公开(公告)号：US08092762B2

公开(公告)日：2012-01-10

申请号：US12624363

申请日：2009-11-23

申请人： Varouj Amirkhanian ,  Bob G. Heitel ,  Ming-Sun Liu ,  Paul Mooney

发明人： Varouj Amirkhanian ,  Bob G. Heitel ,  Ming-Sun Liu ,  Paul Mooney

IPC分类号： A61J1/06

CPC分类号： G01N21/645 ,  G01N27/44721 ,  G01N2021/6463 ,  G01N2021/6484 ,  G01N2201/08

摘要： The present invention provides for an interface mechanism in a bio-separation instrument that makes interface connections to a multi-channel cartridge. The interface mechanism precisely positions the cartridge in relation to the support elements in the instrument (e.g., high-voltage, gas pressure, incident radiation and detector), and makes automated, reliable and secured alignments and connections between various components in the cartridge and the support elements in the supporting instrument. The interface mechanism comprises pneumatically or electromechanically driven actuators for engaging support elements in the instrument to components on the cartridge. After the cartridge has been securely received by the interface mechanism, the connection sequence is initiated. The interface provides separate high voltage and optical connections for each separation channel in the cartridge, thus providing channel-to-channel isolation from cross talk both electrically and optically.

摘要翻译： 本发明提供了生物分离仪器中的接口机构，其使接口连接到多通道盒。 接口机构将盒相对于仪器中的支撑元件（例如，高压，气体压力，入射辐射和检测器）精确定位，并且使得盒中的各种部件之间的自动化，可靠和可靠的对准和连接 配套仪器中的支撑元件。 接口机构包括气动或机电驱动的致动器，用于将仪器中的支撑元件接合到盒上的部件。 在通过接口机构安全接收到盒式磁带后，启动连接顺序。 该接口为盒中的每个分离通道提供单独的高电压和光学连接，从而提供电气和光学上的串扰通道间通道隔离。

公开(公告)号：US06870165B2

公开(公告)日：2005-03-22

申请号：US10277961

申请日：2002-10-21

申请人： Varouj Amirkhanian ,  Ming-Sun Liu

发明人： Varouj Amirkhanian ,  Ming-Sun Liu

IPC分类号： G01N27/447 ,  G01N21/64

CPC分类号： G01N27/44782 ,  G01N27/44721

摘要： A multi-channel and multi-color bio-separation detection method and apparatus in which a single detector is coupled to a plurality of radiation sources, in a one detector/many radiation sources configuration. Each radiation source directs radiation at a detection zone of a single separation channel, and a single detector is applied to detect light emissions from the detection zones associated with several radiation sources. The radiation sources are activated to direct radiation at the detection zone in a predetermined sequence and further in a cyclic manner, with the detector output synchronized to the radiation sources by a controller. Bio-separation may be conducted simultaneously in all the channels in parallel, with detection time-staggered and/or time multiplexed with respect to the light sources. In one embodiment, low cost light emitting diodes may be used as radiation sources. In another aspect, the detection scheme is configured for radiation induced fluorescence detection in an capillary electrophoresis instrument.

摘要翻译： 一种多通道和多色生物分离检测方法和装置，其中单个检测器以一个检测器/许多辐射源配置耦合到多个辐射源。 每个辐射源将辐射引导到单个分离通道的检测区域，并且应用单个检测器来检测与多个辐射源相关联的检测区域的光发射。 辐射源被激活以以预定的顺序以进一步的循环方式在检测区域引导辐射，其中检测器输出通过控制器与辐射源同步。 可以在所有通道中同时进行生物分离，并且相对于光源的检测时间交错和/或时间多路复用。 在一个实施例中，低成本发光二极管可以用作辐射源。 另一方面，检测方案被配置用于毛细管电泳仪中的辐射诱导荧光检测。

公开(公告)号：US20050016852A1

公开(公告)日：2005-01-27

申请号：US10823382

申请日：2004-04-12

申请人： Varouj Amirkhanian ,  Bob Heitel ,  Ming-Sun Liu ,  Paul Mooney

发明人： Varouj Amirkhanian ,  Bob Heitel ,  Ming-Sun Liu ,  Paul Mooney

IPC分类号： B01L99/00 ,  G01N21/64 ,  G01N27/447 ,  A61B17/10 ,  C12M1/00

CPC分类号： G01N27/44782 ,  G01N27/44721 ,  G01N2021/6463 ,  G01N2021/6484 ,  G01N2201/08

摘要： The present invention provides for an interface mechanism in a bio-separation instrument that makes interface connections to a multi-channel cartridge. The interface mechanism precisely positions the cartridge in relation to the support elements in the instrument (e.g., high-voltage, gas pressure, incident radiation and detector), and makes automated, reliable and secured alignments and connections between various components in the cartridge and the support elements in the supporting instrument. The interface mechanism comprises pneumatically or electromechanically driven actuators for engaging support elements in the instrument to components on the cartridge. After the cartridge has been securely received by the interface mechanism, the connection sequence is initiated. The interface provides separate high voltage and optical connections for each separation channel in the cartridge, thus providing channel-to-channel isolation from cross talk both electrically and optically.

摘要翻译： 本发明提供了生物分离仪器中的接口机构，其使接口连接到多通道盒。 接口机构将盒相对于仪器中的支撑元件（例如，高压，气体压力，入射辐射和检测器）精确定位，并且使得盒中的各种部件之间的自动化，可靠和可靠的对准和连接 配套仪器中的支撑元件。 接口机构包括气动或机电驱动的致动器，用于将仪器中的支撑元件接合到盒上的部件。 在通过接口机构安全接收到盒式磁带后，启动连接顺序。 该接口为盒中的每个分离通道提供单独的高电压和光学连接，从而提供电气和光学上的串扰通道间通道隔离。

公开(公告)号：US06529275B2

公开(公告)日：2003-03-04

申请号：US09887872

申请日：2001-06-22

申请人： Varouj Amirkhanian ,  Ming-Sun Liu

发明人： Varouj Amirkhanian ,  Ming-Sun Liu

IPC分类号： G01N2125

CPC分类号： G01N27/44721

摘要： In a bio-separation system, the detection zone for optical detection of sample analytes is located at a widened zone along the separation channel. In one embodiment of the present invention, the widened detection zone is a micro-bore collar having a micro-channel that coaxially surrounds the exit of a capillary column that defines a capillary channel. A separation support medium including a running buffer fills the capillary column and the collar. In another aspect of the present invention, incident radiation for detection of separated analytes is directed at the detection zone and/or emitted radiation is collected axially along the separation medium, instead of through the boundary walls of the detection zone. In a further aspect of the present invention, the optical detection configuration may be scaled up and implemented in a mult-channel CE system that comprises multiple capillary separation channels.

摘要翻译： 在生物分离系统中，用于光学检测样品分析物的检测区位于沿着分离通道的加宽区域。 在本发明的一个实施例中，加宽的检测区域是具有同轴地围绕限定毛细管通道的毛细管柱的出口的微通道的微孔套环。 包括运行缓冲液的分离支持介质填充毛细管柱和套环。 在本发明的另一方面，用于检测分离的分析物的入射辐射指向检测区，和/或发射的辐射沿着分离介质轴向收集，而不是通过检测区的边界壁。 在本发明的另一方面，可以在包括多个毛细管分离通道的多通道CE系统中放大并实现光学检测配置。

公开(公告)号：US08114349B2

公开(公告)日：2012-02-14

申请号：US11022313

申请日：2004-12-23

申请人： Varouj Amirkhanian ,  Ming-Sun Liu ,  Paul Mooney

发明人： Varouj Amirkhanian ,  Ming-Sun Liu ,  Paul Mooney

IPC分类号： G01N15/06 ,  B01D57/02 ,  B01D15/08

CPC分类号： G01N27/44721 ,  G01N21/645 ,  G01N27/44704 ,  G01N27/44782 ,  G01N35/00732 ,  G01N2021/6463 ,  G01N2021/6484 ,  G01N2035/00782

摘要： A reusable bio-analysis cartridge that includes a built-in mechanism to track various parameters and usage data. The tracking mechanism includes a non-volatile rewritable memory “smart-key” that is associated with the cartridge to provide automatic tracking dedicated to the cartridge. The key may be physically coupled to the cartridge with good high voltage insulating properties. When the cartridge is used in an instrument, the associated key is inserted into an I/O interface to communicate with the instrument. The instrument may be configured to “authenticate” the cartridge and conduct an integrity check to determine if the particular cartridge has the correct properties (e.g., gel-chemistry, serial no., Patient I.D.) for the particular sample analysis to be conducted. Further, the instrument may communicate/record information concerning usage of the cartridge (e.g., usage history, test parameters, and perhaps test results). Such information provides an update to the stored information from the previous use of the cartridge.

摘要翻译： 一种可重复使用的生物分析盒，包括内置机制，用于跟踪各种参数和使用数据。 跟踪机构包括与盒相关联的非易失性可重写存储器“智能钥匙”，以提供专用于盒的自动跟踪。 键可以物理地耦合到具有良好的高电压绝缘性能的盒。 当在仪器中使用墨盒时，相关键将被插入I / O接口以与仪器通信。 仪器可以被配置为“认证”墨盒并进行完整性检查以确定特定墨盒是否具有用于进行特定样品分析的正确性质（例如，凝胶化学，序列号，患者I.D.）。 此外，仪器可以传达/记录关于盒的使用的信息（例如，使用历史，测试参数和可能的测试结果）。 这样的信息提供了来自先前使用盒的存储的信息的更新。

公开(公告)号：US20110155572A1

公开(公告)日：2011-06-30

申请号：US12961362

申请日：2010-12-06

申请人： Varouj Amirkhanian ,  Ming-Sun Liu

发明人： Varouj Amirkhanian ,  Ming-Sun Liu

IPC分类号： G01N27/447 ,  C12M1/34 ,  G01N27/453

CPC分类号： G01N21/6428 ,  G01N21/645 ,  G01N27/44721 ,  G01N27/44743 ,  G01N27/44782 ,  G01N2021/6463 ,  G01N2021/6484

摘要： An integrated bio-analysis system incorporates built-in sample preparation capabilities. In one aspect of the present invention, a bio-analysis instrument is provided with a built-in sample preparation device based on PCR (or thermal cycling block/module). In one embodiment of the present invention, a peltier unit in the sample preparation device provides thermal cycling of samples supported in a multi-well tray. In another aspect of the present invention, a CE instrument is provided with a built-in sample preparation capability, which may comprise a sample preparation (bio-molecular reaction) device based on thermal cycler type. In another aspect of the present invention, a PCR device is provided with a built-in analysis device, such as a CE device, for verifying the results of the PCR (bio-molecular reaction) process.

摘要翻译： 集成的生物分析系统集成了内置的样品制备功能。 在本发明的一个方面，生物分析仪器具有基于PCR（或热循环块/模块）的内置样品制备装置。 在本发明的一个实施例中，样品制备装置中的珀耳帖单元提供支撑在多孔盘中的样品的热循环。 在本发明的另一方面，向CE仪器提供内置的样品制备能力，其可以包含基于热循环仪类型的样品制备（生物分子反应）装置。 在本发明的另一方面，PCR装置具有用于验证PCR（生物分子反应）过程的结果的内置分析装置，例如CE装置。

公开(公告)号：US07309409B2

公开(公告)日：2007-12-18

申请号：US10059993

申请日：2002-01-28

申请人： Varouj Amirkhanian ,  Ming-Sun Liu ,  Paul Mooney

发明人： Varouj Amirkhanian ,  Ming-Sun Liu ,  Paul Mooney

IPC分类号： G01N27/26

CPC分类号： G01N27/44782 ,  G01N27/44721

摘要： A bio-separation system using an efficient, compact, portable, interchangeable, reusable, recyclable, multi-channel cartridge, has integrated pre-aligned optics and an integrated reagent reservoir. The cartridge supports, for example, multiple capillaries for CE separation. An integrated reservoir containing a separation support medium (e.g., a gel buffer) is common to all capillaries. The chemistry of the medium and the characteristics of the capillaries (e.g., capillary size, coating and length) are defined for each cartridge. Different cartridges can be easily interchanged in the bio-separation system to suit the particular sample based separation. The reservoir is coupled to an air pressure pump that pressurizes the gel reservoir to purge and fill the capillaries with buffer as the separation support medium. In another aspect of the present invention, optics requiring fine alignment with respect to the detection zones (such as fiber optics for directing incident radiation and/or radiation emissions) are integrated into the cartridge.

摘要翻译： 使用高效，紧凑，便携，可互换，可再利用的多通道盒的生物分离系统具有集成的预对准光学器件和集成的试剂储存器。 盒支持例如用于CE分离的多个毛细管。 包含分离支持介质（例如，凝胶缓冲液）的集成储存器对于所有毛细管是共同的。 介质的化学性质和毛细管的特性（例如，毛细管尺寸，涂层和长度）是针对每个墨盒定义的。 在生物分离系统中可以容易地互换不同的墨盒，以适应特定的基于样品的分离。 储存器联接到空气压力泵，该压力泵对凝胶储存器进行加压，以用作为分离支撑介质的缓冲液吹扫和填充毛细管。 在本发明的另一方面，需要相对于检测区（例如用于引导入射辐射和/或辐射发射的光纤的精细对准）的光学器件集成到盒中。

公开(公告)号：US08500980B1

公开(公告)日：2013-08-06

申请号：US11977726

申请日：2007-10-24

申请人： Varouj Amirkhanian ,  Ming-Sun Liu

发明人： Varouj Amirkhanian ,  Ming-Sun Liu

IPC分类号： G01N27/447 ,  G01N27/453

CPC分类号： G01N27/44704

摘要： A cost-effective multi-channel capillary gel-electrophoresis system for highly efficient, nucleic acid-based analysis, in particular HLA SSP (Human Leukocyte Antigen Sequence Specific Primer) typing applications. Twelve DNA samples are automatically injected, electrophoretically separated, detected and analyzed simultaneously by using a multiple usage and disposable multi-capillary gel-cartridge. Using commercially available DNA size markers as indicators, the system provides high resolving power with 12-channel separations in less than 1.5 minutes. The system can hold a total of 96 samples in a PCR plate that can automatically be analyzed within 25 minutes for a full plate of the HLA SSP kits.

摘要翻译： 用于高效，基于核酸的分析，特别是HLA SSP（人类白细胞抗原序列特异性引物）分型应用的具有成本效益的多通道毛细管凝胶电泳系统。 通过使用多次使用和一次性多毛细管凝胶柱，同时自动注射，电泳分离，检测和分析12个DNA样品。 使用市售的DNA大小标记作为指标，该系统在不到1.5分钟的时间内提供具有12通道分离的高分辨能力。 该系统可以在PCR板中容纳96个样品，其可以在25分钟内自动分析整个HLA SSP试剂盒。

公开(公告)号：US07846315B2

公开(公告)日：2010-12-07

申请号：US10973828

申请日：2004-10-25

申请人： Varouj Amirkhanian ,  Ming-Sun Liu

发明人： Varouj Amirkhanian ,  Ming-Sun Liu

IPC分类号： G01N27/00 ,  G01N33/48

CPC分类号： G01N21/6428 ,  G01N21/645 ,  G01N27/44721 ,  G01N27/44743 ,  G01N27/44782 ,  G01N2021/6463 ,  G01N2021/6484

摘要： An integrated bio-analysis system incorporates built-in sample preparation capabilities. In one aspect of the present invention, a bio-analysis instrument is provided with a built-in sample preparation device based on PCR (or thermal cycling block/module). In one embodiment of the present invention, a peltier unit in the sample preparation device provides thermal cycling of samples supported in a multi-well tray. In another aspect of the present invention, a CE instrument is provided with a built-in sample preparation capability, which may comprise a sample preparation (bio-molecular reaction) device based on thermal cycler type. In another aspect of the present invention, a PCR device is provided with a built-in analysis device, such as a CE device, for verifying the results of the PCR (bio-molecular reaction) process.

摘要翻译： 集成的生物分析系统集成了内置的样品制备功能。 在本发明的一个方面，生物分析仪器具有基于PCR（或热循环块/模块）的内置样品制备装置。 在本发明的一个实施例中，样品制备装置中的珀耳帖单元提供支撑在多孔盘中的样品的热循环。 在本发明的另一方面，向CE仪器提供内置的样品制备能力，其可以包含基于热循环仪类型的样品制备（生物分子反应）装置。 在本发明的另一方面，PCR装置具有用于验证PCR（生物分子反应）过程的结果的内置分析装置，例如CE装置。

公开(公告)号：US07208072B2

公开(公告)日：2007-04-24

申请号：US10349316

申请日：2003-01-21

申请人： Varouj Amirkhanian ,  Ming-Sun Liu ,  Paul Mooney

发明人： Varouj Amirkhanian ,  Ming-Sun Liu ,  Paul Mooney

IPC分类号： G01N27/26

CPC分类号： G01N27/44721 ,  G01N27/44782

摘要： A bio-separation instrument using a multi-segment cartridge. The cartridge includes a plurality of efficient, compact, portable, interchangeable, reusable, recyclable, modular, multi-channel segments. Each segment supports multiple capillaries for CE separation. Each segment has an integrated reservoir containing a buffer/gel common to all the capillaries. Air pressure can be supplied to the reservoir through the periphery of each segment. Each segment has an integrated LED array board directly coupled to capillaries for providing excitation light. Optical fibers of a fiber bundle are individually guided through the periphery of each segment to the capillaries for emission collection. The fiber bundle delivers emissions to a detector that can read the emissions in a time-staggered multiplexed scheme. Each segment includes electrodes electrically coupled to a voltage source through the periphery of the segment for effecting CE separation. Providing each segment with pneumatic and voltage connections on the periphery and direct coupling LED's allow the segments to easily stack together for integration into the instrument.

摘要翻译： 一种使用多分段筒的生物分离仪。 盒包括多个高效，紧凑，便携，可互换，可重复使用，可回收，模块化的多通道段。 每个段支持多个毛细管用于CE分离。 每个段具有一个集成的储存器，其中包含所有毛细管共同的缓冲液/凝胶。 可以通过每个段的周边向贮存器供应空气压力。 每个段都有一个集成的LED阵列板，直接连接到毛细管上，用于提供激发光。 纤维束的光纤被单独地引导通过每个段的周边到毛细管用于排放收集。 光纤束将发射发射到可以时间交错多路复用方案读取发射的检测器。 每个段包括通过该段的周边电耦合到电压源的电极，用于实现CE分离。 为每个段提供气动和电压连接在外围和直接耦合LED允许段很容易堆叠在一起集成到仪器。