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1. 发明申请

WO2018170139A1 NEUROMUSCULAR JUNCTION: NMJ-ON-CHIP 审中-公开
公开(公告)号：WO2018170139A1
公开(公告)日：2018-09-20
申请号：PCT/US2018/022455
申请日：2018-03-14
申请人： EMULATE, INC. , CEDARS-SINAI MEDICAL CENTER
发明人： KERNS, S. Jordan , WEN, Norman , HAMILTON, Geraldine , HINOJOSA, Christopher David , FRASER, Jacob , KARALIS, Catherine , SAREEN, Dhruv , KAUS, Anjoscha , MANDEFRO, Berhan , PARK, Hyoung Shin , KUJALA, Ville
IPC分类号： B01L3/00 , C12N5/077 , C12N5/0793
摘要： The invention relates to culturing motor neuron cells together with skeletal muscle cells in a fluidic device under conditions whereby the interaction of these cells mimic the structure and function of the neuromuscular junction (NMJ) providing a NMJ- on-chip. Good viability, formation of myo-fibers and function of skeletal muscle cells on fluidic chips allow for measurements of muscle cell contractions. Embodiments of motor neurons co-cultures with contractile myo-fibers are contemplated for use with modeling diseases affecting NMJ's, e.g. Amyotrophic lateral sclerosis (ALS).

2. 发明申请

WO2017136462A3 SYSTEMS AND METHODS FOR GROWTH OF INTESTINAL CELLS IN MICROFLUIDIC DEVICES 审中-公开
公开(公告)号：WO2017136462A3
公开(公告)日：2017-08-10
申请号：PCT/US2017/016079
申请日：2017-02-01
申请人： EMULATE, INC. , CEDARS-SINAI MEDICAL CENTER
发明人： KERNS, Jordan , WEN, Norman , LUCCHESI, Carol , HINOJOSA, Chris , FRASER, Jacob , PUERTA, Jefferson , HAMILTON, Geraldine , BARRETT, Robert , SVENDSEN, Clive , LEVNER, Daniel , TARGAN, Stephen R. , WORKMAN, Michael , SAREEN, Dhruv , RAJAMANI, Uthra , CASSANDRA, Magdelena
IPC分类号： C12N5/02 , C12N5/074 , C12N5/0793 , C12N5/0797
摘要： Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.

3. 发明申请

WO2018044885A1 DEVELOPMENT OF SPINAL CORD ON A MICROFLUIDIC CHIP 审中-公开
标题翻译：微流控芯片脊髓的研制
公开(公告)号：WO2018044885A1
公开(公告)日：2018-03-08
申请号：PCT/US2017/049115
申请日：2017-08-29
申请人： EMULATE, INC. , CEDARS-SINAI MEDICAL CENTER
发明人： KERNS, Jordan , WEN, Norman , LUCCHESI, Carol , HINOJOSA, Christopher , FRASER, Jacob , HAMILTON, Geraldine , VATINE, Gad , SANCES, Sam , SVENDSEN, Clive , LEVNER, Daniel , SAREEN, Dhruv
IPC分类号： C12N5/071 , C12N5/079 , C12N5/0793 , C12N5/0797 , C12N15/85
摘要： The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.
摘要翻译：本发明涉及在细胞模拟血脑屏障的结构和功能的条件下，在流体装置中培养脑内皮细胞以及任选的星形胶质细胞和神经元。在微流体装置中培养这种细胞，不管是单独还是与其他细胞组合，都比现有系统更成熟和/或分化。

4. 发明申请

WO2017136462A2 SYSTEMS AND METHODS FOR GROWTH OF INTESTINAL CELLS IN MICROFLUIDIC DEVICES 审中-公开
标题翻译：用于在微流体装置中生长肠细胞的系统和方法
公开(公告)号：WO2017136462A2
公开(公告)日：2017-08-10
申请号：PCT/US2017/016079
申请日：2017-02-01
申请人： EMULATE, INC. , CEDARS-SINAI MEDICAL CENTER
发明人： KERNS, Jordan , WEN, Norman , LUCCHESI, Carol , HINOJOSA, Chris , FRASER, Jacob , PUERTA, Jefferson , HAMILTON, Geraldine , BARRETT, Robert , SVENDSEN, Clive , LEVNER, Daniel , TARGAN, Stephen R. , WORKMAN, Michael , SAREEN, Dhruv , RAJAMANI, Uthra , CASSANDRA, Magdelena
IPC分类号： C12N5/071
CPC分类号： C12N5/0696 , C12M23/16 , C12N5/0679 , C12N2501/11 , C12N2501/119 , C12N2501/16 , C12N2501/24 , C12N2501/415 , C12N2501/998 , C12N2506/45 , C12N2535/00
摘要： Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.
摘要翻译：片上器官是用于在微米大小的腔室中培养活细胞以模拟组织和器官的生理功能的微流体装置。这些装置中的工程化图案化和连续流体流动允许培养具有生理相关特征的肠细胞并持续暴露于细菌，同时保持细胞活力，从而允许研究炎性碗状疾病。然而，现有的肠细胞不具有所有生理学相关的亚型，不具有遗传变异库，或允许研究其他重要的细胞演员如免疫细胞。使用iPSC衍生的上皮细胞（包括IBD患者特异性细胞）通过捕获疾病的多面性质允许优越的疾病模型。

5. 发明申请

WO2017070224A1 MICROFLUIDIC MODEL OF THE BLOOD BRAIN BARRIER 审中-公开
标题翻译：血脑屏障的微流体模型
公开(公告)号：WO2017070224A1
公开(公告)日：2017-04-27
申请号：PCT/US2016/057724
申请日：2016-10-19
申请人： EMULATE, INC. , CEDARS-SINAI MEDICAL CENTER
发明人： KERNS, Jordan , WEN, Norman , LUCCHESI, Carol , HINOJOSA, Chris , FRASER, Jacob , HAMILTON, Geraldine , VATINE, Gad , SANCES, Sam , SVENDSEN, Clive , LEVNER, Daniel , SAREEN, Dhruv
IPC分类号： C12M1/34 , C12M3/00 , C12N5/0793 , C12N5/0797
CPC分类号： C12M23/16 , C12M25/02 , C12M35/08 , C12N5/0618 , C12N5/069 , C12N2506/45 , C12N2531/00 , C12N2535/10
摘要： The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.
摘要翻译：本发明涉及在细胞模拟血脑屏障的结构和功能的条件下，在流体装置中培养脑内皮细胞以及任选的星形胶质细胞和神经元。在微流体装置中培养这种细胞，不管是单独还是与其他细胞组合，都比现有系统更成熟和/或分化。

6. 发明申请

WO2017096282A1 DEVICES AND METHODS FOR SIMULATING A FUNCTION OF A LIVER TISSUE 审中-公开
标题翻译：用于模拟肝组织功能的装置和方法
公开(公告)号：WO2017096282A1
公开(公告)日：2017-06-08
申请号：PCT/US2016/064795
申请日：2016-12-02
申请人： EMULATE, INC.
发明人： HAMILTON, Geraldine , JANG, Kyung, Jin , HANEY, Suzette , RONXHI, Janey , KODELIA, Konstantia , PARK, Hyoung, Shin , SLIZ, Josiah, Daniel , PETROPOLIS, Debora , LEVNER, Daniel
IPC分类号： A61K35/407 , C12N5/00 , C12N5/071
CPC分类号： A61K35/407 , C12N5/067 , C12N2502/28 , C12N2533/52 , C12N2533/90
摘要： Provided herein relates to devices for simulating a function of a tissue and methods of using the same. In some embodiments, the devices can be used to simulate a function of a human liver tissue. In some embodiments, the devices can be used to simulate a function of a dog liver tissue. Endothelial cell culture media for long-term culture of endothelial cells are also described herein.
摘要翻译：这里提供的用于模拟组织功能的装置和使用该装置的方法。在一些实施例中，这些装置可以用于模拟人体肝脏组织的功能。在一些实施方式中，装置可以用于模拟狗肝脏组织的功能。本文还描述了用于长期培养内皮细胞的内皮细胞培养基。

7. 发明申请

WO2020154386A1 HIGH-CONTENT IMAGING OF MICROFLUIDIC DEVICES 审中-公开
公开(公告)号：WO2020154386A1
公开(公告)日：2020-07-30
申请号：PCT/US2020/014590
申请日：2020-01-22
申请人： EMULATE, INC.
发明人： JANG, Kyung-Jin , LEVNER, Daniel , KODELLA, Konstantia-Roumvini , RUBINS, Jonathan , PETROPOLIS, Debora, Barreiros , PEEL, Samatha , CORRIGAN, Adam, M. , EHRARDT, Beate , PINTO, Pedro , BOECKELER, Matt , FOSTER, Alison, J. , WILLIAMS, Dominic , HAMILTON, Geraldine , EWART, Lorna, Ewar
IPC分类号： G01N15/14 , G01N33/48 , G02B21/02 , G02B21/24 , G02B21/34
摘要： The present invention is related to high-content microscopy imaging of microfluidic cell culture systems. A method of high-content microfluidic device microscopy is contemplated, along with related statistical analysis and microfluidic device adaptors.

8. 发明申请

WO2018102201A1 IN VITRO EPITHELIAL MODELS COMPRISING LAMINA PROPRIA-DERIVED CELLS 审中-公开
公开(公告)号：WO2018102201A1
公开(公告)日：2018-06-07
申请号：PCT/US2017/062817
申请日：2017-11-21
申请人： EMULATE, INC.
发明人： LEVNER, Daniel , KERNS, S. Jordan , BARRILE, Riccardo , HAMILTON, Geraldine , KARALIS, Catherine , LEVNER, Daniel , LUCCHESI, Carolina , VARONE, Antonio , VILLENAVE, Remi
IPC分类号： C12M3/00 , C12M3/04 , C12M1/34 , G01N33/50
摘要： An in vitro microfluidic "organ-on-chip" is described herein that mimics the structure and at least one function of specific areas of the epithelial system in vivo . In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and the associated tissue specific epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory tissue, e.g., autoimmune disorders involving epithelia and diseases involving epithelial layers. These multicellular, layered microfluidic "organ-on-chip", e.g. "epithelia-on-chip" further allow for comparisons between types of epithelia tissues, e.g., lung (Lung-On-Chip), bronchial (Airway-On-Chip), skin (Skin-On-Chip), cervix (Cervix-On-Chip), blood brain barrier (BBB-On-Chip), etc., in additional to neurovascular tissue, (Brain-On-Chip), and between different disease states of tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic "organ-on-chips" allow identification of cells and cellular derived factors driving disease states in addition to drug testing for reducing inflammation effecting epithelial regions.

9. 发明申请

WO2019153004A1 STEM CELL-BASED LUNG-ON-CHIP MODELS 审中-公开
公开(公告)号：WO2019153004A1
公开(公告)日：2019-08-08
申请号：PCT/US2019/016680
申请日：2019-02-05
申请人： EMULATE, INC.
发明人： NAWROTH, Janna , BARRILE, Riccardo , CONEGLIANO, David , VILLENAVE, Remi , LUCCHESI, Carolina , NGUYEN, Justin , VARONE, Antonio , KARALIS, Catherine , HAMILTON, Geraldine
IPC分类号： C12N5/071 , C12N5/074 , C12N5/16 , C12N5/02 , C12M3/06
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.

10. 发明申请

WO2018217882A1 ADVANCED PULMONARY MODELS 审中-公开
公开(公告)号：WO2018217882A1
公开(公告)日：2018-11-29
申请号：PCT/US2018/034116
申请日：2018-05-23
申请人： EMULATE, INC.
发明人： VILLENAVE, Remi , LUCCHESI, Carolina , NGUYEN, Justin , KARALIS, Catherine , HAMILTON, Geraldine , SALMON, Michael , BADDAL, Buket
IPC分类号： C12N5/22 , C12N5/16
摘要： The present invention relates to microfluidic fluidic systems and methods for the in vitro modeling diseases of the lung and small airway. In one embodiment, the invention relates to a system for testing responses of a microfluidic Small Airway-on- Chip infected with one or more infectious agents (e.g. respiratory viruses) as a model of respiratory disease exacerbation (e.g. asthma exacerbation). In one embodiment, this disease model on a microfluidic chip allows for a) the testing of anti-inflammatory and/or anti-viral compounds introduced into the system, as well as b) the monitoring of the participation, recruitment and/or movement of immune cells, including the transmigration of cells. In particular, this system provides, in one embodiment, an in-vitro platform for modeling severe asthma as "Severe Asthma-on-Chip." In some embodiments, this invention provides a model of viral-induced asthma in humans for use in identifying potentially effective treatments.

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