586 results about "High-throughput screening" patented technology

The embodiment of the invention provides a method for obtaining a tyrosine ammonialyase mutant based on high-throughput screening, the tyrosine ammonialyase mutant and application of the tyrosine ammonialyase mutant. The mutant is subjected to any one of the following amino acid mutations on an amino acid sequence as shown in SEQ ID NO.2: A245G + A247T, and D192V + A245G + A247T. According to the embodiment of the invention, an amino acid sequence as shown in SEQ ID NO.2 is taken as a template (basis), a key active site of the template is subjected to mutation transformation, a mutant library is constructed, and a series of mutants with remarkably improved catalytic activity and / or conversion rate are screened; the tyrosine ammonia lyase mutant provided by the embodiment of the invention can selectively catalyze L-tyrosine to generate p-coumaric acid, and has excellent yield and / or higher yield, which indicates that the mutant has more significant application prospects in catalysis of L-tyrosine to generate p-coumaric acid.

The invention discloses an intelligent control method and system for saline-alkali soil slow-release fertilizer application, and the method comprises the steps: analyzing the space-time trend of soil salinity change and pH dynamic change through a convolutional neural network, judging the matching demand of the fertilizer release rate, and generating a target release curve; the method comprises the following steps: extracting a high-activity strain adapting to a high-salt environment from a salt-tolerant microbial library through a high-throughput screening algorithm, and determining optimal release time interval distribution of strain function activation by combining with the release characteristic of a dynamic release coated fertilizer; if the soil salinity change exceeds a preset threshold value, sensor monitoring data and a target release curve are integrated through a closed-loop control system, and an optimized fertilization amount scheme is obtained; a deep learning model is adopted to analyze the relation between the optimized fertilization amount scheme and soil deep salt distribution, the parameter requirement of depth accurate regulation and control is judged, and a layered fertilization depth control strategy is generated. Through real-time feedback and optimization iteration, accurate improvement and sustainable nutrient management of the saline-alkali soil are realized.

The invention belongs to the technical field of antibacterial peptide activity identification and evaluation, and relates to an antibacterial peptide activity and MIC value combined prediction framework based on cross-modal deep learning, and the framework uses a protein language model ESM2 to respectively carry out token-level semantic embedding coding on an antibacterial peptide sequence and a pathogen protein sequence; performing cross-modal feature extraction and fusion through a multi-branch structure comprising a Mama module, a multi-head self-attention mechanism and DASM 1D convolution; a multi-task decoding structure is adopted to realize antibacterial peptide activity classification and MIC value regression prediction at the same time; according to the method, functional characteristics in the sequence can be effectively mined, the accuracy and generalization ability of antibacterial peptide activity and MIC value prediction are remarkably improved, and a reliable calculation tool is provided for high-throughput screening and rational design of the antibacterial peptide.

The invention discloses a 3-sterone-delta1-dehydrogenase mutant and application of the 3-sterone-delta1-dehydrogenase mutant in preparation of a steroid drug intermediate. The mutant is obtained by performing single mutation or multiple mutation on 551, 468, 48 and 157 sites of an amino acid sequence of 3-sterone-delta1-dehydrogenase as shown in SEQ ID NO: 1. The 3-ketosterone-delta1-dehydrogenase is subjected to molecular modification through directed evolution and semi-rational design, the mutant with improved enzyme activity is screened in a high-throughput mode, the mutant can effectively improve the conversion rate of a substrate 11alpha, 17alpha-dihydroxyprogesterone, and the substrate conversion rate of the mutant ISM-2 is improved to 92.4% compared with 36.7% before mutation.

The invention belongs to the field of biological pharmacy, and discloses a GPCR-based ultramicro drug screening method and application thereof in screening of antipruritic traditional Chinese medicines. According to the invention, an Echo ultrasonic pipetting system is combined with a GPCR function experiment (beta-arrest recruitment) to establish the ultramicro screening method for screening the GPCR ligand. The Echo 550 system utilizes ultrasonic waves to beat liquid into 2.5 nL liquid drops and then transfer the liquid drops into a 384 or 1536 pore plate, rapid and accurate sample adding of at least 2.5 nL (1 / 400 mu L) can be achieved, ultra-micro screening and high-throughput screening can be achieved at the same time, and the method is particularly suitable for screening of itching relieving drugs.

The invention provides a screening platform for chemotherapy combined anti-tumor natural products and application of the screening platform. PTC has tumor cells, interstitial cells, fibroblasts and immune cells from primary epithelium, is rich in cell components, and has advantages in the aspect of tumor microenvironment simulation. Meanwhile, PTC can reproduce tumor heterogeneity, the culture success rate and clinical consistency can reach 90% or above, and the detection period is within two weeks. And the detection result can be read through AI intelligent software, so that the accuracy can be further improved. The screening period can be shortened, the cost is reduced, and the accuracy is improved; according to the platform, high-throughput screening can be carried out in a short time, and the treatment effect of a chemotherapy drug combined anti-tumor natural product drug scheme can be predicted.

The invention relates to a high-throughput screening method and system for a self-assembled single-layer thermal interface material and a medium. The high-throughput screening method comprises the following steps: constructing an interface heat transport simulation system based on a self-assembled monomolecular layer; screening set preparation is carried out on the end group structure, and an end group screening set and a pre-calculation set are constructed; carrying out molecular dynamics simulation on the self-assembled monomolecular layer corresponding to the pre-calculation set to obtain a physical association index; training a machine learning model by taking the physical association index as a machine learning objective function; carrying out machine learning prediction on the uncalculated screening candidate data set based on the trained machine learning model, and carrying out parallel screening of physical association indexes to obtain a simulation verification set; and carrying out molecular dynamics simulation for verification. Compared with the prior art, high-throughput screening of the self-assembled single-layer thermal interface material is achieved, and the method has important significance on solid-liquid interface heat conduction characteristic regulation and control design under data driving.

The invention discloses an intelligent management and control system for small nucleic acid drug high-throughput screening equipment, and the system comprises an equipment information collection module which is used for collecting the operation state data of the high-throughput screening equipment in real time; the equipment environment acquisition module is used for acquiring physical parameters of a microenvironment in which the equipment is located in real time; the user acquisition module is used for acquiring identity and operation behavior data of operators; and the data processing module comprises an equipment health analysis unit which is used for calculating an equipment health index H according to the running state data and generating equipment state management and control information containing the equipment health index H and maintenance suggestions. The method can integrate equipment operation state, microenvironment parameters and personnel operation behavior data, realizes comprehensive risk assessment, generates a regulation and control instruction in real time through a quantitative model, improves the robustness of equipment to cope with complex scenes, trains a decision model based on historical data, identifies potential risks in advance, triggers a joint optimization scheme, and improves the risk assessment efficiency. And the screening efficiency and accuracy of small nucleic acid drugs are ensured.

The present invention is in the field of agricultural pathogen control. Methods and compositions are described for controlling plant diseases caused by pathogens, including fungi and oomycete phytopathogens. Chemicals were screened for activity as autophagy inhibitors. The screening method used a bioluminescence resonance energy transfer (BRET)-based high-throughput screening strategy to identify compounds that inhibit fungal ATG4 cysteine protease-mediated cleavage of ATG8 for autophagosome formation. Ebselen and ebselen analogs were identified as inhibitors of fungal pathogens ATG4-mediated ATG8 processing. Identified chemicals inhibit spore germination, hyphal development, and appressorium formation. The autophagy inhibitors significantly reduced the virulence of pathogens in their corresponding plant hosts. The invention also provides for compositions comprising the same, methods of making the same, and methods of controlling plant disease.

The invention discloses application of a small-molecule inhibitor of stress particles in preparation of tumor treatment drugs, and relates to the technical field of biological medicines. According to the present invention, the high throughput screening is performed on the 'ChemDiv Protein-Protein Interaction (PPI) Library', such that the small molecule inhibitor of the stress particle, i.e., the compound UA-0007373, is obtained; the research finds that the small-molecule inhibitor can effectively inhibit the formation of cell stress particles caused by G3BP1, so that the drug resistance of tumor cells is reduced. Cell experiments prove that the small-molecule inhibitor can effectively inhibit the formation of stress particles induced by anti-cancer drugs. Therefore, a brand new auxiliary compound is provided for chemical drug treatment of cancers, and a new technical thought can be provided for research and development of cancer drugs.

The invention relates to the technical field of molecular biology, in particular to a multichannel virus reporting system based on TAT trans-activation. The invention relates to a multichannel virus reporting system based on TAT trans-activation. The multichannel virus reporting system comprises an activated virus and a reporting cell, the activated virus is a human enterovirus A71 for expressing TAT protein; the reporter cells are cells transfected with reporter plasmids; the reporter plasmid comprises an LTR sequence and a plurality of reporter genes which are started to express by the LTR sequence. When the virus is activated to infect the reporter cell, the TAT protein carried by the virus enters the reporter cell to activate the expression of the downstream reporter gene, and the expression level of the reporter gene can reflect the virus replication condition, so that the screening or mechanism research of related antiviral drugs can be realized. According to the technical scheme, the technical problem that the flexibility, stability and high-throughput screening adaptability of a virus reporting system in the prior art are not ideal can be solved, and the virus reporting system has ideal popularization and application prospects.

The invention discloses a method for improving the synthesis level of L-tryptophan in escherichia coli based on ARTP mutagenesis high-throughput screening, and belongs to the technical field of bioengineering. According to the invention, the L-tryptophan biosensor pSensor-trp3 is constructed, and the L-tryptophan biosensor pSensor-trp3 is good in response under the condition that the exogenous addition concentration range of L-tryptophan is 0-300mg. L <-1 >. High-throughput screening is performed by using a flow cytometry, a dominant mutant strain YB-2 is obtained through iterative mutagenesis, and the shake flask L-tryptophan yield and the sugar-acid conversion rate of the dominant mutant strain YB-2 are 5.68 g.L <-1 > and 0.103 g.g <-1 > respectively and are increased by 11.4% and 10.7%. Through second-generation whole genome re-sequencing comparative analysis, it is speculated that the genes ynfB and waaO possibly have a promoting effect on synthesis of L-tryptophan. The L-tryptophan biosensor used in the invention also provides reference for high-throughput screening and transformation of other related L-tryptophan production strains.

The invention discloses a nano antibody capable of specifically recognizing staphylococcus aureus as well as a preparation method and application of the nano antibody. A ribosome display technology is adopted, a nano antibody pair with a good pairing effect is screened out through construction of a nano antibody display library, three rounds of high-throughput screening and ELISA verification, and the nano antibody pair is used for in-vivo detection of actual pathogenic bacteria in combination with an immunochromatography technology. The nano antibody disclosed by the invention shows high affinity, high specificity and achievable detection limit when being combined with staphylococcus aureus, has the advantages of good stability, low cost and the like compared with a monoclonal antibody, can be produced on a large scale, and has a wide application prospect in the field of staphylococcus aureus detection and analysis.

An automated high throughput screening platform for identification of compounds and genomic constructs having mitochondrial function modulating activity and compounds so identified are provided. Use of such compounds for modulating mitochondrial function are also disclosed. A high-throughput screening method of determining genetic mechanisms of action for therapeutic or toxic agents in genetic or pharmacologic models of disease are also provided.

A system and method for the high throughput screening of small molecule-protein interactions includes first immobilizing selected small molecules on a solid matrix. Immobilization is preferably made by photo affinity labelling in which a linker used to bind the small molecule to the matrix. A cDNA library is established from a broad array of human tissues. The tissue mRNA is converted to cDNA and transferred to a phage genome to make a phage display library which is mixed with small molecules coupled to the beads and incubated. The incubation mixture is washed to remove unbound phage including non-specific and weak binders. The bound phage are amplified and are used in the next round of biopanning. The biopanning cycles are repeated followed by PCR of individual plaques selected from the final biopanning round. The PCR products are barcoded from each small molecule experiment and are pooled followed by Nextgen sequencing.

The invention belongs to the field of biotechnology and environmental governance, and particularly relates to a manganese peroxidase mutant based on high-throughput screening modification and application of the manganese peroxidase mutant to straw degradation. Aiming at the problems of low natural secretion amount, insufficient specific activity, complex preparation process and the like of the existing manganese peroxidase, the method comprises the following steps: firstly, constructing engineering bacteria based on an escherichia coli exocrine system, constructing a mutant library through error-prone PCR in combination with a directed evolution technology, and performing high-throughput screening by utilizing an ABTS colorimetric method; the recombinant manganese peroxidase mutant with high catalytic activity is obtained, and the enzyme activity is improved by 1.29 times compared with that of a wild type. Furthermore, recombinant engineering bacteria are constructed on the basis of a bacillus subtilis exocrine system, and efficient secretion of the mutant enzyme is achieved. The mutant enzyme preparation is used for wheat straw degradation, and the lignin degradation rate reaches 41.37% (improved by 30.09% compared with that of a wild type). The method is simple and convenient in process, low in cost and remarkable in effect, and has a wide industrial application prospect.

The invention discloses a simulated screening and process optimization method of an anhydrous hydrogen fluoride desulfurization adsorbent, and relates to the technical field of anhydrous hydrogen fluoride, and the method comprises the following steps: constructing a database, and establishing a basic screening library; constructing an intelligent screening engine, and performing force field parameter correction on the materials in the basic screening library to capture a high-polarity solvent effect; calculating and extracting adsorption selectivity, Henry coefficients and working capacity indexes, and screening out a primary candidate material set; a core candidate material is optimized; determining an optimal adsorbent model; the microscopic adsorption data of the optimal adsorbent model are converted into macroscopic process parameters, the macroscopic process parameters are imported into a macroscopic process simulator for prediction, and process optimization is completed. According to the method, the strong polar solvent effect is simulated by constructing the corrected force field environment, and high-throughput screening of the adsorption materials is achieved in combination with an active learning strategy; an electronic grade refinement and modification strategy is utilized to optimize adsorption sites, and microcosmic adsorption data and a macroscopic mass transfer model are coupled to realize accurate prediction and optimization of an adsorption process.

The invention discloses a method for high-throughput screening of key genes in a 1, 5-pentamethylene diamine biosynthetic pathway of escherichia coli, and the high-throughput screening is carried out by using a 1, 5-pentamethylene diamine biosensor. The 1, 5-pentamethylene diamine biosensor is a recombinant plasmid obtained by integrating a lysine decarboxylase coding gene cadA and a promoter trc thereof, and a green fluorescent protein (GFP) coding gene and a promoter pyrF thereof into a plasmid skeleton. A fluorescent quantitative flow cytometer is used for screening single-cell thalli with high yield of 1, 5-pentanediamine according to the fluorescence intensity of GFP, key genes can be rapidly screened out from a large number of genes to be screened in a high-throughput mode, and the screening workload and time are greatly saved. According to the application of the key gene in the biosynthetic pathway of the escherichia coli 1, 5-pentanediamine screened by the method disclosed by the invention, the yield of the 1, 5-pentanediamine produced by fermenting the escherichia coli KA30 can be greatly improved, the substrate conversion rate in the fermentation process is improved, the production cost of the 1, 5-pentanediamine is reduced, and the economic benefit is improved.

The invention discloses a method for screening an MOFs material with excellent CH4 adsorption separation performance based on high-throughput calculation, a method for improving the screening efficiency and a preparation method. The screening method comprises the following steps: constructing a screening database of MOFs material structure information; calculating physical and chemical characteristic parameters by utilizing computational chemistry and material simulation software, and further setting a screening standard aiming at CH4 adsorption; carrying out preliminary screening through a high-throughput screening technology; predicting the competitive adsorption behavior of the primarily selected material in the mixed gas by means of a molecular simulation technology, and performing secondary screening; and finally, determining the final MOFs material in combination with an actual application environment. According to the method, the high-performance MOFs material is rapidly and accurately screened out from a large number of materials, the research and development period is effectively shortened, the development cost is reduced, an efficient and feasible solution is provided for resource utilization of ultralow-concentration CH4 in coal mine windblown gas, and energy utilization and environmental protection are assisted.

The invention discloses development and application of a biosensor for detecting L-threonine, and belongs to the field of genetic engineering. The invention provides a construction method of a novel threonine biosensor and an application method for screening L-threonine high-yield mutants in an auxiliary manner through the biosensor. The biosensor can sensitively detect the concentration change of L-threonine. By combining with a high-throughput screening system, L-threonine high-yield strain mutants with improved production performance can be rapidly screened. By means of the biosensor, an L-threonine high-yield mutant LMTM35 is successfully screened from an L-threonine production strain LMT4 mutant library, 166 g / L of L-threonine is accumulated in a 5L fermentation tank after 45 hours, and the saccharic acid conversion rate is 0.67 g / g.

The invention discloses high-throughput screening of lactobacillus plantarum with ethanol degradation capacity and application of the lactobacillus plantarum, and belongs to the technical field of microorganisms. According to the method for high-throughput screening of the ethanol degradation strains, 8340 strains are successfully and rapidly screened, the strains are evaluated in vitro, and the degradation rates of A1H11 strains in vitro for 6 hours are 33.7% and 24.2% respectively under the alcohol concentrations of 10% and 20% (v / v); the resistance to gastric juice is shown, proliferation to a certain degree can be achieved, and the survival rate reaches 106%. And finally obtaining the lactobacillus plantarum which is relatively good in ethanol degradation capability and resistant to gastric acid.

The present application relates to the technical field of high-throughput chemical reactions, and in particular to a sealing process for a well plate, a high-throughput screening method, a well plate heat sealing device, and a high-throughput screening system. The sealing process for a well plate comprises: covering a blind well of a well plate with a film and then carrying out heat sealing, wherein the material for forming the film is consistent with the material of the part of the well plate in contact with the film, and the heat sealing conditions comprise: the heat sealing temperature is 5-65°C higher than the melting point of the material of the film, and the heat sealing time is 0.3-4.5 s. The sealing process can solve the problems of difficulty in single-well sealing of small volume wells in existing well plates and tolerance to only low temperatures of existing sealing processes. Thus, a well plate reaction device is allowed to expand its applicable ranges of reaction temperatures and reaction solvents in high-throughput screening, implementing heating and oscillating reactions, and also implementing chemical reactions under conditions exceeding the boiling points of solvents.

By engineering genetic traits associated with photosynthesis in plants, transgenic plants with increased crop yield can be generated, which will ultimately lead to increased food production in the field. To obtain beneficial genetic traits for enhanced photosynthesis, accelerated evolution is applied under salt stress in a cyanobacteria species, Synechococcus elongatus PCC 7942, by conditionally suppressing its mismatch repair system. Through high-throughput screening for biomass accumulation and sucrose production, it is discovered that specific amino acid changes in the pre-Dl protein of Photosystem II (PSII), encoded by the psbA genes, can improve efficiency of photosynthesis under salt stress, as well as pathogen resistance. Next, the same amino acid changes were made in Arabadopsis and proved that photosynthetic efficiency (measured via growth rate) is also increased in this model vascular plant.

Apparatuses and corresponding methods are provided for determining molecular properties of a molecule. To determine molecular properties of the molecule, a molecule library comprising the molecule is generated, a focused library comprising the molecule is generated by filtering the molecule library; the focused library is attached to a flow cell of the imaging instrument; and a fluid control module of the imaging instrument is controlled to incubate the flow cell with a fluid comprising labelled target molecules. A light source module and an imaging module of the imaging instrument are operated in a selected operational mode such that the light source module illuminates the flow cell and the imaging module captures light generated by fluorescence by the labelled target molecules within the flow cell. Image data is generated based on the captured light and the imaging data is analyzed to determine molecular properties of the at least one molecule.

A well plate can include a plastic component having an array of microwells, each defining a respective opening sized to receive and contain a volume of fluid. A printed circuit board (PCB) material can be arranged against and accessible through the microwell openings, allowing fluid contact with the PCB material at a first side. An array of integrated circuits (ICs) can be individually positioned to correspond with respective microwells and electrically interconnected via conductive interconnections within the PCB material, such as to facilitate electronic assays within standardized well plates for high-throughput screening applications.

The present invention relates generally to the field of molecular biology and concerns a method for high throughput screening and characterization of one or more candidate plant pathogen effect genes and / or one or more candidate plant disease resistance genes in a single plant cell, the method comprises: (i) introducing into a plant protoplast one or more expression cassettes comprising at least one candidate plant pathogen effect gene and / or at least one candidate plant disease resistance gene; (ii) transiently expressing the one or more candidate plant pathogen effect genes and / or the one or more candidate plant disease resistance genes; (iii) measuring reactive oxygen species (ROS) produced by the protoplast; then (iv) separating the plant protoplast producing the ROS; and (v) identifying the introduced at least one candidate plant pathogen effect gene and / or at least one candidate plant disease resistance gene. Alternatively, the protoplast is capable of expressing the selectable marker, thereby allowing for the measurement of modulated selectable marker expression as an alternative indicator for HR activation.

Methods for testing the effects of therapeutic compound candidates on a phenotypic organoid model is provided. Such a method includes steps of generating the phenotypic organoid model on a high throughput screening platform, treating the organoid with a therapeutic compound candidate, and testing one or more effects resulting from treatment with each of the therapeutic compound candidates. The testing method that has led to identification of a method for treating or preventing cysts is provided. That method may include contacting a population of cells with an inotrope, wherein the inotrope prevents cyst formation, shrinks existing cysts, or both. That method may be used to treat cystogenic diseases or conditions such as Polycystic Kidney Disease (PKD).

The invention provides a method for high-throughput rapid screening of food fermentation strains. The method comprises the following steps: mixing a to-be-detected bacterial sample with a culture medium without a yeast product, injecting an obtained mixed bacterial liquid and an oil phase into a liquid drop generation chip, generating liquid drops, and collecting the liquid drops for culture; injecting the cultured liquid drops, the oil phase and SYTOTM16 fluorescent dye liquid into a liquid drop micro-injection chip, collecting the generated liquid drops, injecting the liquid drops and the oil phase into a micro-fluidic sorting chip, carrying out fluorescence detection, collecting target liquid drops, and carrying out demulsification treatment and coating culture. The method can realize rapid and accurate high-throughput screening of target strains, and especially can directly quantify the growth activity of microorganisms under the stress of acid and salt, thereby realizing efficient and accurate screening of acid-resistant and salt-resistant strains. Moreover, the method does not need to carry out gene modification on the strain, avoids the problems of biological safety and technical complexity possibly caused by gene manipulation, retains the natural characteristics of the strain, is suitable for large-scale high-throughput bacterium screening, and has high application value.

According to the liquid drop sorting instrument based on fluorescence detection, an inverted microscope serves as a whole instrument base and is located at the bottom, an XY precise moving platform is fixed to the microscope, a z-axis moving platform is fixed to a simple supporting frame beside the microscope, a fluorescence channel is installed on the z-axis moving platform, and a microfluidic liquid drop sorting module is fixed to the tip end of the fluorescence channel. A fluorescence detection module is arranged on the side wall of the fluorescence channel, the fluorescence detection module and the microfluidic liquid drop sorting module are both connected with the signal end of the FPGA signal processing module, the fluorescence detection module and the microfluidic liquid drop sorting module are controlled through the FPGA, the condition of generated liquid drops is observed through a microscope, the sorting process of the liquid drops is dynamically adjusted, and the quality of the liquid drops is improved. The closed-loop control of fluorescent liquid drop sorting is realized; according to the invention, high-precision and high-throughput liquid drop sorting can be realized, the liquid drop screening efficiency is greatly improved, the target liquid drop can be accurately identified and selected, and the method can be widely applied to the fields of high-throughput screening, single cell analysis, enzyme evolution, drug discovery and the like.

The invention belongs to the field of microbial breeding and fermentation engineering, and particularly relates to a saccharomyces cerevisiae mutagenesis strain with high yield of S-adenosyl-L-methionine as well as a mutagenesis method and application of the saccharomyces cerevisiae mutagenesis strain. Saccharomyces cerevisiae is induced to generate genetic diversity through multiple rounds of ultraviolet mutagenesis, and high-throughput screening is performed in combination with strain color phenotypic difference; and the mutant strain HY2402-Z18 with high yield of S-adenosine-L-methionine and genetic stability is obtained. The SAM yield of the mutagenic strain is increased by 40.1% compared with that of an original strain, the SAM yield reaches 13.44 g / L when the mutagenic strain is fermented for 60 h in a 5 L fermentation tank system, the unit yield reaches 0.156 g / L / OD, and the methionine conversion rate is 75%. After thalli are collected through centrifugation of fermentation liquor, an S-adenosine-L-methionine product with the purity of 98%-100% can be obtained through purification of ion exchange resin, no by-products are accumulated, the yield, the substrate conversion rate and the production efficiency of the S-adenosine-L-methionine can be remarkably improved when the mutagenesis strain is used for fermentation production, and the production cost is reduced. The production cost is effectively reduced, the product purity and quality are improved, and the method is suitable for industrial large-scale production of SAM.