1825 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 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.

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 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 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 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.

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.

The invention relates to a cochlea spiral neuron in-vitro organ as well as a construction method and application thereof, and provides a method for obtaining a mature inner ear neuron by utilizing human pluripotent stem cell differentiation in vitro and further constructing an inner ear neuron in-vitro organ on the basis of the mature inner ear neuron. The internal ear neuron in-vitro organoid function stage obtained by the method and the application thereof are also provided.

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 discloses a multi-brain organ electron complex as well as a construction method and application thereof. The multi-brain organ electronic complex comprises a microelectrode array and a fusion organ attached to the surface of a chip electrode of the microelectrode array through a PDMS film, and the fusion organ can grow for more than or equal to 120 days through culture. The PDMS film is attached to the surface of the MEA chip electrode, so that the stability of combination of the MEA chip electrode and the organoid is remarkably enhanced, the construction efficiency of a multi-brain organoid electron complex is improved, and the continuity of neural signal detection is improved; a high-performance model platform is provided for multi-brain organ research, and the method has a wide application prospect.

The invention provides construction and application of a human pluripotent stem cell-derived heart organoid traditional Chinese medicine extract toxicity test chip. The chip comprises a plurality of micro-cell culture chambers and a micro-fluidic pore channel, heart organoid culture is carried out in the micro-cell culture room, culture media are added in the micro-fluidic channel to maintain the activity of the heart organoid, and traditional Chinese medicine extracts are added to evaluate the toxicity of traditional Chinese medicine. By simulating the reaction of the heart organ, the toxicity of the traditional Chinese medicine can be evaluated, the safety and effectiveness information about the traditional Chinese medicine can be provided, finally, the use of experimental animals can be reduced, and the animal welfare can be improved.

The invention discloses a force-position control bottle cap screwing device and method supporting the digital twinning technology. The force-position control bottle cap screwing device comprises a screwing clamping jaw mechanism used for screwing a bottle cap; the Z-axis executing mechanism and the X-axis executing mechanism are used for adjusting the position of the screwing clamping jaw mechanism, the screwing clamping jaw mechanism is fixed to the output end of the Z-axis executing mechanism, and the Z-axis executing mechanism is fixed to the output end of the X-axis executing mechanism; the force sensor and the position sensor are used for detecting the stress and position information of the screwing clamping jaw mechanism; and the control unit is used for receiving signals of the force sensor and the position sensor and regulating and controlling the stress and the position of the screwing clamping jaw mechanism according to the received signals. The requirement for opening and closing the cell culture fluid bottle cap to take fluid in the intelligent and automatic production process of the organoids can be met, and technical and theoretical possibilities are provided for successful research and development of the intelligent and automatic production line for culturing and observing the organoids.

The invention relates to a high-throughput method for preparing organoid frozen sections, and belongs to the technical field of biology. The invention provides a high-throughput method for preparing an organoid frozen section, the method comprises five steps of fixing, closed permeation, dehydration, embedding and slicing, in the embedding step, an organoid which is sequentially subjected to fixing, closed permeation and dehydration treatment is embedded by using a high-throughput array embedding mold; the high-throughput array embedding mold comprises an embedding box and a micro-deformation material, the micro-deformation material is fixed at the bottom of the embedding box, and a plurality of embedding holes are formed in the micro-deformation material. According to the method, a plurality of organoid samples can be prepared into the organoid frozen sections at the same time under the same condition, the method has the advantage of high throughput, high-throughput and standardized detection of the plurality of organoid samples can be realized under the single experiment condition, the experiment error is reduced, and the result reliability and stability are improved.

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 belongs to the technical field of organoid culture, and particularly relates to a co-differentiated vascularized islet organoid and a construction method thereof. Aiming at the problems that the existing pancreatic islet organ vascularization mostly adopts a co-culture mode, the operation process is long, the difficulty is high, the randomness is realized, the uniformity is poor and the like, the invention provides the construction method of the co-differentiated vascularized pancreatic islet organ. The method comprises the following steps of: sequentially inducing and culturing directional endoderm cells, original intestinal canal cells and posterior preintestinal cells, and adding a culture medium containing VEGF (vascular endothelial growth factor), BMP4 (bone morphogenetic protein 4) and FGF2 (fibroblast growth factor 2) for culturing in subsequent induced differentiation, so as to obtain the co-differentiated vascularized islet organ. Under the condition that exogenous endothelial cells are not added, the iPS cells are directionally differentiated to generate the vascularized islet organ containing beta, alpha and delta cells and vascular endothelial cells for the first time, the vascularized islet organ is more mature than non-vascularized islet organs and has a stronger insulin secretion function, and a new thought and an experimental basis are provided for realizing functional healing of diabetes mellitus.

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 discloses a construction method of a homogenized self-assembled heart organoid, and belongs to the field of organoid. The preparation scheme of the heart organoid provided by the invention is controllable in method and simple in procedure, emphasizes the transition of differentiation from an iPSC 2D level to a 3D self-assembly heart organoid, overcomes the heterogeneity, including size, structure, function and even gene difference, of cross-batch or even same-batch organoid caused by an existing differentiation method, and has good cross-batch reproducibility. The constructed heart organoid contains various cell types and can continuously beat for at least 180 days in vitro, and the heart organoid in the same batch is uniform in height and stable in function. The preparation scheme does not need an engineering scaffold, matrigel and the like, emphasizes self-assembly of heart organs, and better accords with physiological characteristics of a human body.

The invention provides a construction method and application of a blood sinus networked liver organ. According to the method, pluripotent stem cells are co-differentiated into HAND1 < + > mesoderm and endoderm, a front intestine rear endoderm containing KDR < + > mesoderm progenitor cells is generated, a liver endoderm with CD34 < + > / CD31 < + > endothelial progenitor cells is generated, and the blood sinus networked liver organ is formed. The liver organ has a functional blood sinus endothelial network penetrating through the liver cluster, and has the characteristic functions of low-density lipoprotein uptake, human serum albumin removal, mediated secretion of blood coagulation factor 8 and the like. The method provides a new-generation highly bionic research tool for liver disease mechanism analysis, drug screening and regeneration repair.