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公开(公告)号：US07799553B2
公开(公告)日：2010-09-21
申请号：US11139018
申请日：2005-05-25
CPC分类号： B01L3/50273 , B01L3/502753 , B01L7/52 , B01L2200/10 , B01L2200/147 , B01L2300/0803 , B01L2300/0864 , B01L2300/087 , B01L2300/0874 , B01L2300/0887 , B01L2300/1827 , B01L2400/0415 , B01L2400/0421 , B01L2400/0633 , C12Q1/686 , C12Q1/6869 , C12Q2565/518 , C12Q2537/143 , C12Q2565/629
摘要： Methods and apparatus for genome analysis are provided. A microfabricated structure including a microfluidic distribution channel is configured to distribute microreactor elements having copies of a sequencing template into a plurality of microfabricated thermal cycling chambers. A microreactor element may include a microcarrier element carrying the multiple copies of the sequencing template. The microcarrier element may comprise a microsphere. An autovalve at an exit port of a thermal cycling chamber, an optical scanner, or a timing arrangement may be used to ensure that only one microsphere will flow into one thermal cycling chamber wherein thermal cycling extension fragments are produced. The extension products are captured, purified, and concentrated in an integrated oligonucleotide gel capture chamber. A microfabricated component separation apparatus is used to analyze the purified extension fragments. The microfabricated structure may be used in a process for performing sequencing and other genetic analysis of DNA or RNA.
摘要翻译： 提供了基因组分析的方法和装置。 包括微流体分配通道的微制造结构被配置为将具有测序模板的拷贝的微反应器元件分配到多个微制造的热循环室中。 微反应器元件可以包括承载测序模板的多个拷贝的微载体元件。 微载体元件可以包含微球体。 可以使用热循环室，光学扫描器或定时装置的出口处的自动阀，以确保仅一个微球将流入一个热循环室，其中产生热循环延伸碎片。 延伸产物被捕获，纯化和浓缩在一个整合的寡核苷酸凝胶捕获室中。 微量组分分离装置用于分析纯化的延伸片段。 微制造结构可用于进行DNA或RNA的测序和其他遗传分析的过程。
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公开(公告)号：US08420318B2
公开(公告)日：2013-04-16
申请号：US13372376
申请日：2012-02-13
CPC分类号： B01L3/50273 , B01L3/502753 , B01L7/52 , B01L2200/10 , B01L2200/147 , B01L2300/0803 , B01L2300/0864 , B01L2300/087 , B01L2300/0874 , B01L2300/0887 , B01L2300/1827 , B01L2400/0415 , B01L2400/0421 , B01L2400/0633 , C12Q1/686 , C12Q1/6869 , C12Q2565/518 , C12Q2537/143 , C12Q2565/629
摘要： Methods and apparatus for genome analysis are provided. A microfabricated structure including a microfluidic distribution channel is configured to distribute microreactor elements having copies of a sequencing template into a plurality of microfabricated thermal cycling chambers. A microreactor element may include a microcarrier element carrying the multiple copies of the sequencing template. The microcarrier element may comprise a microsphere. An autovalve at an exit port of a thermal cycling chamber, an optical scanner, or a timing arrangement may be used to ensure that only one microsphere will flow into one thermal cycling chamber wherein thermal cycling extension fragments are produced. The extension products are captured, purified, and concentrated in an integrated oligonucleotide gel capture chamber. A microfabricated component separation apparatus is used to analyze the purified extension fragments. The microfabricated structure may be used in a process for performing sequencing and other genetic analysis of DNA or RNA.
摘要翻译： 提供了基因组分析的方法和装置。 包括微流体分配通道的微制造结构被配置为将具有测序模板的拷贝的微反应器元件分配到多个微制造的热循环室中。 微反应器元件可以包括承载测序模板的多个拷贝的微载体元件。 微载体元件可以包含微球体。 可以使用热循环室，光学扫描器或定时装置的出口处的自动阀，以确保仅一个微球将流入一个热循环室，其中产生热循环延伸碎片。 延伸产物被捕获，纯化和浓缩在一个整合的寡核苷酸凝胶捕获室中。 微量组分分离装置用于分析纯化的延伸片段。 微制造结构可用于进行DNA或RNA的测序和其他遗传分析的过程。
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3.发明申请Inline-injection microdevice and microfabricated integrated DNA analysis system using same 有权在线注射微型装置和微制造综合DNA分析系统使用公开(公告)号：US20090035770A1
公开(公告)日：2009-02-05
申请号：US11978224
申请日：2007-10-25
CPC分类号： G01N27/44743 , B01L3/502715 , B01L3/502753 , B01L3/502784 , B01L7/52 , B01L2200/027 , B01L2200/0631 , B01L2200/0673 , B01L2200/10 , B01L2300/0803 , B01L2400/0421 , B01L2400/0487 , G01N1/405
摘要： Methods and microfluidic circuitry for inline injection of nucleic acids for capillary electrophoresis analysis are provided. According to various embodiments, microfabricated structures including affinity-based capture matrixes inline with separation channels are provided. The affinity-based capture matrixes provide inline sample plug formation and injection into a capillary electrophoresis channel. Also provided are methods and apparatuses for a microbead-based inline injection system for DNA sequencing.
摘要翻译： 提供用于毛细管电泳分析的用于在线注射核酸的方法和微流体电路。 根据各种实施方式，提供包括与分离通道一致的基于亲和性捕获矩阵的微制造结构。 基于亲和性的捕获矩阵提供在线样品塞形成和注入毛细管电泳通道。 还提供了用于DNA测序的基于微珠的在线注射系统的方法和装置。
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4.发明授权Inline-injection microdevice and microfabricated integrated DNA analysis system using same 有权在线注射微型装置和微制造综合DNA分析系统使用公开(公告)号：US08841116B2
公开(公告)日：2014-09-23
申请号：US11978224
申请日：2007-10-25
IPC分类号： C12M1/00 , C12M1/34 , C12M3/00 , G01N15/06 , B01D57/02 , C02F1/40 , B01L3/00 , G01N27/447 , G01N1/40 , B01L7/00
CPC分类号： G01N27/44743 , B01L3/502715 , B01L3/502753 , B01L3/502784 , B01L7/52 , B01L2200/027 , B01L2200/0631 , B01L2200/0673 , B01L2200/10 , B01L2300/0803 , B01L2400/0421 , B01L2400/0487 , G01N1/405
摘要： Methods and microfluidic circuitry for inline injection of nucleic acids for capillary electrophoresis analysis are provided. According to various embodiments, microfabricated structures including affinity-based capture matrixes inline with separation channels are provided. The affinity-based capture matrixes provide inline sample plug formation and injection into a capillary electrophoresis channel. Also provided are methods and apparatuses for a microbead-based inline injection system for DNA sequencing.
摘要翻译： 提供用于毛细管电泳分析的用于在线注射核酸的方法和微流体电路。 根据各种实施方式，提供包括与分离通道一致的基于亲和性捕获矩阵的微制造结构。 基于亲和性的捕获矩阵提供在线样品塞形成和注入毛细管电泳通道。 还提供了用于DNA测序的基于微珠的在线注射系统的方法和装置。
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公开(公告)号：US20050287572A1
公开(公告)日：2005-12-29
申请号：US11139018
申请日：2005-05-25
申请人： Richard Mathies , Robert Blazej , Chung Liu , Palani Kumaresan , Stephanie Yeung
发明人： Richard Mathies , Robert Blazej , Chung Liu , Palani Kumaresan , Stephanie Yeung
CPC分类号： B01L3/50273 , B01L3/502753 , B01L7/52 , B01L2200/10 , B01L2200/147 , B01L2300/0803 , B01L2300/0864 , B01L2300/087 , B01L2300/0874 , B01L2300/0887 , B01L2300/1827 , B01L2400/0415 , B01L2400/0421 , B01L2400/0633 , C12Q1/686 , C12Q1/6869 , C12Q2565/518 , C12Q2537/143 , C12Q2565/629
摘要： Methods and apparatus for genome analysis are provided. A microfabricated structure including a microfluidic distribution channel is configured to distribute microreactor elements having copies of a sequencing template into a plurality of microfabricated thermal cycling chambers. A microreactor element may include a microcarrier element carrying the multiple copies of the sequencing template. The microcarrier element may comprise a microsphere. An autovalve at an exit port of a thermal cycling chamber, an optical scanner, or a timing arrangement may be used to ensure that only one microsphere will flow into one thermal cycling chamber wherein thermal cycling extension fragments are produced. The extension products are captured, purified, and concentrated in an integrated oligonucleotide gel capture chamber. A microfabricated component separation apparatus is used to analyze the purified extension fragments. The microfabricated structure may be used in a process for performing sequencing and other genetic analysis of DNA or RNA.
摘要翻译： 提供了基因组分析的方法和装置。 包括微流体分配通道的微制造结构被配置为将具有测序模板的拷贝的微反应器元件分配到多个微制造的热循环室中。 微反应器元件可以包括承载测序模板的多个拷贝的微载体元件。 微载体元件可以包含微球体。 可以使用热循环室，光学扫描器或定时装置的出口处的自动阀，以确保仅一个微球将流入一个热循环室，其中产生热循环延伸碎片。 延伸产物被捕获，纯化和浓缩在一个整合的寡核苷酸凝胶捕获室中。 微量组分分离装置用于分析纯化的延伸片段。 微制造结构可用于进行DNA或RNA的测序和其他遗传分析的过程。
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6.发明授权Microfabricated droplet generator for single molecule/cell genetic analysis in engineered monodispersed emulsions 有权用于工程化单分散乳液中单分子/细胞遗传分析的微型液滴发生器公开(公告)号：US08454906B2
公开(公告)日：2013-06-04
申请号：US12670377
申请日：2008-07-24
CPC分类号： B01L3/0268 , B01F3/0807 , B01F13/0062 , B01F13/1013 , B01F13/1022 , B01J2219/00466 , B01J2219/00468 , B01J2219/005 , B01J2219/00596 , B01J2219/00722 , B01L2200/0673 , B01L2300/0803 , B01L2400/0439 , B01L2400/0481 , G01N35/08 , G01N2035/1034 , Y10T436/2575
摘要： Provided are microfluidic designs and methods for rapid generation of monodisperse nanoliter volume droplets of reagent/target (e.g., molecule or cell) mix in emulsion oil. The designs and methods enable high-throughput encapsulation of a single target (e.g., DNA/RNA molecules or cells) in controlled size droplets of reagent mix. According to various embodiments, a microfabricated, 3-valve pump is used to precisely meter the volume of reagent/target mix in each droplet and also to effectively route microparticles such as beads and cells into the device, which are encapsulated within droplets at the intersection of the reagent channel and an oil channel. The pulsatile flow profile of the microfabricated pumps provides active control over droplet generation, thereby enabling droplet formation with oils that are compatible with biological reactions but are otherwise difficult to form emulsions with.
摘要翻译： 提供了用于在乳液油中快速产生试剂/靶（例如分子或细胞）混合物的单分散纳升体积液滴的微流体设计和方法。 这些设计和方法使得能够在受控尺寸的试剂混合液滴中的单个靶（例如，DNA / RNA分子或细胞）的高通量包封。 根据各种实施例，使用微型三阀泵来精确地测量每个液滴中的试剂/目标混合物的体积，并且还有效地将诸如珠粒和细胞的微粒有效地引入到装置中，该装置被封装在相交处的液滴内 的试剂通道和油通道。 微型泵的脉动流动分布提供了对液滴产生的主动控制，从而使得能够与与生物反应相容的油形成液滴，但是否则难以与乳液形成乳液。
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7.发明申请MICROFABRICATED DROPLET GENERATOR FOR SINGLE MOLECULE/CELL GENETIC ANALYSIS IN ENGINEERED MONODISPERSED EMULSIONS 有权用于单分子乳液中单分子/细胞遗传分析的微生物滴定发生器公开(公告)号：US20100285975A1
公开(公告)日：2010-11-11
申请号：US12670377
申请日：2008-07-24
CPC分类号： B01L3/0268 , B01F3/0807 , B01F13/0062 , B01F13/1013 , B01F13/1022 , B01J2219/00466 , B01J2219/00468 , B01J2219/005 , B01J2219/00596 , B01J2219/00722 , B01L2200/0673 , B01L2300/0803 , B01L2400/0439 , B01L2400/0481 , G01N35/08 , G01N2035/1034 , Y10T436/2575
摘要： Provided are microfluidic designs and methods for rapid generation of monodisperse nanoliter volume droplets of reagent/target (e.g., molecule or cell) mix in emulsion oil. The designs and methods enable high-throughput encapsulation of a single target (e.g., DNA/RNA molecules or cells) in controlled size droplets of reagent mix. According to various embodiments, a microfabricated, 3-valve pump is used to precisely meter the volume of reagent/target mix in each droplet and also to effectively route microparticles such as beads and cells into the device, which are encapsulated within droplets at the intersection of the reagent channel and an oil channel. The pulsatile flow profile of the microfabricated pumps provides active control over droplet generation, thereby enabling droplet formation with oils that are compatible with biological reactions but are otherwise difficult to form emulsions with.
摘要翻译： 提供了用于在乳液油中快速产生试剂/靶（例如分子或细胞）混合物的单分散纳升体积液滴的微流体设计和方法。 这些设计和方法使得能够在受控尺寸的试剂混合液滴中的单个靶（例如，DNA / RNA分子或细胞）的高通量包封。 根据各种实施例，使用微型三阀泵来精确地测量每个液滴中的试剂/目标混合物的体积，并且还有效地将诸如珠粒和细胞的微粒有效地引入装置中，该装置被封装在相交处的液滴内 的试剂通道和油通道。 微型泵的脉动流动分布提供了对液滴产生的主动控制，从而使得能够与与生物反应相容的油形成液滴，但是否则难以与乳液形成乳液。
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