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1.发明授权Nanofabricated separation matrix for analysis of biopolymers and methods of making and using same 失效用于生物聚合物分析的纳米分离基质及其制备和使用方法
公开(公告)号：US06110339A
公开(公告)日：2000-08-29
申请号：US973932
申请日：1997-12-16
申请人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno Maruzzo , John K. Stevens , Marina T. Larson
发明人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno Maruzzo , John K. Stevens , Marina T. Larson
IPC分类号： G01N27/447
CPC分类号： G01N27/44704 , G01N27/44773 , G01N27/44791 , Y10T436/143333
摘要： Separation matrices useful in the formation of solid-state mm- to cm-scale devices for the rapid, high-resolution separation of single-stranded DNA ladder bands generated by the Sanger dideoxy- or Maxam/Gilbert chemical DNA sequencing procedures are formed from a solid support (1) having a plurality of posts (4) disposed on a first major surface thereof to form an obstacle course of posts (4) and pores (5). The posts are arranged in a regular X, Y array and are separated one from another by a distance of 100 nm or less, preferably 10 to 30 nm, and are optionally separated into lanes 2. The separation matrix can be manufactured by first forming a mold, preferably a reusable mold using lithography techniques. The mold is the reverse of the desired pattern of posts and pores of the obstacle course, and is used for casting the obstacle course. The cast obstacle course is then fused to a solid support and separated from the mold. Alternatively, the separation matrix can be formed from a polymer which undergoes specific and quantifiable swelling in the presence of a selected chemical compound. In this case, the matrix is cast on a mold in a conventional manner with a spacing between posts greater than the desired final spacing of 100 nm or less. For use, a buffer solution saturated with the specific chemical agent that controls swelling is added, causing the posts to swell to a defined amount to achieve the desired separation.
摘要翻译： PCT No.PCT / US96 / 09999 Sec。 371日期：1997年12月16日 102（e）日期1997年12月16日PCT提交1996年6月7日PCT公布。 出版物WO96 / 42012 PCT 日期1996年12月27日用于形成固态mm至cm尺度装置的分离基质用于快速，高分辨率分离由Sanger双脱氧或Maxam / Gilbert化学DNA测序产生的单链DNA梯形带 步骤由具有设置在其第一主表面上的多个柱（4）的固体支撑件（1）形成，以形成柱（4）和孔（5）的障碍物路线。 柱以规则的X，Y阵列布置，并且彼此分离一个距离为100nm或更小，优选为10至30nm，并且任选地分离成通道2.分离基体可以通过首先形成 模具，优选使用光刻技术的可重复使用的模具。 模具与障碍物路线的柱和孔的期望图案相反，并且用于铸造障碍物路线。 然后将铸造的障碍物道路融合到固体支撑物并与模具分离。 或者，分离基质可以由在所选择的化合物存在下经历特异性和可定量溶胀的聚合物形成。 在这种情况下，基体以常规方式在模具上铸造，柱之间的间距大于期望的最终间距为100nm或更小。 为了使用，加入饱和了特定化学试剂的缓冲溶液以控制溶胀，导致柱膨胀至规定的量以达到所需的分离。
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2.发明授权Micro-electrophoresis chip for moving and separating nucleic acids and other charged molecules 失效用于移动和分离核酸和其他带电分子的微电泳芯片公开(公告)号：US06176990B1
公开(公告)日：2001-01-23
申请号：US08973933
申请日：1997-12-16
申请人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
发明人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
IPC分类号： G01N27453
CPC分类号： G01N27/44773 , G01N27/44704 , G01N27/44791
摘要： A microelectrophoresis chip comprises a substrate in which there are formed one or more channels, one channel for each sample to be evaluated. The channels extend for the length of the chip, a distance of generally around 1 cm, and are about 1 to 10 &mgr;m wide and 1 to 10 &mgr;m in depth. The channels are filled with a homogeneous separation matrix which acts as an obstacle to the electrophoretic migration of the charged molecules. Microelectrodes disposed in the channels are used to induce an electric field within the homogeneous separation medium. When a voltage is applied across two or more of the microelectrodes, the charged molecules are induced to move and separate according to the electric field density, the type of solvent film, and the charge, shape and size of the charged molecule. The chip may further comprise detectors, such as light polarization detectors, fluorescence emission detectors, biosensors, electrochemical sensors or other microcomponents which may include sites for enzymatic or chemical manipulation of the moved or separated charged molecules.
摘要翻译： 微电泳芯片包括其中形成一个或多个通道的基底，每个待评估样品的通道一个通道。 通道延长芯片的长度，通常约1厘米的距离，宽度约为1至10微米，深度为1至10毫米。 通道充满均匀的分离基质，其作为电荷分子的电泳迁移的障碍。 设置在通道中的微电极用于在均匀分离介质内诱发电场。 当电压施加到两个或更多个微电极上时，根据电场密度，溶剂膜的类型和带电分子的电荷，形状和尺寸，诱导带电分子移动和分离。 芯片还可以包括诸如光偏振检测器，荧光发射检测器，生物传感器，电化学传感器或其它微元件的检测器，其可以包括用于酶或分离带电分子的酶或化学操作的位点。
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3.发明授权Micro-electrophoresis chip for moving and separating nucleic acids and other charged molecules 失效用于移动和分离核酸和其他带电分子的微电泳芯片公开(公告)号：US06261430B1
公开(公告)日：2001-07-17
申请号：US09505659
申请日：2000-02-17
申请人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
发明人： Thomas D. Yager , Paul Waterhouse , Alexandre M. Izmailov , Bruno C. Maruzzo , John K. Stevens , Marina T. Larson
IPC分类号： G01N2726
CPC分类号： G01N27/44773 , G01N27/44704 , G01N27/44791
摘要： A microelectrophoresis chip comprises a substrate in which there are formed one or more channels, one channel for each sample to be evaluated. The channels extend for the length of the chip, a distance of generally around 1 cm, and are about 1 to 10 &mgr;m wide and 1 to 10 &mgr;m in depth. The channels are filled with a homogeneous separation matrix which acts as an obstacle to the electrophoretic migration of the charged molecules. Microelectrodes disposed in the channels are used to induce an electric filed within the homogeneous separation medium. When a voltage is applied across two or more of the microelectrodes, the charged molecules are induced to move and separate according to the electric field density, the type of solvent film, and the charge, shape and size of the charged molecule. The chip may further comprise detectors, such as light polarization detectors, fluorescence emission detectors, biosensors, electrochemical sensors or other microcomponents which may include sites for enzymatic or chemical manipulation of the moved or separated charged molecules.
摘要翻译： 微电泳芯片包括其中形成一个或多个通道的基底，每个待评估样品的通道一个通道。 通道延长芯片的长度，通常约1厘米的距离，宽度约为1至10微米，深度为1至10毫米。 通道充满均匀的分离基质，其作为电荷分子的电泳迁移的障碍。 设置在通道中的微电极用于诱导均匀分离介质内的电场。 当电压施加到两个或更多个微电极上时，根据电场密度，溶剂膜的类型和带电分子的电荷，形状和尺寸，诱导带电分子移动和分离。 芯片还可以包括诸如光偏振检测器，荧光发射检测器，生物传感器，电化学传感器或其它微元件的检测器，其可以包括用于酶或分离带电分子的酶或化学操作的位点。
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4.发明授权Method, compositions and kit for detection and identification of microorganisms 失效用于微生物检测和鉴定的方法，组合物和试剂盒
公开(公告)号：US5888736A
公开(公告)日：1999-03-30
申请号：US807138
申请日：1997-02-27
CPC分类号： B01L7/525 , B01L7/52 , C12Q1/6841 , C12Q1/6858 , C12Q1/6869 , C12Q1/6881 , C12Q1/689 , C12Q1/703 , C12Q2600/156 , G01N2035/00237
摘要： Evaluation of a sample for the presence and qualitative nature of a microorganism can be performed in a single vessel by combining a natural abundance DNA sample with a sequencing mixture containing a primer pair, a thermally stable polymerase such as ThermoSequenase.TM. which incorporates dideoxynucleotides into an extending nucleic acid polymer at a rate which is no less than about 0.4 times the rate of incorporation of deoxynucleotides, nucleotide triphosphate feedstocks, and a chain terminating nucleotide triphosphate. The mixture is processed through multiple thermal cycles for annealing, extension and denaturation to produce a product mixture which is analyzed by electrophoresis.
摘要翻译： 通过将天然丰度DNA样品与含有引物对的测序混合物，热稳定聚合酶如ThermoSequenase TM组合，可以在单个容器中评估样品的存在和定性性质，其将双脱氧核苷酸掺入延伸的 核酸聚合物的速率不低于脱氧核苷酸，核苷酸三磷酸酯原料和链终止核苷酸三磷酸的引入速率的约0.4倍。 通过多个热循环处理混合物进行退火，延伸和变性以产生通过电泳分析的产物混合物。
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公开(公告)号：US5830657A
公开(公告)日：1998-11-03
申请号：US684498
申请日：1996-07-19
申请人： James Leushner , May Hui , James M. Dunn , Marina T. Larson
发明人： James Leushner , May Hui , James M. Dunn , Marina T. Larson
CPC分类号： B01L7/52 , B01L7/525 , C12Q1/6841 , C12Q1/6881 , C12Q1/689 , C12Q1/703 , C12Q2600/156 , C12Q2600/16 , G01N2035/00237
摘要： Sequencing of a selected region of a target nucleic acid polymer in a genomic DNA sample can be performed in a single vessel by combining the sample with a sequencing mixture containing a primer pair, a thermally stable polymerase such as Thermo Sequenase.TM. which incorporates dideoxynucleotides into an extending nucleic acid polymer at a rate which is no less than about 0.4 times the rate of incorporation of deoxynucleotides, nucleotide feedstocks, and a chain terminating nucleotide. The mixture is processed through multiple thermal cycles for annealing, extension and denaturation to produce a product mixture which is analyzed by electrophoresis.
摘要翻译： 基因组DNA样品中靶核酸聚合物的选定区域的测序可以通过将样品与含有引物对的测序混合物，热稳定聚合酶如Thermo Sequenase TM组合而在单个容器中进行，其将二脱氧核苷酸掺入到 以不低于脱氧核苷酸，核苷酸原料和链终止核苷酸并入速率的约0.4倍的速率延伸核酸聚合物。 通过多个热循环处理混合物进行退火，延伸和变性以产生通过电泳分析的产物混合物。
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公开(公告)号：US20120305396A1
公开(公告)日：2012-12-06
申请号：US13584912
申请日：2012-08-14
IPC分类号： G01N27/28
CPC分类号： G01N27/403 , C12Q1/004 , G01N27/30 , G01N27/3272 , Y10T29/49002 , Y10T29/49114 , Y10T29/49117 , Y10T156/1052 , Y10T156/1062 , Y10T156/1074
摘要： Electrochemical test cells are made with precision and accuracy by adhering an electrically resistive sheet having a bound opening to a first electrically conductive sheet. A notching opening is then punched through the electrically resistive sheet and the first electrically conductive sheet. The notching opening intersects the first bound opening in the electrically resistive sheet, and transforms the first bound opening into a notch in the electrically resistive sheet. A second electrically conductive sheet is punched to have a notching opening corresponding to that of first electrically conductive sheet, and this is adhered to the other side of the electrically resistive sheet such that the notching openings are aligned. This structure is cleaved from surrounding material to form an electrochemical cell that has a sample space for receiving a sample defined by the first and second conductive sheets and the notch in the electrically resistive sheet.
摘要翻译： 通过将具有结合开口的电阻片粘附到第一导电片上，精确地和精确地制造电化学测试电池。 然后通过电阻片和第一导电片冲切开切口。 开槽开口与电阻薄片中的第一个开口相交，并将第一个结合开口转变成电阻薄片中的凹口。 第二导电片被冲压成具有与第一导电片相对应的开槽开口，并且其粘接到电阻片的另一侧，使得开槽开口对准。 这种结构从周围的材料上被切割成一个电化学电池，该电化学电池具有用于接收由第一和第二导电片和电阻片中的凹口限定的样品的样品空间。
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公开(公告)号：US08182636B2
公开(公告)日：2012-05-22
申请号：US13052605
申请日：2011-03-21
IPC分类号： B32B38/04 , G01N27/327
CPC分类号： G01N27/403 , C12Q1/004 , G01N27/30 , G01N27/3272 , Y10T29/49002 , Y10T29/49114 , Y10T29/49117 , Y10T156/1052 , Y10T156/1062 , Y10T156/1074
摘要： Electrochemical test cells are made with precision and accuracy by adhering an electrically resistive sheet having a bound opening to a first electrically conductive sheet. A notching opening is then punched through the electrically resistive sheet and the first electrically conductive sheet. The notching opening intersects the first bound opening in the electrically resistive sheet, and transforms the first bound opening into a notch in the electrically resistive sheet. A second electrically conductive sheet is punched to have a notching opening corresponding to that of first electrically conductive sheet, and this is adhered to the other side of the electrically resistive sheet such that the notching openings are aligned. This structure is cleaved from surrounding material to form an electrochemical cell that has a sample space for receiving a sample defined by the first and second conductive sheets and the notch in the electrically resistive sheet.
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公开(公告)号：US20090221308A1
公开(公告)日：2009-09-03
申请号：US12396581
申请日：2009-03-03
申请人： Keith Lerner , Marina T. Larson
发明人： Keith Lerner , Marina T. Larson
IPC分类号： H04W4/00
CPC分类号： H04L67/12
摘要： A system in the form of distributed data-processing and communications hardware components is used to enhance patient compliance with instructions for the taking of medications. The system includes a central server and a plurality of remote stations disposed at medication points-of-supply in communication for data transmission to and from the central server. Upon dispensing of a medication to a patient, the remote station transmits information to the central server and the central server receives and stores the information. The information includes at least a telephonic communication address for the patient, the nature of the medication dispensed and the amount and instructed frequency of taking the medication. The central server transmits an initial message to the patient, for example to a cellular telephone, within a pre-determined period of time following initial receipt of the information from the remote station; and subsequent messages at time intervals determined by the instructed frequency of taking the medication. Responses from the patient may be logged to confirm taking of the medication.
摘要翻译： 分布式数据处理和通信硬件组件形式的系统用于增强患者对服用药物指导的依从性。 该系统包括中央服务器和多个远程站，这些远程站设置在通信中的药物供应点，用于向中央服务器传送数据。 在向患者分配药物时，远程站向中央服务器发送信息，并且中央服务器接收并存储该信息。 所述信息至少包括用于患者的电话通信地址，所分配的药物的性质以及服用药物的量和指示频率。 中央服务器在从远程站初始接收到信息之后的预定时间段内向患者发送初始消息，例如到蜂窝电话; 以及由指示的服药次数确定的时间间隔的随后消息。 可能会记录患者的反应，以确认服用药物。
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公开(公告)号：US08268145B2
公开(公告)日：2012-09-18
申请号：US10908656
申请日：2005-05-20
IPC分类号： G01N27/327
CPC分类号： G01N27/403 , C12Q1/004 , G01N27/30 , G01N27/3272 , Y10T29/49002 , Y10T29/49114 , Y10T29/49117 , Y10T156/1052 , Y10T156/1062 , Y10T156/1074
摘要： Electrochemical test cells are made with precision and accuracy by adhering an electrically resistive sheet having a bound opening to a first electrically conductive sheet. A notching opening is then punched through the electrically resistive sheet and the first electrically conductive sheet. The notching opening intersects the first bound opening in the electrically resistive sheet, and transforms the first bound opening into a notch in the electrically resistive sheet. A second electrically conductive sheet is punched to have a notching opening corresponding to that of first electrically conductive sheet, and this is adhered to the other side of the electrically resistive sheet such that the notching openings are aligned. This structure is cleaved from surrounding material to form an electrochemical cell that has a sample space for receiving a sample defined by the first and second conductive sheets and the notch in the electrically resistive sheet.
摘要翻译： 通过将具有结合开口的电阻片粘附到第一导电片上，精确地和精确地制造电化学测试电池。 然后通过电阻片和第一导电片冲切开切口。 开槽开口与电阻薄片中的第一个开口相交，并将第一个结合开口转变成电阻薄片中的凹口。 第二导电片被冲压成具有与第一导电片相对应的开槽开口，并且其粘接到电阻片的另一侧，使得开槽开口对准。 这种结构从周围的材料上被切割成一个电化学电池，该电化学电池具有用于接收由第一和第二导电片和电阻片中的凹口限定的样品的样品空间。
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公开(公告)号：US5789168A
公开(公告)日：1998-08-04
申请号：US640672
申请日：1996-05-01
申请人： James Leushner , May Hui , James M. Dunn , Marina T. Larson
发明人： James Leushner , May Hui , James M. Dunn , Marina T. Larson
CPC分类号： B01L7/525 , B01L7/52 , C12Q1/6841 , C12Q1/6881 , C12Q1/689 , C12Q1/703 , C12Q2600/156 , C12Q2600/16 , G01N2035/00237
摘要： Amplification and sequencing of a selected region of a target nucleic acid polymer are be performed in a single vessel. The sample is added to an amplification mixture containing a thermally stable polymerase and nucleoside feedstocks. Chain terminating dideoxynucleosides are added either at the beginning of the amplification reaction or during the course of the amplification. A thermally stable polymerase which incorporates dideoxynucleotides into an extending oligonucleotide at a rate which is no less than about 0.4 times the rate of incorporation of deoxynucleosides can be used in the amplification mixture or added with the chain terminating nucleoside.
摘要翻译： 靶核酸聚合物的选定区域的扩增和测序可以在单个容器中进行。 将样品加入到含有热稳定聚合酶和核苷原料的扩增混合物中。 在扩增反应开始时或扩增过程中加入链终止双脱氧核苷。 将扩增寡核苷酸以不低于脱氧核苷的并入速率的约0.4倍的速率掺入延伸寡核苷酸的热稳定聚合酶可以用于扩增混合物中或加入链终止核苷。
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