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    Microfluidic device and method for detecting rare cells
    1.
    发明授权
    Microfluidic device and method for detecting rare cells 有权

    公开(公告)号：US10677708B2

    公开(公告)日：2020-06-09

    申请号：US16100726

    申请日：2018-08-10

    Applicant: The Regents of the University of Michigan

    Inventor： Sunitha Nagrath ,  Hyeun Joong Yoon ,  Eric Lin ,  Max S. Wicha ,  Lianette Rivera Baez ,  Diane M. Simeone

    IPC: G01N15/10 ,  B01L3/00 ,  G01N33/50 ,  G01N33/574 ,  G01N15/02 ,  C12Q1/04 ,  G01N15/00

    Abstract: A microfluidic device for detecting rare cells in a fluid sample comprises the rare cell and other cells. The microfluidic device comprises an inlet for receiving the fluid sample, a labyrinth channel structure in fluid communication with the inlet, and an outlet in fluid communication with the labyrinth channel structure for collecting the rare cells separated from the other cells in the fluid sample. The labyrinth channel structure comprises at least one channel through which the fluid sample flows. The at least one channel has a plurality of segments and a plurality of corners with each corner defined between adjacent segments. The presence of the plurality of corners induces separation of the rare cells from the other cells in the fluid sample as the rare cells move to a first equilibrium position within the at least one channel when a ratio of inertial lift forces (FZ) and Dean flow (FD) of the fluid sample is from 2 to 10.

    Method of reducing the number of EMT and MET type breast cancer stem cells
    2.
    发明授权
    Method of reducing the number of EMT and MET type breast cancer stem cells 有权
    减少EMT和MET型乳腺癌干细胞数量的方法

    公开(公告)号：US09352039B2

    公开(公告)日：2016-05-31

    申请号：US14376923

    申请日：2013-02-08

    Applicant: The Regents of the University of Michigan

    Inventor： Suling Liu ,  Max S. Wicha

    IPC: A61K39/395 ,  A61K31/7088 ,  C12N15/113 ,  A61K45/06 ,  A61K39/00 ,  G01N33/574

    CPC classification number: A61K39/3955 ,  A61K31/7088 ,  A61K39/0011 ,  A61K45/06 ,  A61K2039/507 ,  A61K2039/5154 ,  C12N15/1135 ,  C12N15/1136 ,  C12N15/1138 ,  C12N2310/113 ,  C12N2310/141 ,  C12N2320/31 ,  C12N2330/50 ,  G01N33/57484 ,  A61K2300/00

    Abstract: Compositions, kits, and methods for therapeutic screening, diagnostics, and cancer treatment based on the identification or use of the different states of cancer stem cells, including cancer stem cells in the EMT (epithelial to mesenchymal transition) MET (mesenchymal to epithelial transition), and EMT-MET states are disclosed. In some methods, a subject is treated with one therapeutic that targets EMT cancer stem cells and a second therapeutic that targets MET cancers stem cells. In certain methods, the different states of cancer stem cells are distinguished based on markers CD44+CD24−, EpCam−CD49P+ (for EMT cancers stem cells), ALDH+ and EPCam+CD49r− (for MET cancers stem cells), and CD44+CD24−ALDH+ (for EMT-MET cancer stem cells). In particular methods, micro RNAs are used to transition to one particular cancer stem cell type (e.g., mir-100 for EMT and mir-93 for MET).

    Abstract translation: 基于识别或使用不同状态的癌症干细胞（包括EMT中的癌症干细胞（上皮至间质转换）MET（间质至上皮转换））的治疗筛选，诊断和癌症治疗的组合物，试剂盒和方法 ，并且公开了EMT-MET状态。 在一些方法中，使用靶向EMT癌症干细胞的一种治疗剂和靶向MET癌症干细胞的第二种治疗剂治疗受试者。 在某些方法中，基于标记物CD44 + CD24-，EpCam-CD49P +（用于EMT癌症干细胞），ALDH +和EPCam + CD49r-（对于MET癌症干细胞）和CD44 + CD24来区分不同状态的癌症干细胞 -ALDH +（用于EMT-MET癌症干细胞）。 在特定方法中，微RNA用于转变成特定的癌症干细胞类型（例如，用于EMT的mir-100和用于MET的mir-93）。

    DIFFERENT STATES OF CANCER STEM CELLS
    3.
    发明申请
    DIFFERENT STATES OF CANCER STEM CELLS 有权
    癌症干细胞的不同状态

    公开(公告)号：US20150125469A1

    公开(公告)日：2015-05-07

    申请号：US14376923

    申请日：2013-02-08

    Applicant: The Regents of the University of Michigan

    Inventor： Suling Liu ,  Max S. Wicha

    IPC: A61K39/395 ,  A61K39/00 ,  G01N33/574

    CPC classification number: A61K39/3955 ,  A61K31/7088 ,  A61K39/0011 ,  A61K45/06 ,  A61K2039/507 ,  A61K2039/5154 ,  C12N15/1135 ,  C12N15/1136 ,  C12N15/1138 ,  C12N2310/113 ,  C12N2310/141 ,  C12N2320/31 ,  C12N2330/50 ,  G01N33/57484 ,  A61K2300/00

    Abstract: Compositions, kits, and methods for therapeutic screening, diagnostics, and cancer treatment based on the identification or use of the different states of cancer stem cells, including cancer stem cells in the EMT (epithelial to mesenchymal transition) MET (mesenchymal to epithelial transition), and EMT-MET states are disclosed. In some methods, a subject is treated with one therapeutic that targets EMT cancer stem cells and a second therapeutic that targets MET cancers stem cells. In certain methods, the different states of cancer stem cells are distinguished based on markers CD44+CD24−, EpCam−CD49P+(for EMT cancers stem cells), ALDH+ and EPCam+CD49r− (for MET cancers stem cells), and CD44+CD24−ALDH+ (for EMT-MET cancer stem cells). In particular methods, micro RNAs are used to transition to one particular cancer stem cell type (e.g., mir-100 for EMT and mir-93 for MET).

    Abstract translation: 基于识别或使用不同状态的癌症干细胞（包括EMT中的癌症干细胞（上皮至间质转换）MET（间质至上皮转换））的治疗筛选，诊断和癌症治疗的组合物，试剂盒和方法 ，并且公开了EMT-MET状态。 在一些方法中，使用靶向EMT癌症干细胞的一种治疗剂和靶向MET癌症干细胞的第二种治疗剂治疗受试者。 在某些方法中，基于标记物CD44 + CD24-，EpCam-CD49P +（用于EMT癌症干细胞），ALDH +和EPCam + CD49r-（对于MET癌症干细胞）和CD44 + CD24来区分不同状态的癌症干细胞 -ALDH +（用于EMT-MET癌症干细胞）。 在特定方法中，微RNA用于转变成特定的癌症干细胞类型（例如，用于EMT的mir-100和用于MET的mir-93）。

    ANTI-CXCR1 COMPOSITIONS AND METHODS
    5.
    发明申请
    ANTI-CXCR1 COMPOSITIONS AND METHODS 审中-公开

    公开(公告)号：US20150094362A1

    公开(公告)日：2015-04-02

    申请号：US14566436

    申请日：2014-12-10

    Applicant: The Regents of The University of Michigan

    Inventor： Max S. Wicha ,  Christophe Ginestier

    IPC: A61K31/18 ,  A61K45/06 ,  A61K31/337

    Abstract: The present invention provides methods of treating cancer by administering an IL8-CXCR1 pathway inhibitor (e.g., an anti-CXCR1 antibody or Repertaxin) alone or in combination with an additional chemotherapeutic agent such that non-tumorigenic and tumorigenic cancer cells in a subject are killed. The present invention also provides compositions and methods for detecting the presence of and isolating solid tumor stem cells in a patient (e.g., based on the presence of CXCR1 or FBXO21).

    Microfluidic Device And Method For Detecting Rare Cells
    10.
    发明申请
    Microfluidic Device And Method For Detecting Rare Cells 审中-公开
    用于检测稀有细胞的微流体装置和方法

    公开(公告)号：US20150293010A1

    公开(公告)日：2015-10-15

    申请号：US14439429

    申请日：2013-10-29

    Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

    Inventor： Sunitha Nagrath ,  Hyeun Joong Yoon ,  Eric Lin ,  Max S. Wicha ,  Lianette Rivera Baez ,  Diane M. Simeone

    IPC: G01N15/10 ,  B01L3/00

    CPC classification number: G01N15/1056 ,  B01L3/502715 ,  B01L3/502753 ,  B01L3/502761 ,  B01L2200/0652 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0883 ,  G01N15/0272 ,  G01N33/5005 ,  G01N33/574 ,  G01N2015/0065 ,  G01N2015/008 ,  G01N2015/0288 ,  G01N2015/1006 ,  G01N2015/1081

    Abstract: A microfluidic device for detecting rare cells in a fluid sample comprises the rare cell and other cells. The microfluidic device comprises an inlet for receiving the fluid sample, a labyrinth channel structure in fluid communication with the inlet, and an outlet in fluid communication with the labyrinth channel structure for collecting the rare cells separated from the other cells in the fluid sample. The labyrinth channel structure comprises at least one channel through which the fluid sample flows. The at least one channel has a plurality of segments and a plurality of corners with each corner defined between adjacent segments. The presence of the plurality of corners induces separation of the rare cells from the other cells in the fluid sample as the rare cells move to a first equilibrium position within the at least one channel when a ratio of inertial lift forces (FZ) and Dean flow (FD) of the fluid sample is from 2 to 10.

    Abstract translation: 用于检测流体样品中稀有细胞的微流体装置包括稀有细胞和其它细胞。 微流体装置包括用于接收流体样品的入口，与入口流体连通的迷宫式通道结构，以及与迷宫式通道结构流体连通的出口，用于收集与流体样品中的其它细胞分离的稀有细胞。 迷宫通道结构包括流体样品流过的至少一个通道。 所述至少一个通道具有多个段和多个角，其中每个角在相邻段之间限定。 当惯性提升力（FZ）和Dean流量的比率（FZ）和Dean流动时，多个拐角的存在引起稀少细胞与流体样本中的其它细胞的分离，因为稀有细胞移动到至少一个通道内的第一平衡位置 （FD）为2〜10。

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