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    • 2. 发明授权
    • Method, apparatus and computer program products for determining
quantities of nucleic acid sequences in samples
    • 用于确定样品中核酸序列数量的方法,装置和计算机程序产品
    • US5863736A
    • 1999-01-26
    • US862905
    • 1997-05-23
    • Perry D. Haaland
    • Perry D. Haaland
    • G01N33/50C12M1/00C12N15/09C12Q1/68C12P19/34G06F17/21
    • C12Q1/6851
    • Methods for determining quantities of nucleic acid sequences in samples include the steps of amplifying a plurality of known quantities of a nucleic acid sequence in respective calibration samples and an unknown quantity of a nucleic acid sequence in a test sample, in parallel, during a time interval. These samples may be amplified using an isothermal amplification method such as Strand Displacement Amplification (SDA), or a thermal cycling amplification method such as Polymerase Chain Reaction (PCR), for example. Indicia of the quantities of a nucleic acid sequence being amplified in the calibration and test samples are then measured using conventional techniques, at measurement points in the time interval. Steps are then performed to determine for a first potential cutoff level, a corresponding first set of time points in the time interval at which the indicia of the quantities of a nucleic acid sequence being amplified in each of the calibration samples equal the first cutoff level. This step is then repeated for each of a number of different potential cutoff levels so that respective sets of time points in the time interval can be obtained for each potential cutoff level. According to a preferred aspect of the present invention, a step is then performed to determine, relative to a statistical criterion, which of the sets of points in the time interval better satisfies the statistical criterion against the known quantities of a nucleic acid sequence in the calibration samples. A quantity of a nucleic acid sequence in the test sample is then determined based on the set of points determined to better or best satisfy the statistical criterion. The accuracy of the determination can also be improved using a relatively large number of potential cutoff levels.
    • 用于确定样品中核酸序列数量的方法包括以下步骤:在时间间隔期间并行扩增多个已知量的各校准样品中的核酸序列和测试样品中未知量的核酸序列 。 这些样品可以使用例如Strand Displacement Amplification(SDA)等等温扩增方法或者例如聚合酶链式反应(PCR)等热循环扩增方法进行扩增。 然后在时间间隔的测量点使用常规技术测量在校准和测试样品中扩增的核酸序列的量的标记。 然后执行步骤以确定第一潜在截止水平,即在每个校准样本中放大的核酸序列的量的标记等于第一截止水平的时间间隔内相应的第一组时间点。 然后对于多个不同的潜在截止电平中的每一个重复该步骤,使得可以针对每个潜在截止电平获得时间间隔中的各组时间点。 根据本发明的优选方面,然后执行步骤以相对于统计标准确定时间间隔中的哪组点更好地满足统计标准中的核酸序列的已知量 校准样品。 然后基于确定为更好或最好地满足统计标准的一组点来确定测试样品中的一定数量的核酸序列。 也可以使用相对大量的潜在截止水平来提高确定的准确度。
    • 3. 发明授权
    • Computerized method and apparatus for analyzing nucleic acid assay readings
    • 用于分析核酸测定读数的计算机化方法和装置
    • US06216049B1
    • 2001-04-10
    • US09196123
    • 1998-11-20
    • Harry YangDaniel L. SchwarzChristopher M. EmbresRichard L. MoorePerry D. HaalandPaula V. Johnson
    • Harry YangDaniel L. SchwarzChristopher M. EmbresRichard L. MoorePerry D. HaalandPaula V. Johnson
    • G05B1302
    • G06F19/20
    • A computerized method and apparatus are disclosed for analyzing numerical data pertaining to a sample assay comprising at least one biological or chemical sample. The data include a set of data pertaining to each respective sample, with each set of data including a plurality of values each representing a condition of the sample at a given time. The method and apparatus assign a respective numerical value to each of the data values, mathematically combine the numerical values to generate a total value, compare the total value to a threshold value, and control the system to indicate whether the sample has a predetermined characteristic based on a result of the comparison. Prior to calculation of the sample value, filtering, normalizing and other correcting operations can be performed on the data to correct anomalous values in the data which could adversely affect the accuracy of the results. The method and apparatus perform the described functions by representing the data values as points on a graph having a vertical axis representing the magnitudes of the values and a horizontal axis representing a period of time during which readings of the sample were taken to obtain the data values, identifying points on the graph having an anomalous characteristic, and correcting the anomalous points to produce a corrected plot of points on the graph, with each of the points of the corrected plot representing a magnitude of a corresponding one of the values. An area value is then calculated which represents an approximate area between at least a portion of the corrected plot of points on the graph and the horizontal axis. The area value is compared to a threshold value to determine whether a certain condition exists in the sample to which the set of data pertains.
    • 公开了一种用于分析与包含至少一种生物或化学样品的样品测定有关的数值数据的计算机化方法和装置。 数据包括与每个相应样本相关的一组数据,每组数据包括多个值,每个值表示在给定时间的样本的状况。 该方法和装置为每个数据值分配相应的数值,数学地组合数值以产生总值,将总值与阈值进行比较,并且控制系统以指示样本是否具有基于预定特征的 比较的结果。 在计算样本值之前,可以对数据执行滤波,归一化和其他校正操作,以纠正数据中可能对结果准确性产生不利影响的异常值。 该方法和装置通过将数据值表示为具有表示值的大小的垂直轴的图形的数据值和表示采样的读数以获得数据值的时间段的水平轴来执行所述功能 识别具有异常特征的图上的点,并且校正异常点以产生曲线图上的点的校正图,其中校正曲线的每个点表示对应的一个值的大小。 然后计算面积值,其表示曲线图上的点的校正曲线的至少一部分与水平轴之间的近似面积。 将面积值与阈值进行比较,以确定在该组数据所属的样本中是否存在特定条件。