Vascular intervention diagnosis and treatment device and system, and use thereof

Abstract

Disclosed in the present invention are a vascular intervention diagnosis and treatment device and system, and a use thereof. The vascular intervention diagnosis and treatment device comprises a main body frame, a conductive material layer, and a flexible insulating packaging layer; the main body frame is an elastic support frame; and the conductive material layer is arranged on the main body frame and is configured to form an electrode and a wire. A conductive material layer is arranged on a deformable main body frame and is configured to form an electrode and a wire, so that the electrode and the wire are of an integrated structure, the structure is simple, and the stability is high, and thus the electrode and the wire are not prone to disconnect when subjected to long-term blood flow scouring in blood vessels.

Description

A vascular interventional diagnosis and treatment device, system and application thereof Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a vascular interventional diagnosis and treatment device, system and application thereof. Background Art

[0002] Each organ in the human body is supplied with blood by arteries, which provide oxygen and nutrients to the tissues. The blood then flows back to the heart (atrium) through the veins. If the arterial stenosis reaches a certain degree due to various reasons, tissue and organ ischemia and hypoxia may occur, and even tissue remodeling, damage, and necrosis may occur, resulting in ischemic diseases of various organs (such as coronary artery ischemia causing coronary heart disease). In recent years, with the improvement of technology, methods, hardware, and equipment, vascular interventional diagnosis and treatment has become an increasingly important means in the medical field. It includes interventional diagnosis and treatment of coronary heart disease, renal artery interventional diagnosis and treatment, carotid artery interventional diagnosis and treatment, aortic interventional diagnosis and treatment, and upper and lower limb artery interventional diagnosis and treatment. Existing vascular interventional diagnosis and treatment devices generally include an internal stent, and an electrode sheet is fixed on the internal stent. Then, a thin wire is connected to the electrode sheet by resistance welding and led to a telemetry circuit, thereby realizing the transmission of electrical signals between the intravascular and external circuits to realize the detection of relevant health information. However, since the above-mentioned diagnosis and treatment devices need to intervene in the blood vessels, their size design is small, and the structural stability must be guaranteed during the intervention process and after implantation while minimizing blood flow obstruction. However, the structural stability of existing vascular interventional diagnostic and treatment devices still needs to be improved. For example, the welded joints between the electrodes and thin wires in these devices are easily broken due to the thin wires and the long-term exposure to blood flow. Therefore, there is an urgent need to find a vascular interventional diagnostic and treatment device with strong structural stability.

[0003] Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides a vascular interventional diagnosis and treatment device, system and application thereof.

[0005] A first aspect of the present invention provides a vascular interventional diagnostic and treatment device, comprising:

[0006] A main frame, wherein the main frame is an elastic support frame;

[0007] The conductive material layer is disposed on the main frame and is configured to form electrodes and wires.

[0008] According to the embodiment of the present invention, the vascular interventional diagnosis and treatment device has at least the following beneficial effects: the vascular interventional diagnosis and treatment device arranges a conductive material layer on the elastic main body support frame to configure electrodes and wires, so that the electrodes and wires are an integrated structure with a simple structure and strong stability. It can withstand long-term blood flow erosion in the blood vessel and is not easy to break.

[0009] In some embodiments of the present invention, the main frame is configured to be contractible and expandable along a central axis.

[0010] In some embodiments of the present invention, the main frame is in the shape of a hollow tube.

[0011] In some embodiments of the present invention, the side walls of the main frame are in a mesh structure.

[0012] In some embodiments of the present invention, the electrodes are provided at intersections of the mesh structures on the main frame.

[0013] In some embodiments of the present invention, there are two or more electrodes.

[0014] In some embodiments of the present invention, the electrodes are evenly distributed along the radial direction and / or the axial direction of the main frame.

[0015] In some embodiments of the present invention, the area on the main frame corresponding to the electrode arrangement position constitutes an electrode assembly portion, and the outer contour size of the electrode assembly portion is equal to or greater than the outer contour size of the electrode.

[0016] In some embodiments of the present invention, the electrode assembly portion is provided with an electrode assembly groove, and the electrode is assembled in the electrode assembly groove.

[0017] In some embodiments of the present invention, the material of the main frame is selected from degradable polymer materials; or, the material of the main frame is selected from at least one of shape memory alloys and iron, and a dielectric layer is provided between the main frame and the conductive material layer.

[0018] In some embodiments of the present invention, the material of the dielectric layer is selected from at least one of polyimide (PI), polydimethylsiloxane (PDMS), poly(p-phenylene benzobisoxazole) (PBO), and SU8.

[0019] In some embodiments of the present invention, the shape memory alloy is selected from at least one of Nitinol alloy, cobalt-chromium alloy, and magnesium alloy.

[0020] In some embodiments of the present invention, the electrodes and the wires in the conductive material layer are integrated into one structure.

[0021] In some embodiments of the present invention, the conductive material layer is a metal material layer, a non-metallic conductive material layer, or a composite layer of a non-metallic conductive material layer and a metal material layer.

[0022] In some embodiments of the present invention, the conductive material layer includes a non-precious metal conductive base layer and a precious metal protective layer, and the precious metal protective layer covers the non-precious metal conductive base layer; the non-precious metal conductive base layer is arranged on the surface of the main frame, and the material of the precious metal protective layer is selected from at least one of platinum and gold.

[0023] In some embodiments of the present invention, the thickness of the conductive material layer is less than 5 μm.

[0024] In some embodiments of the present invention, the material of the flexible insulating packaging layer is selected from at least one of polyimide (PI), polydimethylsiloxane (PDMS), poly(p-phenylene benzobisoxazole) (PBO), and SU8.

[0025] In some embodiments of the present invention, the surface of the electrode is provided with a modified layer, which has a biological signal recognition function for identifying and detecting changes in biological signals within blood vessels, and converting the changes in the biological signals into readable electrical signals through the electrode and transmitting them to an external circuit; the biological signals include chemical signals and / or physical signals related to the physiological condition of the organism.

[0026] In some embodiments of the present invention, the material of the modification layer is selected from at least one of enzymes, redox mediators, nanomaterials, antibodies, biotin, nucleic acid aptamers, polymers, ion carriers, and piezoelectric materials.

[0027] In some embodiments of the present invention, the enzyme is selected from at least one of oxidoreductase, transferase, hydrolase, lyase, ligase, and isomerase.

[0028] In some embodiments of the present invention, the oxidoreductase is selected from the group consisting of glucose oxidase, glutamate oxidase, alcohol oxidase, lactate oxidase, amino acid oxidase, cholesterol oxidase, choline oxidase, nicotinamide adenine dinucleotide phosphate oxidase, oxalate oxidase, cytochrome oxidase, bilirubin oxidase, serotoninase, galactose oxidase, glucose dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, aldehyde dehydrogenase, glutamate dehydrogenase, pyruvate dehydrogenase, sorbitol dehydrogenase, formate dehydrogenase, cellobiose dehydrogenase, amino acid dehydrogenase, succinate dehydrogenase, catalase, horseradish peroxidase, lactoperoxidase, glutathione At least one of peptide peroxidase, ascorbate peroxidase, soybean peroxidase, cytochrome peroxidase, thyroid peroxidase, myeloperoxidase, superoxide dismutase, haloperoxidase, thiol peroxidase, 5α-reductase, 5β-reductase, aldehyde reductase, aldose reductase, hydroxymethylglutaryl-CoA reductase, methemoglobin reductase, ribonucleotide reductase, nitroreductase, thioredoxin reductase, dihydrofolate reductase, disulfide reductase, sulfite reductase, cytochrome reductase, imine reductase, fumarate reductase, carboxylic acid reductase, and dimethyl sulfoxide reductase.

[0029] In some embodiments of the present invention, the transferase is selected from at least one of glutathione transferase, acetyltransferase, methyltransferase, transketolase, transaldolase, glycosyltransferase, transketolase, aminoacid transferase, and acyltransferase.

[0030] In some embodiments of the present invention, the hydrolase is selected from at least one of lipase, phosphohydrolase, glycoside hydrolase, acetylhydrolase, nucleotide hydrolase, helicase, peptide hydrolase, urease, and creatinine deiminase.

[0031] In some embodiments of the present invention, the lyase is selected from at least one of a decarboxylase, a dehydrogenase, a dehalogenase, an aspartate ammonia lyase, and a cysteine ​​desulfurase.

[0032] In some embodiments of the present invention, the ligase is at least one selected from tRNA synthetase, succinyl-coenzyme A synthetase, amino acid ligase, DNA ligase, RNA ligase, and carboxylase.

[0033] In some embodiments of the present invention, the isomerase is selected from at least one of a racemase, an epimerase, and a mutase.

[0034] In some embodiments of the present invention, the nanomaterial is selected from at least one of metal nanomaterials, nanoceramics, nanoglass, and nanopolymer materials.

[0035] In some embodiments of the present invention, the antibody is selected from at least one of C-reactive protein antibody, thyrotropin antibody, bilirubin antibody, albumin antibody, carcinoembryonic antigen antibody, alpha-fetoprotein antibody, prostate-specific antigen antibody, cancer antigen 125 antibody, and cortisol antibody.

[0036] In some embodiments of the present invention, the nucleic acid aptamer is selected from at least one of a DNA type oligonucleotide chain and an RNA type oligonucleotide chain.

[0037] In some embodiments of the present invention, the polymer is selected from at least one of polyaniline, polypyrrole, polyacetylene, polycarbazole, polythiophene, polyphenylene methylene, poly(3,4-ethylenedioxythiophene), polystyrene sulfonic acid, chitin, chitosan, polyvinyl chloride, polyvinyl butyral, and Nafion.

[0038] In some embodiments of the present invention, the ion carrier is selected from at least one of potassium ion, sodium ion, calcium ion, magnesium ion, iron ion, zinc ion, manganese ion, copper ion, molybdenum ion, cobalt ion, cobalt ion, chromium ion, chloride ion, sulfate ion, and phosphate ion.

[0039] In some embodiments of the present invention, the piezoelectric material is selected from at least one of single crystal piezoelectric ceramics, polycrystalline piezoelectric ceramics, piezoelectric polymers, and polymer-piezoelectric ceramic composites.

[0040] In some embodiments of the present invention, the vascular interventional diagnosis and treatment device further includes an insulating packaging layer, which is disposed on the conductive material layer, covers the wires and exposes at least a portion of the electrodes.

[0041] In some embodiments of the present invention, the insulating packaging layer is made of at least one material selected from polyimide, polydimethylsiloxane, poly(p-phenylene benzobisoxazole), and SU8.

[0042] In some embodiments of the present invention, the vascular interventional diagnosis and treatment device further includes a buffer protection component, which is disposed at the implantation front end of the vascular interventional diagnosis and treatment device and is configured to reduce the risk of puncturing a blood vessel during the implantation process of the vascular interventional diagnosis and treatment device.

[0043] In some embodiments of the present invention, the vascular interventional diagnosis and treatment device further includes a delivery component configured to deploy and implant the vascular interventional diagnosis and treatment device into a blood vessel.

[0044] The second aspect of the present invention provides a vascular interventional diagnosis and treatment system, comprising any one of the vascular interventional diagnosis and treatment devices provided in the first aspect of the present invention.

[0045] The third aspect of the present invention proposes the use of any one or more vascular interventional diagnostic and treatment devices in in vitro culturing cell constructs, collecting electrical signals from cell constructs, or electrically stimulating cell constructs. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The present invention will be further described below with reference to the accompanying drawings and embodiments, in which:

[0047] FIG1 is a schematic structural diagram of an embodiment of a vascular interventional diagnosis and treatment device according to the present invention;

[0048] FIG2 is a cross-sectional view along line AA in FIG1 ;

[0049] FIG3 is a partial enlarged view of the M area in FIG2 ;

[0050] FIG4 is a schematic structural diagram of the main frame in FIG1 ;

[0051] FIG5 is a schematic structural diagram of the dielectric layer in FIG1 ;

[0052] FIG6 is a schematic structural diagram of the conductive material layer in FIG1 ;

[0053] FIG7 is a schematic structural diagram of the insulating packaging layer in FIG1 . DETAILED DESCRIPTION

[0054] The following describes embodiments of the present invention in detail. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended only to explain the present invention and are not to be construed as limiting the present invention.

[0055] In the description of the present invention, "several" means more than one, "plurality" means more than two, "greater than," "less than," and "exceed" are understood to exclude the number itself, while "above," "below," and "within" are understood to include the number itself. The use of "first" and "second" in the description is solely for the purpose of distinguishing technical features and should not be construed as indicating or implying relative importance, implicitly specifying the number of the indicated technical features, or implicitly specifying the order of the indicated technical features.

[0056] In the description of the present invention, unless otherwise clearly defined, terms such as setting, installing, and connecting should be understood in a broad sense, and technicians in the relevant technical field can reasonably determine the specific meanings of the above terms in the present invention based on the specific content of the technical solution.

[0057] In the description of the present invention, reference to terms such as "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the exemplary expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0058] Please refer to Figures 1 to 7. Figure 1 shows a schematic structural diagram of an embodiment of a vascular interventional diagnosis and treatment device of the present invention. Figure 2 is a cross-sectional view along line AA in Figure 1. Figure 3 is a partial enlarged view of the M area in Figure 2. Figures 4 to 7 are schematic structural diagrams of the main frame, dielectric layer, conductive material layer and flexible insulating packaging layer in Figure 1, respectively. Specifically, as shown in Figures 1 to 4 and Figures 6 to 7, the vascular interventional diagnosis and treatment device includes a main frame 11, a conductive material layer 13 and an insulating packaging layer 14. Among them, the main frame 11 is an elastic support frame, the conductive material layer 13 is provided on the main frame 11, and is configured to form electrodes 131 and wires 132.

[0059] The vascular interventional diagnosis and treatment device is mainly configured for vascular interventional diagnosis and treatment, and the main frame 11 is generally configured to be able to contract and expand along the central axis, and can contract and expand with the blood vessel in the blood vessel to facilitate implantation into the blood vessel and keep the device in contact with the inner wall of the blood vessel for stable support. Specifically, the main frame 11 can be designed to be a hollow tube, such as a hollow circular tube, a hollow C-shaped tube, etc. Through the above tubular structure and elastic deformable design, the adaptability to the blood vessel can be improved, and the compatibility and detection accuracy can be improved. The diameter of the main frame can be designed to be 1 to 10 mm, the length can be designed to be 10 to 100 mm, and the side wall thickness can be designed to be 10 um to 1 mm. In order to further reduce blood flow obstruction, improve the portability of the device structure and reduce the foreign body and discomfort caused by the device intervention in the organism, the main frame 11 can be designed to have a mesh structure on the side wall; of course, in some embodiments, the side wall can also adopt other hollow structure designs, or even no hollow design. The main frame 11 having a mesh structure or other hollow structure can be formed by first providing a base support layer and then hollowing out the base support layer through laser engraving or etching to form the mesh structure or other hollow structure. Alternatively, the main frame 11 having a mesh structure can be woven from a plurality of main strips. In this embodiment, the main frame 11 is a hollow C-shaped tube with mesh-like sidewalls, as shown in FIG4 .

[0060] In addition, the material of the main frame 11 can be selected as needed, and specifically a deformable material with biocompatibility can be selected. For example, a degradable polymer material can be used, or at least one of a shape memory alloy and iron can be used, wherein the shape memory alloy can specifically be selected from at least one of a nitinol alloy, a cobalt-chromium alloy, and a magnesium alloy. In addition, if the material of the main frame 11 is a conductive material (such as a shape memory alloy, iron, etc.), it is necessary to ensure that the main frame 11 and the conductive material layer 13 are electrically isolated. Therefore, it is generally necessary to provide a dielectric layer 12 between the main frame 11 and the conductive material layer 13 to achieve electrical insulation between the main frame 11 and the conductive material layer 13; and if the material of the main frame 11 is an insulating material, such as an insulating degradable polymer material, then the dielectric layer 12 may not be provided between the main frame 11 and the conductive material layer 13. Among them, the material of the dielectric layer 12 can be selected from at least one of polyimide (PI), polydimethylsiloxane (PDMS), polyparaphenylene benzobisoxazole (PBO), and SU8. In this embodiment, the material of the main frame 11 is selected from Nitinol alloy, and a dielectric layer 12 formed of polyimide is disposed between the main frame 11 and the conductive material layer 13 , as shown in FIG. 1 to 3 and FIG. 5 .

[0061] The conductive material layer 13 is specifically provided on the dielectric layer 12 provided on the surface of the main frame 11 or on the main frame 11 composed of insulating material, and its thickness is generally less than 5 μm. The conductive material layer 13 can be provided on the inner side or the outer side of the main frame 11, and can be provided specifically according to the detection needs. For example, if the target detection object of the vascular interventional diagnosis and treatment device is blood, the conductive material layer 13 can be provided on the inner side of the main frame 11; if the target detection or action object of the vascular interventional diagnosis and treatment device is blood vessels or vascular wall cells, such as the vascular interventional diagnosis and treatment device is used to electrically stimulate vascular wall cells, the conductive material layer 13 can be provided on the outer side of the main frame 11. The conductive material layer 13 generally adopts a biocompatible conductive material, including a metal material and / or a non-metallic conductive material. For example, the conductive material layer 13 can be a metal material layer, a non-metallic conductive material layer, or a composite layer of a non-metallic conductive material layer and a metal material layer. Furthermore, to ensure biocompatibility, the metal material layer generally uses a precious metal material, such as platinum or gold. The non-metallic conductive material layer also generally uses a biocompatible non-metallic conductive material, with no specific limitation on the type. If the conductive material layer 13 is a composite of a non-metallic conductive material layer and a metal material layer, and the metal material layer is coated on the outer layer of the non-metallic conductive material layer to isolate and block the non-metallic conductive material layer, the non-metallic conductive material layer may not even be required to be biocompatible, and only the outermost metal material layer needs to be a biocompatible metal material, such as platinum or gold. To save costs or enhance conductivity, the conductive material layer 13 can be designed to be composed of a non-precious metal conductive base layer and a precious metal protective layer covering the non-precious metal conductive base layer. The non-precious metal conductive base layer can be a non-metallic conductive material and / or a non-precious metal-like metal material, such as a non-metallic conductive base layer or a non-precious metal-like metal conductive base layer. The precious metal protective layer can be made of at least one of platinum and gold. The metal material layer can be made by at least one of sputtering, evaporation, and chemical vapor deposition. The metal material layer made by the above methods has good uniformity and strong adhesion stability, which can improve the stability of the structure.

[0062] As shown in FIG6 , the conductive material layer 13 is configured to form electrodes 131 and wires 132, and the electrodes 131 and wires 132 are an integrated structure. During the preparation process, the corresponding conductive material can be first configured to form a conductive material base layer, and then the electrodes 131 and wires 132 can be made by processes such as laser engraving or etching. Since the vascular interventional diagnosis and treatment device itself is relatively small in size, if wires are configured on the main frame mesh structure, the wire size is generally required to be thin, for example, less than 100 μm, or even less than 25 μm, or even less than 10 μm, such as 5 μm, 8 μm, etc., and the connection stability is poor when it is connected to the electrode by resistance welding. However, the above configuration of the conductive material layer 13 to form the electrodes 131 and wires 132 can meet the requirements of thin wires and make the electrodes 131 and wires 132 an integrated structure. They are not easy to break even when subjected to blood flow erosion in the blood vessel for a long time, have strong stability, and are simple in structure.

[0063] The number of electrodes 131 configured on the conductive material layer 13 can be designed to be one or more (such as 2, 3, 5, 8, 10, 15, 20, etc.), and can be set specifically according to actual needs, generally more than two, to achieve multi-point detection or action, improve detection accuracy or action uniformity; and, the electrodes 131 can be evenly arranged along the radial and / or axial direction of the hollow tubular main frame 11 to further improve the detection accuracy or action uniformity, and improve the stability of the structure.

[0064] For a main frame 11 with a mesh-like sidewall structure, as shown in Figures 1 and 4 , electrodes 131 can be positioned at intersections 111 of the mesh structure on the main frame 11, thereby improving the stability of electrodes 131. Specifically, electrodes 131 can be positioned at some or all intersections 111 of the mesh structure on the main frame 11. In some embodiments, electrodes 131 can be positioned between two intersections 111, rather than at the intersections 111 of the mesh structure on the main frame 11. The shape of electrodes 131 can be designed as needed. Generally, a gently curved shape, such as a circle, ellipse, semicircle, or ring, is employed to improve the safety of the structure in the human body. Of course, in some embodiments, electrodes 131 can also adopt other shapes, such as a square. Furthermore, the area on the main frame 11 corresponding to the location of electrodes 131 can be considered to constitute an electrode mounting portion 112. To improve the stability of the electrode structure, the outer dimensions of electrode mounting portion 112 can be designed to be equal to or larger than the outer dimensions of electrodes 131. Specifically, for example, the shape of the electrode assembly portion 112 on the main frame 11 can be designed to be the same as the shape of the electrode 131, and the size of the electrode assembly portion 112 on the main frame 11 can be equal to or slightly larger than the size of the electrode 131; or, the shape of the electrode assembly portion 112 on the main frame 11 can be designed to be different from the shape of the electrode 131, and the size of the electrode assembly portion 112 on the main frame 11 can be larger than the size of the electrode 131, that is, along the radial direction of the main frame 11, the outer contour of the position where the electrode 131 is set on the main frame 11 is larger than the outer contour of the electrode 131. Through the above structural design, the main frame 11 can fully support the electrode 131, further improving the stability of the electrode 131 and the overall structure.

[0065] In some embodiments, an electrode assembly groove may be provided on the electrode assembly portion 112 of the main frame 11, and the electrode 131 may be assembled into the electrode assembly groove. This structural arrangement allows the electrode 131 to be assembled into the electrode assembly groove, which, on the one hand, reduces the thickness of the structure, and, on the other hand, the sidewalls of the electrode assembly groove can limit the position of the electrode 131, preventing it from shifting during use and further improving the structural stability.

[0066] In addition, a modification layer may be provided on the surface of the electrode 131. The modification layer may be specifically configured to have a biosignal recognition function, for identifying and detecting changes in biosignals within the blood vessels, and converting the changes in biosignals into readable electrical signals through the electrodes and transmitting them to an external circuit; biosignals include chemical signals and / or physical signals related to the physiological condition of an organism (such as a human body). Among them, the chemical signal may be a chemical signal generated by a chemical reaction with the modification layer material. For example, during the use of the diagnostic and treatment device, when a specific biomarker within the blood vessel contacts the modification layer modified on the electrode surface with a biosignal recognition function, a chemical reaction occurs between the two. The chemical signal change generated by the chemical reaction will be converted into a readable electrical signal through the electrode and transmitted to an external circuit. The physical signal may be at least one of temperature, blood flow velocity, and blood pressure. For example, during the use of the diagnostic and treatment device, when the above physical signals in the blood vessel change, the change will cause a responsive change in the physical properties of the modification layer on the electrode surface, and the change will be converted into a readable electrical signal through the electrode and transmitted to an external circuit.

[0067] The specific material of the modification layer is not limited as long as it can achieve the above-mentioned biological signal recognition function, and can be one or more of enzymes, redox mediators, nanomaterials, antibodies, biotin, nucleic acid aptamers, polymers, ion carriers, and piezoelectric materials.

[0068] The enzyme includes but is not limited to at least one of oxidoreductase, transferase, hydrolase, lyase, ligase, and isomerase.

[0069] Oxidoreductases include, but are not limited to, glucose oxidase, glutamate oxidase, alcohol oxidase, lactate oxidase, amino acid oxidase, cholesterol oxidase, choline oxidase, nicotinamide adenine dinucleotide phosphate oxidase, oxalate oxidase, cytochrome oxidase, bilirubin oxidase, serotoninase, galactose oxidase, glucose dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, aldehyde dehydrogenase, glutamate dehydrogenase, pyruvate dehydrogenase, sorbitol dehydrogenase, formate dehydrogenase, cellobiose dehydrogenase, amino acid dehydrogenase, succinate dehydrogenase, catalase, horseradish peroxidase, lactoperoxidase, glutathione peroxidase At least one of enzymes, ascorbate peroxidase, soybean peroxidase, cytochrome peroxidase, thyroid peroxidase, myeloperoxidase, superoxide dismutase, haloperoxidase, thiol peroxidase, 5α reductase, 5β reductase, aldehyde reductase, aldose reductase, hydroxymethylglutaryl-CoA reductase, methemoglobin reductase, ribonucleotide reductase, nitroreductase, thioredoxin reductase, dihydrofolate reductase, disulfide reductase, sulfite reductase, cytochrome reductase, imine reductase, fumarate reductase, carboxylic acid reductase, and dimethyl sulfoxide reductase.

[0070] The transferase includes, but is not limited to, at least one of glutathione transferase, acetyltransferase, methyltransferase, transketolase, transaldolase, glycosyltransferase, transketolase, aminoacid transferase, and acyltransferase.

[0071] The hydrolase includes, but is not limited to, at least one of lipase, phosphohydrolase, glycoside hydrolase, acetylhydrolase, nucleotidase, helicase, peptide hydrolase, urease, and creatinine deiminase.

[0072] Lyases include, but are not limited to, at least one of decarboxylase, dehydrogenase, dehalogenase, aspartate ammonia lyase, and cysteine ​​desulfurase.

[0073] The ligase includes, but is not limited to, at least one of tRNA synthetase, succinyl-coenzyme A synthetase, amino acid ligase, DNA ligase, RNA ligase, and carboxylase.

[0074] The isomerase includes, but is not limited to, at least one of a racemase, an epimerase, and a mutase.

[0075] Nanomaterials include, but are not limited to, one or more of metal nanomaterials, nanoceramics, nanoglass, and nanopolymer materials.

[0076] The antibodies include, but are not limited to, one or more of C-reactive protein antibodies, thyroid-stimulating hormone antibodies, bilirubin antibodies, albumin antibodies, carcinoembryonic antigen antibodies, alpha-fetoprotein antibodies, prostate-specific antigen antibodies, cancer antigen 125 antibodies, and cortisol antibodies.

[0077] The nucleic acid aptamer is selected from at least one of a DNA type oligonucleotide chain and an RNA type oligonucleotide chain.

[0078] The polymer is selected from one or more of polyaniline, polypyrrole, polyacetylene, polycarbazole, polythiophene, polyphenylene methylene, poly(3,4-ethylenedioxythiophene), polystyrene sulfonic acid, chitin, chitosan, polyvinyl chloride, polyvinyl butyral, and Nafion.

[0079] The ion carrier is selected from one or more of potassium ion, sodium ion, calcium ion, magnesium ion, iron ion, zinc ion, manganese ion, copper ion, molybdenum ion, cobalt ion, cobalt ion, chromium ion, chloride ion, sulfate ion, and phosphate ion.

[0080] The piezoelectric material is selected from at least one of single crystal piezoelectric ceramics, polycrystalline piezoelectric ceramics, piezoelectric polymers, and polymer-piezoelectric ceramic composites.

[0081] Specifically, among the above-mentioned modifying layer materials, the mechanism of action of some modifying layer materials is as follows: when the vascular interventional diagnostic and treatment device is implanted in a blood vessel and used, if the modifying layer detects a corresponding biological signal change, the modifying layer material will undergo a corresponding chemical reaction, generating or consuming electrons during the chemical reaction. The change in the number of electrons, under the stimulation of the signal of the external circuit, will be conducted through the electrode below the modifying layer and generate an electrical signal, which is ultimately transmitted to the external circuit to form a readable signal. Among them, the enzyme and the redox mediator mainly achieve the above mechanism by cooperating, and the nanomaterial alone or in combination with the redox mediator can also achieve the above mechanism. For example, if glucose oxidase is used as the modifying layer material, but glucose molecules appear in the blood vessel, the glucose oxidase will specifically react with glucose. The electrons generated by the reaction will be transferred to the oxygen in the blood and generate hydrogen peroxide on the electrode surface. The hydrogen peroxide will react chemically under the stimulation of the appropriate external circuit voltage and generate electrons. The electrons will flow from the electrode into the circuit under the drive of the electric field force and generate a readable current signal in the external circuit. The magnitude of the current signal is related to the glucose concentration in the blood vessel, thus, it can be used to judge the glucose concentration in the blood vessel.

[0082] The mechanism of action of some modification layer materials is as follows: When the vascular interventional diagnostic and treatment device is implanted in a blood vessel and used, if the modification layer detects changes in biological signals within the blood vessel, the modification layer material will undergo corresponding chemical changes. After the chemical reaction, the impedance properties of the modification layer will change. This change in impedance properties can be detected by the electrode under the modification layer under the signal excitation of the external circuit and generate an electrical impedance signal. This electrical impedance signal will eventually be transmitted to the external circuit to form a readable signal. Among them, nanomaterials, antibodies, biotin, nucleic acid aptamers, and polymers can all achieve the above mechanism alone or in combination with each other. For example, if cortisol antibodies are used as the modification layer material, when cortisol molecules appear in the blood vessels, the cortisol molecules will specifically chemically bind to the cortisol antibodies. After binding, the impedance of the electrode surface will increase. This impedance signal change can be read in the external circuit. The change in the electrical impedance signal is related to the concentration of cortisol molecules in the blood vessels, and therefore can be used to determine the cortisol concentration in the blood vessels.

[0083] As shown in Figures 1-3 and 7 , insulating encapsulation layer 14 is disposed on conductive material layer 13, specifically covering conductive wires 132 and exposing at least a portion of electrodes 131. Insulating encapsulation layer 14 provides insulation and protection for conductive wires 132. Its material can be selected from at least one of polyimide (PI), polydimethylsiloxane (PDMS), poly(p-phenylene benzobisoxazole) (PBO), and SU8. Of course, in some embodiments, insulating encapsulation layer 14 may be omitted.

[0084] In addition, in some embodiments, in order to improve the safety of the implantation process of the vascular interventional diagnostic and treatment device, the vascular interventional diagnostic and treatment device may further include a buffering and protective component, which is configured to reduce the risk of puncturing a blood vessel during the implantation process of the vascular interventional diagnostic and treatment device. Specifically, the buffering and protective component may be disposed at the implantation front end of the vascular interventional diagnostic and treatment device. In addition, the buffering and protective component may be designed to have an arc-shaped buffering surface at the front end of the intervention. For example, the buffering and protective component may be designed to be spherical, semi-spherical, ellipsoidal, semi-ellipsoidal, etc. By deploying the arc-shaped buffering surface design of the front end of the intervention by the buffering and protective component, it can play an effective buffering and protective role during the deployment and implantation process of the blood vessel, thereby reducing the risk of puncturing the blood vessel.

[0085] In some embodiments, the above-mentioned vascular interventional diagnostic and treatment device can be used in conjunction with an external delivery component during deployment to deploy and implant the vascular interventional diagnostic and treatment device at the target site in the blood vessel. Of course, in some embodiments, the vascular interventional diagnostic and treatment device can also be designed to include a delivery component, which is configured to deploy and implant the vascular interventional diagnostic and treatment device into the blood vessel. The delivery component can be a delivery shaft, which can be configured to pass through the main frame and have one end connected to the deployment front end of the main frame or a buffer protection component provided at the deployment front end of the main frame.

[0086] The above-mentioned vascular interventional diagnosis and treatment device can be applied to a vascular interventional diagnosis and treatment system, and the present invention further proposes a vascular interventional diagnosis and treatment system, which includes any of the above-mentioned vascular interventional diagnosis and treatment devices. Specifically, one end of the wire of the conductive material layer in the vascular interventional diagnosis and treatment device is connected to the electrode on the conductive material layer, and the wire extends along the side wall of the main frame and is configured to be led out for electrical connection with an external device. The external device can be equipped as needed. For example, in some embodiments, the external device is only used to receive the signal data detected by the electrode and transmitted through the wire; or, in some embodiments, in addition to receiving the signal data detected by the electrode and transmitted through the wire, the external device can also process it to obtain target signal data; or, in some embodiments, in addition to receiving and processing the signal data transmitted by the vascular interventional diagnosis and treatment device, the external device can further generate a control signal and transmit the control signal to other devices; or, the external device can be a driving power supply to apply electrical stimulation to the vascular wall cells through the wire and electrode; in addition, other external devices can be configured as needed. In addition, the above-mentioned vascular interventional diagnosis and treatment system can be applied to in vitro culturing cell constructs, collecting electrical signals from cell constructs, and electrically stimulating cell constructs. Furthermore, this application also proposes the application of one or more vascular interventional diagnosis and treatment systems in in vitro culturing cell constructs, collecting electrical signals from cell constructs, or electrically stimulating cell constructs. Furthermore, for vascular interventional diagnosis and treatment devices with modified layers on the electrode surface, the use of different types of modified layer materials can specifically detect corresponding biomarkers. Furthermore, this application also proposes the application of one or more vascular interventional diagnosis and treatment systems in biomarker detection.

[0087] The above-described embodiments merely illustrate several implementations of the present invention. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that variations and improvements are possible without departing from the scope of the present invention, and all such variations and improvements fall within the scope of protection of the present invention.

Claims

1. A vascular interventional diagnostic and therapeutic device, characterized in that: include: A main frame, wherein the main frame is an elastic support frame; The conductive material layer is disposed on the main frame and is configured to form electrodes and wires.

2. The vascular interventional diagnostic and treatment device according to claim 1, characterized in that: The main frame is configured to be contractible and expandable along a central axis.

3. The vascular interventional diagnostic and treatment device according to claim 1, characterized in that: The main frame is in the shape of a hollow tube; Preferably, the side wall of the main frame is a mesh structure; Preferably, the electrodes are arranged at the intersection of the mesh structures on the main frame; Preferably, there are two or more electrodes; Preferably, the electrodes are evenly arranged along the radial direction and / or the axial direction of the main frame.

4. The vascular interventional diagnostic and treatment device according to claim 1, characterized in that: The area on the main frame corresponding to the electrode setting position constitutes an electrode assembly part, and the outer contour size of the electrode assembly part is equal to or larger than the outer contour size of the electrode; Preferably, the electrode assembly portion is provided with an electrode assembly groove, and the electrode is arranged in the electrode assembly groove.

5. The vascular interventional diagnostic and treatment device according to claim 1, characterized in that: The material of the main frame is selected from degradable polymer materials; Alternatively, the material of the main frame is selected from at least one of shape memory alloy and iron, and a dielectric layer is provided between the main frame and the conductive material layer; Preferably, the material of the dielectric layer is selected from at least one of polyimide, polydimethylsiloxane, poly(p-phenylene benzobisoxazole), and SU8; Preferably, the shape memory alloy is selected from at least one of Nitinol alloy, cobalt-chromium alloy and magnesium alloy.

6. The vascular interventional diagnosis and treatment device according to claim 1, characterized in that: The electrodes and the wires in the conductive material layer are in an integrated structure; preferably, the conductive material layer is a metal material layer, a non-metallic conductive material layer, or a composite layer of a non-metallic conductive material layer and a metal material layer; Preferably, the conductive material layer comprises a non-precious metal conductive base layer and a precious metal protective layer, the non-precious metal conductive base layer is arranged on the surface of the main frame, and the precious metal protective layer covers the non-precious metal conductive base layer; the material of the precious metal protective layer is selected from at least one of platinum and gold; Preferably, the thickness of the conductive material layer is less than 5 μm.

7. The vascular interventional diagnosis and treatment device according to any one of claims 1 to 6, characterized in that: The surface of the electrode is provided with a modification layer, and the modification layer has a biological signal recognition function, which is used to recognize and detect changes in biological signals in the blood vessels, and convert the changes in the biological signals into readable electrical signals through the electrode and transmit them to the external circuit; the biological signals include chemical signals and / or physical signals related to the physiological status of the organism; Preferably, the material of the modification layer is selected from at least one of enzymes, redox mediators, nanomaterials, antibodies, biotin, nucleic acid aptamers, polymers, ion carriers, and piezoelectric materials; Preferably, the enzyme is selected from at least one of oxidoreductase, transferase, hydrolase, lyase, ligase and isomerase; Preferably, the oxidoreductase is selected from the group consisting of glucose oxidase, glutamate oxidase, alcohol oxidase, lactate oxidase, amino acid oxidase, cholesterol oxidase, choline oxidase, nicotinamide adenine dinucleotide phosphate oxidase, oxalate oxidase, cytochrome oxidase, bilirubin oxidase, serotoninase, galactose oxidase, glucose dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase, aldehyde dehydrogenase, glutamate dehydrogenase, pyruvate dehydrogenase, sorbitol dehydrogenase, formate dehydrogenase, cellobiose dehydrogenase, amino acid dehydrogenase, succinate dehydrogenase, catalase, horseradish peroxidase, lactoperoxidase, glutathione peroxidase. at least one of: a biotinylated enzyme, an ascorbate peroxidase, a soybean peroxidase, a cytochrome peroxidase, a thyroid peroxidase, a myeloperoxidase, a superoxide dismutase, a haloperoxidase, a thiol peroxidase, a 5α reductase, a 5β reductase, an aldehyde reductase, an aldose reductase, a hydroxymethylglutaryl-CoA reductase, a methemoglobin reductase, a ribonucleotide reductase, a nitroreductase, a thioredoxin reductase, a dihydrofolate reductase, a disulfide reductase, a sulfite reductase, a cytochrome reductase, an imine reductase, a fumarate reductase, a carboxylic acid reductase, and a dimethyl sulfoxide reductase; Preferably, the transferase is selected from at least one of glutathione transferase, acetyltransferase, methyltransferase, transketolase, transaldolase, glycosyltransferase, transketolase, amino acid transferase and acyltransferase; Preferably, the hydrolase is selected from at least one of lipase, phosphohydrolase, glycoside hydrolase, acetylhydrolase, nucleotide hydrolase, helicase, peptide hydrolase, urease and creatinine deiminase; Preferably, the lyase is selected from at least one of a decarboxylase, a dehydrogenase, a dehalogenase, an aspartate ammonia lyase, and a cysteine ​​desulfurase; Preferably, the ligase is selected from at least one of tRNA synthetase, succinyl coenzyme A synthetase, amino acid ligase, DNA ligase, RNA ligase, and carboxylase; Preferably, the isomerase is selected from at least one of a racemase, an epimerase, and a mutase; Preferably, the nanomaterial is selected from at least one of metal nanomaterials, nanoceramics, nanoglass, and nanopolymer materials; Preferably, the antibody is selected from the group consisting of C-reactive protein antibody, thyrotropin antibody, bilirubin antibody, albumin antibody, At least one of carcinoembryonic antigen antibody, alpha-fetoprotein antibody, prostate-specific antigen antibody, cancer antigen 125 antibody, and cortisol antibody; Preferably, the nucleic acid aptamer is selected from at least one of a DNA type oligonucleotide chain and an RNA type oligonucleotide chain; Preferably, the polymer is selected from at least one of polyaniline, polypyrrole, polyacetylene, polycarbazole, polythiophene, polyphenylene methylene, poly(3,4-ethylenedioxythiophene), polystyrene sulfonic acid, chitin, chitosan, polyvinyl chloride, polyvinyl butyral, and Nafion; Preferably, the ion carrier is selected from at least one of potassium ion, sodium ion, calcium ion, magnesium ion, iron ion, zinc ion, manganese ion, copper ion, molybdenum ion, cobalt ion, cobalt ion, chromium ion, chloride ion, sulfate ion, and phosphate ion; Preferably, the piezoelectric material is selected from at least one of single crystal piezoelectric ceramics, polycrystalline piezoelectric ceramics, piezoelectric polymers, and polymer-piezoelectric ceramic composites.

8. The vascular interventional diagnosis and treatment device according to any one of claims 1 to 6, characterized in that: It also includes an insulating packaging layer, which is disposed on the conductive material layer, covers the wires and exposes at least a portion of the electrodes; preferably, the insulating packaging layer is made of at least one selected from polyimide, polydimethylsiloxane, poly(p-phenylene benzobisoxazole), and SU8; Preferably, it further comprises a buffer protection component, which is arranged at the implantation front end of the vascular interventional diagnosis and treatment device and is configured to reduce the risk of puncturing a blood vessel during the implantation process of the vascular interventional diagnosis and treatment device; Preferably, it also includes a delivery component, wherein the delivery component is configured to deploy and implant the vascular interventional diagnosis and treatment device into a blood vessel.

9. A vascular interventional diagnosis and treatment system, characterized in that: A vascular interventional diagnostic and treatment device comprising any one of claims 1 to 8.

10. Use of the vascular interventional diagnosis and treatment system according to claim 9 in in vitro culture of cell constructs, electrical signal acquisition of cell constructs, or electrical stimulation of cell constructs.

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