2493 results about "Organoid" patented technology

This disclosure relates to methods for spatial profiling of analytes present in a biological sample. Also provided are methods for using spatially barcoded substrates to detect a biological analyte in a cell culture, an organism, and organoid. Also provided are methods for using spatially barcoded substrates to detect the temporal profile of a biological analyte.

This disclosure relates to methods for spatial profiling of analytes present in a biological sample. Also provided are methods for using spatially barcoded substrates to detect a biological analyte in a cell culture, an organism, and organoid. Also provided are methods for using spatially barcoded substrates to detect the temporal profile of a biological analyte.

The invention provides a method for drug screening and disease model construction of liver organoid, relates to the technical field of medical research, and adopts multi-modal data acquisition, fusion and intelligent analysis and quantum computing processing to optimize comprehensive application of data, so that the richness, accuracy and analysis efficiency of the data are remarkably improved, and the risk of drug screening and disease model construction of liver organoid is reduced. Multi-source data of genomics, transcriptomics and the like are collected comprehensively, an accurate research system of immune-hepatic disease interaction based on organoid is constructed, an in-vivo complex immune-hepatic disease microenvironment can be highly simulated, the proportion and activation state of immune cells are accurately regulated and controlled in an in-vitro model, functional and phenotypic changes of the immune cells are monitored in real time, and the immune-hepatic disease interaction accuracy is improved. According to the present invention, the interaction mechanism between the immune cells and the liver organ cells is deeply revealed, such that the accurate information basis is provided for the accurate determination of the drug action target, the development of the innovative drug for the immune check point or tumor microenvironment regulation is easily achieved, and the pertinence and the success rate of the drug research and development are substantially improved.

The invention discloses a vascularized immune co-culture organoid chip for simulating a tumor microenvironment. The vascularized immune co-culture organoid chip comprises a chip main body and a bottom plate, a flow channel and a liquid storage tank are arranged in the chip main body; the runners comprise a first runner, a second runner, a third runner and a fourth runner; a compartment is arranged in the middle of the third flow channel; the first flow channel is connected with a first liquid storage tank which is used for injecting a first hydrogel suspension obtained by mixing fibroblasts and hydrogel into the first flow channel; the second flow channel is connected with a second liquid storage tank for injecting a culture solution into the second flow channel; a compartment is arranged in the middle of the third flow channel; the third flow channel is connected with a third liquid storage tank communicated with the compartment, and the compartment is connected with a compartment liquid storage tank; the compartment liquid storage tank is used for injecting a second hydrogel suspension obtained by mixing tumor organs and hydrogel into the compartment, and the third liquid storage tank is used for injecting hydrogel into the third flow channel; and the fourth flow channel is connected with a fourth liquid storage tank for injecting vascular endothelial cell and immune cell suspension into the fourth flow channel. The invention further discloses a vascularized immune co-culture organoid culture method for simulating the tumor microenvironment.

The invention relates to a bone organ constructed based on oxygen-releasing immune hydrogel microspheres and a preparation method and application thereof. An oxygen release material, macrophages and bone marrow mesenchymal stem cells are loaded in the oxygen release immune hydrogel microspheres. And adding the oxygen-releasing immune hydrogel microspheres into a culture medium for culturing to obtain the bone organ constructed based on the oxygen-releasing immune hydrogel microspheres. The oxygen release material (CaO2-HAp) is entrapped in the hydrogel microspheres, so that continuous oxygen supply can be provided in a defect area, the low-oxygen environment is improved, the activity of osteoblasts is improved, osteogenic differentiation is promoted, macrophages are entrapped by the microspheres, the immune microenvironment is regulated and controlled, the release of proinflammatory cytokines is reduced, the osteogenic efficiency is improved, and bone defect repair is accelerated. The micro-fluidic technology is utilized to accurately control the size and shape of the microspheres, so that the microspheres can adapt to irregular bone defects, bone organs are formed through long-term in-vitro culture, and the biological activity and adaptability of the bone repair material are improved.

The invention provides a microfluidic chip, system and method for osteochondral organs, and relates to the technical field of organoid microfluidic chips, the chip comprises a bone microvascular endothelial cell channel, a bone compartment, a cartilage compartment and a synovial fluid channel which are arranged in parallel and in sequence, and permeation areas between the channel and the compartments and between the compartments. According to the scheme, the complex structure and function of a human osteochondral system are effectively simulated, the physiological and pathological processes of human bone joints can be simulated more truly in an in-vitro environment, and a method for establishing a highly-simulated femoral head necrosis model and osteoarthritis model based on the chip is provided. The problems that a traditional model is insufficient in physiological environment simulation, lack of control over dynamic culture conditions, tedious and time-consuming in the construction process, difficult to support high-throughput experiments and the like are solved.

Embodiments of the invention include additional methods and compositions for fabricating organoids. A unique approach has been developed for the rapid aggregation of defined number of cells using a micropillar-based template to limit the size of organoids, which are then more commonly referred to as spheroids. This procedure can be utilized to create in vitro cardiac tissue models (e.g., cardiac organoids) simply, rapidly, and inexpensively. In certain aspects an alginate-gelatin based hydrogel premixed with cardiomyocytes is used in combination with a patterned microfluidic chip / cell culture chamber having an array of micropillars to fabricate 3D cardiac organoids.

The invention provides a 3D biological printing osteochondral organ based on dynamic mechanical regulation and control, and a construction method and application thereof. Compared with the prior art, the invention innovatively provides a biphasic scaffold optimization modification strategy: firstly, an osteochondral hydrogel scaffold with an accurate layered structure is prepared by adopting a 3D biological printing technology, then a cell mechanical transduction signal channel is activated by a dynamic pressure stimulation system, and cartilage / bone biphasic differentiation of stem cells is directionally regulated and controlled; and by constructing a bionic mechanical microenvironment, the obtained osteochondral organ not only keeps excellent biocompatibility, but also has gradient mechanical properties and a clear spatial layered structure (cartilage layer-bone layer), the directional cartilage formation / osteogenic differentiation efficiency of the osteochondral organ is remarkably improved, and the osteochondral organ has a good application prospect. The problems of spatial heterogeneity construction and accurate regulation and control of cell fate in osteochondral tissue engineering are effectively solved, and the method has important application value in the fields of osteochondral defect repair treatment and mechanical stimulation mechanism research.

The invention relates to bionic matrix hydrogel for constructing bone organs and a preparation method of the bionic matrix hydrogel. The bionic matrix hydrogel is prepared from a bone acellular extracellular matrix, a salmon DNA (Deoxyribose Nucleic Acid) network and a calcium phosphate oligomer under the combination of photo-crosslinking and self-assembly physical crosslinking. The acellular extracellular matrix in the bionic matrix hydrogel can simulate organic components in natural bones, the calcium phosphate oligomer can simulate inorganic components in the natural bones, and sufficient phosphate ions can be provided for biomineralization due to introduction of a DNA network. The biomimetic matrix hydrogel can replace Matrigel to act in bone organoid culture, provide a living environment similar to bone tissue for three-dimensional culture cells, enhance substance exchange and signal transduction between cells, promote proliferation, adhesion and osteogenic differentiation of bone marrow mesenchymal stem cells, and further accelerate the process of biomineralization. The invention provides an optional new material for preparing the functional bone organ.

The invention discloses photocuring hydrogel capable of being combined with cytokines and used for tumor organoid culture and application, and belongs to the technical field of organoid culture. According to the invention, the hydrogel which can fix cells, can be combined with cell factors and can realize organoid recovery is developed through norbornene modified heparin, norbornene modified gelatin, sulfydryl four-arm polyethylene glycol, glucan, matrix metal protein peptidomimetic MMP and a photoinitiator. The hydrogel can be used for directly preparing organoids, heparin of various structures can be used, the cost is reduced, the modified heparin can bind factors or matrix protein and can controllably release the factors, the modified gelatin provides amino acid energy for collagen hydrolysate, and the hydrogel is formed by photocuring in a stepwise polymerization mode, is controllable in structure and can be used for preparing collagen collagen. The adjustable bionic modulus and the adjustable bionic stress relaxation are realized. The hydrogel disclosed by the invention can be used for culturing various organs, overcomes the problems of low repeatability, instability and the like in the prior art, and is suitable for the fields of tumor drug evaluation and the like.

The invention relates to a heart organoid and an in-vitro preparation method thereof, and belongs to the technical field of stem cells. The invention provides a heart organoid. The heart organoid is obtained by induced culture of an adherent pluripotent stem cell mass; the adherent pluripotent stem cell mass is obtained by adherent culture of a suspended pluripotent stem cell mass; the suspension pluripotent stem cell mass is obtained by suspension culture of pluripotent stem cells. According to the in-vitro preparation process of the heart organoid, after pluripotent stem cells form balls, the pluripotent stem cell balls are subjected to staged induced differentiation under adherent culture, so that cell subtypes such as epicardial cells and the like can be generated without additional addition or additional stimulation of signal channels, and the heart organoid is more homogeneous. The self-occurring multi-lineage coexisting heart organoid can better simulate biological events derived from multiple cell types and multiple cell subtypes in the early development process of an embryonic heart, and has great application prospects in exploration of pathogenic factors and potential treatment targets of congenital heart diseases.

The invention provides a neuromuscular multi-element coupled organoid micro-fluidic chip, a device and a method. Relates to the technical field of organoid micro-fluidic chips. A first culture chamber, a second culture chamber and a third culture chamber are arranged in a culture layer of the chip; the first culture room is used for culturing nerve cells; the second culture room is used for culturing muscle cells; a microfluidic channel for communicating the first culture chamber with the second culture chamber is arranged between the first culture chamber and the second culture chamber; the third culture room is arranged on the micro-fluidic channel and is used for culturing a neuromuscular joint formed by convergence of axons of nerve cells and muscle cells; a microelectrode array plate is arranged in the circuit layer and is used for performing electrical stimulation and electrophysiological function detection on neuromuscular cells. Through the chip, co-culture of in-vitro nerves and muscle organs can be realized, a complex interaction relationship in a neuromuscular system can be accurately simulated, and the chip can also be used for constructing various neuromuscular related disease models.

The present invention relates to: a method for evaluating the efficacy of an anti-cancer drug, a method for screening an anti-cancer drug, a system for evaluating the efficacy of an anti-cancer drug, or a system for screening an anti-cancer drug, using a mixture of peripheral blood mononuclear cells (PBMC) and a cancer organoid. Specifically, the present invention relates to: a method for evaluating the efficacy of an anti-cancer drug, a method for screening an anti-cancer drug, a system for evaluating the efficacy of an anti-cancer drug, or a system for screening an anti-cancer drug, using a mixture of cytotoxic T cells differentiated from PBMC and cancer organoids. According to the method for evaluating the efficacy of an anti-cancer drug, the screening method, the efficacy evaluation system, or the screening system of the present invention, a tumor microenvironment, i.e. The form in which cancer cells are present in a living body, can be very closely reproduced. Furthermore, since PBMCs derived from normal individuals are used and differentiated into cancer patient-specific cytotoxic T cells, the burden of collecting biological samples such as blood and tissue samples from cancer patients can be reduced, and the efficacy of an anti-cancer drug can be evaluated with high accuracy.

The invention relates to the technical field of biological tissue engineering, and discloses a nerve-blood brain barrier co-culture model, which comprises a culture chip, and nerves and blood brain barriers respectively constructed in upper culture micropores and lower culture micropores of the culture chip. Wherein a semi-permeable membrane is arranged between the lower-layer culture micropores and the upper-layer culture micropores of the culture chip; the nerves are obtained by inoculating neurons / brain organs obtained by stem cell differentiation into the upper culture micropores for co-culture, and the blood brain barrier is obtained by inoculating brain microvascular endothelial cells obtained by stem cell differentiation into one side of the semipermeable membrane in the lower culture micropores for co-culture. The co-culture model is higher in biomimetic property, and can better simulate the structure and function of the blood brain barrier, for example, the co-culture model has a barrier function closer to the physiological level, the selective permeability of a small molecule drug is matched with the in-vivo permeation condition, and the co-culture model has the function of a small molecule related transporter. The invention further discloses a construction method and application.

Aspects of the present invention relate to a pancreatic cancer organoids on a chip device including a microfluidic chip having a top and bottom surface and a thickness therebetween, a central chamber embedded in the microfluidic chip, at least one opening in the top surface of the chip fluidly connected to the central chamber with one or more channels, and a plurality of evenly spaced micropillars arranged in a substantially circular shape within the central chamber such that the central chamber is partitioned into at least a first inner region and a first outer region, wherein the first inner region includes an immunocompetent pancreatic region configured to mimic a pancreatic niche, and the first outer region includes a vascular region configured to mimic an adjacent vascular network.

The invention belongs to the technical field of biological medicine, and particularly relates to a prostate cancer organoid culture medium, a preparation method thereof, a prostate cancer organoid and a culture method thereof. The prostate cancer organ culture medium provided by the invention comprises a basic culture medium and a culture additive, and the culture additive comprises FGF-10 (Fibroblast Growth Factor), Zeaxanthin dipalmitate and Polydatin. In the prostate cancer organoid culture medium provided by the invention, the success rate of organoid culture is greatly improved by utilizing the synergistic effect of the FGF-10, the Zeaxanthin dipalmitate and the Polydatin, the cultured prostate cancer organoid is high in growth speed, the passage frequency is remarkably improved, in-vitro culture can be specifically carried out on prostate cancer tissues of people, and the prostate cancer organoid culture medium has the advantages that the prostate cancer tissue culture efficiency is improved; the survival rate and the formation efficiency of the prostatic cancer organs are further improved.

The invention belongs to the technical field of organoid culture, and particularly relates to a co-differentiated vascularized liver organoid and a construction method thereof. Aiming at the problems that the existing liver organ vascularization mostly adopts a co-culture mode, the operation process is complicated, the cell source heterogeneity is relatively high, the randomness is strong, the uniformity is poor and the like, the invention provides the construction method of the co-differentiated vascularized liver organ. The preparation method comprises the following steps: sequentially inducing and culturing directional endoderm cells, posterior preintestinal cells and hepatic endoderm cells, adding an S1 culture medium containing VEGF to induce and culture for 1-3 days, then adding an S2 culture medium containing VEGF, BMP4 and FGF2 to induce and culture for 3-5 days, and then adding an S3 culture medium containing VEGF to induce and culture for 14-20 days to obtain the co-differentiated vascularized liver organ. According to the method disclosed by the invention, the operation process is simplified, the experiment efficiency is improved, the liver organ which is rich in blood vessel network, high in maturity and of a blood vessel-bile duct structure is obtained, and a foundation is laid for large-scale production and clinical application.

The invention provides a bone organ model as well as a construction method and application thereof, and the method comprises the following steps: arranging a biological material with a micropore array in a cell culture plate to obtain a bone organ chip; suspending the initial stem cells in a culture medium, and promoting the cells to form a spherical structure through cell aggregation or by using a non-adhesive culture surface, so as to obtain cell spheres; and culturing the cell spheres in the bone organ chip by adopting the culture medium for constructing the bone organ model to obtain the bone organ model. The skeletal organ is successfully constructed through in-vitro self-organized 3D co-culture initial stem cells including embryonic stem cells, induced pluripotent stem cells, bone marrow mesenchymal stem cells, osteoblasts, bone cells, all levels of osteogenic precursor cells, osteogenic-like cells and MC3T3-E1 cells, and the skeletal organ can become an important tool for researching and treating bone related diseases.

The invention provides a cognitive function in-vitro simulation method based on a microelectrode array (MEA) and brain organs and application of the cognitive function in-vitro simulation method, and belongs to the crossing field of brain organ in-vitro model construction, neural engineering, brain-like intelligence and the like. In an in-vitro environment, external signal (such as sound) information is converted into electrical stimulation input capable of being perceived by brain organs in an MEA electrical stimulation mode, so that the brain organs gradually learn and identify external signals in repeated electrical stimulation; after elution stimulation for a period of time, the reduction condition of recognition accuracy is observed, namely, the important memory and forgetting process in the cognitive function is simulated. According to the method, the electrophysiological response and the biological mechanism change of the brain organs under external electrical stimulation can be quantitatively evaluated, and a new possibility is provided for exploring the advanced cognitive function by utilizing the brain organs.

A device for modelling physiological and pathophysiological states of the brain is provided. The device comprises a hydrogel with micropattern channels having a length, width and depth. The micropattern channels comprise cells selected from the group consisting of neurons, astrocytes, microglia, oligodendrocytes, neuronal organoids, cancer cells, cancer spheroids, brain tumoral cells and combinations thereof.

The invention provides a pourable tumor organoid vascularization model and a construction method thereof, and relates to the technical field of organoid culture. A temperature-sensitive degradable material and a photo-crosslinking modified temperature-sensitive material are used, the composite stent is printed through two channels, a multi-component gel mask partition curing process is combined, the stability of a perfusion pipeline is improved, and a partitioned highly-bionic complex microenvironment is accurately constructed in a macroscopic three-dimensional space; and constructing to obtain the perfusion tumor organ vascularization model. The model is high in bionic degree and stable in structure, can be applied to deepening cell and microenvironment interaction research and tumor-related drug screening, and has a good application prospect.

The invention relates to organoid culture. The invention provides a human epidermal organoid differential medium, a method for constructing an epidermal model and application of the human epidermal organoid differential medium, the human epidermal organoid differential medium comprises a basic medium component and an additive, and the additive comprises lipid. According to the method, the organoid is directly used for constructing the epidermal model, so that the problem of few cell sources is solved; a lipid component is added into the epidermal organ differentiation culture medium, so that the epidermal organ can enhance the barrier function of the cuticle, further differentiation of the epidermal organ can be effectively promoted by utilizing the epidermal organ differentiation culture medium, and a human epidermal model with a basal layer, a spinous layer, a granular layer and a cuticle which are completely morphologically differentiated is obtained. And the operation is simple, large-batch production is easy to realize, and a reliable tool is provided for in-vitro observation, interference of skin disease generation, injury repair and other life activities.

The present invention relates to the fields of therapy and drug delivery. More specifically, disclosed herein are therapeutic methods and pharmaceutical compositions for treating disorders of blood-tissue barrier-shielded organs that harbour substantive populations of post-mitotic neurons, such as the organs derived from neural tube that include the central nervous system and the eye. The disclosed methods and compositions involve localised administration into such organs of an effector component that targets an intracellular biological target, in combination with a saponin component that enhances effective uptake of the effector component into the cells and / or that enhances effective routing of the effector component inside the cells where the biological target is present. For example, the effector component can be an oligonucleotide therapeutic that is targeting a gene product associated with the disorder of the CNS and / or of the eye. Due to cellular uptake-stimulating and / or endosomal escape enhancing effects of the saponin component, the presented herein neuropharmaceutical and ophthalmic compositions for the localised administration into the CNS and / or into the eye, respectively, can be formulated with lower concentrations of the effector component and / or at lower volumes, which confers safety-benefits to the neurons and to the comfort of the patient.

The present invention belongs to the field of organoid chips. Provided is a multiple-organoid co-culture micro-fluidic chip, comprising organoid micro-fluidic chip cells, each organoid micro-fluidic chip cell being divided into an upper layer and a lower layer which are bonded to each other, the upper layer being sequentially provided with an organoid culture medium perfusion channel, a first channel barrier, an organoid culture chamber, a second channel barrier and a vascular endothelial culture channel, and the lower layer being provided with a micro-perfusion network channel. The chip ensures specific nutrition and microenvironment for each organoid and helps to maintain specific phenotypes for same. In addition, the chip can simulate in-vitro blood flowing, so as to perform signal communication and interaction between organoids, thereby fully simulating the in-vivo environment and interaction for multiple-organ diseases.

The invention provides a drug screening and curative effect evaluation method and system based on a glioma organ-like model, and relates to the technical field of biological material analys.The method includes the steps that a three-dimensional fluorescence image of the glioma organ-like model is collected, signal intensity analysis and compensation processing are carried out, a growth feature mapping model is constructed, and the three-dimensional fluorescence image of the glioma organ-like model is obtained; and phenotypic characteristics for representing the glioma organoid heterogeneity are obtained. Inputting the phenotypic characteristics into a drug response evaluation network, and calculating a drug sensitivity score; the drug molecular feature library and the drug collaborative analysis model are combined, the synergistic interaction index of different drug combinations is calculated, the optimal drug combination is screened, the drug administration dosage and the drug administration time sequence are determined in combination with phenotypic features, and finally an individualized treatment scheme is generated. According to the invention, the curative effect of the drug on the glioma organs can be effectively evaluated, and the optimal drug combination and administration scheme can be screened out, so that the accuracy and effectiveness of glioma treatment are improved.

The invention discloses a construction method and application of a mouse airway organoid inflammation model, and relates to the technical field of biology. The construction method comprises the following steps: (1) taking a mouse airway tissue, digesting with digestive juice, and centrifuging to obtain a cell suspension; (2) centrifuging the cell suspension, discarding the supernatant, adding matrigel, uniformly mixing, incubating, and culturing by using an airway organoid complete medium; (3) adding a cell recovery solution into the cells cultured in the step (2), incubating, degumming, centrifuging, discarding supernatant, adding matrigel, uniformly mixing, incubating, and adding an airway organ complete culture medium for continuous culture; and (4) adding 1-20 [mu] g / ml of LPS into the airway organoid complete culture medium, and incubating. The AO constructed by the invention covers four main cell types of cilia cells, goblet cells, basal cells and rod-like cells, causes epithelial injury in the AO and expression of AO inflammatory factors, and can provide reference for development of CRD new drugs.

A robust nasal organoid culture system and fully characterized 2D and 3D in vitro produced organoids are provided, as well as methods of using the organoids. The nasal organoids comprise a population of differentiated nasal epithelial cells having cellular heterogeneity and molecular markers similar to mature nasal epithelial tissue. Improved methods for producing two-dimensional and three-dimensional nasal organoids are also provided. These methods generally require a two-phase culture system, i.e., amplification and differentiation culture. The provided nasal organoids are suitable for reproducing nasal tissue complexity, for mimicking respiratory diseases, studying barrier function and drug delivery, high throughput drug screening, and assessing the effects of pathogens and environmental toxins on nasal respiratory epithelium.

The present disclosure relates to a method and an apparatus for measuring motility of ciliated cells in a respiratory tract. The method includes the operations of: acquiring image data including a plurality of frames of respiratory tract organoids; identifying positions of ciliated cells by performing motion-contrast imaging on the image data; when a region of interest (ROI) related to the position of the ciliated cells is selected, measuring a ciliary beat frequency (CBF) related to motility of cilia included in the selected region of interest using cross-correlation between the plurality of frames; and expressing the cilia included in the region of interest in a preset display method on the basis of the range of the measured ciliary beat frequency.

In various aspects, the present invention provides a composition having orthogonally tunable elasticity and viscosity. In some embodiments, the composition comprises an interpenetrating polymer network comprising viscous and elastic polymer networks that are not covalently bonded. In some embodiments, the composition is a viscoelastic hydrogel. In some embodiments, the composition mimics the viscoelasticity of at least one organ, organoid, or tissue of interest (e.g., brain, pancreas, brain tumor, etc.). In various aspects, the present invention provides a device (e.g., 3-dimensional cell culture platform) comprising said composition. In some aspects, the present invention provides a method of preparing said devices. In some embodiments, the method comprises bioprinting.

The invention discloses a culture device for a high-flux biological culture system. The culture device comprises a sealed box body with an inlet and an outlet; the C-shaped supporting mechanism is arranged in the box body; the rotating platform mechanism is arranged in the C-shaped supporting mechanism and is used for placing a culture pore plate; the rotating platform mechanism further comprises a bidirectional clamping mechanism arranged on the tray. Compared with an existing cell or organ-like biological culture device, the cell or organ-like biological culture device has the advantages that the culture environment consistency of all pore plates in the culture process is better, and the disturbance to other pore plates is lower when the pore plates are taken; in the culture and observation process, strict environmental conditions can be maintained, the pore plate does not displace, and a more adaptive space moving range is provided for a monitoring and pipetting integrated device with higher observation and analysis speed, so that the requirements of high throughput and low disturbance of a high throughput biological culture system under the industrial and automatic background can be met; technical and theoretical possibilities are provided for successful cell or organoid culture and observation of an intelligent automatic production line.