The present invention relates to fluidic systems for producing IgG antibodies from co-cultures of white blood cells. In some embodiments, a microfluidic device containing co-cultures of an autologous whole peripheral white blood cell population including B cells, are used for providing antigen specific IgG antibody production from differentiating B cells (plasma cells). More specifically, high levels of IgM and IgG classes of antibodies are harvested from fluids flowing through the device. In some embodiments, IgG is produced during activation in the presence of antigen, including but not limited to therapeutic immunogenic compounds, e.g. engineered antibodies, vaccines, etc. In some embodiments, such co-cultures are further exposed to drug compounds e.g. for preclinical safety testing and individualized personal drug responses. In some embodiments, such antibody producing microfluidic devices are contemplated for use in companion diagnostic and complementary assays.
The invention relates to modeling brain neuronal disease in a microfluidic device, comprising a co-culture of iPS-derived brain endothelial cells; iPS-derived dopaminergic neurons; primary microglia; and primary astrocytes, a Blood-Brain-Barrier (BBB)-Chip and a Brain-Chip. In particular, cross-talk between glial cells (e.g. microglia and astrocytes) with neuronal cells, in further contact with endothelial cells is contemplated for use for identifying drug targets under conditions for inducing in vivo relevant neuronal inflammation, neurodegeneration and neuronal death. Thus, in one embodiment, a microfluidic Brain-Chip comprising a co-culture of brain cells is exposed to a-synuclein preformed fibrils (PFF), a type of pathogenic form of a-synuclein. Such a-synuclein PFF exposure demonstrates an in vivo relevant disease pathogenesis on a microfluidic device as a concentration- and time-controlled manner that may be used for preclinical drug evaluation for diseases related to neuronal inflammation, e.g. Parkinson's disease (PD).
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
3.
METHOD FOR ASSESSING A COMPOUND INTERACTING WITH A TARGET ON EPITHELIAL CELLS
Disclosed herein is a method for assessing a compound interacting with a target on polarized epithelial cells. The method comprising the steps of providing an organ chip comprising a main channel and polarized epithelial cells, wherein the main channel is divided into an apical channel and a basal channel separated by the polarized epithelial cells, wherein the apical side of the polarized epithelial cells is directed towards the apical channel and the basolateral side of the polarized epithelial cells is directed towards the basal channel. Determining the localization and optionally the expression level of the target on the polarized epithelial cells. Administrating the compound and optionally immune cells, preferably peripheral blood mononuclear cells (PBMC) to the basal channel, when the target is localized on the basolateral side of the epithelial cells or administrating the compound and optionally immune cells, preferably peripheral blood mononuclear cells (PBMC) to the apical channel, when the target is localized on the apical side of the epithelial cells. Measuring a parameter of the administration of the compound and the peripheral blood mononuclear cells.
The present invention is related to the field of microfluidics and compound distribution within microfluidic devices and their associated systems. In one embodiment, present invention aims to solve the problem of molecule and compound absorbency into the materials making up laboratory equipment, microfluidic devices and their related infrastructure, without unduly restricting gas transport within microfluidic devices.
B01D 53/22 - Separation of gases or vapoursRecovering vapours of volatile solvents from gasesChemical or biological purification of waste gases, e.g. engine exhaust gases, smoke, fumes, flue gases or aerosols by diffusion
C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
C12M 1/04 - Apparatus for enzymology or microbiology with gas introduction means
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 devices including microfluidic devices, e.g. Skin on-Chip (Skin-Chip), for simulating a physiological response to agents and injury, including tattoo injury. In particular, a Skin-Chip is intended for use in replicating the interaction of tattoo ink with skin on a cellular level, including but not limited to mechanisms of wound healing following a tattoo gun and/or tattoo needle induced skin injury; ink particle effects such as pigment retention, pigment distribution and pigment clearance; inflammatory response to foreign particles, i.e. tattoo ink, etc. Further, effects of tattoo inks on simulated microfluidic skin is extended to determine effects of systemic ink exposure upon other organs through use of organ chips, e.g. liver-chips, kidney-chips, Lymph node-chips, etc. In some embodiments, safer ink formulations, e.g. less toxic ink particles, less toxic ink diluents, etc., are contemplated for development and use over currently available tattoo inks and diluents. Further contemplated is using a Tattooed Skin-Chip for developing rapid and non-toxic methods of removal of Tattoos in human skin.
The present invention relates to microfluidic fluidic devices, methods and systems as microfluidic kidney on-chips, e.g. human Proximal Tubule-Kidney-Chip, Glomerulus (Kidney)- Chip, Collecting Duct (Kidney)-Chip. Devices, methods and systems are described for drug testing including drug transport and renal clearance. Further, such devices, methods and systems are used for determining drug-drug interactions and their effect upon renal transporter functions, importantly, they may be used for pre-clinical and clinical drug development for treating kidney diseases and for personalized medicine.
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.
The present invention relates to a combination of microbes, cell culture systems and microfluidic fluidic systems for use in providing a human Intestine On-Chip with optimal intestinal motility. More specifically, in some embodiments, a microfluidic chip containing intestinal epithelial cells co-cuitured with intestinal endothelial cells in the presence of bacteria, such as probiotic bacteria, may find use in providing an Intestine- On-Chip for testing intestinal motility function. In some embodiments, an Intestine On- Chip may be used for identifying (testing) therapeutic compounds continuing probiotic microbes or compounds for inducing intestinal motility' for use in treating gastrointestinal disorders or diseases related to intestinal function.
The present invention is related to the field of fluidic devices, and in particular, microfluidic cell culture systems. The present invention provides pumping, recirculation and sampling for a microfluidic device or devices. The present invention provides solutions to the control of microfluidics for both terrestrial and space applications, including the control over the movement of fluids in zero gravity or microgravity.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B65D 35/28 - Pliable tubular containers adapted to be permanently deformed to expel contents, e.g. collapsible tubes for toothpaste or other plastic or semi-liquid materialHolders therefor with auxiliary devices for expelling contents
The present invention relates to a combination of cell culture systems and microfluidic fluidic systems for use in providing a human innervated Intestine On-Chip. More specifically, in some embodiments, a microfluidic chip containing intestinal epithelial cells co-cultured with intestinal endothelial cells or intestinal muscle cells, or both, in the presence of induced neural crest cells may find use in providing an innervated Intestine-On-Chip. In some embodiments, an innervated Intestine On-Chip may be used for identifying (testing) therapeutic compounds for use in treating gastrointestinal disorders or diseases.
C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
C12M 3/00 - Tissue, human, animal or plant cell, or virus culture apparatus
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms
C12M 1/12 - Apparatus for enzymology or microbiology with sterilisation, filtration, or dialysis means
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
G01N 1/00 - SamplingPreparing specimens for investigation
12.
HUMAN MICROPHYSIOLOGICAL CELL SYSTEM FOR LIVER DISEASE CONVERSION WITH PROV 1-18585 AND PROV 2-19154
The present invention is related to the field of liver disease. Solid substrates comprising microfluidic channels (e.g., microchips) are configured to support growing and differentiating hepatocytes and are contemplated to provide a suitable environment for the development of fully functional liver tissue. These solid substrates can be used to induce various toxicity conditions in the liver tissue subsequent to the exposure to various chemicals. For example, chronic exposure to ethanol induces a clinical state of alcoholic liver disease in the liver tissue. Alternatively, certain disease states can result in the development of non-alcoholic liver diseases (e.g., non- alcoholic steatohepatitis; NASH).
The present invention relates to microfluidic fluidic devices, methods and systems for use in identifying epigenetic signatures in a range of sample types, e.g., cells established on a "chip" (including but not limited to single cell samples, cell populations, cell layers and whole tissues, such as a biopsy), immune cells, cfDNA, exosomes, and the like. More specifically, in some embodiments, a microfluidic chip containing a sample is contacted with a test compound (e.g. DNA altering test compound, an RNA expression altering test compound, etc.) for use in providing a diagnostic epigenetic signature for that type of sample (or cell type) exposed to that specific test compound. In some embodiments, after contact with a test compound, effluent fluids (e.g. fluids exiting the "chip" that contacted the cells) are derived for testing as a "virtual blood draw." In some embodiments, epigenetic signatures include (but are not limited to) identifying specific combinations of modifications of chromosomes and specific modifications of DNA.
Devices, methods and systems are described for providing controlled amounts of gas, gas pressure and vacuum to microfluidic devices the culturing of cells under flow conditions.
in vitro in vitro 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.
in vitroin vivoin vitroe.g.e.g.e.g., small intestinal duodenum, small intestinal jejunum, small intestinal ileum, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.
The present invention contemplates compositions, devices and methods of simulating biological fluids in a fluidic device, including but not limited to a microfluidic chip. In one embodiment, fluid comprising a colloid under flow in a microfluidic chip has a fluid density or viscosity similar to a bodily fluid, e.g. blood, lymph, lung fluid, or the like. In one embodiment, a fluid is provided as a Theologically biomimetic blood surrogate or substitute for simulating physiological shear stress and cell dynamics in fluidic device, including but not limited to immune cells.
This invention is in the field of surface modification. In particular, the invention relates to the surface modification of microfluidic devices to alter surface hydrophobicity characteristics.
B01J 19/00 - Chemical, physical or physico-chemical processes in generalTheir relevant apparatus
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B05D 3/10 - Pretreatment of surfaces to which liquids or other fluent materials are to be appliedAfter-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials by other chemical means
C08J 3/24 - Crosslinking, e.g. vulcanising, of macromolecules
B29C 35/02 - Heating or curing, e.g. crosslinking or vulcanising
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
H01L 21/027 - Making masks on semiconductor bodies for further photolithographic processing, not provided for in group or
The invention generally relates to a microfluidic platforms or "chips" for testing and conducting experiments on the International Space Station (ISS). More specifically, microfluidic Brain-On-Chip, comprising neuronal and vascular endothelial cells, will he analyzed in both healthy and inflamed states to assess how the circumstances of space travel affect the human brain.
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.
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).
An in vitro microfluidic gut-on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and gastrointestinal epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal tissue, e.g., Crohn's disease, colitis and other inflammatory gastrointestinal disorders. These multicellular, layered microfluidic gut-on-chip further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal deuodejeum, small intestinal ileium, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.
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.
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.
Compositions, devices and methods are described for improving adhesion, attachment, and/or differentiation of cells in a microfluidic device or chip. In one embodiment, one or more ECM proteins are covalently coupled to the surface of a microchannel of a microfluidic device. The microfluidic devices can be stored or used immediately for culture and/or support of living cells such as mammalian cells, and/or for simulating a function of a tissue, e.g., a liver tissue, muscle tissue, etc. Extended adhesion and viability with sustained function over time is observed.
Compositions, devices and methods are described for preventing, reducing, controlling or delaying adhesion, adsorption, surface-mediated clot formation, or coagulation in a microfluidic device or chip. In one embodiment, blood (or other fluid with blood components) that contains anticoagulant is introduced into a microfluidic device comprising one or more additive channels containing one or more reagents that will re-activate the native coagulation cascade in the blood that makes contact with it "on-chip" before moving into the experimental region of the chip.
Methods of removing bubbles from a microfluidic device are described where the flow is not stopped. Methods are described that combine pressure and flow to remove bubbles from a microfluidic device. Bubbles can be removed even where the device is made of a polymer that is largely gas impermeable.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B81B 3/00 - Devices comprising flexible or deformable elements, e.g. comprising elastic tongues or membranes
C12M 1/00 - Apparatus for enzymology or microbiology
C12M 1/36 - Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
F17D 1/08 - Pipe-line systems for liquids or viscous products
F17D 1/20 - Arrangements or systems of devices for influencing or altering dynamic characteristics of the systems, e.g. for damping pulsations caused by opening or closing of valves
28.
DEVICES, SYSTEMS AND METHODS FOR INHIBITING INVASION AND METASTASES OF CANCER
The invention generally relates to a microfluidic platforms or "chips" for testing and understanding cancer, and, more specifically, for understanding the factors that contribute to cancer invading tissues and causing metastases. Tumor cells are grown on microfluidic devices with other non-cancerous tissues under conditions that simulate tumor invasion. The interaction with immune cells can be tested to inhibit this activity by linking a cancer chip to a lymph chip.
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.
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.
A microfluidic device is contemplated comprising an open-top cavity with structural anchors on the vertical wall surfaces that serve to prevent gel shrinkage-induced delamination, a porous membrane (optionally stretchable) positioned in the middle over a microfluidic channel(s). The device is particularly suited to the growth of cells mimicking dermal layers.
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.
Drop-to-drop connection schemes are described for putting a microfluidic device in fluidic communication with a fluid source or another microfluidic device, including but not limited to, putting a microfluidic device in fluidic communication with the perfusion manifold assembly. A perfusion manifold assembly is described that allows for perfusion of a microfluidic device, such as an organ on a chip microfluidic device comprising cells that mimic cells in an organ in the body, that is detachably linked with said assembly so that fluid enters ports of the microfluidic device from a fluid reservoir, optionally without tubing, at a controllable flow rate.
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