetic, preparative sample separation in high-surface-area separation channels with non-convex cross sections 失效
标题翻译：在具有非凸截面的高表面积分离通道中电动，制备样品分离的方法和系统
公开(公告)号：US07524409B2
公开(公告)日：2009-04-28
申请号：US10846147
申请日：2004-05-14
申请人： Daniel T. Chiu , Jason S. Kuo , David S. W. Lim
发明人： Daniel T. Chiu , Jason S. Kuo , David S. W. Lim
IPC分类号： B81B1/00
CPC分类号： G01N23/20
摘要： Embodiments of the present invention employ complexly shaped, high-surface-area channels for separation and purification of molecules, including important biopolymers such as proteins, glycoproteins, polysaccharides, and other molecular components of living cells. The relatively large internal surface areas of the complexly shaped channels employed in embodiments of the present invention provide, in comparison to traditional, simply shaped separation channels, increased heat dissipation during electrokinetic separation, and a decreased tendency for bulk-solution flow. Heat dissipation prevents high temperatures that can denature proteins and that can induce thermal currents within the separation channel. Bulk-solution flow within a separation channel can overwhelm the generally linear, electrical-potential-induced migration of molecules that leads to efficient and well-resolved molecular separations. The complexly shaped channels employed in various embodiments of the present invention can be readily manufactured at microscale dimensions for use in microscale devices, at millimeter-scale dimensions for inclusion in microfluidics devices, and may also be used in larger scale, traditional separation and purification systems.
摘要翻译：本发明的实施方案采用复杂形状的高表面积通道用于分离和纯化分子，包括重要的生物聚合物如蛋白质，糖蛋白，多糖和活细胞的其它分子组分。与传统的简单成型的分离通道相比，在本发明的实施方案中采用的复杂形状的通道的相对较大的内表面积提供了电动分离期间增加的散热性和体积溶液流动的趋势。散热可以预防高温，使蛋白质变性，并能在分离通道内引起热流。分离通道内的体积溶液流可以压倒一般线性的电位诱导的分子迁移，导致有效和良好的分解分离。在本发明的各种实施方案中使用的复杂形状的通道可以容易地以微尺度制造用于微尺寸装置，以毫米级尺寸包含在微流体装置中，并且还可用于较大规模的传统分离和净化系统。

7. 发明申请

US20080248499A1 Methods and Apparatus for the Isolation and Enrichment of Circulating Tumor Cells 有权
标题翻译：循环肿瘤细胞的分离和富集的方法和装置
公开(公告)号：US20080248499A1
公开(公告)日：2008-10-09
申请号：US11766044
申请日：2007-06-20
申请人： Daniel T. Chiu , Jason S. Kuo
发明人： Daniel T. Chiu , Jason S. Kuo
IPC分类号： G01N33/574 , C12M1/00 , C12N5/00
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。

8. 发明授权

US08173413B2 Separation and concentration of biological cells and biological particles using a one-dimensional channel 有权
标题翻译：使用一维通道分离和浓缩生物细胞和生物颗粒
公开(公告)号：US08173413B2
公开(公告)日：2012-05-08
申请号：US11202416
申请日：2005-08-11
申请人： Daniel T. Chiu , Jason S. Kuo
发明人： Daniel T. Chiu , Jason S. Kuo
IPC分类号： C12M1/00
CPC分类号： G01N1/34 , B01L3/50273 , B01L3/502753 , B01L2200/0668 , B01L2300/0681 , B01L2400/0409 , B01L2400/0415 , B01L2400/0487
摘要： This document discloses, among other things, a method and system for a substrate having a bypass region for fluid flow. The substrate includes a plurality of fluid flow channels with each channel configured to concurrently allow fluid flow while precluding passage of a target particle or object.
摘要翻译：本文件尤其公开了一种具有用于流体流动的旁路区域的衬底的方法和系统。衬底包括多个流体流动通道，每个通道构造成同时允许流体流动，同时排除目标颗粒或物体的通过。

9. 发明申请

US20110257894A1 METHOD FOR DECONVOLVING SINGLE-MOLECULE INTENSITY DISTRIBUTIONS FOR QUANTITATIVE BIOLOGICAL MEASUREMENTS 审中-公开
标题翻译：消除用于定量生物测量的单分子强度分布的方法
公开(公告)号：US20110257894A1
公开(公告)日：2011-10-20
申请号：US13155248
申请日：2011-06-07
申请人： Daniel T. Chiu , Sarah Ann Nielsen , Bryant S. Fujimoto , Christopher Lee Kuyper , Jason S. Kuo , Sandra M. Bajjalieh
发明人： Daniel T. Chiu , Sarah Ann Nielsen , Bryant S. Fujimoto , Christopher Lee Kuyper , Jason S. Kuo , Sandra M. Bajjalieh
IPC分类号： G06F17/18 , G06F19/10
CPC分类号： G01N21/6428 , G01N21/6458 , G01N21/648 , G01N2021/6439 , G01N2021/6441 , G01N2021/653
摘要： A method for quantifying fluorescent puncta comprising acquiring at least one first intensity distribution comprising fluorescence intensity values from a plurality of first fluorescent puncta; acquiring at least one second intensity distribution comprising fluorescence intensity values from a plurality of second fluorescent puncta, wherein each second fluorescent puncta has a determined number of fluorescent emitters; determining the relationship between the first and second intensity distributions; and fitting the second intensity distribution to the first intensity distribution to provide a count and distribution of the number of fluorescent emitters within the first fluorescent puncta.
摘要翻译：一种用于量化荧光点的方法，包括从多个第一荧光斑点中获取包含荧光强度值的至少一个第一强度分布; 获取包括来自多个第二荧光点的荧光强度值的至少一个第二强度分布，其中每个第二荧光点具有确定数量的荧光发射器; 确定第一和第二强度分布之间的关系; 以及将所述第二强度分布拟合到所述第一强度分布中以提供所述第一荧光点内的荧光发射体的数量的计数和分布。

10. 发明申请

US20100279321A1 METHODS AND APPARATUS FOR THE ISOLATION AND ENRICHMENT OF CIRCULATING TUMOR CELLS 有权
标题翻译：用于分离和扩增循环肿瘤细胞的方法和装置
公开(公告)号：US20100279321A1
公开(公告)日：2010-11-04
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： G01N33/574 , C12N5/09 , C12M1/12
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。

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