1302 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.

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.

A brain organoid containing optic vesicles generated based on H9 induction and an eye-brain fusion culture method thereof are provided. H9 embryonic stem cell induction is used to generate a brain organoid containing optic vesicles with primitive visual field. Based on an established optic vesicle brain organoid culture system, microscopic imaging is combined with specific marker antibodies related to early retinal development and photoreceptor cell maturation to structurally and functionally identify the brain organoid containing optic vesicles.

Provided are: a method for producing an organoid, the method comprising a step for culturing somatic stem cells in a culture medium containing an agonist of the interferon-γ receptor; and a culture medium for producing an organoid, the culture medium containing an agonist of the interferon-γ receptor.

The invention belongs to the technical field of medical apparatus and instruments, and particularly provides an eye-brain organ complex visual restoration system based on cooperative training, comprising: an eye-brain organ complex construction module for constructing a functional eye-brain organ complex; the signal processing module is used for collecting and processing an initial nerve spike signal generated by the brain organ; the stimulation signal generation module is used for generating an electrical stimulation signal for simulating the response of the photoreceptor through an adaptive modulation algorithm; the signal decoding and mapping module is used for stimulating a brain organ to generate a new nerve spike signal based on the electrical stimulation signal and decoding the new nerve spike signal into an external equipment control instruction; and the closed-loop feedback control module is used for performing closed-loop feedback control and optimization on the eye and brain organ complex visual restoration system based on cooperative training. According to the invention, the visual information in the biological signal can be correctly identified and utilized.

The invention provides an organoid drug reaction whole-course monitoring system, and relates to the technical field of data monitoring, and the system comprises an acquisition module which is used for acquiring a three-dimensional image sequence of an organoid at a set time interval, and monitoring the concentration data of metabolites in a culture solution to obtain multi-source monitoring data; the processing module is used for performing voxelization processing on the three-dimensional image sequence to form a time sequence three-dimensional voxel data set; and the calculation module is used for calculating barycentric coordinates of the organ-like structure based on the three-dimensional space distribution characteristics of the organ-like structure in the time sequence three-dimensional voxel data set, and establishing two mutually orthogonal space analysis axes in the maximum cross section of the organ-like structure by taking the barycentric coordinates as the center. According to the method, comprehensive and dynamic monitoring and evaluation of the organoid drug reaction process are realized through multi-source data collaborative acquisition, standardized spatial analysis, accurate form dynamic extraction, form and metabolism time sequence correlation modeling and real-time time sequence registration evaluation.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The invention belongs to the technical field of biological culture, and particularly relates to a three-dimensional dynamic biological culture device and method. The three-dimensional dynamic biological culture device comprises: a culture chamber unit, which comprises a porous membrane and a chamber body with a first opening, the porous membrane and the chamber body are detachably enclosed to form a first chamber, and the first chamber can accommodate a curable culture medium for providing a growth space for culturing cells; the flow path plate unit comprises a base part, the base part is provided with a circulation groove and a liquid storage opening matched with a liquid storage device storing a culture solution, and the liquid storage opening is communicated with the circulation groove; a plurality of mounting ports which can be matched with the culture room units are formed in the circulating groove and are used for communicating the first chamber with the circulating groove through the porous membrane; and the driving unit and the circulating groove form a circulating loop so as to drive the culture solution in the circulating groove to flow in the plurality of culture room units. According to the invention, dynamic culture of three-dimensional cells, cell spheres and organoid cells can be better realized.

The invention provides a micro-fluidic chip capable of culturing oral squamous cell carcinoma organoid and a preparation method thereof, and relates to the technical field of micro-fluidic chips, the chip comprises a four-layer structure: the first layer is a closed layer, the second layer is a culture solution / drug pool layer (containing a concentration gradient injection channel and a slow flow channel), the third layer is a matrix culture pool layer, and the fourth layer is a matrix culture pool layer. The fourth layer is a matrigel inflow layer (containing an S-shaped flow channel); the second layer and the third layer are integrally formed, and all the layers are connected through oxygen plasma welding; the problems that in the prior art, matrigel is prone to shifting, drug gradient regulation and control is poor, operation is tedious, and adaptability is insufficient are solved, the matrigel and organoids can be stably fixed, the drug concentration gradient can be precisely regulated and controlled, the nutrition supply efficiency is enhanced, the structural integration level and operation convenience are improved, and the application prospect is wide. The method is suitable for oral squamous cell carcinoma organoid culture, drug screening and tumor mechanism research.

The invention discloses an organoid culture and flexible fiber sensor integrated platform and a construction method and application thereof. The integrated platform comprises a flexible template, a flexible frame body and a flexible fiber sensor, a culture chamber is formed by the flexible template and the flexible frame body; the flexible fiber sensors are arranged close to the side wall of the culture chamber, and the flexible fiber sensors comprise two types, one type is obtained through self-contraction, and the other type is obtained through twisting after self-contraction. The constructed integrated platform can reproduce the structure of the heart and the mechanical microenvironment of the heart in vitro, meanwhile, simultaneous monitoring of organoid mechanical-chemical signals is achieved in the myocardial beating process, and the limitation that existing organoid mechanical-chemical signals are difficult to synchronize and obtain in real time is broken through.

The invention provides a micro-fluidic chip, a model for realizing accurate positioning of an organoid and sequential interaction of a tumor microenvironment, and a construction method of the model. The micro-fluidic chip comprises a chip main body and a chip bottom plate, a blood vessel channel, a central channel, a neural immune cell channel and a culture medium channel are sequentially arranged on the lower surface of the chip main body; the chip bottom plate is arranged on the lower surface of the chip main body and seals each channel; one side of the blood vessel channel is communicated with one side of the central channel, the other side of the central channel is communicated with one side of the neural immune cell channel, and the other side of the neural immune cell channel is communicated with one side of the culture medium channel; the upper surface of the chip main body is provided with an open hole, and the open hole penetrates through the chip main body and is communicated with the middle position of the central channel. According to the model manufactured by the micro-fluidic chip, accurate positioning of tumor organs can be realized through combination of an automatic positioning device and physical constraint, and multi-dimensional cell interaction is supported by dynamic environment regulation and control.

The invention discloses a single-shaft adjustable mechanical stretching device for organoids or cells and a stretching culture method. A fixed support and a guide rail are arranged on a fixed base through a guide rail lifting seat, and a sliding block above the guide rail is connected with a stretching movement end through an adapter seat; the stretching moving end and the stretching fixed end are arranged at an interval, a lead screw of a stepping motor on the fixed support is fixedly connected to a coupler, and the coupler is fixedly connected with an adapter through a blocking block; handles on the two sides of the culture chamber are fixed to a stretching fixing base and a stretching fixing end respectively, a stepping motor is started, a lead screw of the stepping motor drives an adapting base to move longitudinally when moving, the longitudinal movement of the adapting base drives a sliding block to move on a guide rail, and then a stretching movement end is made to be far away from / close to the corresponding stretching fixing end; according to the invention, accurate and controllable tensile mechanical stimulation is carried out on different forms of organoids or cells through the replaceable culture chamber and the accurately controllable stepping motor, so that the tissue maturity / calcification degree is obviously changed or the cell differentiation process is adjusted.

The invention provides a pancreatic islet organ capable of efficiently maintaining pancreatic islet beta cell identity and a preparation method and application thereof. Specifically, the invention provides the preparation method for the in-vitro pancreatic islet organ, and the preparation method comprises the following steps: carrying out induced differentiation culture on the ZnT8-knocked-out pluripotent stem cells, so as to obtain the mature pancreatic islet organ. The invention also provides a corresponding transplantation composition and application thereof. The invention discloses that ZnT8 knockout is a key factor for effectively maintaining the identity stability of beta cells in pancreatic islet organs. In addition, the pancreas islet beta cell identity maintenance agent is combined with the ZnT8-knocked-out pancreas islet organ for use, so that the identity stability of the pancreas islet organ beta cell can be obviously maintained. The invention provides a new strategy for transplantation treatment of type 2 diabetes, and has excellent clinical transformation value.

The invention discloses a bone organ chip loaded with a microelectrode array and a use method, and relates to the technical field of organ chips, the bone organ chip is made of a polydimethylsiloxane material, and the bone organ chip comprises a three-layer structure: a top layer, a middle layer and a bottom layer; the middle layer comprises two blood vessel micro-channels, two osteoblast micro-channels and a neuron micro-channel, the channels are separated through columns and micro-columns, and cell interaction in a bone micro-environment is simulated; a microelectrode array is arranged on the top layer and is used for monitoring electrical activity of neurons in real time; the bottom layer is provided with a pneumatic valve which can control opening and closing of the micro-channel. According to the invention, nerve and blood vessel channels are introduced, a nerve-blood vessel-immunoregulation bone microenvironment is constructed, physiological processes such as osteogenesis-blood vessel formation coupling and the like are embodied, intervals of different sizes can enhance intercellular crosstalk and allow blood vessels and neuron axons to selectively pass through, so that the chip can simulate a complex microenvironment of bone tissues, and the microenvironment of the bone tissues can be simulated; and an efficient and accurate in-vitro model is provided for bone disease mechanism research and drug development.

The invention discloses DLL3 serving as a cervical neuroendocrine cancer treatment target and application of the DLL3, and belongs to the technical field of biology. The invention discloses specific expression of a DLL3 gene in cervical neuroendocrine carcinoma (NECC) and application of the DLL3 gene as a therapeutic target. Single cell sequencing and immunohistochemistry find that a DLL3-NOTCH1 / 2 signal axis is activated in NECC, and functional experiments prove that the DLL3-NOTCH1 / 2 signal axis drives malignant progression by promoting tumor proliferation and inducing T cell depletion. In addition, the invention also constructs an NECC organ-TILs co-culture model, and verifies the synergistic effect of the DLL3 targeted drug AMG757 combined with EP chemotherapy. The invention provides new target selection and theoretical basis for precise diagnosis and treatment of NECC, and has important clinical transformation value.

The invention belongs to the technical field of biology, and particularly relates to a high-throughput preparation method of a single-cell-derived organoid based on a microcapsule spherical shell structure, and the preparation method comprises the following steps: preparing an aqueous two-phase microcapsule encapsulated with a single cell, culturing the single cell in the aqueous two-phase microcapsule to obtain the organoid, the substances of the inner phase and / or the outer phase respectively comprise any one or a combination of more of the following substances: methacrylated gelatin, carboxymethyl cellulose, glucan, sodium alginate and polyvinyl alcohol. The invention also provides the organoid prepared by the preparation method and application of the preparation method. According to the invention, the microcapsule with a permeable core-shell structure is formed by packaging the microcapsule in a single-cell form in two-aqueous-phase liquid drops, the wrapping rate is effectively controlled and adjusted on the premise of conforming to Poisson distribution by optimizing parameters, and the single-cell wrapping rate and the organoid single-cell induction efficiency are optimized.

The invention provides preparation, sorting and application of LGE / CGE organoid and GABAergic neurons, and belongs to the field of brain organoid differentiation and GABAergic neurons. The preparation method of the LGE / CGE type organ comprises the following steps: S1, performing embryoid formation and initial culture on the 0th-4th day; s2, performing nerve induction and matrigel embedding on the 5th-11th day; s3, culturing the brain organoid on the 12th day to the 19th day; s4, dynamically culturing and screening the brain organoid on the 20th-35th day; and S5, carrying out differentiation and collection on LCOs of the LGE / CGE type organs after the 35th day. According to the method, the LGE / CGE organs containing the high-purity GABA energy neurons are obtained through differentiation from the brain organs for the first time, the high-purity LGE type GABA energy neurons and the high-purity CGE type GABA energy neurons are obtained through a specific sorting method, and the method has the deep application potential in the fields of disease model construction, medicine research and development and the like.

The invention discloses a construction method and application of an in-vitro callus-like organ, the survival rate of the organ is improved by improving freeze-formed bio-ink, and a stable directional channel structure is further prepared, so that the internal mass transfer problem of the callus-like organ is improved, and the material exchange efficiency is improved. The forming mode of the callus-like organ is simple and effective, the stent material is easy to prepare, and the callus-like organ has mature cross-linking and printing characteristics, is expected to be applied to drug screening research or bone defect repair, is clear in process and simple in composition, and has relatively high operability.

The invention relates to the technical field of image recognition processing, in particular to an automatic organoid labeling method based on machine vision and deep learning, which comprises the following steps: acquiring a to-be-processed image in a high-throughput culture environment, and preprocessing the image; inputting the preprocessed to-be-processed image into a preset digital image processing framework; the digital image processing architecture comprises an image filtering unit, a three-dimensional boundary reconstruction unit and a texture gray analysis unit; generating an independent target area mask through a three-dimensional boundary reconstruction unit; generating a high-density core mask through a texture gray analysis unit; based on the target area mask and the high-density core mask, constructing a three-dimensional geometric topological graph of the organoid; according to the method, the three-dimensional space morphological characteristics of the neighborhood nodes are obtained through processing by means of a numerical iterative aggregation algorithm, and the image feature parameters are output through analysis of the three-dimensional space morphological characteristics.

The invention relates to the technical field of biology, in particular to a composition for preparing a brain organ, the brain organ and application of the brain organ. The invention further discloses a construction method of the brain organ, and on the basis of the method, different stem cells such as ESCs and iPSCs can be utilized to stably construct the three-dimensional brain organ model capable of simulating the medulla oblongata trigeminal nerve. The invention further discloses an organoid assembly which has important application potential in the fields of research on development, functions and related diseases of brain nuclei, drug discovery and the like.

The application discloses a kind of hepatic organoids containing mesenchyme induction method, belong to organoid culture technical field.The method includes the following steps: (1) human embryonic stem cell WIBR3 pretreatment;(2) utilize human embryonic stem cell WIBR3 and induce liver organoids and mesenchymal cells;(3) mesenchymal cells and liver organoid cells are co-cultured, i.e. obtain the hepatic organoids containing mesenchyme.There is beneficial effect: the application changes the culture mode and method of the hepatic organoids containing mesenchyme.The hepatic organoids containing mesenchyme induction method proposed in the application is simple, and mesenchymal cells and other liver cells have the same genetic background source, suitable for the safety evaluation of drug and other chemical substances, liver fibrosis, non-alcoholic hepatitis modeling and pharmacodynamic evaluation.

The invention discloses an application of imatinib mesylate in preparation of a targeted therapeutic drug for gastric signet ring cell carcinoma. The imatinib mesylate has an obvious inhibition effect on the growth of six patients with the pathological type of gastric signet-ring cell carcinoma, the inhibition effect is more obvious along with the increase of the concentration, the concentration and dosage dependency relationship is shown, and the half inhibitory concentration (IC50) is obviously smaller than that of a positive control drug apatinib. The medicine can play a targeted therapeutic role on the gastric signet ring cell carcinoma, and is small in toxic and side effects, economical, practical and low in cost.

The invention provides a vascularized bone organ and a construction method thereof, and a vascularized bone organ model containing a hollow vascular network is constructed by combining a suspension 3D biological printing method, a cell-carrying printing strategy and a sacrificial biological ink material. The vascularized bone organ model has excellent structural stability, mechanical performance, growth and development capability and osteogenesis capability, selected materials and a manufacturing method are simple in process, engineering stable production can be achieved, cells can be blended for a long time for three-dimensional culture, and the vascularized bone organ model has high applicability and research potential.

The invention discloses a high-flux organoid culture liquid core device which comprises an upper cover module, a transwell module and a porous culture plate, more than one culture hole is formed in the porous culture plate, a liquid inlet hole and a liquid outlet hole are formed in the bottom of each culture hole, at least one culture liquid circulation channel is formed in the porous culture plate, and the culture liquid circulation channels are communicated with the culture holes. The culture solution circulation channel comprises an injection port, an input channel, a discharge channel and a discharge port, the injection port is communicated with the input channel, and the discharge channel is communicated with the discharge port; the porous culture plate comprises a plurality of culture holes and a plurality of culture solution circulation channels, each culture solution circulation channel is communicated with an injection port and a discharge port of at least one culture hole, the transwell module comprises more than one transwell chamber, the transwell chambers are matched with the culture holes and placed on the culture holes, and the upper cover module is used for sealing and covering the porous culture plate. According to the liquid core device, a traditional culture plate and a micro-fluidic technology are combined, high-throughput culture of the organoid is achieved, and the homogeneity of the organoid culture tissue is improved due to the fact that a parallel multi-group organoid culture mode is adopted.

Provided are chemically modified silk fibroin and a use thereof in cell and organoid culture. The chemically modified silk fibroin is a product obtained by sequentially carboxylating silk fibroin and modifying same by an organic amine having a phenol group. Also provided is a hydrogel based on the chemically modified silk fibroin. A hydrogel system has a hierarchical structure and mechanical properties similar to those of an extracellular matrix, and exhibits characteristics such as definite composition, controllable physicochemical properties, low cytotoxicity, good biocompatibility, and biodegradability, can support the growth and differentiation of cells and organoids, and is suitable as a matrigel for cell and organoid culture.

The invention belongs to the technical field of biomedicine, and relates to a method for constructing a mouse embryo-derived hypothalamic organ model and application, the invention proposes that a mouse embryo is used for constructing a hypothalamic organ for the first time, and the mouse embryo has a definite development time sequence and genetic operability; the naturally retained vascular endothelial cells and multilineage precursor cells provide unique advantages for constructing a three-dimensional organ containing multiple nucleuses such as a preoptic region, a paraventricular nucleus, an arcuate nucleus and a supraoptic nucleus, and the model not only breaks through the nucleus coverage limitation of the existing iPSCs organ, but also can be used for constructing the three-dimensional organ containing multiple nucleuses such as the preoptic region, the paraventricular nucleus, the arcuate nucleus, the supraoptic nucleus and the like by reconstructing a nerve-blood vessel unit. High-fidelity simulation of complex physiological functions of the hypothalamus is realized, and an irreplaceable technical platform is provided for mechanism analysis of neuroendocrine diseases and high-throughput screening of drugs.

The invention discloses a mouse lung organ and fibroblast co-culture method, which comprises the following steps of: performing in-vitro mouse lung organ culture on mouse lung tissue primary epithelial stem cell spheres (pneumospheroids) in a Transwell upper chamber, and after the lung organs in the Transwell upper chamber are differentiated, replacing with a lower chamber paved with mouse lung fibroblasts, therefore, a gas-liquid interface co-culture system of the mouse lung organ (upper chamber) and the fibroblast (lower chamber) is formed, and the hierarchical structure, morphological characteristics and regeneration function of the upper chamber organ and the phenotype, function and related signal path activation level of the lower chamber fibroblast can be dynamically researched.

The invention relates to the technical field of cell culture, in particular to a dynamic culture device and method for organoids, the dynamic culture device comprises a culture bin and a transverse flow reaction generator, the end, away from the transverse flow reaction generator, of the culture bin is communicated with a liquid supply bin, and the two ends of the culture bin are connected with a second driving unit through a transmission mechanism; the transverse flow reaction generator is rotationally connected with a first driving unit; and vortex bulges / grooves are formed in the inner wall of the culture bin. Under the driving of the second driving unit, the culture bin is driven to rotate; the transverse flow reaction generator is driven by the first driving unit to reciprocate in the axis direction of the culture bin, and liquid in the culture bin collides with the vortex protrusions / grooves in the inner wall of the culture bin under the transverse effect of the transverse flow reaction generator, so that transverse vortexes are formed. The device is simple in structure, can create a culture environment for providing specific mechanical stimulation for the organoid, is beneficial to amplification of the organoid, and improves the structure and function maturity of the organoid.

The utility model relates to the technical field of biological chips, in particular to a multi-tissue co-culture organoid chip which comprises a chip main body, and a plurality of culture hole groups are formed in the chip main body; the culture hole group comprises a first cell culture hole and at least one second cell culture hole communicated with the first cell culture hole, and a porous membrane for cells to pass through is arranged at the communicated part of the first cell culture hole and each second cell culture hole; the mode that the two cell culture holes are communicated and separated through the porous membrane is adopted, organoid co-culture is achieved, meanwhile, the pathological and physiological dynamic microenvironment of tumor tissue can be simulated, the operation process of medicine screening is simplified, and the medicine screening efficiency is greatly improved.