CN102847477B - Magnetic stirring device and stirring method thereof - Google Patents
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Abstract
一种磁力搅拌装置及其搅拌方法,包括线圈和电源两部分,所述的线圈为三对正交的亥姆霍兹线圈和一对麦克斯韦线圈,三对亥姆霍兹线圈的轴向分别对应磁力搅拌装置的X、Y、Z轴,三对亥姆霍兹线圈的轴中心交于坐标原点O,XOY为水平面,OZ轴竖直向上。一对麦克斯韦线圈的轴线与Z轴重合,其轴中心与坐标原点O重合。控制四对线圈中的电流,使得四个线圈产生不同时序的均匀磁场和梯度磁场,推动纳米磁颗粒运动,从而实现纳米磁珠和溶剂的混合。
A magnetic stirring device and a stirring method thereof, comprising two parts, a coil and a power supply, the coils are three pairs of orthogonal Helmholtz coils and a pair of Maxwell coils, and the axes of the three pairs of Helmholtz coils correspond to The X, Y, Z axes of the magnetic stirring device, the axis centers of the three pairs of Helmholtz coils intersect at the coordinate origin O, XOY is the horizontal plane, and the OZ axis is vertically upward. The axes of a pair of Maxwell coils coincide with the Z axis, and the centers of the axes coincide with the coordinate origin O. The currents in the four pairs of coils are controlled so that the four coils generate uniform magnetic fields and gradient magnetic fields with different time sequences to drive the movement of the nano magnetic particles, thereby realizing the mixing of the nano magnetic beads and the solvent.
Description
技术领域 technical field
本发明涉及一种磁力搅拌装置及其搅拌方法,特别涉及纳米磁珠的搅拌混合装置及方法。 The invention relates to a magnetic stirring device and a stirring method thereof, in particular to a stirring and mixing device and a method of nano magnetic beads. the
背景技术 Background technique
纳米磁珠从诞生开始,它就受到了科研工作者的关注,并且在生化分析领域得到成功的应用。近年来,将纳米磁珠包被上特异性抗体、受体、单链DNA,用于分离复杂样品中的靶体,取得巨大成功。与传统的分离方法相比,把纳米磁珠用于复杂组分的生化样品的分离,能够实现分离和富集同时进行,大大提高了分离速度和富集效率,同时也使分析检测的灵敏度大大提高。目前,这种磁性微球已被广泛应用于免疫分析、核酸分离提取、细胞分选、酶的固定等多个领域。 Since the birth of nano magnetic beads, it has attracted the attention of scientific researchers and has been successfully applied in the field of biochemical analysis. In recent years, nano-magnetic beads coated with specific antibodies, receptors, and single-stranded DNA have achieved great success in separating targets in complex samples. Compared with traditional separation methods, the use of nano-magnetic beads for the separation of biochemical samples with complex components can achieve separation and enrichment at the same time, greatly improving the separation speed and enrichment efficiency, and also greatly improving the sensitivity of analysis and detection. improve. At present, this magnetic microsphere has been widely used in many fields such as immunoassay, nucleic acid separation and extraction, cell sorting, and enzyme immobilization. the
在纳米磁场应用中的一个重要步骤是将纳米磁与试剂充分混合。现有的技术一般是将装有样品的试管通过机械振荡的方式实现混合。专利CN201249110Y将含有纳米磁珠的试管放在旋转的两块磁体中间,用磁力使试管底部的磁珠转动达到混合的目的。但该专利有机械运动的电机,控制方式单一,无法调节混合效果。 An important step in the application of nanomagnetic field is to fully mix the nanomagnetic field with the reagent. In the existing technology, the test tubes containing the samples are generally mixed by mechanical vibration. Patent CN201249110Y puts the test tube containing nano-magnetic beads between two rotating magnets, and uses magnetic force to rotate the magnetic beads at the bottom of the test tube to achieve the purpose of mixing. But this patent has the motor of mechanical movement, and control mode is single, can't adjust mixing effect. the
发明内容 Contents of the invention
本发明的目的是克服现有技术的缺点,提出一种磁力搅拌装置及其纳米磁珠搅拌方法。本发明采用一种无机械运动部件的自动化装置实现纳米磁珠与试剂的充分混合,可以改善混合效率并降低实验人员的工作量,并且可以提高装置的可靠性,延长装置的使用寿命。 The purpose of the present invention is to overcome the shortcoming of prior art, propose a kind of magnetic stirring device and nano-magnetic bead stirring method thereof. The invention adopts an automatic device without mechanical moving parts to fully mix the nano magnetic beads and reagents, which can improve the mixing efficiency and reduce the workload of experimenters, and can improve the reliability of the device and prolong the service life of the device. the
本发明采用使可变频率和幅值大小的旋转磁场带动磁场进行混合,具体的技术方案是: The present invention adopts the rotating magnetic field with variable frequency and amplitude to drive the magnetic field to mix, and the specific technical scheme is:
本发明磁场发生装置包括线圈和电源。 The magnetic field generating device of the present invention includes a coil and a power supply. the
所述的线圈包括三对亥姆霍兹线圈和一对麦克斯韦线圈共四对线圈。三对亥姆霍兹线圈按照尺寸从小到大正交安装,三对亥姆霍兹线圈的轴向分别对应磁力搅拌装置的X、Y、Z轴,三对亥姆霍兹线圈对应称为X轴、Y轴、Z轴亥姆霍兹线圈。三对亥姆霍兹线圈的轴中心相交于一点O,该点为直角坐标系OXYZ的原点。XOY为水平平面,OZ轴竖直向上。一对麦克 斯韦线圈的轴线与Z轴重合,该麦克斯韦线圈的轴中心与坐标原点O重合,称为Z轴麦克斯韦线圈。所述的电源为带CPU的四路电流源,X轴、Y轴、Z轴亥姆霍兹线圈和Z轴麦克斯韦线圈各连接一路电流源。Z轴亥姆霍兹线圈产生的磁场沿OZ轴正向,Z轴麦克斯韦线圈在Z轴上产生磁场的梯度沿OZ轴正向。 The coils include three pairs of Helmholtz coils and one pair of Maxwell coils, a total of four pairs of coils. Three pairs of Helmholtz coils are installed orthogonally according to the size from small to large. The axes of the three pairs of Helmholtz coils correspond to the X, Y, and Z axes of the magnetic stirring device, and the three pairs of Helmholtz coils are called X. Axis, Y-axis, Z-axis Helmholtz coils. The axis centers of the three pairs of Helmholtz coils intersect at a point O, which is the origin of the Cartesian coordinate system OXYZ. XOY is a horizontal plane, and the OZ axis is vertically upward. The axis of a pair of Maxwell coils coincides with the Z axis, and the axis center of the Maxwell coil coincides with the coordinate origin O, which is called the Z-axis Maxwell coil. The power supply is a four-way current source with a CPU, and each of the X-axis, Y-axis, Z-axis Helmholtz coil and Z-axis Maxwell coil is connected to one current source. The magnetic field generated by the Z-axis Helmholtz coil is along the positive direction of the OZ axis, and the gradient of the magnetic field generated by the Z-axis Maxwell coil is along the positive direction of the OZ axis. the
所述的电源为带CPU的四路电流源,CPU可分别控制四路电流源输出电流的方向和大小。四对所述的线圈分别连接一路电流源。 The power supply is a four-way current source with a CPU, and the CPU can respectively control the direction and magnitude of the output current of the four-way current source. The four pairs of coils are respectively connected to one current source. the
本发明CPU控制四路电流源按照不同时序向四对线圈输出大小不同的电流,实现纳米磁珠与试剂的混合。其原理及实现方法如下述: In the present invention, the CPU controls four current sources to output currents of different sizes to four pairs of coils according to different time sequences, so as to realize the mixing of nano magnetic beads and reagents. Its principle and implementation method are as follows:
(1)将装有纳米磁珠与试剂的混合液的试管竖直放置在OZ轴线上; (1) Place the test tube containing the mixture of nano-magnetic beads and reagents vertically on the OZ axis;
(2)向Z轴亥姆霍兹线圈中通入电流产生朝向OZ正方向的磁场,场强大于纳米磁珠的饱和磁化强度,使得纳米磁珠磁化; (2) Passing a current into the Z-axis Helmholtz coil generates a magnetic field in the positive direction of OZ, and the field strength is greater than the saturation magnetization of the nano-magnetic beads, making the nano-magnetic beads magnetized;
(3)向Z轴麦克斯韦线圈中通入电流在OZ轴线上产生OZ正方向的梯度磁场,梯度磁场足以使得磁化的纳米磁珠能克服阻力朝OZ正向运动; (3) Feed current into the Z-axis Maxwell coil to generate a gradient magnetic field in the positive direction of OZ on the OZ axis, and the gradient magnetic field is sufficient to enable the magnetized nano-magnetic beads to overcome the resistance and move toward the positive direction of OZ;
(4)当大部分纳米磁珠运动到混合液上部时,停止通向Z轴亥姆霍兹线圈和Z轴麦克斯韦线圈中的电流; (4) When most of the nano-magnetic beads move to the upper part of the mixture, stop the current to the Z-axis Helmholtz coil and the Z-axis Maxwell coil;
(5)在X轴亥姆霍兹线圈和Y轴亥姆霍兹线圈中通入相位差为90度的正弦电流产生XOY平面内的旋转磁场,旋转磁场的场强幅值大于纳米磁珠的饱和磁化强度,使得纳米磁珠磁化;然后在Z轴麦克斯韦线圈中通入电流产生梯度磁场,梯度磁场足以使得磁化的纳米磁珠能克服阻力产生运动; (5) A sinusoidal current with a phase difference of 90 degrees is passed into the X-axis Helmholtz coil and the Y-axis Helmholtz coil to generate a rotating magnetic field in the XOY plane, and the field strength of the rotating magnetic field is greater than that of nano-magnetic beads The saturation magnetization makes the nano-magnetic beads magnetized; then a current is passed through the Z-axis Maxwell coil to generate a gradient magnetic field, and the gradient magnetic field is sufficient to enable the magnetized nano-magnetic beads to overcome resistance and generate motion;
(6)停止通向各线圈中的电流,重复(2)~(5)直到纳米磁珠与试剂混合均匀。 (6) Stop the current to each coil, and repeat (2)-(5) until the nano-magnetic beads and the reagent are evenly mixed. the
本发明的效果和益处是:通过在试管周围加入不同的磁场实现纳米磁珠与试剂的充分混合,整个装置通过改变线圈中的电流来实现混合,方法简单,可通过控制线圈中电流的幅值和频率实现不同的混合效果。 The effect and benefit of the present invention are: by adding different magnetic fields around the test tube to realize the full mixing of nano magnetic beads and reagents, the whole device realizes mixing by changing the current in the coil, the method is simple, and the amplitude of the current in the coil can be controlled and frequency to achieve different mixing effects. the
附图说明 Description of drawings
图1是本发明的磁力搅拌装置示意图; Fig. 1 is a schematic diagram of a magnetic stirring device of the present invention;
图2是本发明的磁力搅拌装置连接示意图。 Fig. 2 is a schematic diagram of the connection of the magnetic stirring device of the present invention. the
具体实施方式 Detailed ways
下面结合附图和具体实施方式进一步说明本发明。 The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. the
本发明磁场发生装置包括线圈2和电源1。 The magnetic field generating device of the present invention includes a coil 2 and a power source 1 . the
如图1所示,所述的线圈2为三对正交亥姆霍兹线圈和一对麦克斯韦线圈。三对正交亥姆霍兹线圈从小尺寸到大尺寸正交嵌套安装,三对亥姆霍兹线圈的轴向对应磁力搅拌装置的X、Y、Z轴。三对亥姆霍兹线圈的轴中心相交于点O,该点为直角坐标系OXYZ的原点。XOY为水平平面,OZ轴竖直向上。一对麦克斯韦线圈的轴线与Z轴重合,该麦克斯韦线圈的轴中心与坐标原点O重合。三对正交亥姆霍兹线圈和一对麦克斯韦线圈分别连接四路电流源,CPU通过控制四路电流源输出电流的大小来控制三个轴向产生的磁场。X轴向的亥姆霍兹线圈为线圈X,Y轴向的亥姆霍兹线圈为线圈Y,Z轴向的亥姆霍兹线圈为线圈Z,Z轴向的麦克斯韦线圈为线圈MZ。 As shown in FIG. 1 , the coils 2 are three pairs of orthogonal Helmholtz coils and a pair of Maxwell coils. Three pairs of orthogonal Helmholtz coils are installed in orthogonal nesting from small to large sizes, and the axes of the three pairs of Helmholtz coils correspond to the X, Y, and Z axes of the magnetic stirring device. The axis centers of the three pairs of Helmholtz coils intersect at point O, which is the origin of the Cartesian coordinate system OXYZ. XOY is a horizontal plane, and the OZ axis is vertically upward. The axes of the pair of Maxwell coils coincide with the Z axis, and the axis centers of the Maxwell coils coincide with the coordinate origin O. Three pairs of orthogonal Helmholtz coils and a pair of Maxwell coils are respectively connected to four current sources, and the CPU controls the magnetic fields generated in three axes by controlling the output current of the four current sources. The Helmholtz coil in the X-axis is coil X, the Helmholtz coil in the Y-axis is coil Y, the Helmholtz coil in the Z-axis is coil Z, and the Maxwell coil in the Z-axis is coil MZ. the
所述的电源1为带CPU的四路电流源,CPU可直接控制每路电流源输出电流的大小。 The power supply 1 is a four-channel current source with a CPU, and the CPU can directly control the output current of each current source. the
图2所示为本发明磁力搅拌装置的整体连接示意图。电流源1~4依次连接X轴向的亥姆霍兹线圈X、Y轴向的亥姆霍兹线圈Y、Z轴向的亥姆霍兹线圈Z、Z轴向的麦克斯韦线圈MZ。 Figure 2 is a schematic diagram of the overall connection of the magnetic stirring device of the present invention. The current sources 1 to 4 are sequentially connected to the Helmholtz coil X of the X axis, the Helmholtz coil Y of the Y axis, the Helmholtz coil Z of the Z axis, and the Maxwell coil MZ of the Z axis. the
本发明磁力搅拌的方法如下: The method of magnetic stirring of the present invention is as follows:
(1)将装有纳米磁珠与试剂的混合液的试管竖直放置在OZ轴线上; (1) Place the test tube containing the mixture of nano-magnetic beads and reagents vertically on the OZ axis;
(2)向线圈Z中通入电流产生朝向OZ正方向的磁场,场强大于纳米磁珠的饱和磁化强度,使得纳米磁珠磁化; (2) Passing a current into the coil Z generates a magnetic field in the positive direction of OZ, and the field strength is greater than the saturation magnetization of the nano-magnetic beads, so that the nano-magnetic beads are magnetized;
(3)向线圈MZ中通入电流在OZ轴线上产生沿OZ正方向的梯度磁场,梯度磁场足以使得磁化的纳米磁珠能克服阻力朝OZ正向运动; (3) Passing current into the coil MZ generates a gradient magnetic field along the positive direction of OZ on the OZ axis, and the gradient magnetic field is sufficient to enable the magnetized nano-magnetic beads to overcome the resistance and move toward the positive direction of OZ;
(4)当大部分纳米磁珠运动到所述混合液上部时,停止通向线圈Z和线圈MZ中的电流; (4) When most of the nano-magnetic beads move to the upper part of the mixture, stop the current to the coil Z and the coil MZ;
(5)线圈X和线圈Y中通入相位差为90度的正弦电流产生XOY平面内的旋转磁场,旋转磁场的场强幅值大于纳米磁珠的饱和磁化强度,使得纳米磁珠磁化;然后在Z轴麦克斯韦线圈中通入电流产生梯度磁场,梯度磁场足以使得磁化的纳米磁珠能克服阻力产生运动; (5) A sinusoidal current with a phase difference of 90 degrees is passed into the coil X and coil Y to generate a rotating magnetic field in the XOY plane, and the field strength amplitude of the rotating magnetic field is greater than the saturation magnetization of the nano-magnetic beads, so that the nano-magnetic beads are magnetized; then A current is passed through the Z-axis Maxwell coil to generate a gradient magnetic field, and the gradient magnetic field is sufficient to enable the magnetized nano-magnetic beads to overcome resistance and generate motion;
(6)停止各线圈中的电流,重复步骤(2)~步骤(5)直到纳米磁珠与试剂混合均匀。改变上述步骤中各个线圈中产生磁场的大小和步骤(5)中的旋转磁场的频率可改变溶液的混合效果。 (6) Stop the current in each coil, and repeat steps (2) to (5) until the nano-magnetic beads and the reagent are evenly mixed. Changing the magnitude of the magnetic field generated in each coil in the above step and the frequency of the rotating magnetic field in step (5) can change the mixing effect of the solution. the
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