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1. 发明申请

US20080206757A1 METHODS AND COMPOSITIONS FOR DETECTING RARE CELLS FROM A BIOLOGICAL SAMPLE 有权
标题翻译：用于从生物样品中检测稀有细胞的方法和组合物
公开(公告)号：US20080206757A1
公开(公告)日：2008-08-28
申请号：US11841972
申请日：2007-08-20
申请人： Ping LIN , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar I. Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu
发明人： Ping LIN , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar I. Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu
IPC分类号： C12Q1/58 , C12N1/20 , G01N33/53
CPC分类号： C12N5/0693 , G01N33/5094 , G01N33/54346 , G01N33/56972 , G01N33/574 , G01N2015/1006 , G01N2015/1402 , G01N2333/70525 , G01N2333/70589 , G01N2800/52 , Y10T436/25375
摘要： The present invention provides methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells. In particular, the present invention includes a debulking step that uses a microfabricated filters for filtering fluid samples and the enriched rare cells can be used in a downstream process such as identifies, characterizes or even grown in culture or used in other ways. The invention also include a method of determining the aggressiveness of the tumor or of the number or proportion of cancer cells in the enriched sample by detecting the presence or amount of telomerase activity or telomerase nucleic acid or telomerase expression after enrichment of rare cells. This invention further provides an efficient and rapid method to specifically remove red blood cells as well as white blood cells from a biological sample containing at least one of each of red blood cells and white blood cells, resulting in the enrichment of rare target cells including circulating tumor cells (CTC), stromal cells, mesenchymal cells, endothelial cells, fetal cells, stem cells, non-hematopoietic cells etc from a blood sample. The method is based upon combination of immuno-microparticles (antibody coated microparticles) and density-based separation. The final enriched target cells can be subjected to a variety of analysis and manipulations, such as flowcytometry, PCR, immunofluorescence, immunocytochemistry, image analysis, enzymatic assays, gene expression profiling analysis, efficacy tests of therapeutics, culturing of enriched rare cells, and therapeutic use of enriched rare cells. In addition, depleted plasma protein and white blood cells can be optionally recovered, and subjected to other analysis such as inflammation studies, gene expression profiling, etc.
摘要翻译：本发明提供从含有其他类型细胞的生物样品中分离和检测稀有细胞的方法和组合物。特别地，本发明包括减压步骤，其使用微制造过滤器来过滤流体样品，并且富集的稀有细胞可以用于下游过程，例如识别，表征甚至在培养中生长或以其它方式使用。本发明还包括通过在稀释细胞富集后检测端粒酶活性或端粒酶核酸或端粒酶表达的存在或数量来确定肿瘤侵袭性或富集样品中癌细胞数量或比例的方法。本发明还提供了一种从含有红细胞和白细胞中的至少一种的生物样品中特异性除去红细胞以及白细胞的有效快速方法，导致稀有靶细胞的富集，包括循环来自血液样品的肿瘤细胞（CTC），基质细胞，间充质细胞，内皮细胞，胎儿细胞，干细胞，非造血细胞等。该方法基于免疫微粒（抗体包被的微粒）和基于密度的分离的组合。最终的富集的靶细胞可以进行各种分析和操作，例如流式细胞术，PCR，免疫荧光，免疫细胞化学，图像分析，酶测定，基因表达谱分析，治疗剂的功效测试，培养富集的稀有细胞和治疗使用富集的稀有细胞。此外，可以任选地回收贫化的血浆蛋白和白细胞，并进行其他分析，例如炎症研究，基因表达谱等。

2. 发明申请

US20050058990A1 Biochip devices for ion transport measurement, methods of manufacture, and methods of use 审中-公开
标题翻译：用于离子传输测量的生物芯片器件，制造方法和使用方法
公开(公告)号：US20050058990A1
公开(公告)日：2005-03-17
申请号：US10858339
申请日：2004-06-01
申请人： Antonio Guia , Jia Xu , Lei Wu , Khachonesin Sithiphong , Maria Spassova , Huimin Tao , George Walker , Mingxian Huang , Guoliang Tao , Steven Saya , Glenn Walker , Zoya Zozulya
发明人： Antonio Guia , Jia Xu , Lei Wu , Khachonesin Sithiphong , Maria Spassova , Huimin Tao , George Walker , Mingxian Huang , Guoliang Tao , Steven Saya , Glenn Walker , Zoya Zozulya
IPC分类号： C12Q1/70 , G01N15/06 , G01N33/487
CPC分类号： G01N33/48728
摘要： The present invention provides biochips for ion transport measurement, ion transport measuring devices that comprise biochips, and methods of using ion transport measuring devices and biochips that allow for the direct analysis of ion transport functions or properties. The present invention provides biochips, devices, apparatuses, and methods that allow for automated detection of ion transport functions or properties. The present invention also provides methods of making biochips and devices for ion transport measurement that reduce the cost and increase the efficiency of manufacture, as well as improve the performance of the biochips and devices. These biochips and devices are particularly appropriate for automating the detection of ion transport functions or properties, particularly for screening purposes.
摘要翻译：本发明提供了用于离子传输测量的生物芯片，包括生物芯片的离子传输测量装置，以及使用离子传输测量装置和允许直接分析离子传递功能或性质的生物芯片的方法。本发明提供允许自动检测离子迁移功能或性质的生物芯片，装置，装置和方法。本发明还提供了制造用于离子传输测量的生物芯片和装置的方法，其降低成本并提高制造效率，以及提高生物芯片和装置的性能。这些生物芯片和装置特别适用于自动化离子迁移功能或性质的检测，特别是用于筛选目的。

3. 发明申请

US20080057505A1 METHODS AND COMPOSITIONS FOR DETECTING RARE CELLS FROM A BIOLOGICAL SAMPLE 审中-公开
公开(公告)号：US20080057505A1
公开(公告)日：2008-03-06
申请号：US11777962
申请日：2007-07-13
申请人： Ping Lin , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu
发明人： Ping Lin , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu
IPC分类号： G01N33/574 , C12Q1/02 , C12Q1/68 , G01N33/00
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/158 , C12Q2600/16 , G01N33/54346 , G01N33/56966 , G01N33/574 , G01N2333/70525 , G01N2333/70589 , G01N2800/52
摘要： The present invention provides methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells. In particular, the present invention includes a debulking step that uses a microfabricated filters for filtering fluid samples and the enriched rare cells can be used in a downstream process such as identifies, characterizes or even grown in culture or used in other ways. The invention also include a method of determining the aggressiveness of the tumor or of the number or proportion of cancer cells in the enriched sample by detecting the presence or amount of telomerase activity or telomerase nucleic acid or telomerase expression after enrichment of rare cells. This invention further provides an efficient and rapid method to specifically remove red blood cells as well as white blood cells from a biological sample containing at least one of each of red blood cells and white blood cells, resulting in the enrichment of rare target cells including circulating tumor cells (CTC), stromal cells, mesenchymal cells, endothelial cells, fetal cells, stem cells, non-hematopoietic cells etc from a blood sample. The method is based upon combination of immuno-microparticles (antibody coated microparticles) and density-based separation. The final enriched target cells can be subjected to a variety of analysis and manipulations, such as flowcytometry, PCR, immunofluorescence, immunocytochemistry, image analysis, enzymatic assays, gene expression profiling analysis, efficacy tests of therapeutics, culturing of enriched rare cells, and therapeutic use of enriched rare cells. In addition, depleted plasma protein and white blood cells can be optionally recovered, and subjected to other analysis such as inflammation studies, gene expression profiling, etc.

4. 发明授权

US08986945B2 Methods and compositions for detecting rare cells from a biological sample 有权
标题翻译：用于从生物样品中检测稀有细胞的方法和组合物
公开(公告)号：US08986945B2
公开(公告)日：2015-03-24
申请号：US11841972
申请日：2007-08-20
申请人： Ping Lin , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar I. Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu , Douglas T. Yamanishi
发明人： Ping Lin , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar I. Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu , Douglas T. Yamanishi
IPC分类号： C12Q1/24 , C12N5/09 , G01N33/50 , G01N33/543 , G01N33/569 , G01N33/574
CPC分类号： C12N5/0693 , G01N33/5094 , G01N33/54346 , G01N33/56972 , G01N33/574 , G01N2015/1006 , G01N2015/1402 , G01N2333/70525 , G01N2333/70589 , G01N2800/52 , Y10T436/25375
摘要： Provided are methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells, particularly including debulking that uses a microfabricated filter for filtering samples. The enriched rare cells can be used in a downstream process such as identification, characterization or growth in culture, or in other ways. Also included is a method of determining tumor aggressiveness or the number or proportion of cancer cells in the enriched sample by detecting telomerase activity, nucleic acid or expression after enrichment of rare cells. Also provided is an efficient, rapid method to specifically remove red and white blood cells from a biological sample containing at least one of the cell types, leading to enrichment of rare target cells including circulating tumor (CTC), stromal, mesenchymal, endothelial, fetal, stem, or non-hematopoietic cells et cetera from a blood sample.
摘要翻译：提供了用于从含有其他类型细胞的生物样品中分离和检测稀有细胞的方法和组合物，特别是包括使用微加工过滤器过滤样品的减粘。富集的稀有细胞可以用于下游过程，例如鉴定，表征或培养生长，或以其他方式。还包括通过检测端粒酶活性，核酸或富集稀有细胞后的表达来确定富集样品中肿瘤侵袭性或癌细胞数量或比例的方法。还提供了一种从含有至少一种细胞类型的生物样品中特异性除去红细胞和白细胞的有效且快速的方法，导致稀有靶细胞的富集，包括循环肿瘤（CTC），基质，间质，内皮，胎儿，茎或非造血细胞等。

5. 发明授权

US08569009B2 Methods and compositions for detecting rare cells from a biological sample 有权
公开(公告)号：US08569009B2
公开(公告)日：2013-10-29
申请号：US11841972
申请日：2007-08-20
申请人： Ping Lin , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar I. Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu
发明人： Ping Lin , Andrea Ghetti , Wenge Shi , Mengjia Tang , Gioulnar I. Harvie , Huimin Tao , Guoliang Tao , Lei Wu , David Cerny , Jia Xu
IPC分类号： C12Q1/24
摘要： Provided are methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells, particularly including debulking that uses a microfabricated filter for filtering samples. The enriched rare cells can be used in a downstream process such as identification, characterization or growth in culture, or in other ways. Also included is a method of determining tumor aggressiveness or the number or proportion of cancer cells in the enriched sample by detecting telomerase activity, nucleic acid or expression after enrichment of rare cells. Also provided is an efficient, rapid method to specifically remove red and white blood cells from a biological sample containing at least one of the cell types, leading to enrichment of rare target cells including circulating tumor (CTC), stromal, mesenchymal, endothelial, fetal, stem, or non-hematopoietic cells et cetera from a blood sample.

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