19744 results about "Biophysics" patented technology

Multiple enzymes may be present in one or more active areas of an electrochemical analyte sensor for detecting one or more different analytes. In particular, an analyte sensor may comprise a sensor tail configured for insertion into a tissue and one or more working electrodes having a glucose-responsive active area and an ethanol-responsive active area to detect glucose and ethanol in vivo.

Provided herein are methods of determining a location of a target analyte in a non-permeabilized biological sample and methods of reducing background binding of an analyte on an array.

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.

An electrophoretic system is provided for analyte capture from a biological sample. The electrophoretic system can be used to permeabilize the sample to allow analytes to be released from the sample. For example, the sample can be contacted with capture probes attached to a substrate, and an electric field created by the electrophoretic system can cause analytes to be released from the cell, and effectively migrate toward and bind to the capture probes attached to the substrate.

Provided herein are systems and methods for analyzing biomolecules (e.g., nucleic acid molecules, proteins). A method of nucleic acid analysis can comprise: (a) providing a sample comprising a cell comprising a target polynucleotide comprising a first exon segment and a second exon segment, wherein the first exon segment and the second exon segment flank opposite ends of a splice junction site of the target polynucleotide. The method can further comprise (b) contacting the cell with: (i) a first probe, wherein the first probe hybridizes to a first target sequence of the first exon segment, and (ii) a second probe, wherein the second probe hybridizes to a second target sequence of the second exon segment. The method can further comprise (c) linking the first probe and the second probe together, thereby generating a probe-linked nucleic acid molecule comprising the first probe and the second probe. The method can further comprise (d) identifying a sequence of the probe-linked nucleic acid molecule or derivative thereof, thereby locating the splice junction site of the target polynucleotide.

Provided herein are methods for analyzing a biological sample that include contacting the biological sample with a non-conductive substrate; and contacting a matrix to a surface of the biological sample. Further methods optionally include performing mass spectrometry analysis; determining presence of a first analyte in the biological sample; and / or analyzing a second analyte on the surface of the biological sample to determine presence of the first and the second analyte in the biological sample.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Systems and methods are provided for stabilization of cells and retention of biomolecules therein for further analysis. Block copolymers are inserted into membranes of biological particles, cell membranes or organelles (e.g., organelle membranes) and polymerized to form an intra-biological particle (e.g., intracellular) polymer network.

Provided are multi-wavelength phototherapy devices, systems and methods for the treatment of a disorder or disease, including multi-wavelength low level light therapy (“PBM”), in particular to multi-wavelength PBM and other phototherapy systems and methods for improving functionality in and / or restoring functionality to a cell and / or tissue through the coordinated and targeted delivery to the cell or tissue of two or more doses of light having distinct wavelengths, wherein the two or more doses of light, when delivered in a coordinated fashion, can stimulate the activity of two or more light sensitive factors that, when activated, provide and / or enhance a desired target cell functionality. Ophthalmic phototherapy devices, systems, and treatment methods to expose an eye to selected multi-wavelengths of light to promote the healing of damaged or diseased eye tissue. The devices include a housing having an interior; an eyepiece disposed on the housing and configured and arranged for placement of an eye of the patient adjacent the eyepiece; a first light source producing a first light beam having a first therapeutic wavelength and disposed within the housing; a second light source producing a second light beam having a second therapeutic wavelength and disposed within the housing, where the second therapeutic wavelength differs from the first therapeutic wavelength by at least 25 nm.

The present invention provides a method and a kit for detecting a target nucleic acid to be detected by using a melting curve. The method includes designing a first primer, a second primer and a detection probe for the target nucleic acid sequence to be detected, performing PCR amplification in a PCR amplification system containing the first primer, the second primer, the detection probe, the sample to be detected, a nicking enzyme and a DNA polymerase, generating a reporter primer that is complementary to the detection probe to form a double-stranded product, obtaining the melting curve of the double-stranded product, and the melting curve of the double-stranded product is the melting curve corresponding to the target nucleic acid to be detected. The method of the present invention is a non-target-dependent melting curve method, and the melting point (T m value) of each double-stranded body can be calculated in advance, solving the problems of melting curve peak shift and easy misjudgment caused by the easy mutation of the target nucleic acid sequence to be detected.

The present disclosure relates to systems, devices, and methods for electroporating. In an embodiment, the present disclosure relates to an electroporation system, comprising at least one electroporation chamber, each electroporation chamber comprising a first electrode and a second electrode, a plurality of ports comprising an inlet port at a first portion of each electroporation chamber, and an outlet port at a second portion of each electroporation chamber, a fluid conduit arranged between the first electrode and the second electrode, the fluid conduit being in fluid communication with the inlet port and the outlet port, and an automated system for electroporation operatively connected to the first electrode and the second electrode of the at least one electroporation chamber.

The present invention provides a method and a kit for detecting a target nucleic acid to be detected through a melting curve. The method includes designing a first primer, a second primer and a detection probe for the target nucleic acid sequence to be detected, performing PCR amplification in a PCR amplification system containing the first primer, the second primer, the detection probe, the sample to be detected, a restriction endonuclease and a DNA polymerase, generating a reporter primer that is complementary to and pairs with the detection probe to form a double-stranded product, obtaining the melting curve of the double-stranded product, and the melting curve of the double-stranded product is the melting curve corresponding to the target nucleic acid to be detected. The method of the present invention is a non-target-dependent melting curve method, and the melting point (T m value) of each double-stranded body can be calculated in advance, solving the problems of melting curve peak shift and easy misjudgment caused by easy mutation of the target nucleic acid sequence to be detected.

The invention belongs to the technical field of hydrogel, and relates to piezoelectric / conductive integrated hydrogel for jaw defect repair, which is prepared from methylacryloyl protein, zwitterionic monomer and titanate piezoelectric particles through ultraviolet crosslinking under the action of a crosslinking agent and a photoinitiator, the hydrogel comprises, by mass, 1.0%-10% of methacrylated protein, 1.0%-10% of zwitterionic monomers, 1.0%-10% of titanate piezoelectric particles and 0.1%-5% of an initiator, and the volume fraction of an accelerant is 0.05%-1.0%. The hydrogel disclosed by the invention has excellent mechanical strength and certain flexibility, can realize piezoelectric and conductive functions of the hydrogel, can effectively promote proliferation, differentiation and mineralization of bone cells under the action of an electric field, accelerates bone tissue repair, and has a more remarkable bone regeneration effect compared with a non-electrical stimulation material in the prior art.

The invention provides a preparation method of mitochondria-targeted antioxidant hybrid vesicles. The preparation method comprises the following steps: S1, preparing and separating adipose-derived stem cell nano-vesicles; s2, preparing a liposome loaded with dihydromyricetin and distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000-triphenylphosphine targeting peptide by an ethanol injection method; and S3, preparing the hybrid nano vesicles loaded with the dihydromyricetin and the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000-triphenylphosphine targeting peptide. The invention also provides the hybrid vesicles prepared by the method and application of the hybrid vesicles in preparation of refractory diabetes wound treatment drugs. The lipidosome and the adipose-derived stem cell nano-vesicles are hybridized to prepare the hybridized vesicles capable of targeting mitochondria and resisting oxidation, the hybridized vesicles are applied to wound treatment for the first time, the problem of oxidative stress of diabetic wounds is solved, wound healing is accelerated, and a new strategy is provided for optimizing mitochondrial function defects and oxidative stress of the diabetic wounds.

The invention discloses a method for promoting dissolution of eggshell membrane protein and preparing chelated calcium through high-pressure crushing. Comprising the following steps: separating and drying eggshells and eggshell membranes of egg shells, and respectively carrying out superfine grinding to obtain eggshell powder and eggshell membrane powder; adding water into the eggshell membrane powder, carrying out high-pressure homogenization, and centrifuging to obtain an eggshell membrane solution; adding eggshell powder into the eggshell membrane solution, adjusting the pH value to 1-3, and adding pepsase for reaction; after the reaction, adjusting the pH value of the eggshell membrane solution to 6.5-7.5, and adding trypsin for reaction; and after the reaction, inactivating the enzyme, centrifuging to take a supernatant, adding absolute ethyl alcohol into the supernatant for alcohol precipitation, and centrifuging to obtain a precipitate, namely the chelated calcium. The technical problem that the eggshell membrane protein is difficult to dissolve out is solved, and a new way is provided for industrial extraction of the eggshell membrane soluble protein.

The invention discloses an arginine decarboxylase diaA enzyme mutant and application thereof in preparation of butanediamine, and belongs to the field of bioengineering. According to the invention, rational charge overturning transformation is simultaneously carried out on a pentamer meridian oligomeric interface and a dimer latitudinal oligomeric interface, so that stable assembly and efficient catalysis of the decamer under the condition of neutral to alkaline pH (7.0-9.0) are realized. Wherein positive charges are introduced into a meridian interface to weaken electrostatic repulsion, and negative charges are introduced into a latitudinal interface to enhance dimer compactness and substrate transfer efficiency. The specific enzyme activity of the representative double mutant AdiAD110K / H736E at pH 8.0 is about 35 times that of a wild type, and the representative double mutant AdiAD110K / H736E keeps a complete decamer state in a pH range of 7.0-9.0. The yield of butanediamine is up to 145.9 g / L under the whole-cell catalysis of the mutant.

The invention discloses an electrical stimulation type nerve regeneration method based on calcium signal regulation and control, and relates to the technical field of electrical stimulation type nerve regeneration, and the method comprises the following steps: based on a Schwann cell population calcium signal response feature set, identifying whether the calcium ion concentration is in a microliter stage which breaks through a lowest activation threshold and does not reach a stable state; judging whether the target nervous tissue is in a calcium signal activation critical state or not based on the behavior mode change of the Schwann cell population; based on the judgment result of the calcium signal activation critical state, an electrical stimulation adjustment control instruction is generated in real time in combination with the calcium ion concentration fluctuation trend and Schwann cell population response characteristics, and the calcium ion concentration stability is optimized and the activation state is maintained by adjusting the electrical stimulation intensity, the electrical stimulation pulse width, the electrical stimulation waveform type and the electrical stimulation application time sequence. According to the method, the problem that a calcium signal is difficult to recognize and dynamically optimize in a microliter stage is solved, and precise maintenance of Schwann cell activation and improvement of nerve regeneration efficiency are realized.

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.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Provided herein are methods of performing multiplex detection of ligand binding kinetics. In some embodiments, the methods include contacting ligands with an array of nucleic acid barcoded oscillators disposed on a first surface of a substrate that comprises an electrically conductive coating, applying an AC electric field to the substrate sufficient to induce the nucleic acid barcoded oscillators to oscillate proximal to the first surface of the substrate, and detecting changes in oscillation amplitudes of the nucleic acid barcoded oscillators over a duration to produce sets of ligand binding data. In some embodiments, the methods also include contacting barcode decoding nucleic acids with the array of nucleic acid barcoded oscillators applying an AC electric field to the substrate sufficient to induce the nucleic acid barcoded oscillators to oscillate proximal to the first surface of the substrate, and detecting changes in oscillation amplitudes of the nucleic acid barcoded oscillators over a duration to produce sets of barcode decoding data.

The invention belongs to the technical field of biomedical materials, and particularly relates to adipose-derived mesenchymal stem cell loaded conductive hydrogel and a preparation method and application thereof, the preparation method comprises the following steps: step S1, after hyaluronic acid is subjected to oxidation treatment, dopamine is grafted to oxidized hyaluronic acid, and oxidized hyaluronic acid-dopamine is obtained; step S2, carrying out amination treatment on gelatin to obtain aminated gelatin; s3, mixing the oxidized hyaluronic acid-dopamine with the aminated gelatin, and carrying out Schiff base crosslinking, so as to obtain hydrogel; and step S4, loading the adipose tissue-derived stromal cells by using the hydrogel. Dopamine is grafted on an oxidized hyaluronic acid macromolecular chain through amidation reaction, the hydrophilicity and the electrical property of the macromolecular chain are improved, a catechol structure is provided to provide possibility for iron ion coordination, the tissue adhesion, the injectability, the mechanical property and the electrical conductivity of the hydrogel are improved, and the hydrogel can be applied to the field of biomedical materials. After being applied to a spinal cord injury rat model, the functional recovery can be promoted.

The invention is based, at least in part, on the discovery that replacement of a key bond in the near-infrared fluorophore with a carbon-carbon bond conjugation to a targeting ligand results in vastly increased stability as compared to NIR fluorophores without such a bond, while preserving ligand and zwitterionic properties. In at least one aspect, the invention provides an imaging agent dye comprising a charge-balanced imaging agent conjugated to a targeting vector, wherein the targeting vector is a PSMA binding vector, such as dPSMA-617 or KUE, a FAP binding vector, a bombesin receptor binding vector, or a somatostatin receptor binding vector, and the charge-balanced imaging agent is ZW-800-1, ZW-830-1, or ZW-700-1-Forte.

The disclosure provides technologies that permit detection and / or characterization of brain biomarkers (e.g., disease-associated biomarkers) in non-CNS samples, including by liquid biopsy (e.g., blood, serum, etc.). Among other things, the present disclosure demonstrates that ultrasound opening of the blood brain barrier can achieve detectable increases in brain-derived materials (e.g., brain-derived proteins, neuron-derived extracellular vesicles, and / or cell-free DNA) in readily-sampled systemic liquids.

The invention discloses a rational copolymerization strategy for improving the stability of an oligomeric structure of acid-induced high-order oligomeric decarboxylase AdiA in a neutral to alkaline environment and application of the rational copolymerization strategy, and belongs to the field of bioengineering. According to the strategy, rational charge overturning transformation is carried out on a pentamer radial oligomeric interface and a dimer weft-wise oligomeric interface at the same time, and stable assembly and efficient catalysis of a decamer under the condition that the pH value is from 7.0 to 9.0 from neutral to alkaline are achieved. Wherein positive charges are introduced into a meridian interface to weaken electrostatic repulsion, and negative charges are introduced into a latitudinal interface to enhance dimer compactness and substrate transfer efficiency. The specific enzyme activity of the representative double mutant AdiAD471K / E467K / H736E is 45.5 times that of a wild type when the pH value is 8.0, and the representative double mutant AdiAD471K / E467K / H736E keeps a complete decamer state when the pH value is 7.0-9.0. The yield of butanediamine is up to 156.5 g / L by using the mutant to catalyze whole cells.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.