CN106802300B - A biological micromanipulator based on visual feedback - Google Patents
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Abstract
Description
技术领域technical field
本发明涉及生物操作仪器技术领域,属于一种使用视觉反馈的显微操作装置,可以对细胞、染色体等目标进行操作和装配作业。The invention relates to the technical field of biological operation instruments, and belongs to a micromanipulation device using visual feedback, which can operate and assemble objects such as cells and chromosomes.
背景技术Background technique
在生物医学工程领域和科研中,存在着大量涉及对细胞、染色体等的显微操作,如单精子注射,胚胎移植前抽取单细胞遗传学诊断,细胞的分离、显微注射、染色体的切割等,这些生物医学实验均涉及对细胞的观察和显微操作,对于这类工作,不但要求操作的精度要高,准确性好,而且要求操作时间短、效率高等。In the field of biomedical engineering and scientific research, there are a large number of micromanipulations involving cells and chromosomes, such as single sperm injection, genetic diagnosis of single cells extracted before embryo transfer, cell separation, microinjection, chromosome cutting, etc. , These biomedical experiments all involve the observation of cells and micromanipulation. For this kind of work, not only high precision and good accuracy are required, but also short operation time and high efficiency are required.
目前,显微操作都是人工通过显微操作仪器来完成的。这种显微操作设备一般包括括以下几部分,隔震台、显微镜、左微操作臂、右微操作臂,微夹持器(细胞吸附装置、微吸管等)、左操纵手柄、右操纵手柄等。其操作方式主要依靠操作人员观察显微镜目镜,在视野范围内根据观察到的微操作臂的位姿信息和细胞位置图像进行判断,并通过操纵手柄控制左右微操作臂进行作业。利用机械装置对人手的动作进行一定比例的缩放或者利用微电机运动,传递到微操作臂的操作工具(左操作臂上安装有微吸管,右操作臂上安装微注射针),使之对细胞进行操作。一般来讲,左微操作臂完成被操作对象的捕捉与固定,右微操作臂对被固定住的操作对象进行显微操作(如基因注射,染色体切割等)。这类显微操作仪通常没有任何控制器,没有任何传感器(显微镜除外)。作业质量易受操作者个人技术、精神状态及心理、情绪的影响。作业时间长,效率低,成本高,精度一致性差,细胞成活率低。At present, micromanipulation is all done manually through micromanipulation instruments. This kind of micromanipulation equipment generally includes the following parts, shock isolation table, microscope, left micromanipulator arm, right micromanipulator arm, microgripper (cell adsorption device, micropipette, etc.), left joystick, right joystick Wait. Its operation method mainly relies on the operator to observe the microscope eyepiece, judge according to the observed position and orientation information of the micro-manipulator arm and the image of the cell position within the field of view, and control the left and right micro-manipulator arms to perform operations through the joystick. Use a mechanical device to scale the movement of the human hand in a certain proportion or use a micro-motor to move, and transmit it to the operating tool of the micro-manipulator arm (the micro-pipette is installed on the left manipulator arm, and the micro-injection needle is installed on the right manipulator arm), so that it can affect the cells to operate. Generally speaking, the left micro-manipulator arm completes the capture and fixation of the manipulated object, and the right micro-manipulator arm performs micromanipulation (such as gene injection, chromosome cutting, etc.) on the fixed manipulated object. Such micromanipulators usually do not have any controllers, and do not have any sensors (except for the microscope). The quality of work is easily affected by the operator's personal technique, mental state, psychology and emotion. Long operation time, low efficiency, high cost, poor precision consistency, and low cell survival rate.
随着新技术的发展,很多图像设备也引入了生物显微操作领域,如很多新型的显微镜都可配备CCD或CMOS相机,可以将物镜视野内的图像通过相机传送到PC端,这样操作人员可以坐在电脑前,观察大屏幕来进行显微操作,这样做的好处是解放了人眼,使得操作人员不必将眼睛一直以固定的姿势放在目镜前。但是这一类的操作,依然是使用人手控制手柄进行操作,比如要将细胞夹持器向注射器移动较长的一端距离,手只能不断的朝一个方向运动或者不断的转动操作码盘。With the development of new technologies, many image devices have also been introduced into the field of biological micromanipulation. For example, many new microscopes can be equipped with CCD or CMOS cameras, which can transmit the images in the field of view of the objective lens to the PC through the camera, so that operators can Sitting in front of the computer and observing the large screen for microscopic operation, the advantage of this is that the human eye is liberated, so that the operator does not have to keep the eye in a fixed posture in front of the eyepiece. However, this type of operation is still operated by using the manual control handle. For example, to move the cell holder to the syringe for a longer distance, the hand can only move in one direction continuously or continuously rotate the operation code wheel.
发明内容Contents of the invention
本发明针对现有技术的不足,提供了一种基于视觉反馈的生物显微操作装置,可以实现对细胞进行精密的显微操作。并且引入了一个新的控制方式,有别于传统的细胞显微操作,可以将所有的工作全部在计算机端完成,不用人手通过手柄去控制微操作器,更加简化了操作,提高了准确性和效率。Aiming at the deficiencies of the prior art, the present invention provides a biological micromanipulation device based on visual feedback, which can realize precise micromanipulation of cells. And it introduces a new control method, which is different from the traditional cell micromanipulation. All the work can be completed on the computer side, without manual control of the micromanipulator through the handle, which simplifies the operation, improves the accuracy and efficiency.
本发明的技术方案如下:一种基于视觉反馈的生物显微操作装置,该装置包括显微图像采集模块、微位移平台、微操作手模块、主控制器和计算机。有别于传统的操作方式,引入了主控制器。The technical scheme of the present invention is as follows: a biological micromanipulation device based on visual feedback, which includes a microscopic image acquisition module, a micro-displacement platform, a micro-manipulator module, a main controller and a computer. Different from the traditional operation mode, the main controller is introduced.
所述的显微图像采集模块为安装在显微镜侧面的CCD相机,CCD相机作为整个操作装置的反馈源,主要功能为捕捉显微镜物镜视野内的图像,并通过USB线缆传送到计算机端进行采集和处理。The microscopic image acquisition module is a CCD camera installed on the side of the microscope. The CCD camera is used as the feedback source of the entire operating device. deal with.
所述的微位移平台包括XY水平平台、显微镜调焦电机和手柄控制器,其中XY水平平台托载被操作对象在垂直于物镜的平面上运动,显微镜调焦电机用来调节显微镜的物镜与被操作对象之间的距离,使得CCD相机采集到的图像足够清晰。手柄控制器是当操作装置工作在手动模式时,用来手动调节被操作对象和物镜之间的位置。The micro-displacement platform includes an XY horizontal platform, a microscope focusing motor and a handle controller, wherein the XY horizontal platform supports the object to be operated and moves on a plane perpendicular to the objective lens, and the microscope focusing motor is used to adjust the objective lens of the microscope and the object to be operated. Operate the distance between objects so that the image captured by the CCD camera is clear enough. The handle controller is used to manually adjust the position between the operated object and the objective lens when the operating device works in manual mode.
所述的微操作手模块包括左操作臂、左夹持器、右操作臂、右操作器、左操作臂驱动器、左操作臂手动控制器、右操作臂驱动器和右操作臂手动控制器,左夹持器安装在左操作臂上,用于夹持和固定细胞,右操作装置固定在右操作臂上,用来对细胞进行穿刺、注射等操作,左操作臂、右操作臂分别由左操作臂驱动器、右操作臂驱动器进行驱动,左操作臂驱动器和右操作臂驱动器连接到主控制器上,左操作臂手动控制器和右操作臂的手动控制器连接到主控制器上,由主控制器负责切换手动模式或计算机模式。The micro-manipulator module includes a left operating arm, a left gripper, a right operating arm, a right operator, a left operating arm driver, a left operating arm manual controller, a right operating arm driver and a right operating arm manual controller, the left The gripper is installed on the left operating arm for clamping and fixing the cells. The right operating device is fixed on the right operating arm for puncturing and injecting the cells. The left operating arm and the right operating arm are respectively operated by the left The driver of the arm and the driver of the right operating arm are driven, the driver of the left operating arm and the driver of the right operating arm are connected to the main controller, the manual controller of the left operating arm and the manual controller of the right operating arm are connected to the main controller, and are controlled by the main controller The controller is responsible for switching between manual mode and computer mode.
所述的主控制器为其他几个模块的控制中枢,其相当于显微操作装置和计算机之间的连接桥梁,主控制器负责将装置的传感器信息、手动控制器的脉冲信息等数据传递到计算机,同时将计算机传递过来的数据转换为控制指令,进而操作相关的模块运动,完成操作功能。The main controller is the control center of several other modules, which is equivalent to the connecting bridge between the micromanipulator and the computer. The main controller is responsible for transferring data such as sensor information of the device and pulse information of the manual controller to the At the same time, the computer converts the data transmitted by the computer into control instructions, and then operates the relevant module movements to complete the operation function.
所述的操作方式为本方案采用了新的控制方式,在主控制器或计算机端选择工作模式为手动模式或计算机模式。手动模式为传统的手工操作方法,而计算机模式则为所有操作全部在计算机端完成。计算机模式下,根据视觉反馈到的距离,通过计算机直接控制显微操作手的长距离移动,进一步解放了人手的操作,而且使得操作更加精确和有效。而且在计算机端的图像处理对要操作的目标进行判断和识别,提高了操作的自动化程度和效率。The described operation mode adopts a new control mode for this scheme, and the working mode is selected as manual mode or computer mode at the main controller or computer side. The manual mode is a traditional manual operation method, while the computer mode means that all operations are completed on the computer side. In the computer mode, according to the distance from the visual feedback, the long-distance movement of the micromanipulator is directly controlled by the computer, which further liberates the operation of the human hand and makes the operation more accurate and effective. Moreover, the image processing on the computer side can judge and identify the target to be operated, which improves the automation degree and efficiency of the operation.
与现有技术相比较,本发明具有如下有益效果:Compared with the prior art, the present invention has the following beneficial effects:
1、本装置根据现有方案的不足进行改进,引入了主控制器,在操作的整个过程中,使用本基于视觉的生物显微操作装置,可以在计算机端完成所有的操作,降低了对专业操作人员的依赖程度,使得操作更为简单、便捷,提高了显微操作的自动化程度。1. This device is improved according to the deficiencies of the existing scheme, and the main controller is introduced. During the whole process of operation, using this vision-based biological micromanipulation device, all operations can be completed on the computer side, reducing the need for professional The degree of dependence on the operator makes the operation simpler and more convenient, and improves the automation of micromanipulation.
2、使用显微视觉作为反馈,能够直接确定操作器和被操作对象的位置,进而根据它们之间的距离利用主控制器操作机械臂相互精准运动,有别于传统的“观察-操作-再观察-再操作”的落后作业模式,提高了操作效率。2. Using microscopic vision as feedback, it can directly determine the position of the manipulator and the operated object, and then use the main controller to control the precise movement of the robotic arms according to the distance between them, which is different from the traditional "observation-operation-re- The backward operation mode of "observation-reoperation" improves the operation efficiency.
3、结合图像处理技术,可以对不同形状的被操作对象和操作器进行匹配,可以更有效的识别如微吸管、微注射针等工具,提高了操作的成功率。3. Combining with image processing technology, it can match different shapes of operated objects and manipulators, and can more effectively identify tools such as micropipettes and microinjection needles, improving the success rate of operations.
附图说明Description of drawings
图1为为本发明一种基于视觉反馈的生物显微操作装置的结构与组成示意图。FIG. 1 is a schematic diagram of the structure and composition of a biological micromanipulation device based on visual feedback according to the present invention.
图中:In the picture:
1、光源 7、左操作臂驱动器 13、左手手轮控制器1. Light source 7. Left operating arm driver 13. Left hand wheel controller
2、左操作臂 8、显微摄像机 14、微位移平台手柄2. Left operating arm 8. Microscopic camera 14. Micro-displacement platform handle
3、左夹持器 9、显微镜 15、右手手轮控制器3. Left gripper 9. Microscope 15. Right hand wheel controller
4、微位移平台 10、调焦电机 16、计算机4. Micro displacement platform 10. Focusing motor 16. Computer
5、右操作器 11、右操作臂驱动器 17、操作手控制器5. Right manipulator 11. Right manipulator arm driver 17. Manipulator controller
6、右操作臂 12、微位移平台控制器6. Right operating arm 12. Micro-displacement platform controller
具体实施方式Detailed ways
下面结合附图和实施例对本发明作进一步的说明。The present invention will be further described below in conjunction with the accompanying drawings and embodiments.
请参见图1所示,本发明为一种基于视觉反馈的生物显微操作装置,包括光源(1)、显微镜(9)、CCD相机(8)、左微操作臂(2)、右微操作臂(6)、计算机(16)、XY微位移平台(4)、左夹持器(3)、右操作装置(5)、主控制器(17)等。在计算机端完成细胞的切割、融合、注射等显微操作。左夹持器(3)为吸管,右操作装置(5)为注射针。Please refer to Fig. 1, the present invention is a biological micromanipulator based on visual feedback, including a light source (1), a microscope (9), a CCD camera (8), a left micromanipulator arm (2), a right micromanipulator Arm (6), computer (16), XY micro-displacement platform (4), left gripper (3), right operating device (5), main controller (17), etc. Microscopic operations such as cell cutting, fusion, and injection are completed on the computer side. The left holder (3) is a suction pipe, and the right operating device (5) is an injection needle.
CCD相机(8)安装于显微镜(9)镜体的侧面,其相当于整个系统的传感器和反馈装置,捕捉显微镜物镜视野下的图像,通过USB线缆传递到计算机进行处理。The CCD camera (8) is installed on the side of the microscope (9) mirror body, which is equivalent to the sensor and feedback device of the whole system, captures the image under the field of view of the microscope objective lens, and transmits it to the computer for processing through the USB cable.
左夹持器(3)、右操作装置(5)分别安装在左微操作臂(2)、右微操作臂(6)上,左微操作臂(2)、右微操作臂(6)是由精密步进电机驱动的三自由度直角坐标式运动平台,左微操作臂(2)、右微操作臂(6)分别由左右驱动器控制,两个驱动器主要是对控制器传来的控制信号进行放大,并将左微操作臂(2)、右微操作臂(6)的限位信号传递给主控制器。The left gripper (3) and the right operating device (5) are installed on the left micro-manipulation arm (2) and the right micro-manipulation arm (6) respectively, and the left micro-manipulation arm (2) and the right micro-manipulation arm (6) are The three-degree-of-freedom rectangular coordinate motion platform driven by a precision stepping motor, the left micro-manipulator arm (2) and the right micro-manipulator arm (6) are controlled by the left and right drivers respectively, and the two drivers are mainly for the control signals sent by the controller Amplify, and transmit the limit signals of the left micro-manipulator arm (2) and the right micro-manipulator arm (6) to the main controller.
主控制器是核心部件,其连接左夹持器(3)、右操作装置(5),并且连接左手手轮控制器(13)、右手手轮控制器(15),并通过USB连接到计算机上。在主控制器上有切换开关,用来切换装置的工作模式为手动操作模式或计算机操作模式。在手动操作模式时,左、右操作手臂由左、右手手轮控制器控制。在计算机操作模式时,左、右操作手臂由计算机控制。The main controller is the core component, which is connected to the left gripper (3), right operating device (5), and connected to the left hand wheel controller (13), right hand wheel controller (15), and connected to the computer via USB superior. There is a switch on the main controller, which is used to switch the working mode of the device to manual operation mode or computer operation mode. In the manual operation mode, the left and right operating arms are controlled by the left and right hand wheel controllers. In the computer operation mode, the left and right operating arms are controlled by the computer.
微位移平台模块由XY微位移平台(4)、调焦电机(10)、微位移平台控制器(12)、微位移平台手柄(14)四部分组成,其中微位移平台(4)为平面XY平台,能够托载被操作物做水平面内的运动,其用来调节被观测对象和显微镜物镜之间的位置。调焦电机(10)是当被观测对象和物镜的位置确定后调节显微镜的焦距,使得从目镜或者相机处观测到的图像足够清晰。微位移平台手柄(14)用来在手动模式下,控制XY微位移平台和调焦电机运动。The micro-displacement platform module is composed of four parts: XY micro-displacement platform (4), focusing motor (10), micro-displacement platform controller (12), and micro-displacement platform handle (14), wherein the micro-displacement platform (4) is a plane XY The platform can carry the operated object to move in the horizontal plane, and it is used to adjust the position between the observed object and the microscope objective lens. The focus motor (10) adjusts the focal length of the microscope after the positions of the observed object and the objective lens are determined, so that the image observed from the eyepiece or the camera is sufficiently clear. The micro-displacement platform handle (14) is used to control the movement of the XY micro-displacement platform and the focusing motor in manual mode.
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CN110108904A (en) * | 2019-05-15 | 2019-08-09 | 北京航空航天大学 | The real-time drift compensating system of atomic force microscope and method of view-based access control model sensing |
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CN115521864A (en) * | 2022-11-29 | 2022-12-27 | 季华实验室 | A Force Feedback Adaptive Micromanipulator for Remote Operation |
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