CN106806039A - Rotary cell support planting unit - Google Patents
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- 238000004113 cell culture Methods 0.000 claims abstract description 8
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- 201000000057 Coronary Stenosis Diseases 0.000 description 1
- 206010011089 Coronary artery stenosis Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000008358 core component Substances 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
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- 238000011081 inoculation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000005486 microgravity Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
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- A—HUMAN NECESSITIES
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- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
- A61F2/07—Stent-grafts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/005—Ingredients of undetermined constitution or reaction products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
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Abstract
本发明提供了一种旋转式细胞支架种植装置,包括装置体和上位机界面。所述装置体内设有核心板和接口板,构成微处理器;微处理器分别与温度传感器及通过固态继电器与加热棒相连,实现恒温控制;微处理器控制CO2传感器与CO2气路、紫外灯及通过驱动器与电机相连,电机机轴上固定有共培养模具,模具内放置细胞培养液与血管内支架,提供无菌种植环境。所述上位机界面通过串口与微处理器连接,上位机界面、红外遥控和液晶显示完成温度、转速、CO2的实时监测与调控、数据存储及显示。本发明解决了血管内支架上细胞生长分布不均、粘附不牢等问题,使用方便,不需要使用CO2恒温培养箱即可独立作业,实现细胞支架的种植功能,具有应用及临床价值。
The invention provides a rotary cell scaffold planting device, which includes a device body and a host computer interface. The device body is provided with a core board and an interface board to form a microprocessor; the microprocessor is connected to a temperature sensor and a heating rod through a solid-state relay to realize constant temperature control; the microprocessor controls the CO2 sensor and the CO2 gas circuit, The ultraviolet lamp is connected to the motor through the driver, and a co-cultivation mold is fixed on the shaft of the motor, and the cell culture solution and the intravascular stent are placed in the mold to provide a sterile planting environment. The host computer interface is connected to the microprocessor through a serial port, and the host computer interface, infrared remote control and liquid crystal display complete the real-time monitoring and control, data storage and display of temperature, rotation speed and CO 2 . The invention solves the problems of uneven cell growth distribution and weak adhesion on the intravascular stent, is easy to use, can work independently without using a CO2 constant temperature incubator, and realizes the planting function of the cell stent, and has application and clinical value.
Description
【技术领域】【Technical field】
本发明涉及医疗器械及组织工程学领域,特别是提出了一种模拟细胞三维培养的旋转式细胞支架种植装置。The invention relates to the fields of medical equipment and tissue engineering, and in particular proposes a rotating cell scaffold planting device for simulating three-dimensional cell culture.
【背景技术】【Background technique】
在冠脉狭窄类心血管类疾病的治疗中,血管内支架的作用举足轻重。目前的血管内支架的研究主要集中在支架载药及可降解方面,但是最终目的都是为了治疗期间的内皮化过程。研究发现,在血管疾病的治疗上,体外细胞种植支架是更为直接的内皮化方法,在同等条件下,内皮细胞种植的支架能取得较好的组织相容性和血液相容性,更有利于心血管疾病的治疗,结合细胞培养工程,细胞支架种植技术应用而生。In the treatment of coronary artery stenosis and cardiovascular diseases, intravascular stents play an important role. The current research on intravascular stents mainly focuses on the drug-loaded and degradable aspects of the stent, but the ultimate goal is for the endothelialization process during treatment. Studies have found that in the treatment of vascular diseases, in vitro cell-planted scaffolds are a more direct method of endothelialization. Under the same conditions, endothelial cell-planted scaffolds can achieve better histocompatibility and blood compatibility, and more It is beneficial to the treatment of cardiovascular diseases, combined with the application of cell culture engineering and cell scaffold planting technology.
细胞支架种植技术是将血管内支架作为细胞载体,在其表面喷涂上一层介质,将基因修饰的细胞种植到支架的表面后,植入体内,以达到细胞接种的目的,从而可以治疗动脉粥样硬化中受损内皮等。细胞支架种植支架带动了细胞支架种植装置的研发。Cell stent planting technology is to use intravascular stent as a cell carrier, spray a layer of medium on its surface, plant genetically modified cells on the surface of the stent, and implant it into the body to achieve the purpose of cell inoculation, so as to treat atherosclerosis Damaged endothelium in sclerosis, etc. The cell scaffold planting scaffold drives the research and development of the cell scaffold planting device.
但是常规的体外静态培养方法由于重力作用,几乎不可能建立体内组织细胞所处的局部三维立体微环境,不能够为组织细胞提供正常生长发育的环境条件,细胞失去原有的立体形态,造成支架上细胞粘附不佳等问题。而细胞三维培养技术又促进了组织工程学的发展,旋转式细胞培养系统通过反应器的不断旋转,模拟微重力环境,为其开创了一个新研究领域。However, due to the effect of gravity, the conventional in vitro static culture method is almost impossible to establish a local three-dimensional microenvironment for tissue cells in the body, and cannot provide environmental conditions for normal growth and development of tissue cells. The cells lose their original three-dimensional shape, resulting in scaffolding problems such as poor cell adhesion. The three-dimensional cell culture technology has promoted the development of tissue engineering. The rotating cell culture system simulates the microgravity environment through the continuous rotation of the reactor, creating a new research field for it.
现有细胞支架种植装置虽然能制备出符合一定要求的细胞支架,但是在实验研究和使用中,暴露出的问题如下:1.支架局部出现生长不均匀、粘附不牢、细胞脱落等现象;2.装置需要借助于CO2恒温培养箱提供相应的培养条件;3.不能批量化生产细胞支架;4.不能动态监视培养环境,缺乏培养条件失调时报警系统;5.设备自动化程度较低,使用繁琐。Although the existing cell scaffold planting device can produce cell scaffolds that meet certain requirements, the problems exposed in the experimental research and use are as follows: 1. The local scaffolds have uneven growth, poor adhesion, and cell shedding; 2. The device needs to provide corresponding culture conditions with the help of a CO 2 constant temperature incubator; 3. Cell scaffolds cannot be produced in batches; 4. The culture environment cannot be dynamically monitored, and there is no alarm system when the culture conditions are out of balance; 5. The degree of automation of the equipment is low, It is cumbersome to use.
【发明专利内容】【Invention patent content】
本发明针对上有技术存在的缺陷,提供了一种旋转式细胞支架种植装置。Aiming at the defects in the prior art, the present invention provides a rotary cell scaffold planting device.
本发明的技术方案如下:旋转式细胞支架种植装置,包括装置体(1)和上位机界面(2)。所述装置体内设有核心板和接口板,构成微处理器;微处理器与温度传感器及通过固态继电器与加热棒相连,实现恒温控制;微处理器控制CO2传感器与CO2气路、紫外灯及通过驱动器与电机相连,电机机轴上固定连接共培养模具,模具内放置细胞培养液与血管内支架,提供无菌种植环境。所述上位机界面通过串口与微处理器连接,上位机界面、红外遥控和液晶显示完成温度、转速、CO2的实时监测与调控、数据存储及显示。本发明解决了血管内支架上细胞生长分布不均、粘附不牢等问题,使用方便,不需要使用CO2恒温培养箱即可独立作业,实现细胞支架的种植功能,具有应用及临床价值。The technical scheme of the present invention is as follows: a rotary cell scaffold planting device includes a device body (1) and a host computer interface (2). The device body is provided with a core board and an interface board to form a microprocessor; the microprocessor is connected to a temperature sensor and a heating rod through a solid state relay to realize constant temperature control; the microprocessor controls the CO2 sensor and the CO2 gas circuit, ultraviolet The lamp is connected to the motor through the driver, and the co-cultivation mold is fixedly connected to the shaft of the motor, and the cell culture solution and the intravascular stent are placed in the mold to provide a sterile planting environment. The host computer interface is connected to the microprocessor through a serial port, and the host computer interface, infrared remote control and liquid crystal display complete the real-time monitoring and control, data storage and display of temperature, rotation speed and CO 2 . The invention solves the problems of uneven cell growth distribution and weak adhesion on the intravascular stent, is easy to use, can work independently without using a CO2 constant temperature incubator, and realizes the planting function of the cell stent, and has application and clinical value.
所述装置体内设有鼓风机,搅拌使培养室温度更均匀,所述培养室的温控范围:37.0±0.1℃,恒温后培养室的温度波动≤0.1℃,CO2浓度为5%。The device is equipped with a blower to make the temperature of the cultivation chamber more uniform. The temperature control range of the cultivation chamber is 37.0±0.1°C. After constant temperature, the temperature fluctuation of the cultivation chamber is ≤0.1°C, and the CO2 concentration is 5%.
所述电机为步进电机,正转、反转的转速均连续可调,转速范围在0~5转/分钟。The motor is a stepping motor, and the rotation speeds of forward rotation and reverse rotation are continuously adjustable, and the rotation speed ranges from 0 to 5 revolutions per minute.
所述微处理器上设有温度及CO2浓度异常报警装置。The microprocessor is provided with an abnormal alarm device for temperature and CO2 concentration.
所述共培养模具内腔直径为60mm,模具上有两个对称支管,直径4mm,便于细胞培养液的更换,共培养模具的一端覆有透气不透液的半透膜,便于气体交换;共培养模具有多个支架固定点,可实现细胞支架的批量化制备。The inner diameter of the co-cultivation mold is 60mm, and there are two symmetrical branch pipes on the mold, with a diameter of 4mm, which is convenient for the replacement of the cell culture solution. One end of the co-cultivation mold is covered with an air-permeable and liquid-impermeable semi-permeable membrane, which is convenient for gas exchange; The culture mold has multiple scaffold fixing points, which can realize the batch preparation of cell scaffolds.
所述装置通过红红外遥控或者上位机即可使用。The device can be used through red and infrared remote control or a host computer.
本发明的有益效果在于:装置实现了自动化控制,使用简单;可进行独立作业,无需借助于CO2恒温培养箱;上位机及报警系统提高了故障监测率,培养条件失调时,可以使我们在第一时间发现问题,避免实验误操作的发生;可提供稳定的共培养环境,使细胞在血管内支架上均匀、牢固生长;多个支架固定点可实现细胞支架的批量化制备,种植效率高,节约时间。The beneficial effects of the present invention are: the device realizes automatic control, and is easy to use; it can perform independent operations without resorting to a CO2 constant temperature incubator; Find problems at the first time to avoid the occurrence of experimental misoperation; can provide a stable co-culture environment, so that cells can grow uniformly and firmly on the intravascular scaffold; multiple scaffold fixing points can realize batch preparation of cell scaffolds, and the planting efficiency is high ,save time.
【附图说明】【Description of drawings】
图1是旋转式细胞支架种植装置的结构示意图;Fig. 1 is a schematic structural view of a rotary cell scaffold planting device;
图2是共培养模具结构示意图;Fig. 2 is a schematic diagram of the co-cultivation mold structure;
图3是CO2气路结构示意图;Figure 3 is a schematic diagram of the structure of the CO2 gas path;
图4是上位机端功能图。Figure 4 is a functional diagram of the host computer.
图中:1.装置体;9.培养室;151.模具体;152.模具盖;153.固定连接件;154.支架固定点;155.支管;156.小槽;157.螺孔;158.孔道。In the figure: 1. device body; 9. cultivation chamber; 151. mold body; 152. mold cover; 153. fixed connector; 154. bracket fixing point; . Holes.
【具体实施方式】【detailed description】
以下所述为本发明专利的具体实施方式。Described below is the specific implementation manner of the patent of the present invention.
如图1所示,该旋转式细胞支架种植装置主要包括装置体1和上位机2。装置体1内设有核心板3和接口板4,构成微处理器,设有开关组,包括设备电源开关、紫外灯开关、鼓风机开关,上位机2或红外遥控上均设有温控、气体控制及转速控制开关。微处理器与温度传感器5及通过固态继电器6与加热棒7相连,装置体1内的鼓风机8搅拌使培养室9温度更均匀,实现培养室9恒温控制,温控范围:37.0±0.1℃,恒温后温度波动≤0.1℃;微处理器控制CO2传感器10与CO2气路11、紫外灯12及通过驱动器13与步进电机14相连,电机机轴上固定连接共培养模具15,模具内放置细胞培养液与血管内支架,电机正、反转转速均连续可调,转速范围在0~5转/分钟,控制CO2浓度为5%。微处理器内载PID控制算法与报警系统,若温度或CO2气路异常时均报警。装置体1上设有红外接收头16与液晶显示屏17,进行红外遥控器的参数设置功能与参数显示功能。As shown in FIG. 1 , the rotary cell scaffold planting device mainly includes a device body 1 and a host computer 2 . The device body 1 is provided with a core board 3 and an interface board 4, which constitute a microprocessor, and a switch group, including a device power switch, an ultraviolet light switch, a blower switch, and a temperature control, gas Control and speed control switch. The microprocessor is connected to the temperature sensor 5 and the heating rod 7 through the solid state relay 6. The blower 8 in the device body 1 stirs to make the temperature of the cultivation chamber 9 more uniform, and realizes the constant temperature control of the cultivation chamber 9. The temperature control range: 37.0±0.1°C, After constant temperature, the temperature fluctuation is less than or equal to 0.1°C; the microprocessor controls the CO2 sensor 10, the CO2 gas circuit 11, the ultraviolet lamp 12, and the stepper motor 14 through the driver 13, and the co-culture mold 15 is fixedly connected to the motor shaft, and the cells are placed in the mold The culture medium and intravascular stent, the forward and reverse rotation speed of the motor are continuously adjustable, the speed range is 0-5 rpm, and the CO2 concentration is controlled at 5%. Microprocessor built-in PID control algorithm and alarm system, if the temperature or CO 2 gas path is abnormal, it will alarm. The device body 1 is provided with an infrared receiving head 16 and a liquid crystal display 17 for performing parameter setting and parameter display functions of the infrared remote controller.
如图2所示,上位机2通过串口18通信,不仅可以设置图中所示的培养环境参数,还可以对其进行同步监测、显示、存储。此外,装置使用时,也可以只使用红外遥控器实现上位机的部分相关操作。As shown in Figure 2, the host computer 2 communicates through the serial port 18, not only can set the cultivation environment parameters shown in the figure, but also can monitor, display and store them synchronously. In addition, when the device is in use, only the infrared remote controller can be used to realize some related operations of the upper computer.
如图3所示,共培养模具15为装置体的核心部件之一,内腔直径为60mm,内置细胞培养液与血管内支架,由模具体151、模具盖152、固定连接件153三部分组成,模具体151底部均匀排列多个血管支架固定点154,插入适当长度牙签,将支架套挂在牙签上即可固定支架,可实现细胞支架的批量化制备;侧面对称开有两个对称支管155,直径4mm,便于细胞培养液的更换。模具盖上开有多个小槽156,在该模具盖的左面覆有透气不透液的半透膜,便于气体交换。用固定连接件153通过螺孔157用螺钉固定模具体151和模具盖152,防止液体漏出,电机机轴通过孔道158,螺母固定,实现旋转培养。As shown in Figure 3, the co-cultivation mold 15 is one of the core components of the device body, with an inner cavity diameter of 60mm, built-in cell culture fluid and intravascular stent, and consists of three parts: a mold body 151, a mold cover 152, and a fixed connector 153 , a plurality of vascular stent fixing points 154 are evenly arranged at the bottom of the mold body 151, a toothpick of an appropriate length is inserted, and the stent can be fixed by hanging the stent cover on the toothpick, which can realize batch preparation of cell scaffolds; two symmetrical branch pipes 155 are symmetrically opened on the side , diameter 4mm, easy to replace the cell culture medium. The mold cover is provided with a plurality of small grooves 156, and the left side of the mold cover is covered with an air-permeable and liquid-tight semi-permeable membrane, which is convenient for gas exchange. Fix the mold body 151 and the mold cover 152 with screws through the screw hole 157 with the fixed connector 153 to prevent the liquid from leaking out.
如图4所示,CO2气路由储气瓶、调速阀、电磁阀组、节流阀、过滤器、微处理器组成。微处理器控制调速阀、电磁阀1、过滤器三者作用首先使CO2气体充满培养室,此后调整调速阀,打开电磁阀2与节流阀,实现微量补气。As shown in Figure 4, the CO2 gas is composed of a gas storage cylinder, a speed regulating valve, a solenoid valve group, a throttle valve, a filter, and a microprocessor. The microprocessor controls the speed regulating valve, solenoid valve 1, and filter to make CO2 gas fill the cultivation chamber first, then adjust the speed regulating valve, open the solenoid valve 2 and the throttle valve, and realize a small amount of gas supplementation.
种植前24h,按下紫外灯开关,对箱体进行灭菌,种植前10min打开气体控制开关,使CO2气体充满培养室。种植时,固定好共培养模具后,按下电源开关与鼓风机开关,设备通电,设置温度及旋转相关参数后按下温控及转速控制开关,同时上位机及液晶显示培养条件。控制器内载PID控制算法与报警系统,此期间,若温度或气路异常时均报警。种植完成时,依次关闭上位机或红外遥控开关组、装置体开关组。24 hours before planting, press the UV light switch to sterilize the box, and turn on the gas control switch 10 minutes before planting to fill the cultivation room with CO2 gas. When planting, after fixing the co-cultivation mold, press the power switch and the blower switch to power on the equipment, set the temperature and rotation related parameters, press the temperature control and speed control switches, and the upper computer and LCD display the cultivation conditions at the same time. The controller is equipped with PID control algorithm and alarm system. During this period, if the temperature or gas path is abnormal, it will alarm. When the planting is completed, turn off the upper computer or the infrared remote control switch group and the device body switch group in turn.
应说明的是,本发明也适用于人工血管上的细胞种植,以上实施仅用以说明本发明的技术方案而非限制,尽管参照较佳实施例对本发明进行了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本发明技术方案的精神和范围,其均应涵盖在本发明的权利要求范围中。It should be noted that the present invention is also applicable to cell implantation on artificial blood vessels. The above implementations are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art Personnel should understand that the technical solution of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solution of the present invention, and all of them should be covered by the claims of the present invention.
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