公开(公告)号：US20020076724A1

公开(公告)日：2002-06-20

申请号：US10008278

申请日：2001-11-05

发明人： Sydney David Finkelstein ,  Patricia Anne Finkelstein

IPC分类号： C12Q001/68 ,  G01N033/48 ,  C12P019/34 ,  G01N001/30

CPC分类号： C12Q1/68 ,  C12Q1/6806 ,  C12Q1/6886 ,  C12Q2600/156

摘要： The present invention pertains to a method for topographic genotyping. The method comprises the steps of placing a biological specimen having DNA of a patient under a microscope. Then there is the step of inspecting the biological specimen microscopically with the microscope. Next there is the step of choosing a microscope size target on the biological specimen based on its histopathologic characteristics. Next there is the step of separating the target from the specimen. Then there is the step of obtaining DNA sequences from the target so the DNA sequences can be amplified. Next there is the step of amplifying the DNA sequences. Then there is the step of detecting mutations in the DNA sequences. The present invention pertains to a method for topographic genotyping. The method comprises the steps of separating a section from a specimen of fixative treated tissue. Then there is the step of obtaining DNA sequences from the section. Next there is the step of amplifying the DNA sequences by cyphaling them in a PCR machine, with each cycle heating them to a temperature no greater than 99null C., and then back to a temperature of 55null C. in 5 minutes. Next there is the step of detecting mutations in the DNA sequences. Preferably, the separating step includes the step of cutting one to three 2-6 micron thick histeologic sections from the specimen.

摘要翻译： 本发明涉及一种用于地形基因分型的方法。 该方法包括将具有病人DNA的生物样本置于显微镜下的步骤。 然后用显微镜显微镜检查生物样本的步骤。 接下来，根据其组织病理学特征，选择生物样本上的显微镜尺寸目标的步骤。 接下来，将目标与试样分开。 然后有从靶获得DNA序列的步骤，以便扩增DNA序列。 接下来是扩增DNA序列的步骤。 那么就有检测DNA序列突变的步骤。 本发明涉及一种用于地形基因分型的方法。 该方法包括从固定处理的组织的样本中分离切片的步骤。 那么就有从该部分获得DNA序列的步骤。 接下来，通过在PCR机中通过cyphaling扩增DNA序列，每个循环将它们加热到不高于99℃的温度，然后在5分钟内回到55℃的温度。 接下来是检测DNA序列中的突变的步骤。 优选地，分离步骤包括从样品切割一至三个2-6微米厚的组织学部分的步骤。

公开(公告)号：US20020064809A1

公开(公告)日：2002-05-30

申请号：US09751666

申请日：2000-12-28

发明人： Mitchell W. Mutz ,  Richard N. Ellson ,  David Soong-Hua Lee

IPC分类号： G01N001/30 ,  G01N033/48 ,  C12N015/01

CPC分类号： B41J2/14008 ,  B01L3/0268 ,  C12M47/04 ,  G01N15/1056 ,  G01N15/1456 ,  G01N29/028 ,  G01N30/02 ,  G01N35/1074 ,  G01N2015/1081 ,  G01N2015/1415 ,  G01N2015/142 ,  G01N2015/1486 ,  G01N2015/149 ,  G01N2035/1039 ,  G01N2035/1048 ,  G01N2035/1062 ,  B01D2015/389

摘要： A method is provided for acoustically ejecting from a container that is preferably a channel, a plurality of particles or localized volumes that can be single living cells contained in fluid droplets toward sites on a substrate surface or alternatively or in addition thereto into containers or channels for deposition at a target array site or a container or channel by acoustic ejection. An integrated cell sorting and arraying system also is provided that is capable of selective sorting, into channels or other containers substantially transected by a common plane, parallel to a surface of the fluid, transecting the container from which cells are ejected by selective ejection of cells with adjustable velocity parallel to the fluid surface, and simultaneously selectively forming an array of cells on a substrate surface comprising an array of substantially planar sites is provided, wherein each site contains a single cell. Additionally provided is a method of forming arrays of single live cells more efficiently, rapidly, flexibly and economically than by other cell array approaches, while permitting efficient, continuous and simultaneous sorting of cells based upon selection by measurement of detectible properties quantitatively or semiquantitatively, and multiple ejection target selections permitting non-binary or severally branched decision making. An integrated system and methods are also provided for ejection of selected particles or circumscribed volumes such as live cells from a continuous stream of particles or circumscribed volumes flowing in fluidic ejection channels into flowing fluidic target channels based upon selection by measurement of detectible properties quantitatively or semiquantitatively, and multiple ejection target selections permitting non-binary or severally branched decision making integrated with the measurement by way of a processor.

摘要翻译： 提供了一种用于从容器中声学喷射的方法，所述容器优选地是通道，多个颗粒或局部体积，其可以是流体液滴中包含在流体液滴中的单个活细胞朝向基底表面上的位置，或者替代地或附加到容器或通道中， 通过声喷射在靶阵列位置沉积或容器或通道。 还提供了一种集成的细胞分选和排列系统，其能够选择性地分选到平行于流体表面的基本上由公共平面横切的通道或其它容器中，从而通过选择性排出细胞来切断细胞被排出的容器 具有平行于流体表面的可调速度，并且同时在包括基本上平面的位置的阵列的基板表面上选择性地形成单元阵列，其中每个位置包含单个单元。 另外提供了一种比通过其他细胞阵列方法更有效，快速，灵活和经济地形成单活细胞阵列的方法，同时基于通过定量或半定量测量可检测性质的选择来有效，连续和同时分选细胞，以及 多个弹出目标选择允许非二进制或多个分支的决策。 还提供了一种集成的系统和方法，用于基于通过定量或半定量测量可检测性质的选择，将选定的颗粒或诸如活细胞的外来体积从连续的颗粒流或流体喷射通道中流动的外接体积喷射到流动的流体目标通道中 以及允许通过处理器与测量集成的非二进制或多个分支决策的多个喷射目标选择。

公开(公告)号：US20020022240A1

公开(公告)日：2002-02-21

申请号：US09783477

申请日：2001-02-14

发明人： Gregory R. Wade ,  Gabriel G. Altmann ,  Stephen G. Altmann ,  Vilma Gejadharsingh Altmann ,  Martine Altmann

IPC分类号： G01N033/574 ,  G01N001/30 ,  G01N033/48

CPC分类号： G01N33/57419 ,  G01N33/56966 ,  G01N2405/04

摘要： This invention provides a method for indicating a high or low risk of developing pathology at specific sites along epithelial tissues, according to a model of carcinogenesis and measurements of activated enterocytes. The method determines the presence and the intensity of a nullpromoting environment,null a region of intestinal epithelial cells which are biochemically programmed as activated enterocytes to develop pathology such as neoplasia or such as cancer in response to certain signals. The model predicts that neoplasia can develop only in such an environment when the promoting influence is sufficiently intense. In which case to provide the ability to identify pathologic tissues If cancer is determined to be present, this method enables one to assess the stage of cancer, which can be used to monitor the effectiveness of therapeutic regimes during the course of treatment for a patient. The method can also be used in the field of cancer research to develop understanding of the etiology of the disease in addition to new treatments for cancer therapy. It also provides an opportunity to use the method as a tool to investigate pathologic development such as pre-cancerous states in animal and cell culture models of diseases.

摘要翻译： 本发明提供了一种用于指示在上皮组织的特定部位发展病理学的高或低风险的方法，根据致癌细胞模型和活化肠细胞的测量。 该方法确定“促进环境”的存在和强度，肠道上皮细胞的区域作为活化的肠细胞进行生物化学编程以响应于某些信号发展出病理学如瘤形成或诸如癌症。 该模型预测，当促进影响足够强烈时，瘤形成只能在这样的环境中发展。 在哪种情况下提供鉴定病理组织的能力如果确定癌症存在，则该方法可以评估癌症的阶段，其可以用于监测治疗期间对于患者的治疗方案的有效性。 除了癌症治疗的新治疗之外，该方法还可用于癌症研究领域，以发展对疾病病因的理解。 它还提供了一种机会，使用该方法作为一种工具，用于调查疾病的动物和细胞培养模型中的病理发展，如癌前状态。

公开(公告)号：US20020022002A1

公开(公告)日：2002-02-21

申请号：US09891883

申请日：2001-06-26

申请人： The Regents of the University of California

发明人： Jorge R. Barrio ,  Andrej Petric ,  Nagichettiar Satyamurthy ,  Gary W. Small ,  Gregory M. Cole ,  Sung-Cheng Huang

IPC分类号： A61K051/00 ,  G01N033/48 ,  G01N001/30 ,  A61K031/519

CPC分类号： A61K51/0406 ,  A61K51/0455 ,  A61K51/0459

摘要： A method for labeling null-amyloid plaques and neurofibrillary tangles in vivo and in vitro, comprises contacting a compound of formula (I): 1 with mammalian tissue. In formula (I), R1 is selected from the group consisting of nullC(O)-alkyl, nullC(O)-alkylenyl-R4, nullC(O)O-alkyl, nullC(O)O-alkylenyl-R4, nullCnullC(CN)2-alkyl, nullCnullC(CN)2-alkylenyl-R4, 2 R4 is a radical selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl; R5 is a radical selected from the group consisting of nullNH2, nullOH, nullSH, nullNH-alkyl, nullNHR4, nullNH-alkylenyl-R4, nullO-alkyl, nullO-alkylenyl-R4, nullS-alkyl, and nullS-alkylenyl-R4; R6is a radical selected from the group consisting of nullCN, nullCOOH, nullC(O)O-alkyl, nullC(O)O-alkylenyl-R4, nullC(O)-alkyl, nullC(O)-alkylenyl-R4, nullC(O)-halogen, nullC(O)NH2, nullC(O)NH-alkyl, nullC(O)NH-alkylenyl-R4; R7 is a radical selected from the group consisting of O, NH, and S; and R8 is N, O or S. R2 and R3 are each independently selected from the group consisting of alkyl and alkylenyl-R10, wherein R10 is selected from the group consisting of nullOH, nullOTs, halogen, spiperone, spiperone ketal and spiperone-3-yl. Alternatively, R2 and R3 together form a heterocyclic ring, optionally substituted with at least one radical selected from the group consisting of alkyl, alkoxy, OH, OTs, halogen, alkylenyl-R10, carbonyl, spiperone, spiperone ketal and spiperone-3-yl. In the compounds of formula (I), one or more of the hydrogen, halogen or carbon atoms can, optionally, be replaced with a radiolabel.

摘要翻译： 一种用于在体内和体外标记β-淀粉样蛋白斑和神经原纤维缠结的方法，包括使式（I）化合物与哺乳动物组织接触。 在式（I）中，R 1选自-C（O） - 烷基，-C（O） - 亚烷基基-R 4，-C（O）O-烷基，-C（O）O-亚烷基 - R4，-C = C（CN）2-烷基，-C = C（CN）2 - 亚烷基-R4，R4为选自烷基，取代烷基，芳基和取代芳基的基团; R5是选自-NH2，-OH，-SH，-NH-烷基，-NHR4，-NH-亚烷基-R4，-O-烷基，-O-亚烷基-R4，-S-烷基的基团 和-S-亚烷基基-R4; R6是选自-CN，-COOH，-C（O）O-烷基，-C（O）O-亚烷基基-R4，-C（O） - 烷基，-C（O） - 亚烷基 -R 4，-C（O） - 卤素，-C（O）NH 2，-C（O）NH-烷基，-C（O）NH-亚烷基基-R4; R7是选自O，NH和S的基团; 并且R 8是N，O或S.R 2和R 3各自独立地选自烷基和亚烷基-R 10，其中R 10选自-OH，-OT，卤素，螺哌
酮，螺哌酮缩酮和螺哌隆 -3-基。 或者，R2和R3一起形成杂环，任选被至少一个选自烷基，烷氧基，OH，OT，卤素，亚烷基-R 10，羰基，螺哌
酮，螺哌酮缩酮和螺哌酮-3-基 。 在式（I）的化合物中，氢，卤素或碳原子中的一个或多个可以任选地被放射性标记代替。

公开(公告)号：US20010051343A1

公开(公告)日：2001-12-13

申请号：US09901014

申请日：2001-07-10

发明人： Wei-Sing Chu

IPC分类号： C12Q001/68 ,  G01N033/567 ,  G01N001/30 ,  G01N033/48

CPC分类号： G01N1/38 ,  G01N1/30 ,  G01N1/44 ,  G01N29/223 ,  G01N2291/02475 ,  G01N2291/02881 ,  Y10T436/11 ,  Y10T436/113332

摘要： Methods of fixing and processing tissue and samples on a membrane by using ultrasound radiation as a part of the method are presented. Ultrasound of a frequency in the range of 0.1-50 MHz is used and the sample or tissue receives 0.1-200 W/cm2 of ultrasound intensity. The use of ultrasound allows much shorter times in the methods. Also presented are apparati comprising transducers of one or of multiple heads for producing the ultrasound radiation and further comprising a central processing unit and optionally comprising one or more sensors. Sensors can include those to measure and monitor ultrasound and temperature. This monitoring system allows one to achieve accurate and optimum tissue fixation and processing without overfixation and tissue damage. The system also allows the performance of antigen-antibody reactions or nucleic acid hybridizations to be completed in a very short time while being highly specific and with a very low or no background.

公开(公告)号：US20040265281A1

公开(公告)日：2004-12-30

申请号：US10819398

申请日：2004-04-07

发明人： Denis Rodgerson ,  Thomas Hirose ,  Rubio Punzalan

IPC分类号： A61K045/00 ,  C12Q001/68 ,  G01N001/30 ,  G01N033/48 ,  C12N005/08

CPC分类号： A61K35/28 ,  G01N33/5091 ,  G01N2800/52

摘要： A system provides individualized nullbaselinenull or internal nullcontrolnull for an individual by collecting cells from the individual at an earlier time point prior to the onset of disease, which can be used as a standard for normalcy and a benchmark or reference for measuring the progression or development of any process the cells undergo. This allows study of biophysical, biochemical, architectural, morphological, functional, or physiological differences between cells collected from an individual at one time to cells collected from the same individual at a later point in time. The comparison between cells collected at different times allows for the study of relative responses of these cells when treated with a variety of chemicals. With this system disease markers can be determined that can aid in diagnosis and discovery of therapeutics for the disease of interest. As a result, this system may provide a basis for the production of patient-specific, as opposed to disease-specific drugs.

摘要翻译： 系统通过在疾病开始之前较早的时间点收集个体的细胞，为个体提供个性化的“基线”或内部“控制”，其可以用作正常的标准，以及用于测量 细胞经历的任何过程的进展或发展。 这允许研究从一个人一次收集的细胞在随后的时间点从相同个体收集的细胞之间的生物物理，生化，建筑，形态，功能或生理差异。 在不同时间收集的细胞之间的比较允许研究当用多种化学物质处理时这些细胞的相对反应。 利用该系统疾病，可以确定可以帮助诊断和发现感兴趣的疾病的治疗剂的标志物。 因此，该系统可能为生产患者特异性而不是疾病特异性药物提供依据。

公开(公告)号：US20040259133A1

公开(公告)日：2004-12-23

申请号：US10826834

申请日：2004-04-15

发明人： Fredrik C. Kamme ,  Bernhard H. Meurers ,  Dmitri Talantov ,  Jingxue Yu

IPC分类号： C12Q001/68 ,  G01N001/30 ,  G01N033/48

CPC分类号： C12Q1/6841 ,  C12N15/1003 ,  G01N1/30

摘要： To preserve RNA in a biological sample for analysis, the sample is incubated with an RNA preservative capable of precipitating RNA in an aqueous solution, such as a triphenylmethane dye (e.g., methyl green, crystal violet, pararosaniline, or tris-(4-aminophenyl)methane), cresyl violet, or cobalt ions. RNA preservation may be used in an immunostaining assay and other histochemical methods.

摘要翻译： 为了保存生物样品中的RNA用于分析，将样品与能够在水溶液中沉淀RNA的RNA防腐剂一起温育，例如三苯基甲烷染料（例如甲基绿，结晶紫，对羟基苯胺或三 - （4-氨基苯基） ）甲烷），甲酚紫或钴离子。 RNA保存可用于免疫染色测定和其他组织化学方法。

公开(公告)号：US20040197839A1

公开(公告)日：2004-10-07

申请号：US10771440

申请日：2004-02-05

申请人： Bioview Ltd.

发明人： Michal Daniely ,  Tal Kaplan ,  Eran Kaplan ,  Avner Freiberger

IPC分类号： G01N033/53 ,  G01N033/574 ,  G01N001/30 ,  G01N033/48

CPC分类号： G01N1/30 ,  G01N33/57484

摘要： The invention provides methods of detecting cancerous cells in biological samples using a double staining/dual imaging approach, which can be used to diagnose cancer. More specifically, the present invention provides methods of diagnosing bladder cancer by a simultaneous scanning of cell morphology and FISH signals of cells derived from a urine sample.

摘要翻译： 本发明提供使用双重染色/双重成像方法检测生物样品中的癌细胞的方法，其可用于诊断癌症。 更具体地，本发明提供了通过同时扫描来自尿液样品的细胞的细胞形态和FISH信号来诊断膀胱癌的方法。

公开(公告)号：US20040191854A1

公开(公告)日：2004-09-30

申请号：US10404879

申请日：2003-03-31

申请人： Cytyc Corporation

发明人： Daniel Lapen ,  Norman Soule ,  Somthouck Lim

IPC分类号： G01N001/30 ,  G01N033/48

CPC分类号： G01N1/30

摘要： A method for treating a biological sample with a Papanicolaou staining process is provided. The method comprises incorporating a detergent treatment into the staining process at any of various steps. The method has been found to advantageously reduce the number of artifacts produced during Papanicolaou staining. Also provided is a sample stained by such a process.

摘要翻译： 提供了一种用Papanicolaou染色方法处理生物样品的方法。 该方法包括在各种步骤的任何步骤中将洗涤剂处理结合到染色过程中。 已经发现该方法有利地减少了在Papanicolaou染色过程中产生的伪影的数量。 还提供了通过这种方法染色的样品。

公开(公告)号：US20040180397A1

公开(公告)日：2004-09-16

申请号：US10794238

申请日：2004-03-05

发明人： Mao-Kuei Chang

IPC分类号： G01N001/30 ,  G01N033/48 ,  C12M001/34

CPC分类号： G01N35/00029 ,  G01N2015/1486

摘要： A quantitative cell-counting slide includes a plurality of counting chambers juxtapositionally formed in the slide; each counting chamber including a first counting portion consisting of a plurality of miniature grids of which each miniature grid may be formed to have a volume of 0.01 micro-liter for counting any kind of cells, and a second counting portion formed on a platform and consisting of a plurality of HPF (High Power Field) volumetric grids each formed to have a quantitative volume of 0.0083 micro-liter generally equal to one HPF volume adapted for cell counting used in urinary sediment microscopic examination.

摘要翻译： 定量细胞计数载玻片包括在幻灯片中并列形成的多个计数室; 每个计数室包括由多个微型栅格组成的第一计数部分，每个微型栅格可以形成每个微型栅格以具有0.01微升的体积用于计数任何种类的单元，以及形成在平台上的第二计数部分， 多个HPF（大功率场）体积格栅，其各自形成为具有0.0083微升的定量体积，通常等于适用于尿沉渣显微镜检查中的细胞计数的一个HPF体积。