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1. 发明授权

US06551843B1 Methods for enhancing binding interactions between members of specific binding pairs 失效
标题翻译：增强特异性结合对成员之间结合相互作用的方法
公开(公告)号：US06551843B1
公开(公告)日：2003-04-22
申请号：US09240939
申请日：1999-01-29
申请人： Galla Chandra Rao , Leon Terstappen , Paul Liberti
发明人： Galla Chandra Rao , Leon Terstappen , Paul Liberti
IPC分类号： G01N3353
CPC分类号： G01N33/54333
摘要： Disclosed is a method that improves the efficiency of reactions between specific binding pairs. By translating one member of the pair through a suspension of the second member, or across a surface to which the second member is immobilized, collision and binding frequencies are greatly increased. The resulting increased binding frequency allows for reduced incubation times and lower incubation temperatures. The enhanced collisions are advantageous for both molecular reactions, in which mixing is not always effective, and cellular reactions, in which the cells may be damaged by mixing.
摘要翻译：公开了一种提高特异性结合对之间的反应效率的方法。通过将该对中的一个构件通过第二构件的悬架或通过固定有第二构件的表面平移，大大增加了碰撞和装订频率。所产生的增加的结合频率允许减少的孵育时间和较低的温育温度。增强的碰撞对于分子反应是有利的，其中混合并不总是有效，以及细胞反应，其中细胞可能被混合而损伤。

2. 发明申请

US20110300551A1 METHOD OF PREDICTING CLINICAL OUTCOMES FOR MELANOMA PATIENTS USING CIRCULATING MELANOMA CELLS IN BLOOD 审中-公开
标题翻译：使用血液循环细胞在血液中预测梅毒患者的临床结果的方法
公开(公告)号：US20110300551A1
公开(公告)日：2011-12-08
申请号：US13155687
申请日：2011-06-08
申请人： Galla Chandra Rao , Mark C. Connelly
发明人： Galla Chandra Rao , Mark C. Connelly
IPC分类号： C12Q1/68 , G01N33/574 , C12Q1/06
CPC分类号： G01N33/5743 , G01N33/57488 , G01N2333/70589 , G01N2333/70596
摘要： The present invention provides an automated method for capturing and detecting circulating melanoma cells (CMC's) in the blood of patients with melanoma. 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.
摘要翻译：本发明提供了一种捕获和检测黑素瘤患者血液中循环黑素瘤细胞（CMC）的自动化方法。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。

3. 发明申请

US20100326587A1 UPON A CARTRIDGE FOR CONTAINING A SPECIMEN SAMPLE FOR OPTICAL ANALYSIS 审中-公开
标题翻译：包含用于光学分析的样品样品的盒子
公开(公告)号：US20100326587A1
公开(公告)日：2010-12-30
申请号：US12876189
申请日：2010-09-06
申请人： Michael Kagan , Galla Chandra Rao , Jerry Prohaska , Tor Alden
发明人： Michael Kagan , Galla Chandra Rao , Jerry Prohaska , Tor Alden
IPC分类号： B32B17/10
CPC分类号： B01L3/508 , B01L2200/0642 , B01L2200/0689 , B01L2300/042 , B01L2300/046 , G01N21/11 , G01N35/0098 , Y10T436/2575
摘要： An improved cartridge for holding a fluid sample with a small volume is disclosed herein. The cartridge has a test chamber and a vestibule through which the test fluids are inserted into the test chamber. Improved grips are flared-out to aid manipulation. The handle portion is reinforced to prevent flexing, and a prefabricated trough along the edge of the land surface prevents introduction of the adhesive into the region for analysis. The cartridge has a stopper having a dual sealing mechanism, which seals the test chamber inlet between the vestibule and the test chamber, and the mouth of the vestibule so that when the stopper is in place, the test chamber is closed to the admission of air or other contaminants. The vestibule is similarly closed against escape of the overflow from the test chamber. The stopper is composed of a single elastomer. An improved locking mechanism has two flexible walls on either side of the handhold that locks into their respective keepers on the cartridge to provide a secure lock. Additionally, an improved method for loading the cartridge allows for an even distribution of magnetically responsive particles contained within a fluid sample to be viewed in an array through the optically clear land surface portion of the cartridge.
摘要翻译：本文公开了一种用于保持具有小体积的流体样品的改进的盒。盒具有测试室和前庭，测试流体通过该前庭插入测试室。改进的手柄被展开以帮助操纵。手柄部分被加强以防止弯曲，并且沿着陆面表面的边缘的预制槽防止粘合剂引入该区域用于分析。盒具有一个具有双重密封机构的塞子，该密封机构密封前庭和测试室之间的测试室入口以及前庭的口，使得当止动器就位时，测试室被关闭以允许空气或其他污染物。前庭也相似地封闭，防止溢出物从测试室逸出。止动器由单个弹性体组成。改进的锁定机构在手柄的任一侧具有两个柔性壁，其锁定在其相应的保持器上，以提供安全的锁定。此外，用于装载盒的改进方法允许包含在流体样品内的磁响应颗粒的均匀分布，以通过盒的光学透明的陆面表面部分在阵列中观察。

4. 发明授权

US07863012B2 Analysis of circulating tumor cells, fragments, and debris 有权
标题翻译：分析循环肿瘤细胞，碎片和碎片
公开(公告)号：US07863012B2
公开(公告)日：2011-01-04
申请号：US10780399
申请日：2004-02-17
申请人： Galla Chandra Rao , Christopher Larson , Madeline Repollet , Herman Rutner , Leon W. M. M. Terstappen , Shawn Mark O'Hara , Steven Gross
发明人： Galla Chandra Rao , Christopher Larson , Madeline Repollet , Herman Rutner , Leon W. M. M. Terstappen , Shawn Mark O'Hara , Steven Gross
IPC分类号： A01N1/02 , G01N33/574 , G01N33/553 , G01N33/00
CPC分类号： G01N33/574 , G01N33/54326 , Y10S436/813 , Y10T436/101666 , Y10T436/25125 , Y10T436/25375
摘要： The methods and reagents described in this invention are used to analyze circulating tumor cells, clusters, fragments, and debris. Analysis is performed with a number of platforms, including flow cytometry and the CellSpotter® fluorescent microscopy imaging system. Analyzing damaged cells has shown to be important. However, there are two sources of damage: in vivo and in vitro. Damage in vivo occurs by apoptosis, necrosis, or immune response. Damage in vitro occurs during sample acquisition, handling, transport, processing, or analysis. It is therefore desirable to confine, reduce, eliminate, or at least qualify in vitro damage to prevent it from interfering in analysis. Described herein are methods to diagnose, monitor, and screen disease based on circulating rare cells, including malignancy as determined by CTC, clusters, fragments, and debris. Also provided are kits for assaying biological specimens using these methods.
摘要翻译：本发明描述的方法和试剂用于分析循环肿瘤细胞，簇，碎片和碎片。使用许多平台进行分析，包括流式细胞术和CellSpotter®荧光显微镜成像系统。分析损伤的细胞已被证明是重要的。然而，有两个损害来源：体内和体外。体内损伤是通过细胞凋亡，坏死或免疫应答发生的。在样品采集，处理，运输，加工或分析过程中发生体外损伤。因此，期望限制，减少，消除或至少限定体外损伤，以防止其干扰分析。本文描述了基于循环稀有细胞（包括由CTC，簇，碎片和碎片确定的恶性肿瘤）来诊断，监测和筛选疾病的方法。还提供了使用这些方法测定生物样品的试剂盒。

5. 发明授权

US07332288B2 Methods and reagents for the rapid and efficient isolation of circulating cancer cells 有权
标题翻译：循环癌细胞快速有效分离的方法和试剂
公开(公告)号：US07332288B2
公开(公告)日：2008-02-19
申请号：US10269579
申请日：2002-10-11
申请人： Leon W. M. M. Terstappen , Galla Chandra Rao , Jonathan W. Uhr , Emilian V. Racila , Paul A. Liberti
发明人： Leon W. M. M. Terstappen , Galla Chandra Rao , Jonathan W. Uhr , Emilian V. Racila , Paul A. Liberti
IPC分类号： G01N33/53 , G01N33/553 , G01N33/546 , C07K17/00 , C07K1/13
CPC分类号： B82Y25/00 , B03C1/01 , G01N33/574 , G01N33/57484 , G01N33/57492 , H01F1/0054
摘要： A highly sensitive assay is disclosed which combines immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis to detect, enumerate and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood and has a greater sensitivity than conventional PCR or immunohistochemistry by 1-2 orders of magnitude. In addition, the assay facilitates the biological characterization and staging of carcinoma cells.
摘要翻译：公开了一种高度敏感的测定法，其将免疫磁性富集与多参数流式细胞术和免疫细胞化学分析结合，以检测，列举和表征血液中的癌细胞。该测定可以检测1ml血液中的一种上皮细胞或更少的灵敏度，并且比常规PCR或免疫组织化学检测灵敏度高1-2个数量级。此外，该测定方法可促进癌细胞的生物学表征和分期。

6. 发明授权

US07011794B2 Upon a cartridge for containing a specimen sample for optical analysis 有权
标题翻译：用于容纳用于光学分析的样本样品的盒
公开(公告)号：US07011794B2
公开(公告)日：2006-03-14
申请号：US10303309
申请日：2002-11-25
申请人： Michael Kagan , Galla Chandra Rao , Jerry Prohaska , Tor Alden
发明人： Michael Kagan , Galla Chandra Rao , Jerry Prohaska , Tor Alden
IPC分类号： B01L3/00
CPC分类号： B01L3/508 , B01L2200/0642 , B01L2200/0689 , B01L2300/042 , B01L2300/046 , G01N21/11 , G01N35/0098 , Y10T436/2575
摘要： An improved cartridge for holding a fluid sample with a small volume is disclosed herein. The cartridge has a test chamber and a vestibule through which the test fluids are inserted into the test chamber. Improved grips are flared-out to aid manipulation. The handle portion is reinforced to prevent flexing, and a prefabricated trough along the edge of the land surface prevents introduction of the adhesive into the region for analysis. The cartridge has a stopper having a dual sealing mechanism, which seals the test chamber inlet between the vestibule and the test chamber, and the mouth of the vestibule so that when the stopper is in place, the test chamber is closed to the admission of air or other contaminants. The vestibule is similarly closed against escape of the overflow from the test chamber. The stopper is composed of a single elastomer. An improved locking mechanism has two flexible walls on either side of the handhold that locks into their respective keepers on the cartridge to provide a secure lock. Additionally, an improved method for loading the cartridge allows for an even distribution of magnetically responsive particles contained within a fluid sample to be viewed in an array through the optically clear land surface portion of the cartridge.
摘要翻译：本文公开了一种用于保持具有小体积的流体样品的改进的盒。盒具有测试室和前庭，测试流体通过该前庭插入测试室。改进的手柄被展开以帮助操纵。手柄部分被加强以防止弯曲，并且沿着陆面表面的边缘的预制槽防止粘合剂引入该区域用于分析。盒具有一个具有双重密封机构的塞子，该密封机构密封前庭和测试室之间的测试室入口以及前庭的口，使得当止动器就位时，测试室被关闭以允许空气或其他污染物。前庭也相似地封闭，防止溢出物从测试室逸出。止动器由单个弹性体组成。改进的锁定机构在手柄的任一侧具有两个柔性壁，其锁定在其相应的保持器上，以提供安全的锁定。此外，用于装载盒的改进方法允许包含在流体样品内的磁响应颗粒的均匀分布，以通过盒的光学透明的陆面表面部分在阵列中观察。

7. 发明授权

US5660990A Surface immobilization of magnetically collected materials 失效
标题翻译：磁性收集材料的表面固定
公开(公告)号：US5660990A
公开(公告)日：1997-08-26
申请号：US516694
申请日：1995-08-18
申请人： Galla Chandra Rao , Paul A. Liberti
发明人： Galla Chandra Rao , Paul A. Liberti
IPC分类号： C12Q1/68 , G01N33/543 , C12Q1/70 , G01N33/53
CPC分类号： C12Q1/6813 , C12Q1/6834 , G01N33/54313 , Y10S436/807 , Y10S436/824 , Y10S977/838 , Y10S977/853 , Y10S977/918 , Y10S977/958 , Y10S977/96
摘要： A method for determining the presence and/or concentration of a target substance e.g. protein, nucleic acid, bioparticle etc. in a fluid sample is provided. The method disclosed combines elements of immunoassays, coated cup assays and magnetic particle separation to effect the quantitation and recovery of an analyte in solution. Also the method ensures the non-reorientation of magnetically collected material by linking the magnetic particles to a collection surface via a specific binding pair. This linkage immobilizes the magnetic-analyte-containing material and thus allows for vigorous washing and reagent addition without significant redistribution or displacement. Thus the assay of this invention offers the speed of diffusion controlled kinetics as in a ferrofluid assay, the speed of collection of labeled target substance as in a magnetic assay as well as the ability to magnetically monolayer the ferrofluid, all of which is combined with the ease of washing and signal detection found in a coated cup assay.
摘要翻译：用于确定靶物质的存在和/或浓度的方法，例如，提供了流体样品中的蛋白质，核酸，生物颗粒等。所公开的方法组合了免疫测定，涂覆杯测定和磁性颗粒分离的元件，以实现溶液中分析物的定量和回收。此外，该方法通过经由特异性结合对将磁性颗粒连接到收集表面来确保磁性收集材料的非重新取向。该连接固定了含有磁性分析物的材料，从而允许剧烈的洗涤和试剂添加，而不会有显着的再分配或位移。因此，本发明的测定提供了如铁磁流体测定中的扩散控制动力学速度，如在磁性测定中收集标记的靶物质的速度以及磁性单层铁磁流体的能力，所有这些都与在涂层杯测定中发现易洗涤和信号检测。

8. 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。

9. 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。

10. 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。

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