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1. 发明授权

US09134237B2 High sensitivity multiparameter method for rare event analysis in a biological sample 有权
公开(公告)号：US09134237B2
公开(公告)日：2015-09-15
申请号：US12181399
申请日：2008-07-29
申请人： Mark Carle Connelly , Frank Coumans , Steve Gross , Mike Kelly
发明人： Mark Carle Connelly , Frank Coumans , Steve Gross , Mike Kelly
IPC分类号： G01N33/574 , G01N33/53 , C12N5/07 , G01N33/566 , G01N33/553 , G01N21/64 , G01N33/50 , G01N33/569 , G01N33/58
CPC分类号： G01N21/6428 , G01N21/6458 , G01N33/5091 , G01N33/5094 , G01N33/569 , G01N33/57488 , G01N33/582 , G01N2021/6441
摘要： A sample of blood containing CTCs, or other cells of interest, is stained with fluorescent markers for image analysis and scanned to identify the presence and location within the cartridge of target cells or subcellular elements. A sample containing desired target cells or subcellular elements is then further processed, in part by photobleaching the sample, so that those same targets may be re-analyzed with additional biomarkers conjugated to the same or different fluorochromes using the same imaging criteria that were used for the initial analysis. The present invention has applications with targets such as circulating epithelial, cells, circulating tumor cells, circulating endothelial cells, leukocytes, lymphocyte subsets, cells containing an organelle or receptor of interest, cellular debris, disrupted cells and their debris, or any other formed element that might be captured and imaged. The invention provides a means to further interrogate individual targets of interest, especially when coupled with genetic analysis such as FISH.

2. 发明授权

US09127302B2 System for the detection and enumeration of suspect target cells in a mixed cell population 有权
标题翻译：用于在混合细胞群体中检测和计数可疑靶细胞的系统
公开(公告)号：US09127302B2
公开(公告)日：2015-09-08
申请号：US12067532
申请日：2006-09-20
申请人： John A Verrant , Arjan G. J. Tibbe , Brad Foulk , Joost F. Swennenhuis , Leon W. M. M. Terstappen , Mark Carle Connelly , Michael T. Kagan
发明人： John A Verrant , Arjan G. J. Tibbe , Brad Foulk , Joost F. Swennenhuis , Leon W. M. M. Terstappen , Mark Carle Connelly , Michael T. Kagan
IPC分类号： C12Q1/68 , G01N33/53 , C12M1/00 , C12M1/34 , A61K39/395 , C12Q1/34
CPC分类号： C12Q1/6886 , C12Q1/34 , C12Q1/6811 , C12Q1/6876 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , C12Q2533/101 , C12Q2531/113 , C12Q2521/301 , C12Q2563/131 , C12Q2563/103
摘要： The invention relates generally to the field of identification of DNA sequences, genes or chromosomes. Methods and composition to obtain Unique Sequence DNA probes are provided. Composition comprises of any double stranded DNA containing Unique Sequences from which the repetitive sequences are eliminated according to the method described in this invention. The invention also relates to the preservation of cells that have been identified after immunomagnetic selection and fluorescent labeling in order to further interrogate the cells of interest. Furthermore the invention relates to genetic analysis of cells that have been identified after immunomagnetic selection and fluorescent labeling.
摘要翻译：本发明一般涉及DNA序列，基因或染色体的鉴定领域。提供了获得独特序列DNA探针的方法和组成。组合物包含根据本发明描述的方法从其中排除重复序列的任何含有唯一序列的双链DNA。本发明还涉及在免疫磁性选择和荧光标记之后鉴定的细胞的保存以进一步询问感兴趣的细胞。此外，本发明涉及在免疫磁性选择和荧光标记之后鉴定的细胞的遗传分析。

3. 发明申请

US20130189675A1 Assay to Capture and Detect Circulating Multiple Myeloma Cells from Blood 有权
标题翻译：测定从血液中捕获和检测循环多发性骨髓瘤细胞
公开(公告)号：US20130189675A1
公开(公告)日：2013-07-25
申请号：US13554623
申请日：2012-07-20
申请人： Steven Gross , Mark Carle Connelly , Galla Chandra Rao , Marielena Mata , Carrie Morano
发明人： Steven Gross , Mark Carle Connelly , Galla Chandra Rao , Marielena Mata , Carrie Morano
IPC分类号： G01N33/574
CPC分类号： G01N33/57492 , B03C1/01 , B03C1/28 , B03C2201/26 , G01N33/57426
摘要： The invention includes methods for isolating circulating multiple myeloma cells as well as method of treating patients suspected of having diseases of abnormal plasma cells.
摘要翻译：本发明包括分离循环多发性骨髓瘤细胞的方法以及治疗怀疑患有异常浆细胞疾病的患者的方法。

4. 发明申请

US20120202189A1 RAPID, SEMI-AUTOMATED METHOD TO DETECT RESPIRATORY VIRUS INFECTED CELLS IN DIRECT SPECIMENS 审中-公开
标题翻译： RAPID，半自动检测直接样本中呼吸道感染细胞的方法
公开(公告)号：US20120202189A1
公开(公告)日：2012-08-09
申请号：US12450846
申请日：2008-04-16
申请人： Mark Carle Connelly , Frank A.W. Coumans , Jimmy Page , Galla Chandra Rao , Joseph Jollick, JR.
发明人： Mark Carle Connelly , Frank A.W. Coumans , Jimmy Page , Galla Chandra Rao , Joseph Jollick, JR.
IPC分类号： G01N21/17
CPC分类号： G01N33/56983 , G01N33/5091 , G01N33/54326 , G01N2333/11
摘要： A novel cytometer system, methods and algorithms which provide a rugged, affordable and easy-to-use device in remote locations. All cells in a biological sample are fluorescently labeled, with target cells also magnetically labeled. Non-magnetically labeled cells are imaged for viability. Labeled sample is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells for observation. A LED illuminates the cells and a CCO camera captures the images of the fluorescent light emitted by the target cells. Image analysis performed with a novel algorithm provides a cell count that can be related to the target cell concentration of the original sample.
摘要翻译：一种新颖的细胞仪系统，方法和算法，可在远程位置提供坚固耐用，价格实惠且易于使用的设备。生物样品中的所有细胞都被荧光标记，靶细胞也被磁性标记。对非磁性标记的细胞进行成像。将标记的样品放置在两个楔形磁体之间，以选择性地移动磁性标记的细胞用于观察。 LED照亮细胞，CCO相机拍摄由靶细胞发出的荧光的图像。用新颖算法进行的图像分析提供了可以与原始样品的靶细胞浓度相关的细胞计数。

5. 发明授权

US07901950B2 Method for assessing disease states by profile analysis of isolated circulating endothelial cells 有权
标题翻译：通过分离的循环内皮细胞的轮廓分析来评估疾病状态的方法
公开(公告)号：US07901950B2
公开(公告)日：2011-03-08
申请号：US11701763
申请日：2007-02-02
申请人： Mark Carle Connelly , Gerald V. Doyle , Galla Chandra Rao , Leon W. M. M. Terstappen
发明人： Mark Carle Connelly , Gerald V. Doyle , Galla Chandra Rao , Leon W. M. M. Terstappen
IPC分类号： G01N33/553 , G01N33/00 , G01N1/00 , G01N1/18
CPC分类号： G01N33/6893 , G01N33/5091 , G01N2800/32 , Y10T436/101666 , Y10T436/107497 , Y10T436/108331 , Y10T436/2525 , Y10T436/25375
摘要： Elevated number of Circulating Endothelial Cells (CEC) have been implicated in disease conditions associated with the formation or destruction of blood vessels such as acute coronary syndrome, thrombocytopenic purpura, sickle cell disease, sepsis, lupus, nephrotic syndromes, rejection of organ transplants, surgical trauma and cancer. This invention provides a method for assessing the levels of CEC which vary between different studies using a sensitive enrichment, imaging, and enumberation analysis. CD146 is one of the most specific endothelium-associated cell-surface antigens which can be used in image cytometry. CEC analysis provides an essential tool in prognostic/diagnostic evaluation in the clinic.
摘要翻译：循环内皮细胞数量增多已经涉及与血管形成或破坏有关的疾病状况，如急性冠状动脉综合征，血小板减少性紫癜，镰状细胞病，败血症，狼疮，肾病综合征，器官移植排斥，外科手术创伤和癌症。本发明提供了一种用于评估使用敏感浓缩，成像和启发分析的不同研究之间变化的CEC水平的方法。 CD146是可用于图像细胞计数的最特异的内皮相关细胞表面抗原之一。 CEC分析为诊所的预后/诊断评估提供了重要的工具。

6. 发明申请

US20090029378A1 High sensitivity multiparameter method for rare event analysis in a biological sample 有权
标题翻译：用于生物样品中罕见事件分析的高灵敏度多参数方法
公开(公告)号：US20090029378A1
公开(公告)日：2009-01-29
申请号：US12181399
申请日：2008-07-29
申请人： Mark Carle Connelly , Frank Coumans , Steve Gross , Mike Kelly
发明人： Mark Carle Connelly , Frank Coumans , Steve Gross , Mike Kelly
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： G01N21/6428 , G01N21/6458 , G01N33/5091 , G01N33/5094 , G01N33/569 , G01N33/57488 , G01N33/582 , G01N2021/6441
摘要： A sample of blood containing CTCs, or other cells of interest, is stained with fluorescent markers for image analysis and scanned to identify the presence and location within the cartridge of target cells or subcellular elements. A sample containing desired target cells or subcellular elements is then further processed, in part by photobleaching the sample, so that those same targets may be re-analyzed with additional biomarkers conjugated to the same or different fluorochromes using the same imaging criteria that were used for the initial analysis. The present invention has applications with targets such as circulating epithelial, cells, circulating tumor cells, circulating endothelial cells, leukocytes, lymphocyte subsets, cells containing an organelle or receptor of interest, cellular debris, disrupted cells and their debris, or any other formed element that might be captured and imaged. The invention provides a means to further interrogate individual targets of interest, especially when coupled with genetic analysis such as FISH.
摘要翻译：含有CTC或其他感兴趣的细胞的血液样品用用于图像分析的荧光标记染色并扫描以鉴定靶细胞或亚细胞元件的盒内的存在和位置。然后进一步处理含有所需靶细胞或亚细胞元件的样品，部分通过光漂白样品进行处理，使得可以使用与用于相同或不同荧光染料的相同成像标准的附加生物标志物重新分析相同的靶标初步分析。本发明具有诸如循环上皮细胞，细胞，循环肿瘤细胞，循环内皮细胞，白细胞，淋巴细胞亚群，含有感兴趣的细胞器或受体的细胞，细胞碎片，破裂的细胞及其碎片或任何其它形成的元件这可能被捕获和成像。本发明提供了进一步询问感兴趣的个体目标的方法，特别是当与FISH等遗传分析相结合时。

7. 发明申请

US20090191535A1 Method of assessing metastatic carcinomas from circulating endothelial cells and disseminated tumor cells 审中-公开
标题翻译：评估循环内皮细胞和弥散性肿瘤细胞的转移癌的方法
公开(公告)号：US20090191535A1
公开(公告)日：2009-07-30
申请号：US12004805
申请日：2007-12-22
申请人： Mark Carle Connelly , Gerald V. Doyle , Galla Chandra Rao , Leon W.M.M. Terstappen
发明人： Mark Carle Connelly , Gerald V. Doyle , Galla Chandra Rao , Leon W.M.M. Terstappen
IPC分类号： A01N1/02 , C12Q1/02
CPC分类号： G01N33/57415 , G01N33/574 , G01N33/57492
摘要： A method for assessing cancer in test subjects is described based upon enumeration of circulating endothelial cells and/or disseminated tumor cells in a test subject. This method is used to quantify disseminated tumor cells. Correlations with circulating tumor cells provides prognostic information with high accuracy in assessing the risk of recurrence in patients with primary breast cancer.
摘要翻译：基于在测试对象中循环内皮细胞和/或扩散的肿瘤细胞的计数来描述用于评估测试受试者中的癌症的方法。该方法用于量化弥散性肿瘤细胞。与循环肿瘤细胞的相关性在准确评估原发性乳腺癌患者复发风险方面提供预后信息。

8. 发明申请

US20090136946A1 Automated Enumeration and Characterization of Circulating Melanoma Cells in Blood 审中-公开
标题翻译：血液中循环黑色素瘤细胞的自动计数和表征
公开(公告)号：US20090136946A1
公开(公告)日：2009-05-28
申请号：US12254188
申请日：2008-10-20
申请人： Mark Carle CONNELLY , Galla Chandra Rao , Leon W.M.M. Terstappen
发明人： Mark Carle CONNELLY , Galla Chandra Rao , Leon W.M.M. Terstappen
IPC分类号： C12Q1/68 , C12Q1/02 , G01N33/574
CPC分类号： G01N33/5743 , G01N33/57488 , G01N2333/70589 , G01N2333/70596
摘要： The CellTracks® System provides a system to enumerate circulating melanoma cells in blood. The system immunomagnetically concentrates epithelial cells, fluorescently labels the cells and identifies and quantifies circulating melanoma cells. The absolute number of circulating melanoma cells detected in the peripheral blood tumor load is, in part, a factor in prediction of survival, time to progression, and response to therapy. Diagnosis and monitoring of melanoma has been limited by the inability to monitor circulating melanoma cells. The present invention provides a method to enumerate circulating melanoma cells in blood samples. Accordingly, this technology provides a means and device for monitoring disease progression in patients with melanoma.
摘要翻译： CellTracks（R）系统提供了一种系统来枚举血液中的循环黑素瘤细胞。该系统免疫磁性浓缩上皮细胞，荧光标记细胞，并鉴定和量化循环黑素瘤细胞。在外周血肿瘤负荷中检测到的循环黑素瘤细胞的绝对数量部分地是预测存活时间，进展时间和对治疗反应的因素。黑色素瘤的诊断和监测受到无法监测循环黑素瘤细胞的限制。本发明提供了一种列举血液样品中循环黑素瘤细胞的方法。因此，该技术提供了用于监测黑素瘤患者疾病进展的手段和装置。

9. 发明授权

US09618515B2 Assay to capture and detect circulating multiple myeloma cells from blood 有权
公开(公告)号：US09618515B2
公开(公告)日：2017-04-11
申请号：US13554623
申请日：2012-07-20
申请人： Steven Gross , Mark Carle Connelly , Galla Chandra Rao , Marielena Mata , Carrie Morano
发明人： Steven Gross , Mark Carle Connelly , Galla Chandra Rao , Marielena Mata , Carrie Morano
IPC分类号： G01N33/551 , G01N33/566 , G01N33/574 , B03C1/01 , B03C1/28
CPC分类号： G01N33/57492 , B03C1/01 , B03C1/28 , B03C2201/26 , G01N33/57426
摘要： The invention includes methods for isolating circulating multiple myeloma cells as well as method of treating patients suspected of having diseases of abnormal plasma cells.

10. 发明授权

US08940493B2 Circulating tumor cell assay 有权
标题翻译：循环肿瘤细胞测定
公开(公告)号：US08940493B2
公开(公告)日：2015-01-27
申请号：US12303243
申请日：2007-05-29
申请人： Antonio Gualberto , Maria Luisa Paccagnella , Carrie L. Melvin , Madeline I. Repollet , David Chianese , Mark Carle Connelly , Leonardus Wendelinus Mathias Marie Terstappen
发明人： Antonio Gualberto , Maria Luisa Paccagnella , Carrie L. Melvin , Madeline I. Repollet , David Chianese , Mark Carle Connelly , Leonardus Wendelinus Mathias Marie Terstappen
IPC分类号： G01N33/574 , G01N33/50 , G01N30/02
CPC分类号： G01N33/57496 , G01N30/02 , G01N33/5023 , G01N33/5064 , G01N33/574 , G01N33/57492 , G01N2333/4742 , G01N2333/4745 , G01N2333/71 , G01N2333/91205 , G01N2458/00 , G01N2800/52 , B01D15/3804
摘要： Methods for the detection, enumeration and analysis of circulating tumor cells expressing insulin-like growth factor-1 receptors (IGF-1R) are disclosed. These methods are useful for cancer screening and staging, development of treatment regimens, and for monitoring for treatment responses, cancer recurrence or the like. Test kits that facilitate the detection, enumeration and analysis of such circulating tumor cells are also provided.
摘要翻译：公开了用于检测，计数和分析表达胰岛素样生长因子-1受体（IGF-1R）的循环肿瘤细胞的方法。这些方法可用于癌症筛查和分期，治疗方案的开发，以及用于治疗反应，癌症复发等的监测。还提供了促进这种循环肿瘤细胞的检测，计数和分析的测试试剂盒。

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