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    STEM CELL-BASED LUNG-ON-CHIP MODELS
    2.
    发明申请
    STEM CELL-BASED LUNG-ON-CHIP MODELS 有权

    公开(公告)号：US20210062129A1

    公开(公告)日：2021-03-04

    申请号：US16983850

    申请日：2020-08-03

    申请人： EMULATE, INC.

    发明人： Janna Nawroth ,  Riccardo Barrile ,  David Conegliano ,  Remi Villenave ,  Carolina Carolina ,  Justin Nguyen ,  Antonio Varone ,  Catherine Karalis ,  Geraldine Hamilton

    IPC分类号： C12M3/06 ,  C12N5/071 ,  C12N5/074

    摘要： An in vitro microfluidic “organ-on-chip” device is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo. In particular, a stem cell-based Lung-on-Chip is described. This in vitro microfluidic system can be used for modeling differentiation of cells on-chip into lung cells, e.g., a lung (Lung-On-Chip), bronchial (Airway-On-Chip; small-Airway-On-Chip), alveolar sac (Alveolar-On-Chip), etc., for use in modeling disease states of derived tissue, i.e. as healthy, pre-disease and diseased tissues. Additionally, stem cells under differentiation protocols for deriving (producing) differentiated lung cells off-chips may be seeded onto microfluidic devices at any desired point during the in vitro differentiation pathway for further differentiation on-chip or placed on-chip before, during or after terminal differentiation. Additionally, these microfluidic “stem cell-based Lung-on-Chip” allow identification of cells and cellular derived factors driving disease states in addition to drug testing for diseases, infections and for reducing inflammation effecting lung alveolar and/or epithelial regions. Further, fluidic devices are provided seeded with primary alveolar cells for use in providing a functional Type II and Type I cell layer, wherein Type II cells express and secrete surfactants, such as Surfactant B (Surf B; SP-B) and Surfactant C (Surf C; SP-C), which were detectable at the protein level by antibody staining in Type II cells. A number of uses are contemplated for the devices and cells, including but not limited to, for use under inflammatory conditions, in drug development and testing, and for individualized (personalized) medicine. Moreover, an ALI-M was developed for supporting multiple cell types in co-cultures with functional Type II and Type I cells.

    COMPOSITIONS AND METHODS OF USING PARTIAL GEL LAYERS IN A MICROFLUIDIC DEVICE
    5.
    发明申请
    COMPOSITIONS AND METHODS OF USING PARTIAL GEL LAYERS IN A MICROFLUIDIC DEVICE 有权

    公开(公告)号：US20220106547A1

    公开(公告)日：2022-04-07

    申请号：US17514659

    申请日：2021-10-29

    申请人： Emulate, Inc.

    发明人： Debora Barreiros Petropolis ,  Remi Villenave ,  Janna Nawroth ,  Tanvi Shroff ,  S. Jordan Kerns ,  Antonio Varone

    IPC分类号： C12M3/06 ,  C12M1/12 ,  C12N5/071

    摘要： The present invention relates to the use of gels for cell cultures, including but not limited to microfluidic devices and transwell devices, for culturing cells, such as organ cells, e.g. airway cells, intestinal cells, etc., and co-culturing cells, (e.g. parenchymal cells and endothelial cells, etc). As one example, the use of gels results in improved lung cell cultures, such as when using transwells and microfluidic devices, (e.g. for culturing healthy airway epithelial cells, culturing diseased airway epithelial cells, e.g., CF epithelial cells that are ciliated). The present invention relates to fluidic devices, methods and systems for use with gel layers within a microfluidic device. In particular, a partial gel layer is disposed within a microchannel of a microfluidic device. For example, a partial gel layer has a thickness ranging between approximately 20-100 μm. A dilute partial gel layer of less than 100 μm may be formed from a polymer solution of 0.5 mg/ml. A cell-permeable partial gel layer having a thickness ranging between approximately 20-50 μm may be formed from a polymer solution of 1-3 mg/ml. A partial gel layer may be formed by a hydrodynamic shearing technique. Such thin gel layers can support a variety of cell cultures, including but not limited to single cells, cell populations, cell layers, differentiated cell layers, and/or primary tissues. The present invention is related to the field of imaging and image processing. In particular, the invention is related to imaging that supports the determination of cell membrane cilia beating frequency. For example, methods described herein encompass cilia beat frequency in the context of membrane region and/or distances between regions. Alternatively, the methods described here encompass cilia beat synchrony and correlation of beat frequency between cell membrane regions.