CN108760485A - A kind of equipment for the detection of micro-nano-scale substance physical characteristic - Google Patents
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Abstract
本发明公开了一种用于微纳米尺度物质物理特性检测的设备,包括支撑架、高精度定位平台和对焦装置,支撑架由上支撑板和下支撑板组成,高精度定位平台由具有三自由度的纳米精度位移台和具有两自由度的微米精度位移台组成,微米精度位移台和纳米精度位移台从下到上依次设置于上支撑板上方,纳米精度位移台上设有样品台,上支撑板顶部通过连接杆设置有三角形安装板,三角形安装板上设有探针升降电机和探针夹持器,探针夹持器上夹持有探针;对焦装置包括显微镜镜筒、对焦电机、CCD视频传感器和物镜,物镜和CCD视频传感器安装在显微镜镜筒上,显微镜镜筒安装于对焦电机,下支撑板上安装有具有二自由度的粗调位移台,对焦电机安装于粗调位移台。
The invention discloses a device for detecting the physical characteristics of micro-nano scale substances, including a support frame, a high-precision positioning platform and a focusing device. The support frame is composed of an upper support plate and a lower support plate, and the high-precision positioning platform has three freedoms. degree of nano-precision translation stage and a micron-precision translation stage with two degrees of freedom. The micron-precision translation stage and the nano-precision translation stage are arranged above the upper support plate in sequence from bottom to top. The nano-precision translation stage is equipped with a sample stage. The top of the support plate is provided with a triangular mounting plate through the connecting rod, and the triangular mounting plate is provided with a probe lifting motor and a probe holder, and the probe holder holds a probe; the focusing device includes a microscope lens barrel, a focusing motor , CCD video sensor and objective lens. The objective lens and CCD video sensor are installed on the microscope lens barrel. tower.
Description
技术领域technical field
本发明涉及一种专用于微纳米尺度物质的物理特性的设备,具体涉及一种用于微纳尺度粒子(如聚合物粒子)、微纳尺度活体生物材料(细胞、蛋白质、DNA等)的物理特性检测的设备。The present invention relates to a kind of equipment dedicated to the physical properties of micro-nanoscale substances, in particular to a physical device for micro-nanoscale particles (such as polymer particles) and micro-nanoscale living biological materials (cells, proteins, DNA, etc.) Devices for feature detection.
背景技术Background technique
癌症目前被诊断为是全球第二大死因,在2012年全世界癌症患者有1410万,并且估计到2035年,这个数字将会达到2400万,提高对癌症的状况和发展过程的手段是非常紧要的任务。2007年,哈佛-麻省理工健康科学与技术部门的Subra Suresh总结目前癌细胞研究现状并指出癌细胞的机械特性与正常细胞具有显著区别,在过去的几年里,单细胞生物学研究中已经进行了单个细胞的纳米机械和电生理学性质的探索。然而,迄今为止的大多数研究是经验性的,缺乏对机理的理解,因此对癌症治疗的作用是有限的。因此,研发高精度的单个细胞机械特性检测技术对揭示癌细胞的发展及产生原因来说是紧急和重要的。Cancer is currently diagnosed as the second leading cause of death in the world. In 2012, there were 14.1 million cancer patients worldwide, and it is estimated that by 2035, this number will reach 24 million. It is very urgent to improve the means of understanding the status and development of cancer task. In 2007, Subra Suresh of the Harvard-MIT Department of Health Science and Technology summarized the current status of cancer cell research and pointed out that the mechanical properties of cancer cells are significantly different from normal cells. In the past few years, single-cell biology research has been The exploration of the nanomechanical and electrophysiological properties of individual cells was performed. However, most of the studies to date are empirical and lack mechanistic understanding, thus their impact on cancer therapy is limited. Therefore, it is urgent and important to develop high-precision single-cell mechanical property detection technology to reveal the development and cause of cancer cells.
同时,深入研究微纳尺度物质的物理学特性有利于揭示物质的性质及变化过程,对于材料领域、生物领域的发展具有重大的推动作用。At the same time, an in-depth study of the physical properties of matter at the micro-nano scale is conducive to revealing the nature and change process of matter, and has a significant role in promoting the development of the field of materials and biology.
发明内容Contents of the invention
本发明的目的是为了克服现有技术中的不足,提供一种用于微纳米尺度物质物理特性检测的设备,主要涉及对微纳米尺度物质的实时观测、确定微纳米尺度物质和探针的相对位置关系、高精度纳米级的物理参数检测、高精度探针定位、高精度探针力和位移施加的功能实现。The purpose of the present invention is to overcome the deficiencies in the prior art and provide a device for detecting the physical characteristics of micro-nanoscale substances, which mainly involves real-time observation of micro-nanoscale substances and determining the relative relationship between micro-nanoscale substances and probes. Functional realization of positional relationship, high-precision nanoscale physical parameter detection, high-precision probe positioning, high-precision probe force and displacement application.
本发明的目的是通过以下技术方案实现的:The purpose of the present invention is achieved through the following technical solutions:
一种用于微纳米尺度物质物理特性检测的设备,包括支撑架、高精度定位平台和对焦装置,所述支撑架由上支撑板和下支撑板组成,所述高精度定位平台由具有三自由度的纳米精度位移台和具有两自由度的微米精度位移台组成,所述微米精度位移台和纳米精度位移台从下到上依次设置于所述上支撑板的上方,所述纳米精度位移台上设有样品台,所述上支撑板、微米精度位移台和纳米精度位移台中心均相对应地设有用于为显微镜提供观测空间的通孔,所述上支撑板顶部还通过连接杆设置有三角形安装板,三角形安装板上设有探针升降电机和探针夹持器,所述探针夹持器通过所述探针升降电机驱动,探针夹持器上夹持有探针,探针可为MEMS力探针或极细导电探针或其它物理参数探针;对焦装置包括显微镜镜筒、对焦电机、CCD视频传感器和物镜,所述物镜和CCD视频传感器安装在所述显微镜镜筒上,显微镜镜筒安装于所述对焦电机,所述下支撑板上安装有具有二自由度的粗调位移台,对焦电机安装于所述粗调位移台。A device for detecting the physical properties of substances at the micro-nano scale, including a support frame, a high-precision positioning platform and a focusing device, the support frame is composed of an upper support plate and a lower support plate, and the high-precision positioning platform is composed of a three-freedom degree of nano-precision translation stage and a micron-precision translation stage with two degrees of freedom. There is a sample stage on the top, and the center of the upper support plate, the micron-precision translation stage and the nano-precision translation stage are correspondingly provided with through holes for providing observation space for the microscope, and the top of the upper support plate is also provided with a connecting rod A triangular mounting plate, the triangular mounting plate is provided with a probe lifting motor and a probe holder, and the probe holder is driven by the probe lifting motor, and the probe holder holds a probe. The needle can be a MEMS force probe or a very fine conductive probe or other physical parameter probe; the focusing device includes a microscope lens barrel, a focus motor, a CCD video sensor and an objective lens, and the objective lens and the CCD video sensor are installed in the microscope lens barrel On the top, the microscope lens barrel is installed on the focus motor, on the lower support plate is installed a coarse adjustment translation platform with two degrees of freedom, and the focus motor is installed on the coarse adjustment translation platform.
与现有技术相比,本发明的技术方案所带来的有益效果是:Compared with the prior art, the beneficial effects brought by the technical solution of the present invention are:
1.通过将高倍数光学显微镜和探针装置利用跨精度的纳米级、微米级位移台有效的结合在一起,通过较低成本实现对微纳米尺度物质的实时观测、定位、对针和检测。1. By effectively combining the high-magnification optical microscope and the probe device with the nano-scale and micron-scale translation stages with high precision, the real-time observation, positioning, needle alignment and detection of micro-nano scale substances can be realized at a low cost.
2.利用将中空的纳米位移台和微米位移台相结合,为高倍数倒置镜筒式光学显微镜提供观测和移动空间,避免和探针部分的运动相互干扰,解决高倍数显微镜工作空间过小的问题,实现低成本、快速的、操作方便的高精度微纳米尺度物质物理特性检测,且有利于推动微纳米尺度物质物理特性研究发展。2. Using the combination of hollow nanometer displacement stage and micrometer displacement stage, it provides observation and moving space for high magnification inverted lens barrel optical microscope, avoids mutual interference with the movement of the probe part, and solves the problem that the working space of high magnification microscope is too small To achieve low-cost, fast, and easy-to-operate high-precision detection of physical properties of micro-nano-scale substances, and to promote the research and development of physical properties of micro-nano-scale substances.
3.可利用MEMS的高精度测量特性来实现癌细胞机械、电学特性测量工作的可能。3. The high-precision measurement characteristics of MEMS can be used to realize the possibility of measuring the mechanical and electrical characteristics of cancer cells.
附图说明Description of drawings
图1为本发明的立体结构示意图;Fig. 1 is the three-dimensional structure schematic diagram of the present invention;
图2为本发明的正视结构示意图。Fig. 2 is a schematic diagram of the front view structure of the present invention.
附图标记:1、探针升降电机,2、探针夹持器,3、探针,4、样品台,5、物镜,6、纳米精度位移台,7、微米精度位移台,8、上支撑板,9、下支撑板,10、连接杆,11、三角形安装板,12、显微镜镜筒,13、CCD视频传感器,14、对焦电机,15、粗调位移台。Reference signs: 1. Probe lifting motor, 2. Probe holder, 3. Probe, 4. Sample stage, 5. Objective lens, 6. Nano-precision translation stage, 7. Micron-precision translation stage, 8. Upper Support plate, 9, lower support plate, 10, connecting rod, 11, triangular mounting plate, 12, microscope lens barrel, 13, CCD video sensor, 14, focusing motor, 15, coarse adjustment displacement stage.
具体实施方式Detailed ways
为能进一步了解本发明的发明内容、特点及功效,兹例举以下实施例,并配合附图详细说明如下:In order to further understand the invention content, characteristics and effects of the present invention, the following examples are given, and detailed descriptions are as follows in conjunction with the accompanying drawings:
请参阅图1和图2,一种用于微纳米尺度物质物理特性检测的设备,高精度探针3,所述的高精度探针3通过螺栓安装在探针夹持器2上,探针夹持器2通过螺栓连接在探针升降电机1的可动部位上,实现探针的升降,探针升降电机1通过连接杆10和三角形安装板11安装在上支撑板8上;样品台4通过螺栓与具有X、Y、Z三自由度的纳米精度位移台6可动部分通过螺栓固定连接在一起、纳米精度位移台6叠放在具有X、Y两自由度的微米精度位移台7可动部分上并通过螺栓相互连接,微米精度位移台7机架通过螺栓连接固定在上支撑板8上;高倍数的物镜5以及CCD视频传感器13安装在显微镜镜筒12上,显微镜镜筒12通过镜筒夹具安装在对焦电机14上、对焦电机14通过安装板安装在具有X、Y两自由度的手动粗调位移台15上,粗调位移台15通过螺栓连接安装在下支撑板9上。Please refer to Fig. 1 and Fig. 2, a kind of equipment for the detection of the physical characteristics of micro-nano scale material, high-precision probe 3, described high-precision probe 3 is installed on the probe holder 2 by bolt, the probe The holder 2 is connected to the movable part of the probe lifting motor 1 by bolts to realize the lifting of the probe. The probe lifting motor 1 is installed on the upper support plate 8 through the connecting rod 10 and the triangular mounting plate 11; the sample stage 4 The movable part of the nano-precision translation stage 6 with three degrees of freedom of X, Y, and Z is connected together by bolts, and the nano-precision translation stage 6 is stacked on the micron-precision translation stage 7 with two degrees of freedom of X and Y. The moving part is connected to each other by bolts, and the frame of the micron-precision displacement stage 7 is fixed on the upper support plate 8 by bolts; the high-magnification objective lens 5 and the CCD video sensor 13 are installed on the microscope barrel 12, and the microscope barrel 12 passes The lens barrel fixture is installed on the focusing motor 14, and the focusing motor 14 is installed on the manual coarse adjustment translation platform 15 with two degrees of freedom of X and Y through the mounting plate, and the coarse adjustment translation platform 15 is installed on the lower support plate 9 through bolt connection.
具体的,本实施例中上支撑板8、微米精度位移台7和纳米精度位移台6的上均相对应地设有用于为显微镜提供观测空间的通孔。Specifically, in this embodiment, the upper support plate 8 , the micron precision translation stage 7 and the nanometer precision translation stage 6 are respectively provided with through holes for providing observation space for the microscope.
本发明的工作原理如下:The working principle of the present invention is as follows:
首先确定探针3针尖在显微镜成像中的位置,利用显微镜对焦电机14将物镜5对焦在探针针尖附近距离,使用粗调位移台15调节显微镜位置,使探针3针尖位于成像范围之内,配合探针升降电机1和粗调位移台15并利用CCD视频传感器13判断是否成功对焦到探针针尖,记录此时探针升降电机1和对焦电机14位置数据以及探针针尖在显示器中的位置。利用探针升降电机1带动探针上升以免在放置样品时损坏探针,然后将放置样品的载玻片或培养皿放在样品台4上面。物镜5通过高倍数的物镜镜头放大样品,实现对微纳米尺度物质轮廓的清晰观察,调节显微镜对焦电机14上下运动,利用CCD视频传感器13产生的图像确定是否对焦到微纳米尺度物质上。First determine the position of the needle tip of the probe 3 in the microscope imaging, use the microscope focus motor 14 to focus the objective lens 5 at a distance near the probe tip, and use the coarse adjustment stage 15 to adjust the position of the microscope so that the needle tip of the probe 3 is within the imaging range. Cooperate with the probe lifting motor 1 and the coarse adjustment stage 15 and use the CCD video sensor 13 to judge whether the probe tip is successfully focused, and record the position data of the probe lifting motor 1 and focus motor 14 and the position of the probe tip on the display at this time . Utilize the probe lifting motor 1 to drive the probe up so as not to damage the probe when placing the sample, and then put the slide glass or petri dish on which the sample is placed on the sample stage 4 . The objective lens 5 magnifies the sample through a high-magnification objective lens to realize clear observation of the outline of the micro-nano scale material, adjust the microscope focus motor 14 to move up and down, and use the image generated by the CCD video sensor 13 to determine whether to focus on the micro-nano scale material.
使用微米精度位移台7对样品进行移动,通过CCD视频传感器13寻找目标物质。将目标物质通过微米精度位移台7大致移动到探针针尖下方,然后利用纳米精度位移台6进行水平方向精确位置调节,实现探针3针尖正对在目标物质中心。The sample is moved by a micron-precision displacement stage 7, and the target substance is searched for by a CCD video sensor 13. The target substance is roughly moved below the probe tip through the micron-precision translation stage 7, and then the nano-precision translation stage 6 is used to adjust the precise position in the horizontal direction, so that the needle tip of the probe 3 is directly aligned with the center of the target substance.
下降探针升降电机1,使其刚刚接触目标物质,通过检测MEMS探针3的电信号变化以及CCD视频传感器13的图像确定接触是否成功。然后利用纳米精度位移台6高精度的Z方向进给运动实现探针3对物质的压入。记录纳米精度位移台6的Z向进给距离以及MEMS探针3的电信号数值计算得到的物理参数值。如果采用MEMS力感应探针,通过Hertz接触模型,利用位移和力曲线计算得到物质的杨氏模量以及松弛时间,以及计算微纳尺度物质刚度和粘弹性系数等,或通过导电探针,检测物质的电学特性等。The probe lifting motor 1 is lowered so that it just touches the target substance, and whether the contact is successful is determined by detecting the change of the electrical signal of the MEMS probe 3 and the image of the CCD video sensor 13 . Then, the high-precision Z-direction feed motion of the nano-precision displacement stage 6 is used to realize the pressing of the probe 3 into the substance. Record the Z-direction feed distance of the nano-precision displacement stage 6 and the physical parameter values calculated from the electrical signal values of the MEMS probe 3 . If a MEMS force sensing probe is used, the Young’s modulus and relaxation time of the material can be calculated by using the displacement and force curves through the Hertz contact model, and the stiffness and viscoelastic coefficient of the micro-nano scale material can be calculated, or the conductive probe can be used to detect electrical properties of matter, etc.
综上,本发明可准确、方便、高效地测量微纳米尺度物质的物理特性。In summary, the present invention can accurately, conveniently and efficiently measure the physical properties of micro-nano-scale substances.
本发明并不限于上文描述的实施方式。以上对具体实施方式的描述旨在描述和说明本发明的技术方案,上述的具体实施方式仅仅是示意性的,并不是限制性的。在不脱离本发明宗旨和权利要求所保护的范围情况下,本领域的普通技术人员在本发明的启示下还可做出很多形式的具体变换,这些均属于本发明的保护范围之内。The present invention is not limited to the embodiments described above. The above description of the specific embodiments is intended to describe and illustrate the technical solution of the present invention, and the above specific embodiments are only illustrative and not restrictive. Without departing from the gist of the present invention and the scope of protection of the claims, those skilled in the art can also make many specific changes under the inspiration of the present invention, and these all belong to the protection scope of the present invention.
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