123results about How to "Reduce phototoxicity" patented technology

In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest.

Compounds and compositions of said compounds along with methods of use of compounds are disclosed for treating ophthalmic conditions related to mislocalization of opsin proteins, the misfolding of mutant opsin proteins and the production of toxic visual cycle products that accumulate in the eye. Compounds and compositions useful in the these methods, either alone or in combination with other therapeutic agents, are also described.

The invention provides a fluorescent probe represented by the formula (I), wherein R1 and R2 are independently selected from H or an aromatic vinyl group, and at least one of R1 and R2 is the aromatic vinyl group; R3 is selected from H, F, Cl, Br, OH, OCH3, N(CH3)2 or C1-C6 alkyl; and R4 is selected from C1-C6 alkyl. Compared with the prior art, because the fluorescent probe provided by the invention has a relatively large electronic conjugated system and plane, the intensity of the intramolecular charge transfer effect can affect the molecular fluorescence emission intensity; when the fluorescent probe and the G-quadruplex generate a specific action, the flexibility of intramolecular rotatable double bonds is restricted, the intramolecular charge transfer effect is enhanced, and the fluorescence is also enhanced significantly; moreover, the fluorescent probe provided by the invention has the advantages of low biotoxicity, phototoxicity and photobleaching property, good light stability, good water solubility and good cell membrane permeability.

The invention discloses a fluorescent probe, a preparation method thereof and an application of the fluorescent probe for detecting a nucleic acid G-quadruplex structure. The probe is provided with a structure in a general formula (I) is simple and stable in structure and easy to prepare. The probe can be used for specific detection of a nucleic acid G-quadruplex secondary structure, and the G-quadruplex secondary structure in solution can be rapidly detected by a fluorescence spectrometer or direct visual inspection under irradiation of a fluorescent lamp. The probe can be used for detecting the nucleic acid G-quadruplex structure in agarose gel or polyacrylamide gel and can also be used for detecting, marking or displaying existence or distribution of the G-quadruplex structure in living cells. Fluorescent materials have efficient and specific recognition capability for the nucleic acid G-quadruplex structure, have the advantages of excellent cell membrane permeability, low photo-induced toxicity, biological toxicity and photo-bleaching performance and the like, and overcome the shortcomings of high cost, high equipment requirement, complicated technical operation and the like in other detection methods.

The invention relates to a manufacture method for an anti-ultraviolet nanometer zinc oxide compound powder. It includes the following steps: mixing nanometer zinc oxide powder with dispersing agent, and deionized water; using silicate as raw material, by controlling the pH value of reacting liquid, taking silicon dioxide surface modification; taking organic modification to the surface, after washing and drying, the nanometer zinc oxide compound powder would be gained. The invention has the advantages of simple technology, low cost, strong repeatability, etc. It has bright application prospect.

The invention discloses a super-resolution fluorescence microscopic apparatus based on photoactivation and structured light illumination. The apparatus comprises a light source module having a first laser for fluorescence activation, a second laser for fluorescence excitation, and a frequency selection switching module for switching between the two lasers; a regulation unit for regulating a light beam output from the light source module to two beams of p polarized light and two beams of s polarized light capable of interference and for changing the interference phase difference of the two groups of light beams; a dichroic mirror, on the surface of which interference fringes are formed via the two beams of p polarized light and two beams of s polarized light, and which reflects a mesh structured light illumination comprising bright spots and dark spots in array distribution and taken as an irradiation sample; and an imaging unit comprising a converging module for changing the spacing between interference fringes, a microobjective projecting a light beam emerging from the converging module to the microobjective of a sample, and a camera for conducting stimulated radiation fluorescence imaging of the sample. The invention further discloses a super-resolution fluorescence microscopic method based on photoactivation and structured light illumination.

A surgical microscope (1) for ophthalmology includes a tube unit (4) which permits viewing an area (5) of surgery, especially a forward section of the eye, through a microscope main objective (2). The surgical microscope (1) includes an illuminating system (10) which makes available the illuminating light to illuminate the surgical area (5), especially the forward section of the eye. To provide daylight-like illuminating light, the illuminating system includes a xenon illuminating light source (11) or a metal halogen illuminating light source. At least one interference filter (22, 23) is provided in the illuminating beam path (15a). The cutoff frequency of the interference filter lies such that illuminating light in the ultraviolet range is filtered out and illuminating light in the visible wavelength range is attenuated, if at all, to an insignificant extent in order to reduce the phototoxicity of the illuminating light for the human eye.

The invention discloses a bilateral biotin-phthalocyanine zinc conjugate as well as preparation and application thereof. According to the conjugate disclosed by the invention, a biotin-cell growth-promoting factor (which is a critical micronutrient for cells to maintain normal functions, growth and reproduction) is used as a tumor target and is covalently connected onto a phthalocyanine zinc photosensitizer capable of being used for a photodynamic therapy, thus obtaining a third-generation anti-cancer photosensitizer for targeted therapy. Meanwhile, according to the conjugate, the biotin instead of a phthalocyanine zinc derivative acts a research object, human breast cancer cell MCF-7 and human embryo lung inoblast HELF act as subject cell lines respectively, a research regarding the in-vitro anti-cancer activity of the biotin is developed, and a prodrug suitable for a molecular targeted therapy is screened out, and a foundation is laid for applying the biotin instead of the phthalocyanine zinc derivative to the targeted therapy of cancers. The compound, namely the conjugate disclosed by the invention, is relatively simple in synthesis method, easily available in raw materials, low in cost, fewer in side reactions, relatively high in yield, easy to purify and beneficial for industrial production.

The invention relates to a near infrared fluorescence probe adopting nile blue as a parent, a preparation method thereof and applications thereof. The fluorescence probe has a structure shown as the general formula I as the attached drawing 1. The fluorescence probe can effectively improve deficiencies of tumor labeling fluorescence probes at present, can sensitively and accurately response to target cells COX-2 expression amount of which is abnormal, and is suitable for effective specific near infrared fluorescence probes labeling living tumor cells. The fluorescence probe provided by the invention is simple in synthesis and products are easy to obtain. The fluorescence probe provided by the invention has a very low fluorescence background in non-tumor cells and high fluorescence signals in tumor cells, and has strong specific labeling function for tumor cells. In addition, compounds of the type have good cell membrane permeability, low biotoxicity, low phototoxicity and low photobleaching capability and can locate a special organelle of a certain kind tumor cell.

The invention discloses a high-speed large-view-field digital scanning light sheet microscopic imaging system. The system comprises a light source module, a transverse view field expansion module, a scanning module, an illumination module and a detection module which are sequentially arranged according to a light path, light generated by the light source module passes through the transverse view field expansion module to obtain an effective view field for expanding a final illumination area. The scanning module scans a line beam received from the transverse view field expansion module into a surface beam, the illumination module performs fluorescence excitation by adopting a beam splitter, a first illumination objective lens and a second illumination objective lens, and the detection module realizes fluorescence detection imaging by adopting a line detector. The axial resolution is improved, the influence of phototoxicity and photobleaching on a sample is reduced, the imaging has higher resolution and contrast ratio by using the linear array detector, the imaging speed is higher, and the cost of the detector is saved.

The invention discloses a preparation method of targeted ferroferric oxide-porphyrin containing composite nanoparticles, and relates to a preparation method of composite nanoparticles. The preparation method disclosed by the invention aims at solving the problems that a photosensitizer is high in accumulation effect within normal tissues and even performs a photochemical reaction under a dark light because a photosensitizer fluorescence signal is low in intensity and low in selective uptake for tumour tissues, existing in photodynamic diagnosis and therapy. The method comprises the following steps: 1, preparing magnetic ferroferric oxide nanoparticles coated by silicon dioxide; 2, preparing a porphyrin compound; 3, preparing a porphyrin compound bound by a silane reagent; 4, preparing a porphyrin-folic acid compound; and 5, preparing the targeted ferroferric oxide-porphyrin containing composite nanoparticles. The preparation method based on the magnetic ferroferric oxide-porphyrin composite nanoparticles and disclosed by the invention integrates magnetofluid thermal therapy, magnetic targeting and photodynamic therapy as a therapy means for tumours. The preparation method disclosed by the invention is used for preparing the targeted ferroferric oxide-porphyrin containing composite nanoparticles.

Use of a biocompatible dye, for example patent blue V or brilliant blue R, for the production of a dye agent for non-cytotoxic visualisation of cells, in particular delimiting or separating membranes in the human or animal body, in particular in the eye.

Methods for evaluating micrometastases in a tissue region of a subject are described. The methods include administering to the subject a detectably effective amount of a tumor-targeted photoactivatable immunoconjugate; allowing a sufficient amount of time for the tumor-targeted photoactivatable immunoconjugate to enter micrometastases in the tissue region; illuminating the tumor-targeted photoactivatable immunoconjugate; obtaining an image of the tissue region of the subject using a fluorescent imaging device, and evaluating the micrometastases in the tissue region by conducting algorithmic analysis of the image. Methods of treating micrometastases in a tissue region of a subject are also described.

The invention provides a pH-sensitive conjugate with a high signal activation effect, micelle, and a preparation method and application thereof. The pH-sensitive conjugate comprises a hydrophilic chain segment and a hydrophobic chain segment, wherein the hydrophilic chain segment is mainly a strongly hydrophilic polymer such as polyethylene glycol, and the hydrophobic chain segment is a polyalkylaminoacrylate having a tertiary amino structure as shown in the formula 1, wherein each symbol is as defined in the specification. The hydrophobic chain segment contains marker molecules. By modifyingthe hydrophobic chain segment of the polymer with the marker molecules, the pH response activation of photodynamic effect can be realized and the phototoxicity to normal tissues can be reduced. In addition, the invention also provides the application of the pH-sensitive conjugate and micelle in photodynamic therapy of tumors, skin diseases and ophthalmic diseases and in combination with photothermal therapy, chemotherapy and immunotherapy.

The invention provides a composite sound sensitizer. The composite sound sensitizer includes a matrix and an organic sound sensitizer body loaded on the matrix, and the matrix refers to manganese dioxide. The invention further provides a preparation method of the composite sound sensitizer. The composite sound sensitizer has the advantages of low phototoxicity, high bioavailability, high tumor enrichment and the like.

The invention provides a sonodynamic liposomal material, a preparation method and an application thereof in preparing pharmorubicin composite liposomal. The liposomal material comprises 10-40mg of lecithin, 10mg of cholesterol, 5mg of chlorin, 3-5mL of saline citrate buffer solution of which the pH is 4-5 and 0.1-1mL of surfactant. The sonodynamic liposomal material mainly relates to the composite liposomal of pharmorubicin and sonochemical agent chlorin. The preparation method comprises the following steps of: combining the pharmorubicin and the chlorin into the lecithin with a film dispersion method-pH gradient method to form the composite liposomal; and better targeting the pharmorubicin composite liposomal into a tumor tissue to dually kill a tumor cell. The sonodynamic liposomal material is used for treating various tumors and has a good development prospect.

The present invention provides a compound represented by the following formula (I): wherein: Ring A represents an optionally substituted piperazine ring, an optionally substituted morpholine ring, or an optionally substituted bromopiperazine ring; R1 and R2 are the same or different from each other, and represent a hydrogen atom or optionally substituted lower alkyl; R3 and R4 are the same or different from each other, and represent a hydrogen atom or halogenated or non-halogenated lower alkyl; R3 to R7 are the same or different from each other, and represent a hydrogen atom, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted cycloakyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic ring, optionally substituted amino, or acyl; and represents a single bond or double bond, wherein R2 and R3 do not exist when carbon atoms respectively adjacent to R2: and R3 form a double bond, and there is no case where all of R1 to R7 are hydrogen atoms, and R1 and R2; may form a ring together with an adjacent carbon atom; or a salt thereof.

The invention belongs to the field of nanobiomedicine diagnosis and treatment, and mainly relates to preparation of an organic / inorganic composite nano material system with high biocompatibility and application of the organic / inorganic composite nano material system in biological two-photon imaging and dual photosensitization dynamic therapy. According to the preparation disclosed by the invention, by adoption of an supramolecular self-assembling driver of a metal porphin complex, a functional metal-organic framework material ZnTPyP-MOF, so that the physical and chemical characteristics of an original assembling molecule ZnTPyP are retained, and the original assembling molecule ZnTPyP is endowed with new optical and structural characteristics. The MOF is used as a kernel for growing titanium oxide serving as a shell coated with a layer of polylysine, thus obtaining a high-performance two-photon diagnosis and treatment nano biological probe. The nano probe is high in biological safety and dispersity; and the ZnTPyP-MOF is high in two-photon absorption and fluorescence emission performance and realizes the photosensitization dynamic therapy under activation of two photons. The organic / inorganic composite nano material system can be widely applied to in-situ fluorescence diagnosis and treatment of various diseases, particularly the cancer, and has very important in clinical medicine.

Provided is a head-mounted micro light sheet microscope. A probe emits a light sheet to excite an object to be measured, and collects a fluorescence signal produced by the object to be measured according to an emitted light sheet signal to obtain the fluorescence imaging information of the object to be measured. The imaging probe can be fixed to the head of a free moving animal. The object to be measured is excited by the light sheet, and fluorescence is collected in a direction perpendicular to the light sheet to carry out imaging. Light sheet scanning is used to replace the point scanning imaging mode featuring slow imaging. During excitation of the object to be measured, the light sheet has good optical layer selection capability and large excitation area. Therefore, the imaging speed and the signal-to-noise ratio are improved, and the light toxicity is reduced. The head-mounted micro light sheet microscope is suitable for long-time living imaging. A high-contrast image can be obtained. Real-time imaging of the brain of a free moving animal is realized.

A 1,4-dihydroxy-6-methyl-2-pyridone compound having structural formula (I), and a preparation method and application thereof are provided. The compound has good antibacterial activity in vitro against bacteria such as staphylococcus aureus, streptococcus, Escherichia coli, and has a stronger antibacterial activity against Gram-positive bacteria than against Gram-negative bacteria; and also has good antibacterial activity against fungi such as Candida albicans and Candida Krusei, so that the compound can be used as a drug for preventing and curing bacterial and fungal infections.

The invention relates to a production process of refined petroleum emulsion in water and belongs to the field of pesticide manufacturing process. The refined petroleum emulsion in water is made from refined petroleum, film-forming agent, emulsifiers, plant nutrients, defoaming agent, stabilizers, antifreezing agent and deionized water, by uniform dispersion using a high-speed shear mixing emulsifier. The refined petroleum emulsion is innoxious and non-irritant or low-toxic or low-irritant to animals and human beings, is harmless to crops, has environmental affinity, enhances the resistance of crops, and can promote the growth of crops. The refined petroleum emulsion can kill main insect pests, regulate the growth of crops, enhance resistance to cold and diseases and increase the yield of crops. The invention has the advantages of use of water as solvent, reduced waste of resources, no discharge of three wastes, environmental friendliness, scientific formulation, advanced process, low cost and good effect.

Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and / or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, coumarins, cyanines, bimanes, and difluoroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer. The rate of electron transfer, fluorescence intensity, and quenching are altered in response to changes in transmembrane potential.

The invention discloses an application of near infrared bioluminescence dye to living cell imaging; living cell imaging using near infrared bioluminescence dye is completed by the steps of cell culture, dye solution preparation, dyeing and imaging; the invention employs near infrared bioluminescence dye, thereby minimizing damages of cells and tissues caused by light source, and reducing interference of autofluorescence with more thorough dyeing; the near infrared fluorescence dye has specificity for mitochondrial or RNA.

The invention discloses a nano sunscreen agent, a preparation method, and an application thereof. The nano sunscreen agent includes a zeolite imidazate framework structure material and an organic sunscreen agent which is sealed in the framework material. The zeolite imidazate framework structure material coats the surface of the organic sunscreen agent. The nano sunscreen agent has gentle synthesis conditions and short reaction time, can effectively inhibit contact between the organic sunscreen agent and skin and reduce direct contact between the organic sunscreen agent and an active oxygen substance, ROS, generated after photo-activation and skin, so that a series of phototoxicities caused by transdermal absorption of the nano sunscreen agent is prevented. The product is a novel nano sunscreen agent material.

A fluorescence microscopy method includes a trained deep neural network. At least one 2D fluorescence microscopy image of a sample is input to the trained deep neural network, wherein the input image(s) is appended with a digital propagation matrix (DPM) that represents, pixel-by-pixel, an axial distance of a user-defined or automatically generated surface within the sample from a plane of the input image. The trained deep neural network outputs fluorescence output image(s) of the sample that is digitally propagated or refocused to the user-defined surface or automatically generated. The method and system cross-connects different imaging modalities, permitting 3D propagation of wide-field fluorescence image(s) to match confocal microscopy images at different sample planes. The method may be used to output a time sequence of images (e.g., time-lapse video) of a 2D or 3D surface within a sample.

The invention discloses a super-resolution imaging method and system by utilizing square lattice structure light illumination, and the method mainly comprises the following steps: forming a lattice structure light field on a sample plane, and carrying out the phase shift through controlling a light field modulation device; acquiring a fluorescence image illuminated by the lattice structure light;and utilizing a frequency domain reconstruction algorithm to obtain a super-resolution image. Compared with common striped structured light, the square lattice structure light has lower light dose under the same peak intensity, the phototoxicity of the system can be greatly reduced, living cells can be observed for a longer time, and in addition, only phase shift needs to be carried out on the illumination pattern in the imaging process without rotation, so that polarization control in the imaging process is simplified to a great extent, the complexity of the system can be reduced, and the construction cost of the system is effectively reduced.

The invention discloses a method for testing photodynamic therapy assisted by operative treatment on mouse mammary tumor cells. The method comprises the following steps: preparing a fluorescent nanoparticle solution; culturing the mouse mammary tumor cells; inoculating the mouse mammary tumor cells at oxter of mice of 6 weeks; two weeks later, dividing the mice into a control group, a mere exairesis group, a mere photodynamic therapy group and an exairesis and photodynamic therapy group; killing residue tumor with operation together with photodynamic therapy, namely, 12 hours before operation, injecting the prepared fluorescent nanoparticle solution into the mice of different groups, irradiating with white light for 15 minutes, and respectively monitoring sizes of tumor; after confirming that the tumor of the experiment groups is eliminated, inoculating same tumor cells at backs of the mice of different groups, and continuously monitoring development of the tumor inoculated later. The method has the advantages that a photosensitizer with a property of aggregation-induced emission, and exairesis, are combined, and the defects of radical cure limit, slow treatment and postoperative recurrence of a conventional method can be solved.

The invention provides a composite nanomaterial of organic naphthalene and inorganic phosphate, and the composite nanomaterial has the structure of general formula I shown in the description. The composite nanomaterial can perform identification, adsorption, clearance and transport of the heavy metal in the living cell, and can show obvious different identification signals in the adsorption process of the heavy metal in the living cell. The material has a certain level of water solubility, has good membrane permeability, and has low biotoxicity, phototoxicity, and photobleaching property. The spectral region of the material has enough large difference with the spectral region of the biological sample.