公开(公告)号：US06485625B1

公开(公告)日：2002-11-26

申请号：US09336848

申请日：1999-06-21

申请人： John W. Simpson ,  Jonathan M. Rothberg ,  Gregory T. Went ,  Marie Carmen Ruiz-Martinez ,  Gregory T. Mulhern

发明人： John W. Simpson ,  Jonathan M. Rothberg ,  Gregory T. Went ,  Marie Carmen Ruiz-Martinez ,  Gregory T. Mulhern

IPC分类号： G01N2326

CPC分类号： B01J19/0093 ,  G01N27/44708 ,  G01N27/44721 ,  G01N27/44782 ,  G01N27/44791

摘要： This invention is an integrated instrument for the high-capacity electrophoretic analysis of biopolymer samples. It comprises a specialized high-voltage, electrophoretic module in which the migration lanes are formed between a bottom plate and a plurality of etched grooves in a top plate, the module permitting concurrent separation of 80 or more separate samples. In thermal contact with the bottom plate is a thermal control module incorporating a plurality of Peltier heat transfer devices for the control of temperature and gradients in the electrophoretic medium. Fragments are detected by a transmission imaging spectrograph which simultaneously spatially focuses and spectrally resolves the detection region of all the migration lanes. The spectrograph comprises a transmission dispersion element and a CCD array to detect signals. Signal analysis comprises the steps of noise filtering, comparison in a configuration space with signal prototypes, and selection of the best prototype. Optionally post-processing is done by a Monte-Carlo simulated annealing algorithm to improve results. Optionally, an array of micro-reactors can be integrated into the instrument for the generation of sequencing reaction fragments directly from crude DNA samples.

摘要翻译： 本发明是用于生物聚合物样品的高容量电泳分析的综合仪器。 它包括专门的高压电泳模块，其中迁移通道形成在顶板和顶板中的多个蚀刻凹槽之间，该模块允许同时分离80个或更多个单独的样品。 与底板热接触的是热控制模块，其包含多个用于控制电泳介质中的温度和梯度的珀尔帖传热装置。 通过透射成像光谱仪检测片段，其同时空间聚焦并光谱地解析所有迁移通道的检测区域。 该光谱仪包括用于检测信号的透射色散元件和CCD阵列。 信号分析包括噪声滤波，配置空间与信号原型的比较以及最佳原型的选择。 可选地，后处理通过蒙特卡罗模拟退火算法完成以改善结果。 任选地，可以将微反应器阵列整合到仪器中，以直接从粗DNA样品产生测序反应片段。