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    • 3. 发明授权
    • Virtual DNA sequencer
    • 虚拟DNA测序仪
    • US5776767A
    • 1998-07-07
    • US570994
    • 1995-12-12
    • John K. StevensJames M. DunnGregory DeeJames W. Cassidy
    • John K. StevensJames M. DunnGregory DeeJames W. Cassidy
    • G01N27/447G06F19/00C12M3/00
    • G01N27/44782
    • A virtual DNA sequencer combines a plurality of individual DNA sequencers. Samples of DNA or other nucleic acid from subjects are prepared and allocated in real time to particular lanes or sets of lanes in electrophoresis plates of the individual sequencers, with records kept of the allocations. The data resulting from the electrophoresis runs is collected and collated according to the identities of the subjects. The individual sequencers are networked, and each individual sequencer is preferably equipped with a data buffer large enough to accommodate all or substantially all of a data run, thus protecting the virtual sequencer from loss of valuable data in the event that the network is disrupted for some portion of the time of the data run. In this way, a plurality of sequencers is virtually the same as a single sequencer with a very large number of tracks each of which can run for a much longer sequencing run than an individual sequencer.
    • 虚拟DNA测序仪组合了多个单独的DNA测序仪。 来自受试者的DNA或其他核酸的样品被制备并实时分配到各个定序器的电泳板中的特定泳道或泳道组,并保存有分配记录。 根据受试者的身份收集和整理电泳运行产生的数据。 各个顺控程序被联网,并且每个单独的定序器优选地配备有足够大的数据缓冲器,以容纳所有或基本上所有的数据运行,从而在网络被中断的情况下保护虚拟定序器免于丢失有价值的数据 部分时间的数据运行。 以这种方式,多个定序器与具有非常大数量的轨道的单个定序器几乎相同,每个轨道可以运行比单个定序器更长的排序运行。
    • 4. 发明授权
    • High dynamic range apparatus for separation and detection of
polynucleotide fragments
    • 用于分离和检测多核苷酸片段的高动态范围装置
    • US6014213A
    • 2000-01-11
    • US819910
    • 1997-03-18
    • Paul WaterhouseAlexandre M. IzmailovHenryk ZaleskiJohn A. RenfrewJames W. Cassidy
    • Paul WaterhouseAlexandre M. IzmailovHenryk ZaleskiJohn A. RenfrewJames W. Cassidy
    • G01N27/447G01N30/86G01N21/00
    • G01N30/8603G01N27/44721
    • A high dynamic range apparatus for separation and detection of polynucleotide fragments has a housing adapted to receive an electrophoresis gel holder containing an electrophoresis gel loaded with fluorophore-labeled samples; one or more laser diodes for providing radiation of a frequency suitable for excitation of the fluorophore which irradiates a an array of excitation/detection sites on the electrophoresis gel; an array of detectors aligned with the excitation/detection sites for collecting fluorescent emissions; and one or more components for increasing the dynamic range of the instrument by at least an order of magnitude. These components, which can be used individually or in combination include detectors that are connected to a signal processing system that modulates the period of signal integration employed so that large signals are totaled at short time intervals and smaller signals are totaled at longer time intervals; the use of a beam splitter to produces a high intensity beam of emitted light and a low intensity beam of emitted light from each excitation/detection site; and a device for modulating the intensity of the excitation beam can be used to improve the dynamic range of the instrument.
    • 用于分离和检测多核苷酸片段的高动态范围装置具有适于接收含有装载有荧光团标记的样品的电泳凝胶的电泳凝胶保持器的壳体; 用于提供适于激发荧光团的频率的辐射的一个或多个激光二极管,其照射电泳凝胶上的激发/检测位点阵列; 与用于收集荧光发射的激发/检测部位对准的检测器阵列; 以及用于将仪器的动态范围增加至少一个数量级的一个或多个组件。 可以单独或组合使用的这些组件包括连接到信号处理系统的检测器,该信号处理系统调制所采用的信号积分的周期,以便以较短的时间间隔合计大信号,并以更长的时间间隔合计较小的信号; 使用分束器产生高强度发射光束和来自每个激发/检测部位的低强度发射光束; 并且可以使用用于调制激发光束的强度的装置来改善仪器的动态范围。
    • 5. 发明授权
    • Electrophoresis and fluorescence detection apparatus
    • 电泳和荧光检测仪
    • US5712476A
    • 1998-01-27
    • US624789
    • 1996-03-27
    • John A. RenfrewJames W. Cassidy
    • John A. RenfrewJames W. Cassidy
    • G01N27/447G01N30/86H01J40/14
    • G01N27/44721G01N30/8603
    • An improved electrophoresis and fluorescence detection apparatus has an electromagnetic radiation sensor juxtaposed with a sensing region. The output signal from the electromagnetic radiation sensor is a current signal, and the current signal is converted to a voltage signal. The voltage signal is summed with a programmable offset generated by an inexpensive eight-bit D/A converter. The offset signal is selected to establish a lower starting point for the dynamic range of the A/D conversion, and is selected to null some or all of the background electromagnetic radiation level. The summed signal is amplified and integrated in an integrator. The integrator is switchable under program control. The integrator is switched on for long and short intervals. The short intervals permit sensing over a dynamic range accommodating very high levels of fluorescence; very high peaks may be measured and features of the peaks distinguished. The long intervals permit sensing over a dynamic range that is optimized for the peaks associated with the smaller peaks of individual nucleotides. In this way, the dynamic range of the A/D convertor is set to permit the highest possible resolution over the range of interest during the time in which the sequencing of the nucleotides takes place. The sequencer is fast and economical and yields data with high resolution.
    • 改进的电泳和荧光检测装置具有与感测区域并置的电磁辐射传感器。 来自电磁辐射传感器的输出信号是电流信号,电流信号被转换为电压信号。 电压信号与由便宜的8位D / A转换器产生的可编程偏移相加。 选择偏移信号以建立A / D转换的动态范围的较低起始点,并且被选择为零部分或全部背景电磁辐射水平。 求和信号被放大并集成在积分器中。 集成商可在程序控制下切换。 积分器长时间和短的间隔打开。 短时间间隔允许在适应非常高水平荧光的动态范围内进行感测; 可以测量非常高的峰,并区分峰的特征。 长间隔允许感测针对与各个核苷酸的较小峰相关的峰优化的动态范围。 以这种方式,A / D转换器的动态范围被设置为允许在发生核苷酸的测序的时间期间在感兴趣的范围内具有最高可能的分辨率。 音序器是快速和经济的,并产生高分辨率的数据。
    • 6. 发明授权
    • Electrophoresis and fluorescence detection method
    • 电泳和荧光检测方法
    • US5786142A
    • 1998-07-28
    • US452719
    • 1995-05-30
    • John A. RenfrewJames W. Cassidy
    • John A. RenfrewJames W. Cassidy
    • G01N27/447G01N30/86C12Q1/68B01D61/42C25B1/00G01N15/06
    • G01N27/44721G01N30/8603
    • An improved electrophoresis and fluorescence detection method for nucleotide sequences comprises a fluorescence sensing region along the path of nucleotide detection, coupled with amplification and integration in an integrator of output signals in the form of activity peaks. The output signal, which is converted to a voltage signal, is summed with a programmable offset generated by an inexpensive eight-bit D/A converter. The offset signal is selected to establish a lower starting point for the dynamic range of analog-digital conversion, and is selected to null some or all of the background fluorescence level. The integrator is switchable under program control. The integrator is switched on for long and short integration intervals. The short intervals permit sensing over a dynamic range accommodating very high levels of fluorescence; very high peaks may be measured and features of the peaks distinguished. The long intervals permit sensing over a dynamic range that is optimized for the peaks associated with the smaller peaks of individual nucleotides. In this way, the dynamic range of the analog-digital conversion permits the highest possible resolution over the range of interest during the time in which the sequencing of the nucleotides takes place. The method of nucleotide sequencing and analysis is fast, economical, and yields data with high resolution.
    • 用于核苷酸序列的改进的电泳和荧光检测方法包括沿着核苷酸检测途径的荧光感测区域,以及在活性峰形式的输出信号的积分器中的放大和积分。 转换为电压信号的输出信号与由廉价的八位D / A转换器产生的可编程偏移相加。 选择偏移信号以建立模拟数字转换的动态范围的较低起始点,并选择为零部分或全部背景荧光水平。 集成商可在程序控制下切换。 积分器接通长和短的积分间隔。 短时间间隔允许在适应非常高水平荧光的动态范围内进行感测; 可以测量非常高的峰,并区分峰的特征。 长间隔允许感测针对与各个核苷酸的较小峰相关联的峰优化的动态范围。 以这种方式,模拟数字转换的动态范围允许在发生核苷酸测序的时间内在感兴趣的范围内达到最高可能的分辨率。 核苷酸测序和分析的方法快速,经济,并且产生高分辨率的数据。