公开(公告)号：US08835110B2

公开(公告)日：2014-09-16

申请号：US13120060

申请日：2009-11-04

Applicant: Tza-Huei Wang ,  Kelvin J. Liu ,  Ie-Ming Shih

Inventor： Tza-Huei Wang ,  Kelvin J. Liu ,  Ie-Ming Shih

IPC: C12Q1/68

CPC classification number: C12Q1/6825 ,  C12Q2563/107 ,  C12Q2525/204

Abstract: The present invention relates, e.g., to a method for determining the size distribution of DNA molecules in a sample comprising cell-free nucleic acid, comprising labeling the DNA with a fluorescent dye in a stoichiometric manner, subjecting the DNA to molecular spectroscopy (e.g., cylindrical illumination confocal spectroscopy), analyzing suitable fluorescent burst parameters of the labeled DNA, and conducting single molecule DNA integrity analysis of the labeled DNA molecules in the sample. In one embodiment of the invention, the method is used as a diagnostic method for detecting cancer.

Abstract translation: 本发明涉及例如用于确定包含无细胞核酸的样品中DNA分子的大小分布的方法，包括以化学计量方式用荧光染料标记DNA，对DNA进行分子光谱学（例如， 圆柱形照明共焦光谱），分析标记DNA的合适的荧光突变参数，并对样品中标记的DNA分子进行单分子DNA完整性分析。 在本发明的一个实施方案中，该方法用作检测癌症的诊断方法。

公开(公告)号：US08637301B2

公开(公告)日：2014-01-28

申请号：US13147742

申请日：2010-03-02

Applicant: Jeff Tza-Huei Wang ,  Kelvin J. Liu ,  Christopher M. Puleo ,  Tushar D. Rane

Inventor： Jeff Tza-Huei Wang ,  Kelvin J. Liu ,  Christopher M. Puleo ,  Tushar D. Rane

IPC: C12M1/00 ,  C12M1/36 ,  C12M1/34 ,  G01N15/06 ,  G01N21/64 ,  G02B21/06

CPC classification number: C12Q1/6825 ,  B01L3/502753 ,  B01L3/502769 ,  B01L7/52 ,  B01L2200/0678 ,  B01L2200/10 ,  B01L2300/088 ,  B01L2400/0481 ,  B01L2400/0655 ,  G01N1/38 ,  G01N15/1484 ,  G01N21/6458 ,  G01N2001/4027 ,  G01N2015/0038 ,  G01N2015/1493 ,  G01N2021/6419 ,  G01N2021/6421 ,  Y10T436/143333

Abstract: A microfluidic device for a confocal fluorescence detection system has an input channel defined by a body of the microfluidic device, a sample concentration section defined by the body of the microfluidic device and in fluid connection with the input channel, a mixing section defined by the body of the microfluidic device and in fluid connection with the concentration section, and a detection region that is at least partially transparent to illumination light of the confocal fluorescence detection system and at least partially transparent to fluorescent light when emitted from a sample under observation as the sample flows through the detection region.

Abstract translation: 用于共焦荧光检测系统的微流体装置具有由微流体装置的主体限定的输入通道，由微流体装置的主体限定并与输入通道流体连接的样品浓度部分，由身体限定的混合部分 的微流体装置，并且与浓缩部分流体连接;以及检测区域，其对于共焦荧光检测系统的照明光至少部分透明，并且当从作为样品的观察样品发射时对荧光至少部分透明 流过检测区域。

公开(公告)号：US20120135874A1

公开(公告)日：2012-05-31

申请号：US13260212

申请日：2010-05-06

Applicant: Jeff Tza-Huei Wang ,  Kelvin J. Liu ,  Christopher M. Puleo

Inventor： Jeff Tza-Huei Wang ,  Kelvin J. Liu ,  Christopher M. Puleo

IPC: G01N21/64 ,  B01L3/00 ,  C40B30/04 ,  B82Y15/00

CPC classification number: C12Q1/6844 ,  C12Q2563/143 ,  C12Q2549/119 ,  C12Q2537/149

Abstract: The present invention relates, e.g., to a method for detecting a nucleic acid molecule of interest in a sample comprising cell-free nucleic acids, comprising fluorescently labeling the nucleic acid molecule of interest, by specifically binding a fluorescently labeled nanosensor or probe to the nucleic acid of interest, or by enzymatically incorporating a fluorescent probe or dye into the nucleic acid of interest, illuminating the fluorescently labeled nucleic acid molecule, causing it to emit fluorescent light, and measuring the level of fluorescence by single molecule spectroscopy, wherein the detection of a fluorescent signal is indicative of the presence of the nucleic acid of interest in the sample.

Abstract translation: 本发明涉及例如用于检测包含无细胞核酸的样品中感兴趣的核酸分子的方法，其包括通过将荧光标记的纳米传感器或探针特异性结合到核酸上来荧光标记感兴趣的核酸分子 酸，或通过将荧光探针或染料酶促并入感兴趣的核酸，照射荧光标记的核酸分子，使其发射荧光，并通过单分子光谱法测量荧光水平，其中检测 荧光信号指示样品中感兴趣的核酸的存在。

公开(公告)号：US20110171741A1

公开(公告)日：2011-07-14

申请号：US13120060

申请日：2009-11-04

Applicant: Tza-Huei Wang ,  Kelvin J. Liu ,  Ie-Ming Shih

Inventor： Tza-Huei Wang ,  Kelvin J. Liu ,  Ie-Ming Shih

IPC: G01N33/52

CPC classification number: C12Q1/6825 ,  C12Q2563/107 ,  C12Q2525/204

Abstract: The present invention relates, e.g., to a method for determining the size distribution of DNA molecules in a sample comprising cell-free nucleic acid, comprising labeling the DNA with a fluorescent dye in a stoichiometric manner, subjecting the DNA to molecular spectroscopy (e.g., cylindrical illumination confocal spectroscopy), analyzing suitable fluorescent burst parameters of the labeled DNA, and conducting single molecule DNA integrity analysis of the labeled DNA molecules in the sample. In one embodiment of the invention, the method is used as a diagnostic method for detecting cancer.

Abstract translation: 本发明涉及例如用于确定包含无细胞核酸的样品中DNA分子的大小分布的方法，包括以化学计量方式用荧光染料标记DNA，对DNA进行分子光谱学（例如， 圆柱形照明共焦光谱），分析标记DNA的合适的荧光突变参数，并对样品中标记的DNA分子进行单分子DNA完整性分析。 在本发明的一个实施方案中，该方法用作检测癌症的诊断方法。

公开(公告)号：US08248609B2

公开(公告)日：2012-08-21

申请号：US12612300

申请日：2009-11-04

Applicant: Tza-Huei Wang ,  Kelvin J. Liu

Inventor： Tza-Huei Wang ,  Kelvin J. Liu

IPC: G01J3/46

CPC classification number: G01J3/02 ,  G01J3/0208 ,  G01J3/0229 ,  G01J3/024 ,  G01J3/10 ,  G01J3/44

Abstract: A cylindrical illumination confocal spectroscopy system has a fluidic device having a fluid channel defined therein, an objective lens unit arranged proximate the fluidic device, an illumination system in optical communication with the objective lens unit to provide light to illuminate a sample through the objective lens unit, and a detection system in optical communication with the objective lens unit to receive at least a portion of light that passes through the objective lens unit from the sample. The illumination system includes a beam-shaping lens unit constructed and arranged to provide a substantially planar illumination beam that subtends across, and is longer than, a lateral dimension of the fluid channel.

Abstract translation: 圆柱形照明共焦光谱系统具有其中限定有流体通道的流体装置，靠近流体装置布置的物镜单元，与物镜单元光学连通的照明系统，以提供通过物镜单元照射样品的光 以及与所述物镜单元光学通信以从所述样品接收经过所述物镜单元的至少一部分光的检测系统。 照明系统包括光束整形透镜单元，其被构造和布置成提供对准流体通道的横向尺寸并且比其更长的基本上平面的照明光束。

公开(公告)号：US20110287976A1

公开(公告)日：2011-11-24

申请号：US13147742

申请日：2010-03-02

Applicant: Jeff Tza-Huei Wang ,  Kelvin J. Liu ,  Christopher M. Puleo ,  Tushar D. Rane

Inventor： Jeff Tza-Huei Wang ,  Kelvin J. Liu ,  Christopher M. Puleo ,  Tushar D. Rane

IPC: C40B30/10 ,  C40B60/12

CPC classification number: C12Q1/6825 ,  B01L3/502753 ,  B01L3/502769 ,  B01L7/52 ,  B01L2200/0678 ,  B01L2200/10 ,  B01L2300/088 ,  B01L2400/0481 ,  B01L2400/0655 ,  G01N1/38 ,  G01N15/1484 ,  G01N21/6458 ,  G01N2001/4027 ,  G01N2015/0038 ,  G01N2015/1493 ,  G01N2021/6419 ,  G01N2021/6421 ,  Y10T436/143333

Abstract: A microfluidic device for a confocal fluorescence detection system has an input channel defined by a body of the microfluidic device, a sample concentration section defined by the body of the microfluidic device and in fluid connection with the input channel, a mixing section defined by the body of the microfluidic device and in fluid connection with the concentration section, and a detection region that is at least partially transparent to illumination light of the confocal fluorescence detection system and at least partially transparent to fluorescent light when emitted from a sample under observation as the sample flows through the detection region.

Abstract translation: 用于共焦荧光检测系统的微流体装置具有由微流体装置的主体限定的输入通道，由微流体装置的主体限定并与输入通道流体连接的样品浓度部分，由身体限定的混合部分 的微流体装置，并且与浓缩部分流体连接;以及检测区域，其对于共聚焦荧光检测系统的照明光至少部分透明，并且当从作为样品的观察样品发射时对荧光至少部分透明 流过检测区域。

公开(公告)号：US20100118300A1

公开(公告)日：2010-05-13

申请号：US12612300

申请日：2009-11-04

Applicant: Tza-Huei Wang ,  Kelvin J. Liu

Inventor： Tza-Huei Wang ,  Kelvin J. Liu

IPC: G01J3/04

CPC classification number: G01J3/02 ,  G01J3/0208 ,  G01J3/0229 ,  G01J3/024 ,  G01J3/10 ,  G01J3/44

Abstract: A cylindrical illumination confocal spectroscopy system has a fluidic device having a fluid channel defined therein, an objective lens unit arranged proximate the fluidic device, an illumination system in optical communication with the objective lens unit to provide light to illuminate a sample through the objective lens unit, and a detection system in optical communication with the objective lens unit to receive at least a portion of light that passes through the objective lens unit from the sample. The illumination system includes a beam-shaping lens unit constructed and arranged to provide a substantially planar illumination beam that subtends across, and is longer than, a lateral dimension of the fluid channel, the substantially planar illumination beam having a diffraction limited thickness in a direction substantially orthogonal to the lateral dimension of the fluid channel. The substantially planar illumination beam incident upon the fluidic device has a width that is substantially longer than the lateral dimension of the fluid channel such that the substantially planar illumination beam has an illumination intensity that is uniform across the lateral dimension of the fluid channel to within ±10%. The detection system comprises an aperture stop defining a substantially rectangular aperture having a longitudinal dimension and a transverse dimension. The aperture stop is arranged so that the substantially rectangular aperture is confocal with an illuminated portion of the fluid channel such that the transverse dimension of the substantially rectangular aperture substantially subtends the lateral dimension of the fluid channel without extending substantially beyond the fluid channel and allows light to pass from only a uniform excitation region while occluding light from outside the uniform excitation region, and the lateral dimension of the substantially rectangular aperture substantially matches the diffraction limited thickness of the planar illumination beam.