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    High throughput method for accurate prediction of compound-induced liver injury
    1.
    发明授权
    High throughput method for accurate prediction of compound-induced liver injury 有权

    公开(公告)号：US11321826B2

    公开(公告)日：2022-05-03

    申请号：US16093139

    申请日：2017-04-11

    Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

    Inventor： Daniele Zink ,  Nur Faezah Begum Akbar Hussain ,  Lit Hsin Loo ,  Ah Wah Lam

    IPC: G06K9/00 ,  G06T7/00 ,  G16H50/20 ,  G16H30/40 ,  G16B20/00 ,  G01N33/50 ,  G01N33/533

    Abstract: A method and system for predicting liver injury in vivo due to hepatocyte damage by a test compound are provided. The method includes acquiring images of fluorescently stained cells obtained from a cell culture in which the cells have been treated with a dose-range of at least the test compound and its vehicle. The cells may be hepatic cells including primary or immortalized hepatocytes, hepatoma cells or induced pluripotent stem cell-derived hepatocyte-like cells. The acquired images are segmented. The method further includes extracting and analyzing one or more phenotypic features from the segmented images, wherein the one or more phenotypic features are selected from the group of intensity, textural, morphological, or ratiometric features consisting of (a) features of DNA, (b) features of RELA (NF-KB p65), and (c) features of actin filaments at different subcellular regions and d) features of cellular organelles and their substructures in the segmented images. Finally, the method includes normalizing results from the treated samples to vehicle controls and predicting the probability of liver injury by the test compound based on test compound-induced normalized changes of the extracted and selected phenotypic features using machine learning methods.

    Thermoresponsive Microcarrier System and Uses Thereof
    2.
    发明申请
    Thermoresponsive Microcarrier System and Uses Thereof 审中-公开

    公开(公告)号：US20200149001A1

    公开(公告)日：2020-05-14

    申请号：US16473266

    申请日：2018-01-22

    Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

    Inventor： Jackie Y. Ying ,  Leng Leng Chng ,  Daniele Zink ,  Aysha Farwin

    IPC: C12N5/00 ,  C08F293/00 ,  C08L53/00 ,  C12N5/0775

    Abstract: There is provided a polymeric microsphere comprising a thermally responsive monomer crosslinked with a functional group monomer, wherein the functional group monomer comprises at least one of a carboxylic acid functional group or an amine functional group. The thermally responsive monomer is preferably N-isopropylacrylamide (NIPAM), and the microspheres preferably comprise a coating of polymerized catecholamines (e.g. DOPA). There is also provided a method of preparing the polymeric microsphere and uses of the polymeric microsphere in culturing, harvesting, or expanding stem cells or stromal cells. Preferably, the cells, e.g. hMSCs (human mesenchymal stem/stromal cells), are expanded or harvested in serum-free and xeno-free medium.

    BIOREACTOR UNIT FOR USE IN BIOARTIFICIAL KIDNEY DEVICE
    4.
    发明申请
    BIOREACTOR UNIT FOR USE IN BIOARTIFICIAL KIDNEY DEVICE 有权
    生物工程设备用于生物科技设备

    公开(公告)号：US20150076066A1

    公开(公告)日：2015-03-19

    申请号：US14395810

    申请日：2013-04-22

    Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

    Inventor： Daniele Zink ,  Yar Oo Zay

    IPC: A61M1/34 ,  B01D63/02

    CPC classification number: A61M1/3489 ,  A61M1/3417 ,  A61M1/3434 ,  A61M1/3472 ,  B01D63/02

    Abstract: There is provided a bioreactor device having cells, including human primary proximal tubule cells (HPTCs) or HPTC-like cells on the exterior surface of hollow fiber membranes included within the device. Also provided are bioartificial kidney devices incorporate the bioreactor device and methods of using such devices.

    Abstract translation: 提供了具有细胞的生物反应器装置，其包括在装置内的中空纤维膜的外表面上包括人类初级近端小管细胞（HPTC）或HPTC样细胞。 还提供了包括生物反应器装置的生物人造肾装置和使用这种装置的方法。

    IN VITRO ASSAY FOR PREDICTING RENAL PROXIMAL TUBULAR CELL TOXICITY
    7.
    发明申请
    IN VITRO ASSAY FOR PREDICTING RENAL PROXIMAL TUBULAR CELL TOXICITY 审中-公开
    用于预测肾脏原发性管状细胞毒性的体外测定

    公开(公告)号：US20150197802A1

    公开(公告)日：2015-07-16

    申请号：US14416020

    申请日：2013-07-22

    Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

    Inventor： Daniele Zink ,  Yao Li

    IPC: C12Q1/68 ,  G01N33/68

    CPC classification number: C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/142 ,  C12Q2600/158 ,  C12Q2600/16 ,  G01N33/5014 ,  G01N33/5044 ,  G01N33/6869 ,  G01N2333/5412 ,  G01N2333/5421

    Abstract: There is provided an in vitro assay for screening a test compound for toxicity in renal proximal tubular cells. The method comprises contacting a test compound with a test population of renal proximal tubular cells; and determining the expression level of an interleukin in the test population, the interleukin being interleukin-6 (IL-6) or interleukin-8 (IL-8), or both. Expression levels of the interleukin in the test population being greater than expression levels in a control population of renal proximal tubular cells not contacted with the test compound is indicative that the test compound is toxic for renal proximal tubular cells.

    Abstract translation: 提供了用于在肾近端肾小管细胞中筛选测试化合物毒性的体外测定。 该方法包括使测试化合物与肾近端肾小管细胞的测试群体接触; 测定白细胞介素-6（IL-6）或白细胞介素-8（IL-8）或白细胞介素8（IL-8）中白细胞介素的表达水平。 测试群体中白介素的表达水平大于未与测试化合物接触的肾近端肾小管细胞的对照群体中的表达水平，这表明测试化合物对肾近端肾小管细胞具有毒性。

    In vitro assay for predicting renal proximal tubular cell toxicity
    10.
    发明授权
    In vitro assay for predicting renal proximal tubular cell toxicity 有权
    用于预测肾近端肾小管细胞毒性的体外测定

    公开(公告)号：US09568466B2

    公开(公告)日：2017-02-14

    申请号：US14416016

    申请日：2013-07-22

    Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

    Inventor： Daniele Zink ,  Yao Li

    IPC: G01N33/50

    CPC classification number: G01N33/5014 ,  G01N33/5026 ,  G01N33/5044 ,  G01N2333/47 ,  G01N2333/4712 ,  G01N2458/00

    Abstract: There is provided an in vitro assay for screening a test compound for toxicity in renal proximal tubular cells. The method comprises contacting a test compound with a test population of renal proximal tubular cells; and examining one or more cell morphology features, examining one or more cytoskeleton features, and/or determining cell numbers of the renal proximal tubular cells in the test population and comparing such cell morphology, arrangement of cytoskeletal components and/or cell count with the respective features of a control population. A change in one or more cell morphology features, a change in arrangement of one or more cytoskeleton features or a decrease in cell numbers of the test population relative to the control population is indicative that the test compound is toxic for renal proximal tubular cells.

    Abstract translation: 提供了用于在肾近端肾小管细胞中筛选测试化合物毒性的体外测定。 该方法包括使测试化合物与肾近端肾小管细胞的测试群体接触; 并检查一个或多个细胞形态特征，检查一个或多个细胞骨架特征，和/或确定测试群体中肾近端肾小管细胞的细胞数，并将细胞骨架成分和/或细胞计数与相应的细胞形态 控制人口的特点。 一个或多个细胞形态特征的改变，一个或多个细胞骨架特征的排列变化或测试群体相对于对照群体的细胞数量的减少表明该测试化合物对肾近端肾小管细胞有毒性。

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