Multi-degree-of-freedom magnetic tweezers manipulation method and system

Abstract

The application belongs to the technical field of magnetic tweezers control, and discloses a multi-degree-of-freedom magnetic tweezers control method and system. The application discards the control mode of traditional magnetic tweezers relying on magnetic attraction, and instead uses a special gradient magnetic field configuration, so that the magnetic ball is subjected to magnetic repulsion force in a direction away from a zero magnetic field point, and the magnetic repulsion force is proportional to the distance of the magnetic ball to the zero point, thereby realizing linear and direct force control relationship. By changing the current of the gradient field coil to move the spatial position of the magnetic field zero point, the magnetic repulsion force can be linearly adjusted, so as to realize precise and decoupled control of three-dimensional translation of the magnetic ball; further, by controlling the net torque exerted by the zero point around the movement of the magnetic ball, three-dimensional rotation control is realized. The system has fast response speed, high control precision and good stability, solves the problems of limited control degree of freedom, difficult decoupling, complex system and weak anti-interference ability in the prior art, and has wide application in the fields of biomedicine, nanomaterial research, atomic-level manufacturing and micro-nano electromechanical systems.

Description

Technical Field

[0001] This invention belongs to the field of magnetic tweezers manipulation technology, and more specifically, relates to a multi-degree-of-freedom magnetic tweezers manipulation method and system. Background Technology

[0002] At the forefront of nanotechnology, advanced materials, and life sciences, in-situ, quantitative, and multi-dimensional mechanical manipulation and measurement of nanoscale objects (such as single proteins, DNA molecules, organelles, quantum dots, or functionalized nanoparticles) are crucial for revealing their physicochemical properties, biological functional mechanisms, and achieving precise nanoscale manufacturing. For example, in single-molecule biophysics, it is necessary to precisely apply piconewton-level forces to measure the stepping mechanism of molecular motors or the energy barrier of protein folding; in nanomaterials science, it is necessary to manipulate nanoparticles for non-contact assembly or to test their mechanical properties; in cell biology, it is hoped that controllable forces and torques can be applied to organelles inside living cells to study their mechanical responses. Therefore, at the extremely microscopic scale (typically from hundreds of nanometers to micrometers) in liquid and near-physiological environments, it is essential to develop a "nanomanipulator" capable of multi-degree-of-freedom, high-precision, and rapid response to targets, much like a human hand manipulates macroscopic objects.

[0003] When the scale of manipulation enters the micro-nano realm, the dominant rules of the classical physical world give way to fluctuations and interface effects. At this point, two fundamental challenges are faced: First, strong Brownian motion random disturbances, whose energy (on the order of kBT) is comparable to the energy scale required for manipulation, seriously interfere with the stability and precision of control; second, existing manipulation technologies are severely limited in terms of the degree of freedom of motion or the magnitude of the force.

[0004] Current mainstream technologies such as atomic force microscopy (AFM) probes, optical tweezers, and traditional magnetic tweezers all have inherent limitations: AFM is a contact-based technique, which can easily damage samples and makes it difficult to achieve complex three-dimensional manipulations; while optical tweezers can perform non-contact manipulation, their force range is limited (typically <100 pN), and the laser thermal effect caused by a larger force range may damage biological samples. In this field, magnetic manipulation technology (magnetic tweezers) is considered one of the most promising solutions for microscopic mechanical research due to its advantages such as non-contact operation, good biocompatibility, strong penetration, and the ability to generate relatively large forces (pN to nN). By manipulating functionalized magnetic microspheres to indirectly apply forces to connected targets, it has become the gold standard for single-molecule force spectroscopy in the field of biomechanics.

[0005] However, existing magnetic tweezers technology faces a long-standing core bottleneck: severely limited degrees of freedom of motion. Currently, both traditional magnetic tweezers based on the mechanical movement of permanent magnets and advanced magnetic tweezers based on planar microcoil arrays have limited independent and decoupled degrees of freedom. Achieving complete six-degree-of-freedom (6-DOF) dexterous manipulation—arbitrary translation (X, Y, Z) and rotation (pitch, yaw, roll) around any axis of the magnetic sphere in three-dimensional space—remains an unresolved problem in this field. The root of this bottleneck lies in the physical principles: traditional magnetic manipulation relies on applying an attractive force to the magnetic sphere and shaping a complex magnetic field distribution in space to guide its movement. The attractive force F_att is inversely proportional to the square of the distance r² (F_att ∝ 1 / r²), meaning that the force rapidly decreases as the distance between the magnetic sphere and the magnetic field source (or virtual center of force) increases, leading to nonlinear control, limited accuracy, and susceptibility to interference. To increase the degrees of freedom, the magnetic field structure must be made extremely complex. This not only results in a large system with high control coupling, but also leads to mutual interference between the degrees of freedom, making it difficult to achieve truly independent decoupled control. More importantly, this "field traction"-based approach does not fundamentally address the primary source of interference—Brownian motion at the microscopic scale—and typically relies on subsequent signal filtering or feedback compensation for passive defense, with limited effectiveness.

[0006] Therefore, developing a novel magnetic drive control mechanism that is theoretically sound and can simultaneously achieve independent multi-degree-of-freedom drive and active suppression of Brownian motion is not only an essential step in propelling nanotechnology from "simple pulling and twisting" to "omnidirectional dexterity," but also a key to unlocking high-fidelity mechanical experiments in living cells and complex fluid environments, possessing significant scientific and technological value. Summary of the Invention

[0007] In view of the above-mentioned defects or improvement needs of the existing technology, the present invention provides a multi-degree-of-freedom magnetic tweezers manipulation method and system, the purpose of which is to achieve complete decoupling control of multi-degree-of-freedom, reduce control complexity, and improve control stability and control accuracy.

[0008] To achieve the above objectives, this invention proposes a multi-degree-of-freedom magnetic tweezers manipulation method, comprising: A stable gradient magnetic field is generated, which covers the target control area where the magnetic sphere is located. The gradient magnetic field has a zero magnetic field point within the workspace. The magnetized magnetic sphere is located outside the target control area outside the zero magnetic field point, and the magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant, so that the relative distance between the zero magnetic field point and the magnetic sphere is proportional to the magnetic repulsive force on the magnetic sphere. The magnetic repulsive force is a force that moves away from the zero magnetic field point. The workspace includes a two-dimensional workspace and a three-dimensional workspace. The magnitudes of the magnetic field gradients and gradient magnetic field strengths in each orthogonal direction of the workspace are changed to alter the position of the zero magnetic field point. When the change in the position of the zero magnetic field point causes a change in the relative distance between the zero magnetic field point and the magnetic sphere, translational control of the magnetic sphere in a target vector direction away from the zero magnetic field point is achieved. When the change in the position of the zero magnetic field point causes a change in the relative orientation between the zero magnetic field point and the magnetic sphere, rotational control of the magnetic sphere is achieved. The rotational control includes pitch, yaw, and roll control.

[0009] Furthermore, by configuring a set of gradient field coils in each of the N directions of the workspace, each set of gradient field coils includes two gradient field coils with opposite magnetic poles, so that after current is passed through the gradient field coils, the zero magnetic field point is formed in the target control area between the two magnetic poles, and the gradient magnetic field is formed around the zero magnetic field point, and the magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant. By adjusting the current in the two gradient field coils in each direction, the magnitude of the magnetic field gradient and the gradient magnetic field strength in each orthogonal direction of the working space are changed, thereby changing the position of the zero magnetic field point. Wherein, when the workspace is a two-dimensional workspace, N≥2, and there are at least two non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in two orthogonal directions; when the workspace is a three-dimensional workspace, N≥3, and there are at least three non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in three orthogonal directions. When the workspace is a two-dimensional workspace and the N directions are N orthogonal directions, N=2; when the workspace is a three-dimensional workspace and the N directions are N orthogonal directions, N=3.

[0010] Furthermore, it also includes: moving the relative positions between the two gradient field coils in each direction to change the distribution area of ​​the gradient magnetic field so that the gradient magnetic field covers the target control area.

[0011] Furthermore, it also includes: real-time detection of the current pose of the magnetic ball, comparison of the current pose with the target pose, and dynamic adjustment of the current in the two gradient field coils in each direction using a closed-loop control algorithm to correct the position of the zero magnetic field point so that the current pose and the target pose are close to being consistent. Or / and, prior to generating the gradient magnetic field, the method further includes generating a background magnetic field covering the target manipulation area, the background magnetic field being used to magnetize the magnetic sphere in the initial stage.

[0012] This invention also provides a multi-degree-of-freedom magnetic tweezers manipulation system, comprising: A gradient magnetic field generating unit is used to generate a stable gradient magnetic field that covers the target control area where the magnetic sphere is located. The gradient magnetic field has a zero magnetic field point within the workspace. The magnetized magnetic sphere is located within the target control area outside the zero magnetic field point, and the magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant, so that the relative distance between the zero magnetic field point and the magnetic sphere is proportional to the magnetic repulsive force experienced by the magnetic sphere. The magnetic repulsive force is a force directed away from the zero magnetic field point. The workspace includes a two-dimensional workspace and a three-dimensional workspace. The real-time control module is used to change the magnitude of the magnetic field gradient and gradient magnetic field strength in each orthogonal direction of the workspace to change the position of the zero magnetic field point. When the change in the position of the zero magnetic field point causes a change in the relative distance between the zero magnetic field point and the magnetic ball, the module enables translational control of the magnetic ball in the target vector direction away from the zero magnetic field point. When the change in the position of the zero magnetic field point causes a change in the relative orientation between the zero magnetic field point and the magnetic ball, the module enables rotational control of the magnetic ball. The rotational control includes pitch, yaw, and roll control.

[0013] Furthermore, the gradient magnetic field generating unit includes a set of gradient field coils arranged in each of the N directions of the workspace. Each set of gradient field coils includes two gradient field coils with opposite magnetic poles, so that when current is passed through the gradient field coils, the zero magnetic field point is formed in the target control area between the two magnetic poles, and the gradient magnetic field is formed around the zero magnetic field point. The magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant. The real-time control module is used to change the position of the zero magnetic field point by adjusting the current in the two gradient field coils in each direction, thereby changing the magnitude of the magnetic field gradient and gradient magnetic field strength in each orthogonal direction of the workspace. Wherein, when the workspace is a two-dimensional workspace, N≥2, and there are at least two non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in two orthogonal directions; when the workspace is a three-dimensional workspace, N≥3, and there are at least three non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in three orthogonal directions. When the workspace is a two-dimensional workspace and the N directions are N orthogonal directions, N=2; when the workspace is a three-dimensional workspace and the N directions are N orthogonal directions, N=3.

[0014] Furthermore, the real-time control module is also used to move the relative position between the two gradient field coils in each direction to change the distribution area of ​​the gradient magnetic field so that the gradient magnetic field covers the target control area.

[0015] Furthermore, it also includes an interferometric scattering imaging detection module for real-time detection of the current pose of the magnetic sphere; The real-time control module is used to compare the current pose with the target pose and dynamically adjust the current in the two gradient field coils in each direction using a closed-loop control algorithm to correct the position of the zero magnetic field point so that the current pose and the target pose are close to being consistent. Or / and, it also includes a static magnetic field source for generating a background magnetic field covering the target manipulation area prior to generating the gradient magnetic field, the background magnetic field being used to magnetize the magnetic sphere in the initial stage.

[0016] Furthermore, the diameter of the magnetic sphere is from micrometers to nanometers, and its surface is optimized to reduce friction and adhesion. The gradient field coil contains an iron core and adopts a multi-layer coil structure, and uses eddy current optimization distribution technology to reduce eddy currents.

[0017] The present invention also provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the multi-degree-of-freedom magnetic tweezers manipulation method as described in any of the preceding claims.

[0018] In summary, the above-described technical solutions conceived in this invention can achieve the following beneficial effects: (1) This invention completely breaks free from the constraints of traditional magnetic tweezers that rely on nonlinear attractive forces, and innovatively utilizes linear magnetic repulsion as the source of manipulation. This fundamental shift brings multiple advantages: the linear force control relationship (the relative distance between the zero magnetic field point and the magnetic ball is proportional to the magnetic repulsion force on the magnetic ball) makes the manipulation more precise, the response more direct, and reduces the control complexity; by controlling the zero-point motion to indirectly drive the magnetic ball, the complex six-degree-of-freedom control problem in the three-dimensional workspace (pitch, yaw, and roll three rotational degrees of freedom control and translation control in three orthogonal directions in the three-dimensional workspace) is reduced to the three-dimensional motion control of the zero point (the motion of the zero magnetic field point in space), which greatly simplifies the logic and naturally decouples the degrees of freedom; based on the principle of magnetic repulsion, the magnetic ball tends to move away from the field source and boundary, effectively avoiding non-specific adsorption problems; in addition, the deep potential well formed by the high gradient magnetic field significantly enhances the system's inherent ability to resist Brownian motion interference from an energy perspective. For magnetic tweezers manipulation in a three-dimensional workspace, this invention provides a new and superior technical path for achieving truly agile, stable, and precise nanoscale six-degree-of-freedom manipulation.

[0019] In summary, the core of this invention lies in abandoning the traditional magnetic tweezers' manipulation mode, which relies on the attraction of magnetic fields. In this mode, the force is inversely proportional to the square of the distance, leading to nonlinear control, limited precision, and susceptibility to interference. Instead, this invention utilizes a special gradient magnetic field configuration, subjecting the magnetic sphere to a magnetic repulsive force directed away from the zero magnetic field point. The magnitude of this repulsive force is proportional to the distance from the magnetic sphere to the zero point, achieving a linear and direct force control relationship. By changing the current in the coil of the gradient field generator to move the spatial position of the zero magnetic field point, the magnetic repulsive force can be linearly adjusted, thereby achieving precise and decoupled control of the three-dimensional translational motion of the magnetic sphere. Furthermore, by controlling the net torque applied to the zero point's motion around the magnetic sphere, three-dimensional rotational control is achieved. The system exhibits fast response speed, high control precision, and good stability, solving the problems of limited control freedom, difficult decoupling, system complexity, and weak anti-interference capabilities in existing technologies. It has wide applications in biomedicine, nanomaterials research, atomic-level manufacturing, and micro / nano-electromechanical systems. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of a multi-degree-of-freedom magnetic tweezers manipulation method in an embodiment of the present invention.

[0021] Figure 2 This is a top view schematic diagram of the magnetic tweezers manipulation system in an embodiment of the present invention.

[0022] Figure 3 This is a schematic diagram of the gradient field coil structure in an embodiment of the present invention.

[0023] Figure 4 This is a schematic diagram of the gradient magnetic field around the zero magnetic field point in an embodiment of the present invention. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0025] Example 1 This invention proposes a novel manipulation paradigm based on "gradient magnetic field repulsion." The core physical principle of this paradigm differs significantly from the traditional "attraction" model. This invention constructs a gradient magnetic field with a zero-magnetic-field point. From this point outwards, the magnetic field strength in all directions of space exhibits a linear increasing trend (i.e., a constant positive gradient exists, and the magnetic field strength gradient in all directions of space is constant). When a magnetized magnetic sphere is placed at a non-zero position in this field, it will experience a force that always moves away from the zero point. This force is magnetically repulsive, and crucially, its magnitude is directly proportional to the distance from the center of the magnetic sphere to the zero point of the magnetic field, exhibiting a linear relationship. This linear repulsive relationship fundamentally overturns the nonlinear attractive force (inverse square law) relied upon by traditional magnetic tweezers. The linear relationship means that the force and distance control are in a one-to-one correspondence, resulting in a direct response, greatly simplifying high-precision control algorithms, and providing better predictability and stability.

[0026] Based on this principle of linear repulsion, the control logic of this invention undergoes a fundamental transformation: from complexly controlling the distribution of the entire spatial magnetic field to "pull" the magnetic ball, to simply controlling the movement of a zero-dimensional geometric point (i.e., the zero point of the magnetic field) in space. Under the action of linear repulsion, the magnetic ball will automatically tend to follow the moving zero point, thereby completing the preset movement.

[0027] As a specific implementation method, translational manipulation is achieved by adjusting the current combination of multiple sets of gradient field coils to change the coordinates of the zero magnetic field point in three-dimensional space. Two gradient field coils are configured in each of the three orthogonal directions in three-dimensional space, or two gradient field coils are configured in each of multiple directions. Each direction contains at least three non-coplanar direction vectors, enabling the generation of gradient magnetic fields in the three orthogonal directions. The like magnetic poles of the two gradient field coils are opposite each other, so that after current is passed through the two gradient field coils, a zero magnetic field point is formed in the target manipulation region between the two like magnetic poles, and a gradient magnetic field is formed around the zero magnetic field point. Since the translation in each orthogonal direction is independently controlled by the corresponding current component, decoupling in the three orthogonal directions is naturally achieved.

[0028] Rotational manipulation is achieved by controlling the zero point of the magnetic field to move in a circular or more complex trajectory around the current position of the magnetic sphere, thereby applying a net magnetic torque to the sphere. A uniform static background magnetic field is mainly used to magnetize the superparamagnetic sphere in the initial stage, enabling it to acquire a stable magnetic moment.

[0029] In other embodiments, translation and rotation manipulation can also be achieved in other ways. As long as the method is based on the physical principle of "gradient magnetic field repulsion" of this invention, it is within the protection scope of this invention.

[0030] The specific plan is as follows: like Figure 1As shown, this embodiment of the invention provides a multi-degree-of-freedom magnetic tweezers manipulation method, comprising: Step S1: Provide a static magnetic field source to generate a stable background magnetic field, ensuring the magnetic sphere can exist stably within the control area. The background magnetic field covers the target control area where the magnetic sphere is located. By precisely controlling the strength and direction of the background magnetic field, the initial positioning and control of the magnetic sphere are achieved. The main function of the background magnetic field is to magnetize the paramagnetic or superparamagnetic magnetic sphere in the initial stage, enabling it to obtain a stable magnetic moment consistent with the direction of the background magnetic field, thereby ensuring that the magnetic sphere can produce a clear and effective mechanical response in the subsequent gradient magnetic field. In the main control stage of this invention, the direction and magnitude of the background magnetic field generally remain basically unchanged, and the realization of six-degree-of-freedom control does not depend on the dynamic changes of the background magnetic field.

[0031] As an alternative implementation, the magnetic spheres are in the micrometer to nanometer size, such as 10 nanometers to 100 micrometers in diameter. Their surfaces are optimized to reduce friction and adhesion, resulting in high magnetic stability. In this embodiment of the invention, the magnetic spheres are 200 nm diameter Fe3O4 particles coated with silica to reduce adhesion, thereby optimizing their dispersibility and biocompatibility. The magnetic moments of the magnetic spheres are stable and do not degrade under the influence of a magnetic field. Since the 200 nm magnetic spheres themselves have very weak magnetism (paramagnetic or superparamagnetic), the background magnetic field and the generated gradient magnetic field can cause the paramagnetic nanospheres to reach magnetic saturation, ensuring that the magnetic spheres have maximum magnetic response capability and further improving the stability of control.

[0032] As an optional implementation, the static magnetic field source employs an electromagnetic coil made of high-permeability material, and the structure of the electromagnetic coil is optimized to make the magnetic field strength adjustable and ensure magnetic field uniformity. In this embodiment of the invention, the static magnetic field strength is adjustable between 0.5T and 2T, and the uniformity error is less than 5%.

[0033] Step S2: Construct a gradient magnetic field and establish control relationships. A stable spatial gradient magnetic field is generated, which contains a zero magnetic field point within the two-dimensional or three-dimensional workspace. The zero magnetic field point is the point where the magnetic field strength is zero. From this zero magnetic field point, the magnetic field strength gradient along each direction of the workspace is constant. The spatial gradient magnetic field covers the target control area where the magnetic sphere is located, and the magnetized magnetic sphere is located outside the target control area of ​​the zero magnetic field point. At this time, the spatial gradient magnetic field interacts with the magnetic sphere. Under the influence of the spatial gradient magnetic field, the magnetic sphere experiences a magnetic repulsive force that is directed away from the zero magnetic field point and whose magnitude is proportional to the distance from the magnetic sphere to the zero magnetic field point. Under the influence of this magnetic repulsive force, a torque (translational control) or a torque (rotational control) in any direction can be generated on the magnetic sphere. That is, the magnetic sphere will experience a net magnetic force pointing towards the high field strength region, thereby achieving positional movement and attitude rotation.

[0034] As a specific implementation, a set of gradient field coils is configured in each of the N directions of the multidimensional workspace. When the multidimensional workspace is two-dimensional, N≥2, and there are at least two non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions can generate gradient magnetic fields in two orthogonal directions (generating a gradient magnetic field can be decomposed into gradients in two orthogonal directions). When the multidimensional workspace is three-dimensional, N≥3, and there are at least three non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions can generate gradient magnetic fields in three orthogonal directions (generating a gradient magnetic field can be decomposed into gradients in three orthogonal directions). Preferably, when the N directions are N orthogonal directions in a two-dimensional workspace, N=2; when the N directions are N orthogonal directions in a three-dimensional workspace, N=3, and so on. Figure 2 As shown.

[0035] Each set of gradient field coils contains two gradient field coils with their like magnetic poles facing each other. When current is passed through each of the two gradient field coils, a zero magnetic field point is formed within the target control region between the two like magnetic poles. A gradient magnetic field with a constant magnetic field strength gradient is then formed around the zero magnetic field point. The magnetic sphere is located at any point within the target control region outside the zero magnetic field point. Figure 3 As shown and Figure 4 As shown.

[0036] Since the magnetic sphere itself has very weak magnetism, in this embodiment of the invention, the two gradient field coils in each direction contain an iron core to increase the strength of the gradient magnetic field.

[0037] In this embodiment of the invention, an example is given by arranging two gradient field coils with opposite magnetic poles in each of the three orthogonal directions (X, Y, Z) of a three-dimensional workspace. Gradient magnetic field generating units are arranged in the three orthogonal directions (X, Y, Z) of the three-dimensional workspace. Each unit contains three independently controlled pairs of electromagnetic coils. Besides the orthogonal arrangement, in other embodiments, they can also be arranged along three non-coplanar directions. When a specific current is applied to each pair of coils (such as an anti-Helmholtz coil), a magnetic field zero point is generated in its symmetrical center region. By adjusting the current ratio of the three pairs of coils, a magnetic field zero point can be synthesized at any specified location within the working cavity. From this zero point, the magnetic field strength in all directions of space increases linearly, forming a high gradient field. A magnetized magnetic sphere (such as a 200-nanometer diameter Fe3O4 sphere) is placed in this field, ensuring that its initial position is not at the zero point. At this time, the magnetic sphere will experience a magnetic force pointing away from the zero point; this force is a magnetic repulsion force. The fundamental difference from existing technologies lies in the fact that the magnitude of this repulsive force (F) is directly proportional to the distance (d) from the center of the magnetic sphere to the zero point (O), i.e., F ∝ d, exhibiting a linear relationship. In contrast, in existing magnetic tweezers technology, the relationship between the attractive force (F_att) on the magnetic sphere and the distance (r) to the center of force is F_att ∝ 1 / r², which is a non-linear inverse square relationship. The linearity of this invention makes force control more direct, precise, and stable. By comprehensively adjusting the magnitude and direction of the current flowing through the two gradient field coils in the X, Y, and Z directions, the magnitude and intensity of the magnetic field gradient in each orthogonal direction are changed, thereby changing the coordinates of the zero magnetic field point in three-dimensional space, thus changing the relative distance between the zero magnetic field point and the magnetic sphere, and consequently changing the magnitude and direction of the magnetic repulsive force on the magnetic sphere. Within a certain range (within the target control area), the magnitude of the magnetic repulsive force is directly proportional to the distance. Therefore, by manipulating the magnitude of the magnetic repulsive force on the magnetic sphere, translational manipulation of the magnetic sphere in a vector direction away from the zero magnetic field point can be achieved.

[0038] As an optional implementation, the gradient field coil employs a multi-layer coil structure and uses eddy current optimization distribution technology to reduce eddy currents. Silver alloy wires can be used to reduce resistance, lower eddy currents, and improve gradient field efficiency. By changing the magnitude of the current flowing through the coil, the position of the zero magnetic field point can be precisely adjusted, thereby changing the magnitude and direction of the force on the magnetic sphere and ensuring that the magnetic field gradient is above 10 T / m. In this embodiment of the invention, the gradient field coil is wound with multi-layer silver alloy wires and equipped with a water-cooling system to ensure the generation of a high gradient field above 10 T / m. The magnetic field gradient exists from the zero magnetic field point to any direction, ensuring controlled movement of the magnetic sphere in any direction.

[0039] Step S3: Achieve translational control. The core of translational control is moving the zero point of the magnetic field. By changing the magnitude of the magnetic field gradient and gradient magnetic field strength in each orthogonal direction of the multidimensional workspace (two orthogonal directions for a two-dimensional workspace, and three orthogonal directions for a three-dimensional workspace), the relative distance between the zero point of the magnetic field and the magnetic ball is changed (the relative distance between the zero point of the magnetic field and the magnetic ball is changed by changing the position of the zero point of the magnetic field). Within a certain range (within the target control area), the magnitude of the magnetic repulsion force on the magnetic ball is proportional to the distance from the zero magnetic field point. Therefore, by changing the relative distance between the zero magnetic field point and the magnetic ball, the magnitude of the magnetic repulsion force on the magnetic ball can be controlled, thus achieving translational control of the magnetic ball in the target vector direction away from the zero magnetic field point.

[0040] As a specific implementation method, the real-time control module calculates the path that the magnetic field zero point needs to move based on the desired trajectory of the magnetic ball. By rapidly adjusting the magnitude and direction of the current in each coil pair in the gradient magnetic field generating unit, the magnetic field zero point is driven to move continuously in three-dimensional space. Since the magnetic ball is subjected to a linear repulsive force proportional to the distance (the relative distance between the zero magnetic field point and the magnetic ball), it will stably follow the moving zero point, thereby accurately completing the translation in the X, Y, and Z directions, and thus achieving translation in the target direction. Each translational degree of freedom is independently controlled by the current of different coils, achieving natural decoupling.

[0041] In this embodiment of the invention, under the action of a gradient magnetic field, the magnetic sphere is subjected to a magnetic force, and the magnetic force formula is: Where F represents the magnetic force exerted on the magnetic sphere under the influence of the gradient magnetic field. Let B be the volume of the magnetic sphere, and B be the magnetic field strength of the gradient magnetic field. The permeability of free space, B represents the magnetic field gradient at the location of the magnetic sphere. By controlling the magnetic field gradient... The magnitude and direction of the magnetic field strength B of the gradient magnetic field allow for precise control of the magnetic force, thereby enabling manipulation of the corresponding degrees of freedom in the direction of the magnetic field.

[0042] Step S4: Achieve rotational control. The core of rotational control is to make the zero magnetic field point orbit the magnetic sphere. By changing the relative position of the zero magnetic field point and the magnetic sphere, the zero magnetic field point is controlled to orbit the magnetic sphere along each axis, thereby achieving rotational control of the magnetic sphere. The rotational control of the magnetic sphere includes control of three degrees of freedom: pitch, yaw, and roll.

[0043] As a specific implementation method, the real-time control module comprehensively adjusts the magnitude and direction of the current flowing through the two gradient field coils in the X, Y, and Z directions, changing the relative orientation of the zero magnetic field point and the magnetic sphere, thereby achieving rotational control of the magnetic sphere. For example, to make the magnetic sphere rotate (roll) around the Z-axis, the real-time control module can drive the zero magnetic field point to make rapid, minute circular motions in a plane perpendicular to the Z-axis and including the current position of the magnetic sphere. During this dynamic process, the magnetic sphere is subjected to a magnetic repulsive force with constantly changing directions, and its net torque is not zero, thus driving the magnetic sphere to rotate around the Z-axis. By changing the axis of the zero-point orbital motion (changing the relative orientation of the zero magnetic field point and the magnetic sphere), rotational control around the X, Y, and Z axes can be achieved separately, namely pitch, yaw, and roll. Translational control in three orthogonal directions and rotational control in three degrees of freedom (pitch, yaw, and roll) constitute a six-degree-of-freedom magnetic tweezers control.

[0044] As an optional implementation, the real-time control module is also used to move the relative positions between the two gradient field coils in various directions to change the distribution area of ​​the gradient magnetic field, so that the gradient magnetic field can cover the target control area. In this way, after the position of the target control area changes, it is ensured that the target control area is always covered by the gradient magnetic field.

[0045] This invention achieves magnetic tweezers manipulation by adjusting the current of multiple coils, without moving the physical coils, through the principle of electromagnetic superposition, virtually moving the zero magnetic field point and changing the gradient field direction within the control area, rather than relying on mechanical movement. Physical movement is only used to expand the macroscopic working range. This electronic control method is the key to achieving high-frequency response (sub-millisecond / nanosecond level) and can resist high-frequency Brownian motion.

[0046] Step S5: Integrated feedback achieves closed-loop control. The interferometric scattering imaging detection module performs high-speed, high-precision imaging of the magnetic sphere, calculating its actual pose in real time, including its three-dimensional position and orientation (or two-dimensional position and orientation), and feeding this information back to the real-time control module. The real-time control module compares the actual pose with the target pose and uses a closed-loop control algorithm (such as model predictive control) to dynamically adjust the magnitude and direction of the current flowing through the two gradient field coils in each direction. This corrects the trajectory of the zero point of the magnetic field, thereby counteracting interferences such as Brownian motion and fluid resistance, achieving high-precision, robust multi-degree-of-freedom tracking and control. The advanced control algorithm integrated in the real-time control module can achieve sub-millisecond response and sub-nanometer control accuracy.

[0047] In this embodiment of the invention, five degrees of freedom control (two translational degrees of freedom and three rotational degrees of freedom) in two-dimensional space is achieved by distributing two independent coils in each of the two orthogonal directions in two-dimensional space. Alternatively, independent coils can be distributed in multiple directions in three-dimensional space, and six degrees of freedom control in three-dimensional space can be achieved by superimposing magnetic field vectors.

[0048] In this embodiment of the invention, the interferometric scattering imaging detection module employs a high numerical aperture objective lens, a uniform illumination source, and a high-sensitivity camera, combined with image denoising and enhancement algorithms to ensure nanometer-level positioning accuracy and millisecond-level temporal resolution. It monitors the position of a 200-nanometer magnetic sphere in real time, effectively improving the signal-to-noise ratio and 3D positioning accuracy. For 3D manipulation, multi-plane imaging or depth-of-field extension techniques are used to ensure high-precision positioning within a limited depth of field. In this embodiment, the magnetic sphere acts as a "handle" connected to the target microscopic sample. The linear magnetic repulsion force generated by the magnetic tweezers is indirectly and non-destructively transmitted to the sample through the magnetic sphere, achieving precise mechanical measurement and manipulation. Experiments demonstrate that the manipulation force in this embodiment covers the range from 0.1 piconewtons to tens of nanonewtons, meeting the needs of research in fields such as biomechanics and atomic-level manufacturing.

[0049] Example 2 This invention provides a computer-readable storage medium storing a computer program thereon, which, when executed by a processor, implements the steps of the multi-degree-of-freedom magnetic tweezers manipulation method described in Embodiment 1 above.

[0050] Specifically, the memory may include high-speed random access memory, as well as non-volatile memory, such as hard disks, RAM, plug-in hard disks, smart media cards (SMC), secure digital (SD) cards, flash cards, at least one disk storage device, flash memory device, or other volatile solid-state storage devices.

[0051] The relevant technical solutions are the same as above, and will not be repeated here.

[0052] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for manipulating magnetic tweezers with multiple degrees of freedom, characterized in that, include: A stable gradient magnetic field is generated, which covers the target control area where the magnetic sphere is located. The gradient magnetic field has a zero magnetic field point within the workspace. The magnetized magnetic sphere is located outside the target control area outside the zero magnetic field point, and the magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant, so that the relative distance between the zero magnetic field point and the magnetic sphere is proportional to the magnetic repulsive force on the magnetic sphere. The magnetic repulsive force is a force that moves away from the zero magnetic field point. The workspace includes a two-dimensional workspace and a three-dimensional workspace. The magnitudes of the magnetic field gradients and gradient magnetic field strengths in each orthogonal direction of the workspace are changed to alter the position of the zero magnetic field point. When the change in the position of the zero magnetic field point causes a change in the relative distance between the zero magnetic field point and the magnetic sphere, translational control of the magnetic sphere in a target vector direction away from the zero magnetic field point is achieved. When the change in the position of the zero magnetic field point causes a change in the relative orientation between the zero magnetic field point and the magnetic sphere, rotational control of the magnetic sphere is achieved. The rotational control includes pitch, yaw, and roll control.

2. The multi-degree-of-freedom magnetic tweezers manipulation method according to claim 1, characterized in that, By configuring a set of gradient field coils in each of the N directions of the workspace, each set of gradient field coils includes two gradient field coils with opposite magnetic poles, so that after current is passed through the gradient field coils, the zero magnetic field point is formed in the target control area between the two magnetic poles, and the gradient magnetic field is formed around the zero magnetic field point, and the magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant. By adjusting the current in the two gradient field coils in each direction, the magnitude of the magnetic field gradient and the gradient magnetic field strength in each orthogonal direction of the working space are changed, thereby changing the position of the zero magnetic field point. Wherein, when the workspace is a two-dimensional workspace, N≥2, and there are at least two non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in two orthogonal directions; when the workspace is a three-dimensional workspace, N≥3, and there are at least three non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in three orthogonal directions. When the workspace is a two-dimensional workspace and the N directions are N orthogonal directions, N=2; when the workspace is a three-dimensional workspace and the N directions are N orthogonal directions, N=3.

3. The multi-degree-of-freedom magnetic tweezers manipulation method according to claim 2, characterized in that, Also includes: The relative positions between the two gradient field coils in each direction are moved to change the distribution area of ​​the gradient magnetic field, so that the gradient magnetic field covers the target control area.

4. The multi-degree-of-freedom magnetic tweezers manipulation method according to claim 2 or 3, characterized in that, Also includes: The current pose of the magnetic ball is detected in real time and compared with the target pose. The current in the two gradient field coils in each direction is dynamically adjusted using a closed-loop control algorithm to correct the position of the zero magnetic field point, so that the current pose is close to the target pose. Or / and, prior to generating the gradient magnetic field, the method further includes generating a background magnetic field covering the target manipulation area, the background magnetic field being used to magnetize the magnetic sphere in the initial stage.

5. A multi-degree-of-freedom magnetic tweezers manipulation system, characterized in that, include: A gradient magnetic field generating unit is used to generate a stable gradient magnetic field that covers the target control area where the magnetic sphere is located. The gradient magnetic field has a zero magnetic field point within the workspace. The magnetized magnetic sphere is located within the target control area outside the zero magnetic field point, and the magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant, so that the relative distance between the zero magnetic field point and the magnetic sphere is proportional to the magnetic repulsive force experienced by the magnetic sphere. The magnetic repulsive force is a force directed away from the zero magnetic field point. The workspace includes a two-dimensional workspace and a three-dimensional workspace. The real-time control module is used to change the magnitude of the magnetic field gradient and gradient magnetic field strength in each orthogonal direction of the workspace to change the position of the zero magnetic field point. When the change in the position of the zero magnetic field point causes a change in the relative distance between the zero magnetic field point and the magnetic ball, the module enables translational control of the magnetic ball in the target vector direction away from the zero magnetic field point. When the change in the position of the zero magnetic field point causes a change in the relative orientation between the zero magnetic field point and the magnetic ball, the module enables rotational control of the magnetic ball. The rotational control includes pitch, yaw, and roll control.

6. The multi-degree-of-freedom magnetic tweezers manipulation system according to claim 5, characterized in that, The gradient magnetic field generating unit includes a set of gradient field coils arranged in each of the N directions of the workspace. Each set of gradient field coils includes two gradient field coils with opposite magnetic poles, so that when current is passed through the gradient field coils, the zero magnetic field point is formed in the target control area between the two magnetic poles, and the gradient magnetic field is formed around the zero magnetic field point. The magnetic field strength gradient along each direction of the workspace from the zero magnetic field point is constant. The real-time control module is used to change the position of the zero magnetic field point by adjusting the current in the two gradient field coils in each direction, thereby changing the magnitude of the magnetic field gradient and gradient magnetic field strength in each orthogonal direction of the workspace. Wherein, when the workspace is a two-dimensional workspace, N≥2, and there are at least two non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in two orthogonal directions; when the workspace is a three-dimensional workspace, N≥3, and there are at least three non-coplanar direction vectors in the N directions, so that the N sets of gradient field coils in the N directions generate gradient magnetic fields in three orthogonal directions. When the workspace is a two-dimensional workspace and the N directions are N orthogonal directions, N=2; when the workspace is a three-dimensional workspace and the N directions are N orthogonal directions, N=3.

7. The multi-degree-of-freedom magnetic tweezers manipulation system according to claim 6, characterized in that, The real-time control module is also used to move the relative position between the two gradient field coils in each direction to change the distribution area of ​​the gradient magnetic field so that the gradient magnetic field covers the target control area.

8. The multi-degree-of-freedom magnetic tweezers manipulation system according to claim 6 or 7, characterized in that, It also includes an interferometric scattering imaging detection module for real-time detection of the current pose of the magnetic sphere; The real-time control module is used to compare the current pose with the target pose and dynamically adjust the current in the two gradient field coils in each direction using a closed-loop control algorithm to correct the position of the zero magnetic field point so that the current pose and the target pose are close to being consistent. Or / and, it also includes a static magnetic field source for generating a background magnetic field covering the target manipulation area prior to generating the gradient magnetic field, the background magnetic field being used to magnetize the magnetic sphere in the initial stage.

9. The multi-degree-of-freedom magnetic tweezers manipulation system according to claim 8, characterized in that, The magnetic spheres have diameters ranging from micrometers to nanometers, and their surfaces are optimized to reduce friction and adhesion. The gradient field coil contains an iron core and adopts a multi-layer coil structure, and uses eddy current optimization distribution technology to reduce eddy currents.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the program is executed by the processor, it implements the multi-degree-of-freedom magnetic tweezers manipulation method as described in any one of claims 1-4.

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