CN219024109U - Microfluidic device - Google Patents
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- CN219024109U CN219024109U CN202320019262.7U CN202320019262U CN219024109U CN 219024109 U CN219024109 U CN 219024109U CN 202320019262 U CN202320019262 U CN 202320019262U CN 219024109 U CN219024109 U CN 219024109U
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Abstract
Description
技术领域technical field
本实用新型涉及微流体控制技术领域,尤其涉及一种微流控设备。The utility model relates to the technical field of microfluid control, in particular to a microfluid control device.
背景技术Background technique
微流控是一个基于在物理、化学、生物、流体动力学、微电子和材料科学等多学科交叉的次新研究领域。微流控被认为是能够使用数十至数百微米尺寸的通道处理或操纵少量(10-9~10-18L)流体的系统科学和技术。近年来,随着微流控设备和技术被成功用于以脂质纳米粒(lipid nanoparticles,LNP)为载体的mRNA新冠疫苗的研发和生产,越来越多不同的mRNA疫苗,比如预防疟疾、人类免疫缺陷病毒、流感和癌症等疫苗,都在采取该研究手段进行产品研究。微流控设备和技术作为制备核酸载体LNP的关键手段目前得到了各个领域,尤其是医药行业,前所未有的关注。Microfluidics is a new research field based on the intersection of physics, chemistry, biology, fluid dynamics, microelectronics and material science. Microfluidics is considered to be a system science and technology capable of handling or manipulating small volumes (10 -9 ~ 10 -18 L) of fluids using channels of tens to hundreds of microns in size. In recent years, as microfluidic devices and technologies have been successfully used in the development and production of mRNA COVID-19 vaccines based on lipid nanoparticles (LNP), more and more different mRNA vaccines, such as preventing malaria, Vaccines such as human immunodeficiency virus, influenza and cancer are all using this research method for product research. As the key means of preparing nucleic acid carrier LNP, microfluidic equipment and technology have received unprecedented attention from various fields, especially the pharmaceutical industry.
在脂质纳米粒LNP的制备中,微流控装置和技术呈现出了诸多优势,例如操作相对简便快速,可以快速优化LNP制备条件,条件温和,容易实现生产放大等。这些优势不仅促使了采用微流控装置和技术制备的LNP被用作RNA递送平台,也使得实验室级别的使用被放大到实际的产品生产应用中。目前,以LNP为基础的RNA、DNA、核糖核蛋白、药物和其他纳米粒子递送平台都在采用微流控设备和技术进行研究开发。将来,微流控设备和技术很有可能被作为LNP制备的行业标准手段。核酸/基因治疗是一个具有广泛应用前景和价值的新兴领域,作为最具优势的、制备关键递送载体的设备和技术将是这个领域至关重要的一环。In the preparation of lipid nanoparticles LNP, microfluidic devices and technologies present many advantages, such as relatively simple and fast operation, quick optimization of LNP preparation conditions, mild conditions, and easy production scale-up. These advantages have not only prompted LNPs prepared with microfluidic devices and techniques to be used as RNA delivery platforms, but also enabled laboratory-level use to be scaled up to actual product production applications. Currently, LNP-based RNA, DNA, ribonucleoprotein, drug and other nanoparticle delivery platforms are being researched and developed using microfluidic devices and technologies. In the future, microfluidic devices and techniques are likely to be used as industry standard means for LNP preparation. Nucleic acid/gene therapy is an emerging field with broad application prospects and value. As the most advantageous equipment and technology for preparing key delivery vectors, it will be a crucial part of this field.
目前,市面上产品化的微流控设备主要包括NanoAssemblr和ILiNP的产品。国内市场上也主要是以此类进口设备为主,设备采用的芯片因程序设定只能使用一次,这使得微流控的使用成本相当昂贵。此外,目前用于小剂量研发的微流控设备(例如NanoAssemblr产品)还主要存在以下几点不足:单次混合最大容量12ml,不能满足大体积样品制备的使用要求;混合最大速度16ml/min,不能满足液体高速度混合的使用场景要求;兼容注射器类型有限,只能匹配1ml的注射器。然而,国内能够代替进口设备的国内自主研发的自动化微流控设备却还非常有限,因此研制出能够实现不同计型、不同混合速度、兼容性高、两相液体精准快速混合的微流控机构具有重大意义。At present, the commercialized microfluidic devices on the market mainly include NanoAssemblr and ILiNP products. The domestic market is mainly based on this kind of imported equipment. The chips used in the equipment can only be used once due to the program setting, which makes the use of microfluidics quite expensive. In addition, the current microfluidic devices (such as NanoAssemblr products) used for small-dose research and development still have the following main shortcomings: the maximum volume of single mixing is 12ml, which cannot meet the requirements for large-volume sample preparation; the maximum mixing speed is 16ml/min, It cannot meet the requirements of high-speed mixing of liquids; the types of compatible syringes are limited, and only 1ml syringes can be matched. However, domestic self-developed automated microfluidic equipment that can replace imported equipment is still very limited. Therefore, a microfluidic mechanism that can achieve different meter types, different mixing speeds, high compatibility, and precise and rapid mixing of two-phase liquids has been developed. has great significance.
实用新型内容Utility model content
本实用新型所要解决的技术问题是提供一种构造简约、大屏触控交互体验好、操作便捷、自动化程度高、制备稳定、精确度高、可自动化精确控制原料液体的进液量及进液速度、实现不同计型、不同混合速度的两相液体的精准快速混合的一种微流控设备。The technical problem to be solved by the utility model is to provide a simple structure, good interactive experience of large-screen touch control, convenient operation, high degree of automation, stable preparation, high precision, automatic and precise control of the liquid intake and liquid intake of the raw material liquid. A microfluidic device that achieves precise and rapid mixing of two-phase liquids of different meter types and different mixing speeds.
为解决上述技术问题,本实用新型的技术方案是:一种微流控设备,包括壳体,所述壳体的内部安装有推送液机构,所述推送液机构的上方连通有微流液相混合机构,所述微流液相混合机构的下方连通有接液机构,所述壳体的上部安装有触屏交互控制机构,所述触屏交互控制机构控制连接所述推送液机构、所述微流液相混合机构和所述接液机构。In order to solve the above-mentioned technical problems, the technical proposal of the present utility model is: a microfluidic device, including a casing, a pushing liquid mechanism is installed inside the casing, and a microfluidic liquid phase is connected above the pushing liquid mechanism. A mixing mechanism, a liquid contacting mechanism is connected under the microfluidic liquid phase mixing mechanism, a touch screen interactive control mechanism is installed on the upper part of the housing, and the touch screen interactive control mechanism controls and connects the pushing liquid mechanism, the The microfluidic liquid phase mixing mechanism and the liquid contact mechanism.
作为优选的技术方案,所述推送液机构包括安装在所述壳体内底部的两个推送液安装座,每个所述推送液安装座上分别垂直安装有一根滑台螺杆,每根所述滑台螺杆上分别安装有推送液推子,所述推送液安装座上安装有初始位置检测传感器。As a preferred technical solution, the pushing liquid mechanism includes two pushing liquid mounting seats installed at the inner bottom of the housing, each of the pushing liquid mounting seats is respectively vertically installed with a slide table screw, and each of the sliding table screws Pushing liquid faders are respectively installed on the screw rods of the platform, and initial position detection sensors are installed on the pushing liquid mounting base.
作为优选的技术方案,所述推送液推子包括安装在所述滑台螺杆上的推子本体,所述推子本体的上部通过推子接触板轴承铰接有推子接触板,所述推子本体的下部固定安装有推子支撑结构,所述推子支撑结构上安装有触发传感器,所述推子接触板的下表面与所述触发传感器弹性接触。As a preferred technical solution, the pushing liquid clipper includes a clipper body installed on the screw rod of the slide table, the upper part of the clipper body is hinged with a clipper contact plate through a clipper contact plate bearing, and the clipper The lower part of the main body is fixedly installed with a clip support structure, and a trigger sensor is installed on the clip support structure, and the lower surface of the clip contact plate is in elastic contact with the trigger sensor.
作为优选的技术方案,所述接液机构包括固定安装在所述壳体内上部的混合液接收装置支撑体,所述混合液接收装置支撑体的底面上设有半圆形槽位,所述半圆形槽位内安装有半圆环形的旋转收液结构体,所述旋转收液结构体的一侧设有旋转收液机构齿轮,所述混合液接收装置支撑体的底面上还安装有与所述旋转收液机构齿轮相啮合的旋转收液机构驱动齿轮。As a preferred technical solution, the liquid contact mechanism includes a mixed liquid receiving device support body fixedly installed in the upper part of the housing, a semicircular slot is provided on the bottom surface of the mixed liquid receiving device support body, and the semicircular slot A semi-circular rotating liquid receiving structure is installed in the circular slot, one side of the rotating liquid collecting structure is provided with a rotating liquid collecting mechanism gear, and the bottom surface of the support body of the mixed liquid receiving device is also installed with the The driving gear of the rotating liquid collecting mechanism meshed with the gear of the rotating liquid collecting mechanism.
作为优选的技术方案,所述混合液接收装置支撑体的中间部位设置有两个收集试管夹具结构,所述收集试管夹具结构上分别安装有接液离心管和样品收集离心管。As a preferred technical solution, two collection test tube clamp structures are arranged in the middle of the support body of the mixed liquid receiving device, and the liquid-contacting centrifuge tube and the sample collection centrifuge tube are respectively installed on the collection test tube clamp structure.
作为优选的技术方案,所述微流液相混合机构包括安装在所述混合液接收装置支撑体顶部的芯片,所述芯片内部设有微流混合通道,所述微流混合通道的一端设有两个进液口、所述微流混合通道的另一端设有一个出液口,所述旋转收液结构体的中间位置设置有两个与所述进液口相对应的注射器放置连接孔,所述注射器放置连接孔内分别安装有进液注射器,所述出液口与所述接液离心管和所述样品收集离心管配合使用。As a preferred technical solution, the microfluidic liquid phase mixing mechanism includes a chip installed on the top of the support of the mixed liquid receiving device, a microfluidic mixing channel is provided inside the chip, and one end of the microfluidic mixing channel is provided with Two liquid inlets, the other end of the microfluidic mixing channel is provided with a liquid outlet, and the middle position of the rotating liquid receiving structure is provided with two syringe placement connection holes corresponding to the liquid inlet, Liquid inlet syringes are respectively installed in the connecting holes of the syringes, and the liquid outlets are used in conjunction with the liquid contact centrifuge tube and the sample collection centrifuge tube.
作为优选的技术方案,所述芯片为Y型结构芯片或T型结构芯片。As a preferred technical solution, the chip is a Y-shaped structure chip or a T-shaped structure chip.
作为优选的技术方案,所述壳体的前面开设有开口,所述开口上安装有开门。As a preferred technical solution, an opening is opened on the front of the housing, and a door is installed on the opening.
作为优选的技术方案,所述触屏交互控制机构的触摸屏与水平面呈75°角。As a preferred technical solution, the touch screen of the touch screen interactive control mechanism forms an angle of 75° with the horizontal plane.
由于采用了上述技术方案,一种微流控设备,包括壳体,壳体的内部安装有推送液机构,推送液机构的上方连通有微流液相混合机构,微流液相混合机构的下方连通有接液机构,壳体的上部安装有触屏交互控制机构,触屏交互控制机构控制连接推送液机构、微流液相混合机构和接液机构;本实用新型的有益效果是:Due to the adoption of the above technical solution, a microfluidic device includes a housing, a liquid pushing mechanism is installed inside the housing, a microfluidic liquid phase mixing mechanism is connected above the liquid pushing mechanism, and a microfluidic liquid phase mixing mechanism is connected below the microfluidic liquid phase mixing mechanism. Connected with a liquid contact mechanism, the upper part of the housing is equipped with a touch screen interactive control mechanism, which controls and connects the push liquid mechanism, the micro-flow liquid phase mixing mechanism and the liquid contact mechanism; the beneficial effects of the utility model are:
(1)设备构造简约、自动化程度高、友好的交互解决方案、制备精度高。本实用新型通过自动化精确控制两个通道原液进入微流液相混合机构内的进液量及进液速度,达到精确控制两组液相混合的配比。(1) The equipment has a simple structure, a high degree of automation, a friendly interactive solution, and high preparation accuracy. The utility model achieves precise control of the mixing ratio of two groups of liquid phases through automatic and precise control of the feed volume and speed of two channel raw liquids entering the micro-fluid liquid phase mixing mechanism.
(2)触屏交互控制机构,包括触摸屏,微控制芯片,各传感器部件等,组成完整系统。UI界面美观、直观,便捷操作,反馈的工作状态和流程直观明了。(2) Touch screen interactive control mechanism, including touch screen, micro-control chip, various sensor components, etc., to form a complete system. The UI interface is beautiful, intuitive, and easy to operate, and the feedback of the working status and process is intuitive and clear.
(3)推送液机构结合多种传感器,收集运动过程数据,精确送液的精度,自动化处理液相制备过程中的运动。(3) The liquid pushing mechanism is combined with a variety of sensors to collect movement process data, accurately deliver the liquid, and automatically process the movement in the liquid phase preparation process.
(4)微流液相混合机构可兼容多种型号的注射器,并配备了重新开发的软件调试系统。该设计可针对新增注射器的各种参数进行测试,并可在测试完成后加入该注射器作为本实用新型使用。(4) The microfluidic liquid phase mixing mechanism is compatible with various types of syringes, and is equipped with a redeveloped software debugging system. The design can be tested for various parameters of the newly added syringe, and after the test is completed, the syringe can be added to be used as the utility model.
(5)本实用新型可用于更高流速的液相混合样品的制备,例如高于16ml/min流速的LNP的制备。本实用新型使用更大扭矩的驱动电机,并采用重新设计的软件系统和供电系统。本实用新型采用的驱动电机可实现高精度、大负载驱动注推机构。本实用新型使用的软件系统可以进一步细分驱动单元的脉冲发送,从而实现液相高流速混合。(5) The utility model can be used for the preparation of liquid-phase mixed samples with a higher flow rate, for example, the preparation of LNP with a flow rate higher than 16ml/min. The utility model uses a driving motor with a larger torque, and adopts a redesigned software system and power supply system. The driving motor adopted in the utility model can realize high-precision and large-load driving injection and pushing mechanism. The software system used in the utility model can further subdivide the pulse transmission of the driving unit, so as to realize the mixing of the liquid phase at a high flow rate.
(6)接液机构采用半圆状环形运动机构,并设置两组收集试管夹具结构。收集试管夹具结构采用的是200度的圆弧结构设计,该设计便于收集液体的试管或者离心管的固定和取放操作。半圆形机构围绕微流液相混合机构布置,不仅节省了结构空间,更是完美的实现了废液与目标液体的接收和更替运动。该设计具有对称结构样式,设备配重平衡,设备运行稳定,外形设计美观。(6) The liquid contact mechanism adopts a semi-circular circular motion mechanism, and two sets of clamp structures for collecting test tubes are set. The collection test tube fixture structure adopts a 200-degree arc structure design, which is convenient for fixing and picking and placing the test tube or centrifuge tube for collecting liquid. The semicircular mechanism is arranged around the microfluidic liquid phase mixing mechanism, which not only saves the structure space, but also perfectly realizes the receiving and replacement movement of waste liquid and target liquid. The design has a symmetrical structure style, the equipment has a balanced counterweight, the equipment operates stably, and the appearance design is beautiful.
(7)本实用新型的壳体采用左边开门设计,更加符合人体工学,使用操作更加便利。(7) The housing of the utility model adopts the design of opening the door on the left side, which is more ergonomic and more convenient to use and operate.
(8)本实用新型的混合液相流速范围0~200ml/min,适用范围更广。可用于前期工艺探索和后期工艺放大等多种业务场景。(8) The flow rate of the mixed liquid phase of the present invention ranges from 0 to 200ml/min, and has a wider application range. It can be used in various business scenarios such as pre-process exploration and post-process amplification.
附图说明Description of drawings
以下附图仅旨在于对本实用新型做示意性说明和解释,并不限定本实用新型的范围。其中:The following drawings are only intended to illustrate and explain the utility model schematically, and do not limit the scope of the utility model. in:
图1是本实用新型一种微流控设备的开门打开状态结构示意图;Fig. 1 is a schematic diagram of the structure of a microfluidic device of the present invention in the open state of the door;
图2是本实用新型一种微流控设备的开门关闭状态结构示意图;Fig. 2 is a schematic structural diagram of a microfluidic device of the present invention in the state of opening and closing the door;
图3是本实用新型一种微流控设备的内部结构示意图;3 is a schematic diagram of the internal structure of a microfluidic device of the present invention;
图4是本实用新型一种微流控设备的推送液机构的局部放大图;Fig. 4 is a partially enlarged view of a liquid pushing mechanism of a microfluidic device of the present invention;
图5是本实用新型一种微流控设备的接液机构的局部放大图之一;Fig. 5 is one of the partially enlarged views of the liquid-contacting mechanism of a microfluidic device of the present invention;
图6是本实用新型一种微流控设备的接液机构的局部放大图之二;Fig. 6 is the second partial enlarged view of the liquid-contacting mechanism of a microfluidic device of the present invention;
图7是本实用新型一种微流控设备的微流液相混合机构的结构示意图;Fig. 7 is a structural schematic diagram of a microfluidic liquid phase mixing mechanism of a microfluidic device of the present invention;
图8是本实用新型一种微流控设备的推送液推子的结构示意图;Fig. 8 is a schematic structural view of a pushing fluid pusher of a microfluidic device of the present invention;
图9是本实用新型一种微流控设备的芯片的内部结构示意图;9 is a schematic diagram of the internal structure of a chip of a microfluidic device of the present invention;
图10是本实用新型一种微流控设备的芯片的外部结构示意图;Fig. 10 is a schematic diagram of the external structure of a chip of a microfluidic device of the present invention;
图中:1-壳体;2-触摸屏;3-推送液机构;31-推送液安装座;32-滑台螺杆;33-推子本体;34-初始位置检测传感器;35-推子接触板轴承;36-推子接触板;37-推子支撑结构;38-触发传感器;4-微流液相混合机构;41-芯片;42-微流混合通道;43-进液口;44-出液口;45-注射器放置连接孔;46-进液注射器;5-接液机构;51-混合液接收装置支撑体;52-旋转收液结构体;53-旋转收液机构齿轮;54-旋转收液机构驱动齿轮;55-收集试管夹具结构;56-接液离心管;57-样品收集离心管;6-开门。In the figure: 1-housing; 2-touch screen; 3-push liquid mechanism; 31-push liquid mount; 32-slide screw; 33-fader body; 34-initial position detection sensor; 35-fader contact plate Bearing; 36-fader contact plate; 37-fader support structure; 38-trigger sensor; 4-microfluidic liquid phase mixing mechanism; 41-chip; 42-microfluidic mixing channel; 43-liquid inlet; 44-outlet Liquid port; 45-syringe placement connection hole; 46-injection syringe; 5-liquid contact mechanism; 51-support body of mixed liquid receiving device; 52-rotary liquid receiving structure; The driving gear of the liquid receiving mechanism; 55-the fixture structure of the collection test tube; 56-the liquid-contacting centrifuge tube; 57-the sample collection centrifuge tube; 6-opening the door.
具体实施方式Detailed ways
下面结合附图和实施例,进一步阐述本实用新型。在下面的详细描述中,只通过说明的方式描述了本实用新型的某些示范性实施例。毋庸置疑,本领域的普通技术人员可以认识到,在不偏离本实用新型的精神和范围的情况下,可以用各种不同的方式对所描述的实施例进行修正。因此,附图和描述在本质上是说明性的,而不是用于限制权利要求的保护范围。Below in conjunction with accompanying drawing and embodiment, further set forth the utility model. In the following detailed description, certain exemplary embodiments of the present invention are described by way of illustration only. Needless to say, those skilled in the art would realize that the described embodiments may be modified in various different ways, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and description are illustrative in nature and not intended to limit the scope of the claims.
如图1至图10共同所示,一种微流控设备,包括壳体1,壳体1的内部安装有推送液机构3,推送液机构3的上方连通有微流液相混合机构4,微流液相混合机构4的下方连通有接液机构5,壳体1的上部安装有触屏交互控制机构,触屏交互控制机构控制连接推送液机构3、微流液相混合机构4和接液机构5;推送液机构3、接液机构5均容置于壳体1内;微流液相混合机构4包括两个进液口43、微流混合通道42和一个出液口44。进液口43和出液口44通过微流混合通道42相连通,推送液机构3能够推送原料液体于进液口43内,接液机构5能够接收自出液口44的微流体混合液。As shown in Figures 1 to 10, a microfluidic device includes a
本实用新型具有以下优点:The utility model has the following advantages:
(1)设备构造简约、自动化程度高、友好的交互解决方案、制备精度高。本实用新型通过自动化精确控制两个通道原液进入微流液相混合机构4内的进液量及进液速度,达到精确控制两组液相混合的配比。(1) The equipment has a simple structure, a high degree of automation, a friendly interactive solution, and high preparation accuracy. The utility model achieves precise control of the mixing ratio of the two groups of liquid phases through automatic and precise control of the feed volume and speed of the raw liquids of the two channels into the micro-flow liquid
(2)触屏交互控制机构,包括触摸屏2,微控制芯片41,各传感器部件等,组成完整系统。UI界面美观、直观,便捷操作,反馈的工作状态和流程直观明了。(2) The touch screen interactive control mechanism, including the
(3)推送液机构3结合多种传感器,收集运动过程数据,精确送液的精度,自动化处理液相制备过程中的运动。(3) The
(4)微流液相混合机构4可兼容多种型号的进液注射器46,并配备了重新开发的软件调试系统。该设计可针对新增进液注射器46的各种参数进行测试,并可在测试完成后作为本实用新型使用。(4) The microfluidic liquid-
(5)本实用新型可用于更高流速的液相混合样品的制备,例如高于16ml/min流速的LNP的制备。本实用新型使用更大扭矩的驱动电机,并采用重新设计的软件系统和供电系统。本实用新型采用的驱动电机可实现高精度、大负载驱动注推机构。本实用新型使用的软件系统可以进一步细分驱动单元的脉冲发送,从而实现液相高流速混合。(5) The utility model can be used for the preparation of liquid-phase mixed samples with a higher flow rate, for example, the preparation of LNP with a flow rate higher than 16ml/min. The utility model uses a driving motor with a larger torque, and adopts a redesigned software system and power supply system. The driving motor adopted in the utility model can realize high-precision and large-load driving injection and pushing mechanism. The software system used in the utility model can further subdivide the pulse transmission of the driving unit, so as to realize the mixing of the liquid phase at a high flow rate.
(6)接液机构5采用半圆状环形运动机构,并设置两组收集试管夹具结构55。收集试管夹具结构55采用的是200度的圆弧结构设计,该设计便于收集液体的试管或者离心管的固定和取放操作。半圆形机构围绕微流液相混合机构4布置,不仅节省了结构空间,更是完美的实现了废液与目标液体的接收和更替运动。该设计具有对称结构样式,设备配重平衡,设备运行稳定,外形设计美观。(6) The liquid-contacting
(7)本实用新型的壳体1采用左边开门设计,更加符合人体工学,使用操作更加便利。(7) The
(8)本实用新型的混合液相流速范围0~200ml/min,适用范围更广。可用于前期工艺探索和后期工艺放大等多种业务场景。(8) The flow rate of the mixed liquid phase of the present invention ranges from 0 to 200ml/min, and has a wider application range. It can be used in various business scenarios such as pre-process exploration and post-process amplification.
如图1、图3、图4和图8共同所示,推送液机构3包括安装在壳体1内底部的两个推送液安装座31,每个推送液安装座31上分别垂直安装有一根滑台螺杆32,每根滑台螺杆32上分别安装有推送液推子,推送液安装座31上安装有初始位置检测传感器34。推送液机构3用于将原料液按设定比例和速度推送入芯片41的微流混合通道42。壳体1内部纵向布置两组滑台螺杆32,两个推送液推子安装在两组滑台螺杆32上随螺杆运动而运动,两组初始位置检测传感器34安装在两组滑台螺杆32末端固定位置,用于精准定位推送液推子的初始位置。推送液推子跟随滑台螺杆32向上移动时,对进液注射器46进行推送,将两支进液注射器46内的药物推入微流液相混合机构4内进行混合,推送液机构3还包括动力驱动装置,动力驱动装置主要采用滑台螺杆32和步进电机相结合的驱动技术。本实用新型利用精度最高的滚珠丝杆滑台对两相液体进行推送,再利用步进电机驱动在程序控制下驱动MCU的高级定时器精确输出指定高频率PWM波形,从而实现精确控制推送速度和距离。本实用新型在主控软件通过进一步细分输出PWM,可实现最大移动精确度0.0006mm。动力驱动机构结合了滑台螺杆32和步进电机驱动技术的自身优势,从而实现了高精度,高测试重复性的液体混合的自动化精确定位推送。As shown in Figure 1, Figure 3, Figure 4 and Figure 8, the pushing
如图1、图3、图4和图8共同所示,推送液推子包括安装在滑台螺杆32上的推子本体33,推子本体33的上部通过推子接触板轴承35铰接有推子接触板36,推子本体33的下部固定安装有推子支撑结构37,推子支撑结构37上安装有触发传感器38,推子接触板36的下表面与触发传感器38弹性接触。推子接触板36通过推子接触板轴承35连接到推子本体33上,可上下小范围活动,触发传感器38安装在推子接触板36的下方,位于推子支撑结构37的内部,触发传感器38弹性支撑推子接触板36。As shown in Fig. 1, Fig. 3, Fig. 4 and Fig. 8 together, the pushing fluid fader includes a
如图1、图3、图5、图6和图7共同所示,接液机构5包括固定安装在壳体1内上部的混合液接收装置支撑体51,混合液接收装置支撑体51的底面上设有半圆形槽位,半圆形槽位内安装有半圆环形的旋转收液结构体52,旋转收液结构体52的一侧设有旋转收液机构齿轮53,混合液接收装置支撑体51的底面上还安装有与旋转收液机构齿轮53相啮合的旋转收液机构驱动齿轮54。接液机构5拥有独特的环形运动结构,旋转收液机构驱动齿轮54与设置在旋转收液结构体52的旋转收液机构齿轮53啮合,驱动旋转收液结构体52实现左右旋转运动。收集试管夹具结构55设置在驱动旋转收液结构体52半圆的中间位置,其上可安装接液离心管56和样品收集离心管57用于接收从芯片41输出的混合液体。As shown in Fig. 1, Fig. 3, Fig. 5, Fig. 6 and Fig. 7, the
如图1、图3、图5和图6共同所示,混合液接收装置支撑体51的中间部位设置有两个收集试管夹具结构55,收集试管夹具结构55上分别安装有接液离心管56和样品收集离心管57。在两液相推注初期,混合比例未达到设定参数前的混合液体被作为废液由接液离心管56收集。在达到设定混合参数时的样品由样品收集离心管57收集。接液离心管56和样品收集离心管57可以根据参数设定由系统实现自动切换操作。As shown in Fig. 1, Fig. 3, Fig. 5 and Fig. 6, the middle part of the
如图1、图3、图5、图7、图9和图10共同所示,微流液相混合机构4包括安装在混合液接收装置支撑体51顶部的芯片41,芯片41内部设有微流混合通道42,微流混合通道42的一端设有两个进液口43、微流混合通道42的另一端设有一个出液口44,旋转收液结构体52的中间位置设置有两个与进液口43相对应的注射器放置连接孔45,注射器放置连接孔45内分别安装有进液注射器46,出液口44与接液离心管56和样品收集离心管57配合使用。微流液相混合机构4可配合内部Y型结构芯片41和T型结构芯片41使用。如图9所示,以Y型结构芯片41为例进行说明,微流液相混合机构4带有两个螺纹接口,即两个进液口43,可实现和两个进液注射器46的紧密衔接,确保无泄漏产生。在推送液机构3的精准驱动下,两相液体在微流液相混合机构4内实现快速的混合。As shown in Fig. 1, Fig. 3, Fig. 5, Fig. 7, Fig. 9 and Fig. 10, the microfluidic liquid
如图1和图2共同所示,壳体1的前面开设有开口,开口上安装有开门6。壳体1采用左边开门设计,更加符合人体工学,使用操作更加便利。As shown in Fig. 1 and Fig. 2 together, an opening is opened on the front of the
如图1和图2共同所示,触屏交互控制机构的触摸屏2与水平面呈75°角。触屏交互控制机构用于对本实用新型的液体推进体积,推进速度比例,进样总流速,废液体积,和收集样品体积等进行设定。触屏交互控制机构采用内核的STM32F7系列超高性能MCU平台。通过触屏交互控制UI对样品制备参数进行设置、实现对驱动的控制和对多种传感器的控制,从而实现了设备的自动化操作。As shown in Figure 1 and Figure 2 together, the
本实用新型的工作流程:Work process of the present utility model:
将两个进液注射器46通过注射器放置连接孔45分别与芯片41的两个进液口43相连接;将接液离心管56和样品收集离心管57放置于收集试管夹具结构55内,跟随旋转收液结构体52转动;而后,在触屏交互控制机构设置两相液体体积分别为3ml和12ml,总流速为16ml/min,废液收集为0.5ml。接着,通过初始化设置,两个推送液推子通过两组滑台螺杆32随螺杆运动,在两组初始位置检测传感器34的控制下精准定位于推送液推子的初始位置。最后,通过触屏交互控制机构的启动程序,推送液推子通过两组滑台螺杆32将两相液体按照设定比例和流速进行推进,同时接液离心管56在收集完成设定体积废液后,通过旋转收液机构驱动齿轮54移动出接液位置,样品收集离心管57移动到接液位置进行样品收集。在完成设定程序,样品制备完成后,液体推送运动将停止,样品收集离心管57可取下。在两相液体推送过程中,如若其中一相液体低于设定参数,推送液机构3将提前停止运动。Connect the two
本实用新型使用滑台螺杆32结合步进电机,使用内核的STM32F7系列超高性能MCU的平台开发一套集触屏交互控制UI,精确实时步进电机驱动,多种传感器驱动紧密结合配合工作,实现自动化精确定位推送液体混合的装置。步进电机驱动:编写程序,驱动MCU的高级定时器精确输出指定高频率PWM波形,实现精确控制推送速度和距离。MCU可输出PWM频率范围:20HZ~100KHZ。在主控软件通过进一步细分输出PWM,可实现最大移动精确度是0.0006mm。对于精确混合两相液体意义重大。The utility model uses the sliding
本实用新型核心部件工作过程:在触屏交互控制机构分别设置两个通道的推送液体的量和速度,系统获取到设置的数值,经过计算转换成对应PWM数量和PWM频率。之后数据发送给驱动,在MCU设置具体定时器相关寄存器数据,之后启动定时器工作。定时器工作不占用MCU主进程,避免了由主线程运行造成的时序影响驱动步进电机的精确性。因此两个通道步进电机开始按照设定运动,推动各自通道注射器,通过芯片41进行混合。The working process of the core components of the utility model: the amount and speed of the pushing liquid of the two channels are respectively set in the touch screen interactive control mechanism, and the system obtains the set value, which is converted into the corresponding PWM quantity and PWM frequency through calculation. Then the data is sent to the driver, and the specific timer-related register data is set in the MCU, and then the timer is started to work. The timer work does not occupy the main process of the MCU, which avoids the timing impact caused by the main thread running on the accuracy of driving the stepper motor. Therefore, the stepper motors of the two channels start to move according to the setting, and push the syringes of the respective channels to mix through the
本实用新型独有的环形运动结构,用于收集废液和目标样品的结构。其结构简单巧妙,可有效减少设备体积,并且对称结构样式,有利于设备配重的平衡,提高了设备运行的稳定性,提高了设计美感。The unique circular motion structure of the utility model is used for collecting waste liquid and target samples. Its structure is simple and ingenious, which can effectively reduce the volume of the equipment, and the symmetrical structure style is conducive to the balance of the counterweight of the equipment, improves the stability of the equipment operation, and improves the design aesthetics.
本实用新型设计之初就考虑到单次混合容量,速度,和兼容多种型号注射器的使用场景。为了满足大容量混合的情况,设计使用有效行程更大丝杆滑台机构,同时有效负载也相应提高。设备软件系统也针对大容量混合做好的优化与适配。一些列的改进措施保证了设备有效完成大容量液相混合的需求。At the beginning of the design of the utility model, the single mixing capacity, speed, and use scenarios compatible with various types of syringes have been taken into consideration. In order to meet the situation of large-capacity mixing, the design uses a screw slide mechanism with a larger effective stroke, and the effective load is also increased accordingly. The equipment software system is also optimized and adapted for large-capacity mixing. A series of improvement measures ensure that the equipment can effectively complete the large-capacity liquid-phase mixing requirements.
本实用新型兼容多种型号的注射器,软件系统开发了一套调试系统,用于针对新增注射器的各种参数进行测试。待测试完成,即可加入该注射器作为本设备使用。The utility model is compatible with various types of syringes, and the software system has developed a set of debugging system for testing various parameters of the newly added syringes. After the test is completed, the syringe can be added and used as the device.
本实用新型不仅可以用于前期l~20ml/min流速范围的低流速纳米药脂质物处方筛选,更突破性的解决了传统微流控装置不能工艺放大的问题,最高流速可以支持到200ml/min。The utility model can not only be used for the screening of low-flow-velocity nano-medicine lipids in the range of 1-20ml/min in the early stage, but also solves the problem that the traditional microfluidic control device cannot be scaled up, and the maximum flow rate can support up to 200ml/min. min.
本实用新型其设备构造简单、自动化程度高、操作方便、制备精度较高,使用微混合装置制备微流体混合液,通过自动化精确控制原料液体的进入微混合装置内的进液量及进液速度,以精确控制各原料液体之间的配比,另外,接液机构5的不同接液管之间可自动切换,能够实现制备的微流体混合液的多剂量连续制备。The utility model has the advantages of simple equipment structure, high degree of automation, convenient operation, and high preparation precision. The microfluid mixed liquid is prepared by a micro-mixing device, and the amount and speed of the raw material liquid entering the micro-mixing device are precisely controlled through automation. , to accurately control the ratio of the various raw material liquids, in addition, the different liquid receiving tubes of the
本实用新型制备经典LNP处方情况表:The utility model prepares the classic LNP prescription situation table:
通过本实用新型,采用阳离子Dlin-MC3-DMA经典LNP处方,以包括阳离子,胆固醇,辅助磷脂DOPC,PEG2000-DSPE在内的四组分按照摩尔比50:38:10:2溶解在乙醇中得到10ml的脂质乙醇溶液;将表达萤火虫荧光素酶的pDNA质粒稀释在pH 4的醋酸钠溶液中,按照下表1中的参数设定,得到pDNA/MC3LNP,得到的LNP的粒径尺寸、分布及包封率如下表1。Through this utility model, the cationic Dlin-MC3-DMA classic LNP prescription is adopted, and four components including cationic, cholesterol, auxiliary phospholipid DOPC, and PEG2000-DSPE are dissolved in ethanol according to the molar ratio of 50:38:10:2 to obtain 10ml lipid ethanol solution; Dilute the pDNA plasmid expressing firefly luciferase in the sodium acetate solution of
表1制备经典LNP处方情况表Table 1 Preparation of classic LNP prescription situation table
上述PDI表示粒子的分散性指数,数据结果证实了本实用新型得到的包裹DNA的基因药物粒径尺寸小、分散性好、包封率高。本实用新型制备的pDNA/MC3 LNP,在小鼠的体内实验中呈现良好pDNA递送效果,小鼠体内萤火虫荧光素酶的表达量与注射剂量成相性关,并在14天内都有稳定表达。The above-mentioned PDI represents the dispersibility index of the particles, and the results of the data confirm that the DNA-encapsulating gene drug obtained by the utility model has a small particle size, good dispersibility, and high encapsulation efficiency. The pDNA/MC3 LNP prepared by the utility model shows a good pDNA delivery effect in the in vivo experiment of mice, and the expression level of firefly luciferase in the mice is correlated with the injection dose, and has a stable expression within 14 days.
本申请中涉及软件、电路程序的技术特征,其功能的实现属于现有技术,本申请技术方案的实质是对硬件部分的组成以及连接关系进行的改进,并不涉及软件程序或电路结构本身的改进。This application involves the technical features of software and circuit programs, and the realization of its functions belongs to the prior art. The essence of the technical solution of this application is to improve the composition and connection relationship of hardware parts, and does not involve the software program or circuit structure itself. Improve.
在本实用新型的描述中,需要理解的是,术语“上”、“下”、“前”、“后”、“左”、“右”、“顶”、“底”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本实用新型和简化描述,而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作,因此不能理解为对本实用新型的限制。In describing the present utility model, it should be understood that the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", The orientation or positional relationship indicated by "outside" is based on the orientation or positional relationship shown in the drawings, which is only for the convenience of describing the utility model and simplifying the description, rather than indicating or implying that the referred device or element must have a specific orientation , are constructed and operated in a specific orientation and therefore cannot be construed as limiting the invention.
以上显示和描述了本实用新型的基本原理、主要特征及本实用新型的优点。本行业的技术人员应该了解,本实用新型不受上述实施例的限制,上述实施例和说明书中描述的只是说明本实用新型的原理,在不脱离本实用新型精神和范围的前提下,本实用新型还会有各种变化和改进,这些变化和改进都落入要求保护的本实用新型范围内。本实用新型要求保护范围由所附的权利要求书及其等效物界定。The basic principles, main features and advantages of the present utility model have been shown and described above. Those skilled in the industry should understand that the utility model is not limited by the above-mentioned embodiments. The above-mentioned embodiments and descriptions only illustrate the principles of the utility model. Without departing from the spirit and scope of the utility model, the utility model The new model also has various changes and improvements, and these changes and improvements all fall within the scope of the claimed utility model. The scope of protection required by the utility model is defined by the appended claims and their equivalents.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117414882A (en) * | 2023-12-08 | 2024-01-19 | 东富龙生命科技有限公司 | Nanomedicine production equipment based on microfluidic technology |
| CN118681612A (en) * | 2024-08-23 | 2024-09-24 | 苏州艾特森制药设备有限公司 | Preparation control method based on droplet microfluidics technology |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117414882A (en) * | 2023-12-08 | 2024-01-19 | 东富龙生命科技有限公司 | Nanomedicine production equipment based on microfluidic technology |
| CN117414882B (en) * | 2023-12-08 | 2025-12-16 | 东富龙生命科技有限公司 | Nanometer medicine production facility based on micro-fluidic technology |
| CN118681612A (en) * | 2024-08-23 | 2024-09-24 | 苏州艾特森制药设备有限公司 | Preparation control method based on droplet microfluidics technology |
| CN118681612B (en) * | 2024-08-23 | 2024-12-20 | 苏州艾特森制药设备有限公司 | Preparation control method based on droplet microfluidics technology |
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