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公开(公告)号：US06352838B1
公开(公告)日：2002-03-05
申请号：US09545150
申请日：2000-04-07
申请人： Peter A. Krulevitch , Robin R. Miles , Xiao-Bo Wang , Raymond P. Mariella , Peter R. C. Gascoyne , Joseph W. Balch
发明人： Peter A. Krulevitch , Robin R. Miles , Xiao-Bo Wang , Raymond P. Mariella , Peter R. C. Gascoyne , Joseph W. Balch
IPC分类号： C12A168
CPC分类号： C12N15/101 , C12Q1/6806 , C12Q2565/629 , C12Q2565/125
摘要： Manipulation of DNA molecules in solution has become an essential aspect of genetic analyses used for biomedical assays, the identification of hazardous bacterial agents, and in decoding the human genome. Currently, most of the steps involved in preparing a DNA sample for analysis are performed manually and are time, labor, and equipment intensive. These steps include extraction of the DNA from spores or cells, separation of the DNA from other particles and molecules in the solution (e.g. dust, smoke, cell/spore debris, and proteins), and separation of the DNA itself into strands of specific lengths. Dielectrophoresis (DEP), a phenomenon whereby polarizable particles move in response to a gradient in electric field, can be used to manipulate and separate DNA in an automated fashion, considerably reducing the time and expense involved in DNA analyses, as well as allowing for the miniaturization of DNA analysis instruments. These applications include direct transport of DNA, trapping of DNA to allow for its separation from other particles or molecules in the solution, and the separation of DNA into strands of varying lengths.
摘要翻译： 溶液中DNA分子的操作已成为用于生物医学测定，识别有害细菌试剂和解码人类基因组的遗传分析的重要方面。 目前，制备用于分析的DNA样品所涉及的大部分步骤都是手动进行的，是时间，劳动和设备密集型的。 这些步骤包括从孢子或细胞中提取DNA，将DNA与其他颗粒和溶液中的分子（例如灰尘，烟雾，细胞/孢子碎片和蛋白质）分离，以及将DNA本身分离成特定长度的细丝 。 电穿孔（DEP）是一种可极化粒子响应于电场梯度移动的现象，可用于以自动方式操作和分离DNA，大大减少DNA分析所涉及的时间和费用，并允许 DNA分析仪器的小型化。 这些应用包括直接转运DNA，捕获DNA以使其与溶液中的其它颗粒或分子分离，并将DNA分离成不同长度的链。
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公开(公告)号：US06289695B1
公开(公告)日：2001-09-18
申请号：US09441916
申请日：1999-11-17
IPC分类号： C03B2320
CPC分类号： C03B23/203 , Y02P40/57 , Y10T428/10
摘要： An improved apparatus and method for vacuum fusion bonding of large, patterned glass plates. One or both glass plates are patterned with etched features such as microstructure capillaries and a vacuum pumpout moat, with one plate having at least one hole therethrough for communication with a vacuum pumpout fixture. High accuracy alignment of the plates is accomplished by a temporary clamping fixture until the start of the fusion bonding heat cycle. A complete, void-free fusion bond of seamless, full-strength quality is obtained through the plates; because the glass is heated well into its softening point and because of a large, distributed force that is developed that presses the two plates together from the difference in pressure between the furnace ambient (high pressure) and the channeling and microstructures in the plates (low pressure) due to the vacuum drawn. The apparatus and method may be used to fabricate microcapillary arrays for chemical electrophoresis; for example, any apparatus using a network of microfluidic channels embedded between plates of glass or similar moderate melting point substrates with a gradual softening point curve, or for assembly of glass-based substrates onto larger substrates, such as in flat panel display systems.
摘要翻译： 一种用于大型图案化玻璃板的真空熔接的改进的装置和方法。 一个或两个玻璃板被图案化，具有蚀刻特征，例如微结构毛细管和真空泵出护城河，其中一个板具有穿过其中的至少一个孔，用于与真空抽出固定装置连通。 板的高精度对准是通过临时夹紧装置实现的，直到熔合结合热循环开始。 通过板获得完整，无空隙的无缝，全强度质量的熔合键; 因为玻璃被加热到其软化点，并且由于大的分布力，其被开发出来，其将两个板压在炉环境（高压）和板之间的沟槽和微结构之间的压力差中（低 压力）由于抽真空。 该装置和方法可用于制造用于化学电泳的微毛细管阵列; 例如，使用嵌入玻璃板或具有逐渐软化点曲线的类似中等熔点基材之间的微流体通道网络的任何装置，或用于将玻璃基底料装配到诸如平板显示系统的较大基板上。
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公开(公告)号：US06301931B1
公开(公告)日：2001-10-16
申请号：US09448308
申请日：1999-11-24
IPC分类号： C03B2320
CPC分类号： C03B23/203 , Y02P40/57 , Y10T428/10
摘要： An improved apparatus and method for vacuum fusion bonding of large, patterned glass plates. One or both glass plates are patterned with etched features such as microstructure capillaries and a vacuum pumpout moat, with one plate having at least one hole therethrough for communication with a vacuum pumpout fixture. High accuracy alignment of the plates is accomplished by a temporary clamping fixture until the start of the fusion bonding heat cycle. A complete, void-free fusion bond of seamless, full-strength quality is obtained through the plates; because the glass is heated well into its softening point and because of a large, distributed force that is developed that presses the two plates together from the difference in pressure between the furnace ambient (high pressure) and the channeling and microstructures in the plates (low pressure) due to the vacuum drawn. The apparatus and method may be used to fabricate microcapillary arrays for chemical electrophoresis; for example, any apparatus using a network of microfluidic channels embedded between plates of glass or similar moderate melting point substrates with a gradual softening point curve, or for assembly of glass-based substrates onto larger substrates, such as in flat panel display systems.
摘要翻译： 一种用于大型图案化玻璃板的真空熔接的改进的装置和方法。 一个或两个玻璃板被图案化，具有蚀刻特征，例如微结构毛细管和真空泵出护城河，其中一个板具有穿过其中的至少一个孔，用于与真空抽出固定装置连通。 板的高精度对准是通过临时夹紧装置实现的，直到熔合结合热循环开始。 通过板获得完整，无空隙的无缝，全强度质量的熔合键; 因为玻璃被加热到其软化点，并且由于大的分布力，其被开发出来，其将两个板压在炉环境（高压）和板之间的沟槽和微结构之间的压力差中（低 压力）由于抽真空。 该装置和方法可用于制造用于化学电泳的微毛细管阵列; 例如，使用嵌入玻璃板或具有逐渐软化点曲线的类似中等熔点基材之间的微流体通道网络的任何装置，或用于将玻璃基底料装配到诸如平板显示系统的较大基板上。
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4.发明授权Extended length microchannels for high density high throughput electrophoresis systems 失效用于高密度高通量电泳系统的扩展长度微通道
公开(公告)号：US06153076A
公开(公告)日：2000-11-28
申请号：US5499
申请日：1998-01-12
申请人： James C. Davidson , Joseph W. Balch
发明人： James C. Davidson , Joseph W. Balch
IPC分类号： G01N27/447 , G01N30/60 , G01N27/26
CPC分类号： G01N27/44791 , G01N30/6095
摘要： High throughput electrophoresis systems which provide extended well-to-read distances on smaller substrates, thus compacting the overall systems. The electrophoresis systems utilize a high density array of microchannels for electrophoresis analysis with extended read lengths. The microchannel geometry can be used individually or in conjunction to increase the effective length of a separation channel while minimally impacting the packing density of channels. One embodiment uses sinusoidal microchannels, while another embodiment uses plural microchannels interconnected by a via. The extended channel systems can be applied to virtually any type of channel confined chromatography.
摘要翻译： 高通量电泳系统，可在更小的基板上提供延长的读取距离，从而压缩整个系统。 电泳系统利用高密度阵列的微通道进行电泳分析，延长阅读长度。 微通道几何形状可以单独使用或联合使用以增加分离通道的有效长度，同时最小程度上影响通道的堆积密度。 一个实施例使用正弦微通道，而另一个实施例使用由通孔相互连接的多个微通道。 扩展通道系统可以应用于几乎任何类型的通道限制色谱。
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公开(公告)号：US5980713A
公开(公告)日：1999-11-09
申请号：US705447
申请日：1996-08-29
申请人： James C. Davidson , Joseph W. Balch
发明人： James C. Davidson , Joseph W. Balch
IPC分类号： G01N1/00 , C12M1/00 , C12N15/09 , G01N1/10 , G01N27/447 , G01N27/416
CPC分类号： G01N27/44743
摘要： A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.
摘要翻译： 用于带电分子的微注射器样品递送系统。 注射器用于收集和输送受控量的带电分子样品用于后续分析。 注射器输送系统可以缩放到大量（> 96），用于样品输送到大规模并行的高通量分析系统。 注射器系统的本质是电场可控加载尖端，其包括多孔材料的一部分。 通过将适当的极性偏置电位施加到注射器尖端，带电分子将迁移到多孔材料中，并且通过反转极性偏置电位，分子被喷射或强制离开尖端。 本发明具有用于摄取带电生物分子（例如蛋白质，核酸，聚合物等）以用于递送至分析系统的应用，并且可用于自动化样品递送系统中。
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公开(公告)号：US5746901A
公开(公告)日：1998-05-05
申请号：US628309
申请日：1996-04-05
IPC分类号： G01N27/447 , G01N27/26
CPC分类号： G01N27/44791
摘要： A hybrid slab-microchannel gel electrophoresis system. The hybrid system permits the fabrication of isolated microchannels for biomolecule separations without imposing the constraint of a totally sealed system. The hybrid system is reusable and ultimately much simpler and less costly to manufacture than a closed channel plate system. The hybrid system incorporates a microslab portion of the separation medium above the microchannels, thus at least substantially reducing the possibility of non-uniform field distribution and breakdown due to uncontrollable leakage. A microslab of the sieving matrix is built into the system by using plastic spacer materials and is used to uniformly couple the top plate with the bottom microchannel plate.
摘要翻译： 混合板 - 微通道凝胶电泳系统。 混合系统允许制造分离的微通道用于生物分子分离，而不施加全密封系统的约束。 混合系统可重复使用，并且最终比封闭的通道板系统简单得多且制造成本更低。 混合系统包含微通道上方的分离介质的微尺度部分，因此至少显着降低了由于不可控的泄漏引起的非均匀场分布和击穿的可能性。 通过使用塑料隔板材料将筛分基质的microslab内置在系统中，并用于将顶板与底部微通道板均匀地接合。
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公开(公告)号：US06372328B1
公开(公告)日：2002-04-16
申请号：US09426413
申请日：1999-10-25
申请人： James C. Davidson , Joseph W. Balch
发明人： James C. Davidson , Joseph W. Balch
IPC分类号： B32B300
CPC分类号： C03B23/203 , Y10S228/903 , Y10T29/49826 , Y10T428/24562 , Y10T428/2457 , Y10T428/24612 , Y10T428/24744
摘要： A process for effectively bonding arbitrary size or shape substrates. The process incorporates vacuum pull down techniques to ensure uniform surface contact during the bonding process. The essence of the process for bonding substrates, such as glass, plastic, or alloys, etc., which have a moderate melting point with a gradual softening point curve, involves the application of an active vacuum source to evacuate interstices between the substrates while at the same time providing a positive force to hold the parts to be bonded in contact. This enables increasing the temperature of the bonding process to ensure that the softening point has been reached and small void areas are filled and come in contact with the opposing substrate. The process is most effective where at least one of the two plates or substrates contain channels or grooves that can be used to apply vacuum between the plates or substrates during the thermal bonding cycle. Also, it is beneficial to provide a vacuum groove or channel near the perimeter of the plates or substrates to ensure bonding of the perimeter of the plates or substrates and reduce the unbonded regions inside the interior region of the plates or substrates.
摘要翻译： 用于有效地粘合任意尺寸或形状的基底的方法。 该工艺采用真空拉拔技术，以确保在接合过程中均匀的表面接触。 用于粘合具有适度熔点的逐渐软化点曲线的基材（例如玻璃，塑料或合金等）的工艺的本质涉及施加主动真空源以排空基板之间的间隙，同时在 同时提供正的力来保持要接合的部件接触。 这使得能够提高接合过程的温度以确保达到软化点，并且填充小的空隙区域并与相对的基板接触。 该方法在两个板或基板中的至少一个包含可用于在热粘合循环期间在板或基板之间施加真空的通道或凹槽时是最有效的。 此外，有利的是在板或基板的周边附近提供真空槽或通道，以确保板或基板的周边的粘合，并且减少板或基板的内部区域内的未结合区域。
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8.发明授权公开(公告)号：US06319379B1
公开(公告)日：2001-11-20
申请号：US09379378
申请日：1999-08-23
IPC分类号： G01N2726
CPC分类号： G01N30/16 , G01N27/44743 , G01N30/6095 , G01N2030/285 , G01N2030/562 , G01N30/466
摘要： A sample injection method for horizontal configured multiple chromatography or electrophoresis units, each containing a number of separation/analysis channels, that enables efficient introduction of analyte samples. This method for loading when taken in conjunction with horizontal microchannels allows much reduced sample volumes and a means of sample stacking to greatly reduce the concentration of the sample. This reduction in the amount of sample can lead to great cost savings in sample preparation, particularly in massively parallel applications such as DNA sequencing. The essence of this method is in preparation of the input of the separation channel, the physical sample introduction, and subsequent removal of excess material. By this method, sample volumes of 100 nanoliter to 2 microliters have been used successfully, compared to the typical 5 microliters of sample required by the prior separation/analysis method.
摘要翻译： 用于水平配置的多个色谱或电泳单元的样品注射方法，每个包含多个分离/分析通道，能够有效地引入分析物样品。 当与水平微通道结合使用时，这种加载方法允许大大减少样品体积和样品堆叠的手段，以大大降低样品的浓度。 样品量的减少可以在样品制备中节省大量成本，特别是在大规模并行应用如DNA测序中。 该方法的本质在于准备分离通道的输入，物理样品引入和随后的多余材料的去除。 通过这种方法，与以前的分离/分析方法所需的典型5微升样品相比，成功地使用了100纳升至2微升的样品体积。
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公开(公告)号：US6131410A
公开(公告)日：2000-10-17
申请号：US39522
申请日：1998-03-16
IPC分类号： C03B23/203 , C03B23/20 , B32B31/04
CPC分类号： C03B23/203 , Y02P40/57 , Y10T428/10
摘要： An improved apparatus and method for vacuum fusion bonding of large, patterned glass plates. One or both glass plates are patterned with etched features such as microstructure capillaries and a vacuum pumpout moat, with one plate having at least one hole therethrough for communication with a vacuum pumpout fixture. High accuracy alignment of the plates is accomplished by a temporary clamping fixture until the start of the fusion bonding heat cycle. A complete, void-free fusion bond of seamless, full-strength quality is obtained through the plates; because the glass is heated well into its softening point and because of a large, distributed force that is developed that presses the two plates together from the difference in pressure between the furnace ambient (high pressure) and the channeling and microstructures in the plates (low pressure) due to the vacuum drawn. The apparatus and method may be used to fabricate microcapillary arrays for chemical electrophoresis; for example, any apparatus using a network of microfluidic channels embedded between plates of glass or similar moderate melting point substrates with a gradual softening point curve, or for assembly of glass-based substrates onto larger substrates, such as in flat panel display systems.
摘要翻译： 一种用于大型图案化玻璃板的真空熔接的改进的装置和方法。 一个或两个玻璃板被图案化，具有蚀刻特征，例如微结构毛细管和真空泵出护城河，其中一个板具有穿过其中的至少一个孔，用于与真空抽出固定装置连通。 板的高精度对准是通过临时夹紧装置实现的，直到熔合结合热循环开始。 通过板获得完整，无空隙的无缝，全强度质量的熔合键; 因为玻璃被加热到其软化点，并且由于大的分布力，其被开发出来，其将两个板压在炉环境（高压）和板之间的沟槽和微结构之间的压力差中（低 压力）由于抽真空。 该装置和方法可用于制造用于化学电泳的微毛细管阵列; 例如，使用嵌入玻璃板或具有逐渐软化点曲线的类似中等熔点基材之间的微流体通道网络的任何装置，或用于将玻璃基底料装配到诸如平板显示系统的较大基板上。
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公开(公告)号：US5589136A
公开(公告)日：1996-12-31
申请号：US492678
申请日：1995-06-20
IPC分类号： C12N15/09 , B01J19/00 , B01L7/00 , B81B1/00 , B81C3/00 , C12M1/00 , C12Q1/68 , G01N21/03 , G01N21/05 , G01N21/69 , G01N21/76 , B01L3/00
CPC分类号： G01N21/69 , B01J19/0046 , B01J19/0093 , B01L7/52 , G01N21/0332 , G01N21/76 , B01J2219/00828 , B01J2219/00853 , B01J2219/00873 , B01J2219/00889 , B01J2219/00891 , B01J2219/00912 , B01J2219/00936 , B01J2219/00945 , B01J2219/00952 , B81C3/00 , G01N2021/0346 , G01N21/05
摘要： A silicon-based sleeve type chemical reaction chamber that combines heaters, such as doped polysilicon for heating, and bulk silicon for convection cooling. The reaction chamber combines a critical ratio of silicon and silicon nitride to the volume of material to be heated (e.g., a liquid) in order to provide uniform heating, yet low power requirements. The reaction chamber will also allow the introduction of a secondary tube (e.g., plastic) into the reaction sleeve that contains the reaction mixture thereby alleviating any potential materials incompatibility issues. The reaction chamber may be utilized in any chemical reaction system for synthesis or processing of organic, inorganic, or biochemical reactions, such as the polymerase chain reaction (PCR) and/or other DNA reactions, such as the ligase chain reaction, which are examples of a synthetic, thermal-cycling-based reaction. The reaction chamber may also be used in synthesis instruments, particularly those for DNA amplification and synthesis.
摘要翻译： 一种硅基套管型化学反应室，其结合加热器，例如用于加热的掺杂多晶硅和用于对流冷却的体硅。 反应室将硅和氮化硅的临界比与待加热材料（例如液体）的体积相结合，以便提供均匀的加热，但低功率要求。 反应室还将允许将二次管（例如塑料）引入到包含反应混合物的反应套筒中，从而减轻任何潜在的材料不相容性问题。 反应室可用于任何用于合成或加工有机，无机或生物化学反应的化学反应体系，例如聚合酶链式反应（PCR）和/或其它DNA反应，例如连接酶链式反应，其为实施例 的合成，热循环反应。 反应室也可用于合成仪器，特别是用于DNA扩增和合成的仪器。
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