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1.发明授权Method and apparatus for measuring multiple optical properties of biological specimens 失效用于测量生物样本的多种光学性质的方法和装置
公开(公告)号：US5107422A
公开(公告)日：1992-04-21
申请号：US583075
申请日：1990-09-14
CPC分类号： G01N15/147 , G06K9/00127
摘要： The invention relates to an apparatus and methods for generating multiparameter optical data that characterize a population of cells. The invention includes the steps of scanning the cell population with a beam to produce sets of digital data samples, each sample set of digital data representing multiparameter optical interactions from a specific location within the cell population; storing the digital data, e.g., in a computer memory; locating a cell within the population, e.g., by comparing the digital data to a preselected threshold value; defining a neighborhood around the digital data representing the located cell; estimating a background level for the neighborhood based upon digital data corresponding to locations outside the neighborhood; and correcting each of the samples corresponding to the neighborhood with the estimated neighborhood background level to generate the optical data. The invention further relates to specific methods of background correction and data calibration as well as specific sampling features to enable precise estimates of multiple cellular constituents or other cell properties at high rates of speed.
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公开(公告)号：US5523207A
公开(公告)日：1996-06-04
申请号：US324265
申请日：1994-10-17
CPC分类号： C12Q1/6841 , Y10T436/143333
摘要： A method for the accurate counting of DNA probe spots in cell nuclei wherein anomalies caused by a two dimensional measurement of a three dimensional cell sample are eliminated from evaluation. DNA probe spots in cell nuclei which are counted by means of Fluorescent In Situ Hybridization (FISH) include cells wherein probe spots of different contoured cells are overlaid or are detected as being adjacent one another with resultant erroneous diagnostic results such as with cancer detection or prognosis. A gating fluorescent value is determined by clusters of fluorescence in regions of non-anomalous values of fluorescence determined by plotting peak fluorescent value against area. The loci of the non-anomalous peak values cluster in specifically definable regions whereby fluorescent values for cells which deviate from the gating fluorescent value, are discounted in the preparation of histograms or other diagnostic measurements.
摘要翻译： 一种用于准确计数细胞核中DNA探针斑点的方法，其中从三维细胞样品的二维测量引起的异常从评估中消除。 通过荧光原位杂交（FISH）计数的细胞核中的DNA探针斑点包括其中不同轮廓细胞的探针点被重叠或被检测为彼此相邻的细胞，导致错误诊断结果，例如癌症检测或预后 。 门控荧光值由通过绘制峰值荧光值与面积确定的荧光非异常值区域中的荧光簇确定。 非特异性峰值的位点集中在特定可定义区域，其中偏离门控荧光值的细胞的荧光值在制备直方图或其他诊断测量中被折扣。
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公开(公告)号：US5885840A
公开(公告)日：1999-03-23
申请号：US798488
申请日：1997-02-10
CPC分类号： G01N33/52 , G01N15/1475 , G01N2015/1006
摘要： A method for increasing the accuracy and the types of data measurements of laser scanned dye stained cells, in a single sample, by means of multiple assays, utilizing cell positions as a factor in merging data measurements. Change in lasers, use of different cell dye stains and different treating reagents provide additional data regarding cells of the sample and fixing of cell positions in the first assay permits merging of the data obtained in subsequent assays.
摘要翻译： 在单个样品中，通过多次测定，利用细胞位置作为合并数据测量的因素，增加激光扫描的染色染色细胞的数据测量的精度和类型的方法。 改变激光，使用不同的细胞染料污渍和不同的处理试剂提供关于样品细胞的另外的数据，并且在第一次测定中固定细胞位置允许合并后续测定中获得的数据。
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公开(公告)号：US5793969A
公开(公告)日：1998-08-11
申请号：US585183
申请日：1996-01-11
CPC分类号： G01N1/2813 , G02B21/26 , G02B21/34 , G06F19/321 , G06F19/366 , G01N2001/282
摘要： A network system for review and analysis of computer encoded microscope slides and specimens which were originally computer encoded from a microscope (attached via an encoder device to a local computer site), during an initial examination. The encoding includes parameters of viewing locations and events of interest on the slide, with such information being stored on a networked file server. The encoding also includes information regarding the manner in which the initial examination was conducted, for quality control purposes. The computer encoded information is retrievable at all remote locations of the network (either local or connected via modem) for supervisor review or for pathologist analysis. The network is further constituted by microscope sites having similar computer encoding devices attached thereto, which function, in this aspect, as computer terminals of the network. For enhanced analysis, the computer terminals have direct access to patient background information, e.g., such as from an HIS (hospital information system) for simultaneous slide analysis review in relation to the medical history of the patient. For diagnostic support, the computer terminals are networked with an on-line library of cell type images for comparison with the slide being examined. Slide diagnosis is either directly with the original slide on the microscope or with a scanned image of the slide stored in the network server or CD-ROM and retrieved on the computer terminal. The microscope is optionally motor driven, with computer control, to re-scan slides or slide images only at designated sites.
摘要翻译： 在初次检查期间，用于检查和分析计算机编码的显微镜载玻片和标本的网络系统，其最初由计算机从显微镜编码（通过编码器装置附接到本地计算机站点）进行编码。 编码包括在幻灯片上观看位置和感兴趣的事件的参数，其中这些信息被存储在联网的文件服务器上。 编码还包括关于进行初步检查的方式的信息，用于质量控制目的。 计算机编码的信息可以在网络的所有远程位置（本地或通过调制解调器连接）检索，以供主管审查或用于病理学家分析。 该网络由具有附接到其上的类似计算机编码装置的显微镜站点进一步构成，在该方面，其作为网络的计算机终端。 为了增强分析，计算机终端可以直接访问患者背景信息，例如来自HIS（医院信息系统），用于与病人的病史有关的同时幻灯片分析审查。 对于诊断支持，计算机终端与网络图像的网格库联网，以便与被检查的幻灯片进行比较。 幻灯片诊断直接与显微镜上的原始幻灯片或存储在网络服务器或CD-ROM中的幻灯片的扫描图像并在计算机终端上检索。 显微镜可选择由电机驱动，具有电脑控制功能，只能在指定的位置重新扫描幻灯片或幻灯片图像。
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公开(公告)号：US5427910A
公开(公告)日：1995-06-27
申请号：US987679
申请日：1992-12-09
IPC分类号： G01N33/50 , C12N15/09 , C12Q1/68 , G01N33/566
CPC分类号： C12Q1/6841 , Y10S435/81
摘要： A method of characterizing the chromosomes in a sample of cells by fixing the cell sample on a substrate, contacting the cell sample with a nucleic acid probe having a detectable label under conditions that allow the probe to hybridize preferentially to a chromosome in the cells to form a hybridized complex, optically detecting each labeled complex in the sample, defining a predetermined number of neighboring labeled complexes as a group, generating a distance parameter based on the distance between the position of a group and the position of the next neighboring labeled complex, and comparing the distance parameter for each group to a standard distance value to characterize the chromosomes in the cells of the sample.
摘要翻译： 通过将细胞样品固定在底物上来表征细胞样品中的染色体的方法，使细胞样品与具有可检测标记的核酸探针在允许探针优先与细胞中的染色体杂交形成的条件下接触， 杂交的复合物，光学检测样品中的每个标记的复合物，将预定数量的相邻的标记复合物定义为一组，基于组的位置和下一个相邻的标记复合物的位置之间的距离产生距离参数，以及 将每组的距离参数与标准距离值进行比较，以表征样本细胞中的染色体。
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公开(公告)号：US5602674A
公开(公告)日：1997-02-11
申请号：US491414
申请日：1995-06-16
申请人： Mark Weissman , Louis Kamentsky , Lee D. Kamentsky
发明人： Mark Weissman , Louis Kamentsky , Lee D. Kamentsky
CPC分类号： G02B21/34 , G01N1/2813 , G02B21/00 , G02B21/26 , G01N2001/282
摘要： A computerized specimen encoder for use with microscope analysis and pathological studies. The slide encoder is attached to the movable microscope stage, whereby X-Y plane movement and location, is correlated to examination of a specimen on an identified slide, with information marking and location being directly correspondingly written on computer storage media, during the examination. The information marking is in the form of computer generated indicia which are placed at a computer image location of the slide at predetermined time intervals. Subsequent use of the computer-stored information, coupled with the slide encoder, in a slide re-examination, permits independent retrieval of such information and location on the slide. The encoder device is provided with a grayscale marker which marks in varying shades of gray, ranging from white to black, the time spent by a slide screener on a particular portion of the specimen and the number of times spent viewing a particular portion of the specimen.
摘要翻译： 用于显微镜分析和病理学研究的计算机化标本编码器。 幻灯片编码器安装在可移动显微镜载物台上，由此X-Y平面运动和位置与检查中的样本相关，在检查期间将信息标记和位置直接相应地写在计算机存储介质上。 信息标记是以计算机生成的标记的形式，以预定的时间间隔放置在幻灯片的计算机图像位置。 随后使用计算机存储的信息（与幻灯片编码器一起）在幻灯片重新检查中，允许在幻灯片上独立地检索这样的信息和位置。 编码器装置设置有灰度标记，其以不同的灰色阴影标记，范围从白色到黑色，滑动筛选器在样本的特定部分上花费的时间和观察特定部分的样本的次数 。
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公开(公告)号：US07424371B2
公开(公告)日：2008-09-09
申请号：US11018515
申请日：2004-12-21
申请人： Lee D. Kamentsky
发明人： Lee D. Kamentsky
CPC分类号： C12Q1/6813
摘要： A sample nucleic acid sequence is compared against a database to find a matching sequence. In one embodiment, this comparison is accomplished with a table look-up approach that involves using sequences with collapsed homopolymer regions.
摘要翻译： 将样品核酸序列与数据库进行比较以找到匹配序列。 在一个实施方案中，该比较是通过使用具有塌陷均聚物区域的序列的表查找方法来实现的。
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公开(公告)号：US5633945A
公开(公告)日：1997-05-27
申请号：US318233
申请日：1994-10-05
申请人： Lee D. Kamentsky
发明人： Lee D. Kamentsky
IPC分类号： G01N33/48 , C12Q1/68 , G01N15/14 , G01N21/64 , G01N21/78 , G01N33/50 , G01N33/52 , G06F19/00 , G06K9/36
CPC分类号： G01N33/5005 , C12Q1/68 , G01N15/1456 , G01N21/6428 , G01N21/6458 , G01N2015/1486 , Y10S435/808
摘要： Cell samples, stained with a fluorescent dye, taken up by DNA in the individual cells, are scanned with a cytometer, which measures the integrated value of fluorescent light/cell. The integrated values of all of the cells are compiled to create an histogram of cell counts versus integrated fluorescent light, representing a cell population of (a) cells having a complement of DNA, but not in the process of division (G.sub.0 phase), (b) cells having two full compliments of DNA, but which have not actually divided into two cells (G.sub.2 phase) and (c) cells which are in the process of replicating their DNA (S, separation phase). The percentages of cells in each of the phases, represented in the histogram as separated peaks of sizes proportional to the G.sub.0 and G.sub.2 populations, and separation S phase population, aids in the prognosis of a patient's cancer development. More serious malignancy is indicated by increased S and G.sub.2 phase populations. Errors, e.g., resulting from statistical errors, focusing problems, inaccurate measurement of background, etc., in the integrated values and compilation of cells in the histogram, affect the accuracy and prognostic value of the peaks and separation phase, and are corrected by a method, wherein the convolution of error function with the signal function (representing the number of cells, as determined by the florescence measurements, with a DNA content of a specified value), is modeled and the error function removed, by deconvolution, from the G.sub.0 and G.sub.2 peaks and the S phase.
摘要翻译： 用荧光染料染色的细胞样品，用单个细胞中的DNA吸收，用测量荧光/细胞的积分值的细胞仪扫描。 所有细胞的积分值被编译成产生细胞计数直方图，而不是整合的荧光，代表（a）具有DNA补体的细胞的细胞群，而不是分裂过程（G0期），（ b）具有两个完全补充DNA但是实际上没有分为两个细胞（G2期）和（c）正在复制其DNA（S，分离期）的细胞的细胞。 在直方图中表示的每个相中的细胞百分比表示为与G0和G2群体成比例的大小分离的峰和分离S期群体，有助于患者癌症发展的预后。 更严重的恶性肿瘤由增加的S和G2期种群表现。 错误，例如，由于统计学差错，聚焦问题，背景校准不准确等原因导致的直方图中的细胞积分值和编码，影响峰和分离阶段的准确性和预后价值，并由 方法，其中建模误差函数与信号函数（表示通过荧光测量确定的细胞数目，具有指定值的DNA含量）的卷积，并且通过去卷积从G0去除误差函数 G2峰和S期。
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