公开(公告)号：US20060115380A1

公开(公告)日：2006-06-01

申请号：US11294012

申请日：2005-12-05

申请人： Michael Kagan ,  Galla Rao ,  Jerry Prohaska ,  Tor Alden

发明人： Michael Kagan ,  Galla Rao ,  Jerry Prohaska ,  Tor Alden

IPC分类号： B01L9/00

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。

公开(公告)号：US20050181463A1

公开(公告)日：2005-08-18

申请号：US10780399

申请日：2004-02-17

申请人： Galla Rao ,  Christopher Larson ,  Madeline Repollet ,  Herman Rutner ,  Leon Terstappen ,  Shawn O'Hara ,  Steven Gross

发明人： Galla Rao ,  Christopher Larson ,  Madeline Repollet ,  Herman Rutner ,  Leon Terstappen ,  Shawn O'Hara ,  Steven Gross

IPC分类号： G01N33/53 ,  G01N33/543 ,  G01N33/567 ,  G01N33/574

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，包括流式细胞仪和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。

公开(公告)号：US20070154960A1

公开(公告)日：2007-07-05

申请号：US11701763

申请日：2007-02-02

申请人： Mark Connelly ,  Gerald Doyle ,  Galla Rao ,  Leon Terstappen

发明人： Mark Connelly ,  Gerald Doyle ,  Galla Rao ,  Leon Terstappen

IPC分类号： G01N33/567

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加已涉及与血管形成或破坏相关的疾病状况，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。

公开(公告)号：US20060194192A1

公开(公告)日：2006-08-31

申请号：US11413544

申请日：2006-04-28

申请人： Galla Rao ,  Melissa Herman ,  Herman Rutner ,  Leon Terstappen

发明人： Galla Rao ,  Melissa Herman ,  Herman Rutner ,  Leon Terstappen

IPC分类号： C12N5/00 ,  A01N1/02

CPC分类号： A01N1/02 ,  A01N1/0226 ,  A61K31/198 ,  A61K31/727

摘要： Compositions and methods for stabilizing rare cells in blood specimens, preserving the quality of blood specimens, and also serving as cell fixatives are disclosed which minimize losses of target cells (for example, circulating tumor cells) and formation of debris and aggregates from target cells, non-target cells and plasma components, thereby allowing more accurate analysis and classification of circulating tumor cells (CTC) and, ultimately, of tumor burdens in cancer patients. Stabilization of specimens is particularly desirable in protocols requiring rare cell enrichment from blood specimens drawn from cancer patients. Exposure of such specimens to potentially stressful conditions encountered, for example, in normal processing, mixing, shaking, delays due to transporting the blood, has been observed to not only diminish the number of CTC but also to generate debris and aggregates in the blood specimens that were found to interfere with accurate enumeration of target cells, if present. Stabilizers are necessary to discriminate between in vivo CTC disintegration and in vitro sample degredation.

摘要翻译： 公开了用于稳定血液标本中稀有细胞，保持血液标本质量以及用作细胞固定剂的组合物和方法，其使靶细胞（例如循环肿瘤细胞）的损失最小化，并从靶细胞形成碎片和聚集体， 非靶细胞和血浆成分，从而允许更准确地分析和分类循环肿瘤细胞（CTC），最终导致癌症患者的肿瘤负担。 在从癌症患者抽取的血液标本中需要罕见细胞富集的方案中，标本的稳定是特别需要的。 已经观察到这些样品暴露于例如在正常加工，混合，摇动，由于运送血液引起的延迟所遇到的潜在压力条件下，不仅减少了CTC的数量，而且在血样中产生碎片和聚集体 被发现干扰靶细胞的准确计数（如果存在）。 鉴别体内CTC分解和体外样品降解是必需的稳定剂。

公开(公告)号：US20050181353A1

公开(公告)日：2005-08-18

申请号：US10780349

申请日：2004-02-17

申请人： Galla Rao ,  Melissa Herman ,  Herman Rutner ,  Leon Terstappen

发明人： Galla Rao ,  Melissa Herman ,  Herman Rutner ,  Leon Terstappen

IPC分类号： A01N1/02 ,  A61K31/198 ,  A61K31/727

CPC分类号： A01N1/02 ,  A01N1/0226 ,  A61K31/198 ,  A61K31/727

摘要： Compositions and methods for stabilizing rare cells in blood specimens, preserving the quality of blood specimens, and also serving as cell fixatives are disclosed which minimize losses of target cells (for example, circulating tumor cells) and formation of debris and aggregates from target cells, non-target cells and plasma components, thereby allowing more accurate analysis and classification of circulating tumor cells (CTC) and, ultimately, of tumor burdens in cancer patients. Stabilization of specimens is particularly desirable in protocols requiring rare cell enrichment from blood specimens drawn from cancer patients. Exposure of such specimens to potentially stressful conditions encountered, for example, in normal processing, mixing, shaking, delays due to transporting the blood, has been observed to not only diminish the number of CTC but also to generate debris and aggregates in the blood specimens that were found to interfere with accurate enumeration of target cells, if present. Stabilizers are necessary to discriminate between in vivo CTC disintegration and in vitro sample degredation.

摘要翻译： 公开了用于稳定血液标本中稀有细胞，保持血液标本质量以及用作细胞固定剂的组合物和方法，其使靶细胞（例如循环肿瘤细胞）的损失最小化，并从靶细胞形成碎片和聚集体， 非靶细胞和血浆成分，从而允许更准确地分析和分类循环肿瘤细胞（CTC），最终导致癌症患者的肿瘤负担。 在从癌症患者抽取的血液标本中需要罕见细胞富集的方案中，标本的稳定是特别需要的。 已经观察到这些样品暴露于例如在正常加工，混合，摇动，由于运送血液引起的延迟所遇到的潜在压力条件下，不仅减少了CTC的数量，而且在血样中产生碎片和聚集体 被发现干扰靶细胞的准确计数（如果存在）。 鉴别体内CTC分解和体外样品降解是必需的稳定剂。