Micron-sized magnetic control cell micro-clamp system for medical detection and diagnosis

Abstract

The invention discloses a micron-sized magnetic control cell micro-clamp system for medical detection and diagnosis, and relates to the technical field of detection and diagnosis. Stable and controllable cell grabbing, trigger release and transfer can be realized in in-vivo and in-vitro environments, and an important tool is provided for automatic accurate diagnosis and clinical detection of cell-related diseases. The system comprises a micron-sized magnetic control cell micro clamp, an in-vitro magnetic control system and an in-vivo magnetic control system, the in-vitro magnetic control system can generate a first external magnetic field for driving the micron-sized magnetic control cell micro-clamp to perform cell operation in vitro; the in-vivo magnetic control system can generate a second external magnetic field for driving the micron-sized magnetic control cell micro-clamp to carry out cell transportation operation in vivo; the micron-sized magnetic control cell micro clamp comprises two clamp bodies and an elastic piece, the clamp body is formed by processing a hyperelastic photoresist material doped with a superparamagnetic material; the clamp body can be opened or closed under the action of the first external magnetic field or the second external magnetic field so as to grab or release cells.

Description

Technical Field

[0001] The present application relates to the field of medical detection and diagnosis technology, and in particular to a micron-level magnetically controlled cell micro-clamp system for medical detection and diagnosis. Background Art

[0002] With the development of micro-nano robotics, how to precisely manipulate single cells or cell clusters at the micrometer scale so that they can be used for medical detection and diagnosis has become an important research direction in biomedical engineering. Traditional mechanical methods are difficult to meet the precision and flexibility requirements of cell manipulation. In addition, a key issue in cell manipulation is how to fix fragile target cells firmly enough without applying destructive pressure to them. Existing micro-robotics technology generally fixes and transports biological cells and tissues by designing microstructures that capture cells, such as micro-clamps or micro-spirals. However, most of the existing microstructures use static non-enclosed cell compartment structures, such as cylindrical structures with one end open, which has the disadvantage that cells are easily detached during transportation. Magnetic control technology has gradually become an ideal choice for cell manipulation due to its advantages of non-contact, high precision, and remote control. In addition, existing magnetically controlled micromanipulation systems often lack integration and systematization, and cannot be applied to complex operating environments both in vivo and in vitro. Therefore, the development of a micrometer-level magnetically controlled cell micro-clamp system with high integration, real-time performance, and strong applicability has important research value and application prospects. Summary of the invention

[0003] The embodiments of the present application provide a micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis, which can achieve stable and controllable cell capture, triggered release and transport in both in vivo and in vitro environments, providing an important tool for automated and precise diagnosis and clinical detection of cell-related diseases.

[0004] To achieve the above-mentioned objectives, an embodiment of the present application provides a micron-level magnetically controlled cell micro-clamp system for medical detection and diagnosis, including a micron-level magnetically controlled cell micro-clamp, an in vitro magnetic control system and an in vivo magnetic control system; the in vitro magnetic control system can generate a first external magnetic field that drives the micron-level magnetically controlled cell micro-clamp to perform cell operations in vitro; the in vivo magnetic control system can generate a second external magnetic field that drives the micron-level magnetically controlled cell micro-clamp to perform cell transport operations in vivo; the micron-level magnetically controlled cell micro-clamp includes two clamp bodies arranged opposite to each other and an elastic member connected between the clamp bodies; the elastic member can constrain the two clamp bodies in a closed jaw state; the clamp body is made of superelastic photoresist material doped with superparamagnetic material; the clamp body can be opened or closed under the action of the first external magnetic field or the second external magnetic field to grasp or release cells, and transport cells to a preset position.

[0005] Furthermore, when the clamp body is in a closed state, a single cell can be clamped in the jaws.

[0006] Furthermore, the clamp body is a sawtooth-shaped clamp body or a claw-shaped clamp body.

[0007] Furthermore, the fore-and-aft direction of the clamp body is the easy magnetization axis.

[0008] Furthermore, the first external magnetic field and the second external magnetic field are both variable magnetic fields that can be transformed between a rotating uniform magnetic field and a gradient magnetic field; the rotating uniform magnetic field is a rotating uniform magnetic field with variable magnetic field strength; when the first external magnetic field is transformed into a rotating uniform magnetic field with a magnetic field strength greater than 7mT, the micron-scale magnetically controlled cell micro-clamp is driven to roll forward and open; when the first external magnetic field is transformed into a rotating uniform magnetic field with a magnetic field strength less than 7mT, the micron-scale magnetically controlled cell micro-clamp is driven to roll forward and close; when the first external magnetic field is transformed into a gradient magnetic field with a gradient of 0~1T / m or when the second external magnetic field is transformed into a gradient magnetic field with a gradient of 0~5T / m, the micron-scale magnetically controlled cell micro-clamp is driven to translate forward.

[0009] Furthermore, there is an angle between the two clamp bodies; the easy magnetization axis can be deflected by controlling the strength of the first external magnetic field and the second external magnetic field, thereby controlling the angle between the two clamp bodies.

[0010] Furthermore, the in vitro magnetic control system includes a three-dimensional Helmholtz coil, a first data acquisition card, a first power amplifier, a first relay, a first computer and a cell detection module; the three-dimensional Helmholtz coil and the cell detection module are both arranged on a load-bearing bracket; a sample platform is provided at the center of the three-dimensional Helmholtz coil, and the sample platform is used to place a culture dish for culturing cells to be operated; the cell detection module is communicatively connected to the first computer, and the cell detection module can monitor living tissues and cells, and monitor the position of the micron-level magnetically controlled cell micro-clamp in real time; the first data acquisition card is communicatively connected to the first computer; the first relay is electrically connected to the three-dimensional Helmholtz coil; the signal input end of the first power amplifier is connected to the analog signal output end of the first data acquisition card, and the output end of the first power amplifier is connected to the power input end of the first relay.

[0011] Furthermore, the cell detection module includes an optical biological microscope and a microscope camera; the optical biological microscope is an inverted fluorescence microscope, and the objective lens is inverted under the sample platform; the microscope camera is connected to the trinocular port of the optical biological microscope to achieve optical system docking of the microscope camera and the optical biological microscope.

[0012] Furthermore, the in vivo magnetic control system includes a magnetic field generator, a scanning bed, an OCT imaging system, a second computer, a second data acquisition card, a second power amplifier and a second relay; the magnetic field generator includes a main body and a plurality of groups of superconducting electromagnetic coils arranged along the X, Y and Z axis directions on the main body; the main body is an annular or cylindrical structure that can allow the patient scanning bed to pass through; the OCT imaging system can detect the position of the micron-level magnetically controlled cell micro-clamp in the body in real time; the second data acquisition card is communicatively connected to the second computer; the second relay is electrically connected to the superconducting electromagnetic coil; the signal input end of the second power amplifier is connected to the analog signal output end of the second data acquisition card; the output end of the second power amplifier is connected to the power input end of the second relay.

[0013] Compared with the prior art, this application has the following beneficial effects:

[0014] 1. The clamp body of the micron-level magnetically controlled cell micro-clamp in the embodiment of the present application is made of superelastic photoresist material doped with superparamagnetic material, and the clamp body has a large aspect ratio. The two clamp bodies are connected by an elastic member. Therefore, when a weak rotating magnetic field is applied to the micro-clamp through an in vitro or in vivo magnetic control system, the micro-clamp is in a closed state due to the constraint of the elastic member, and flips close to the target cell. When the micro-clamp reaches the target position, a strong rotating magnetic field is applied. Since the head and tail direction of the clamp body is the easy magnetization axis, it will be aligned with the direction of the strong magnetic field. At this time, the clamp body overcomes the resistance of the elastic member and rotates. The micro-clamp is in an open state. After the cell enters the jaws, the strength of the strong magnetic field is reduced, and the micro-clamp clamps the cell and transports the cell to a preset position. Since the micro-clamp is opened and driven by the magnetic field, stable cell transportation and trigger release can be achieved, and by adjusting the opening and closing deformation amplitude of the micro-clamp, it can be used to grab cells or other objects of different geometric shapes and sizes.

[0015] 2. The embodiment of the present application combines in vitro and in vivo magnetic control systems, which can not only complete cell manipulation in laboratory environments, but also perform delicate micromanipulation in complex biological environments in vivo. This dual system design greatly expands the application scenarios of micro-clamps, making them not only suitable for single cell manipulation in in vitro experiments, such as precisely controlling the behavior of cells in a culture dish, but also capable of complex operations such as cell capture and transportation in vivo, such as in blood vessels or other body cavities.

[0016] 3. The optical microscope and OCT imaging system integrated in the embodiment of the present application provide real-time visual feedback for the operation of the micron-level magnetically controlled cell micro-clamp, allowing researchers to accurately monitor the movement state of cells and micro-clamps to ensure the accuracy and safety of the operation. The embodiment of the present application not only brings new possibilities for biomedical research and clinical biological diagnosis, but also provides broad prospects for applications in minimally invasive surgery, drug delivery and other fields. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0018] Figure 1 This is a schematic diagram of the structure of Example 1 of the present application;

[0019] Figure 2 This is a front view of the micrometer-scale magnetically controlled cell micro-clamp in Example 1 of the present application;

[0020] Figure 3 A top view of the micrometer-scale magnetically controlled cell micro-clamp of Example 1 of the present application;

[0021] Figure 4 This is a closed state diagram of the micron-scale magnetically controlled cell micro-clamp of Example 1 of the present application;

[0022] Figure 5 This is a diagram of the open state of the micron-scale magnetically controlled cell micro-clamp of Example 1 of the present application;

[0023] Figure 6 This is a diagram showing the clamping state of the micron-scale magnetically controlled cell micro-clamp of Example 1 of the present application;

[0024] Figure 7 This is a schematic diagram of the structure of the in vitro magnetic control system in Example 1 of the present application;

[0025] Figure 8 The image detected by the cell detection module in Example 1 of the present application;

[0026] Fig. 9 This is a schematic diagram of the structure of the in vivo magnetic control system in Example 1 of the present application;

[0027] Fig.10 The image detected by the OCT imaging system in Example 1 of the present application;

[0028] Fig.11 This is a front view of the micrometer-scale magnetically controlled cell micro-clamp in Example 2 of the present application;

[0029] Fig.12 This is a top view of the micron-scale magnetically controlled cell micro-clamp of Example 2 of the present application. DETAILED DESCRIPTION

[0030] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0031] In the description of the present application, it should be understood that the terms "center", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.

[0032] In the description of the present application, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected" and "connected" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection. For ordinary technicians in this field, they can understand the specific meanings of the above terms in this application according to specific circumstances.

[0033] The terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" can explicitly or implicitly include one or more of the features. In the description of this application, unless otherwise specified, "plurality" means two or more.

[0034] Embodiment 1:

[0035] Reference Figure 1 The present application provides a micron-level magnetically controlled cell micro-clamp system for medical detection and diagnosis, including a micron-level magnetically controlled cell micro-clamp 10, an in vitro magnetic control system 20, and an in vivo magnetic control system 30. The in vitro magnetic control system 20 can generate a first external magnetic field that drives the micron-level magnetically controlled cell micro-clamp to perform cell manipulation in vitro. The in vivo magnetic control system 30 can generate a second external magnetic field that drives the micron-level magnetically controlled cell micro-clamp to perform cell transport operations in vivo.

[0036] Reference Figures 2 to 6The micron-scale magnetically controlled cell micro-gripper 10 comprises two clamp bodies 1 arranged opposite to each other and an elastic member 2 connected between the clamp bodies 1. The elastic member 2 can constrain the two clamp bodies 1 in a closed jaw state. The clamp body 1 is made of a superelastic photoresist material doped with a superparamagnetic material. The clamp body 1 can be opened or closed under the action of a first external magnetic field or a second external magnetic field to grasp or release a cell 3, and transport the cell 3 to a preset position.

[0037] The first external magnetic field is generated by an in vitro magnetic control system 20. The first external magnetic field is a variable magnetic field that can be switched between a rotating uniform magnetic field and a gradient magnetic field, and the magnetic field strength of the rotating uniform magnetic field is variable. When the magnetic field strength of the rotating uniform magnetic field is 15mT, the clamp body 1 can be driven to roll forward and open to grab or release cells; when the magnetic field strength of the rotating uniform magnetic field is 5mT, the clamp body 1 can be driven to roll forward and close to transport cells to a preset position. For ease of description, the magnetic field with a magnetic field strength of 15mT is referred to as a strong magnetic field, and the magnetic field with a magnetic field strength of 5mT is referred to as a weak magnetic field.

[0038] The gradient magnetic field has a gradient of 0~1T / m.

[0039] The second external magnetic field is generated by the in vivo magnetic control system 30. The second external magnetic field is a variable magnetic field that can be switched between a rotating uniform magnetic field and a gradient magnetic field, and the magnetic field strength of the rotating uniform magnetic field is variable. When the magnetic field strength of the rotating uniform magnetic field is 15mT, the clamp body 1 can be driven to roll forward and open to grab or release cells; when the magnetic field strength of the rotating uniform magnetic field is 5mT, the clamp body 1 can be driven to roll forward and close to transport cells to a preset position. The gradient magnetic field is a gradient magnetic field with a gradient of 0~5T / m.

[0040] The clamp body 1 contains magnetic material and will have a magnetic moment when an external magnetic field is applied. The clamp body 1 has a large aspect ratio in structure. After being placed in the magnetic field, the length direction (head-to-tail direction) of the clamp body 1 is the easy magnetization axis and will be aligned with the direction of the strong magnetic field.

[0041] The clamp body 1 is a serrated clamp body. A jaw is formed between the two clamp bodies 1, and a grabbing tooth 11 is provided on the inner side of the jaw. The grabbing tooth 11 can prevent slipping out when grabbing a tiny object (such as sperm), and can limit the grasped object in the jaw. Under normal conditions, the jaw of the micro clamp is closed by the elastic member 2, and the angle between the two clamp bodies 1 is an acute angle when closed. The angle between the two clamp bodies 1 can be controlled by controlling the intensity of the rotating uniform magnetic field. That is, when an external strong magnetic field is applied, the two clamp bodies 1 will be aligned with the direction of the external magnetic field, and the angle between the two is reduced to near zero degrees, and the micro clamp is in an open state, that is, the two are parallel to each other and the distance between the two is greater than the diameter of the cell 3. After reducing the intensity of the external magnetic field, the jaw tends to close under the action of the elastic member 2, and the micro clamp is in a clamping state, which can clamp a single cell 3 in the jaw, thereby preventing the cell 3 from being lost during the movement of the micro clamp.

[0042] The elastic member 2 is made of a low elastic modulus photoresist material doped with a superparamagnetic material, and has the characteristics of low rigidity and high elastic deformation, which can ensure that the micro clamp will not damage the cell 3 during the opening and closing process.

[0043] Reference Figure 1 , Figure 7 and Figure 8 The in vitro magnetic control system 20 is a high-precision magnetic field control system for generating and controlling a three-dimensional alternating magnetic field, thereby accurately controlling the movement and operation of the micro-clamp. The in vitro magnetic control system 20 includes a three-dimensional Helmholtz coil 21, a first data acquisition card 22, a first power amplifier 23, a first relay (not shown), a first computer, a cell detection module and a sample platform 291. The first computer includes a first computer host 24 and a first computer display 25. The cell detection module includes an optical biological microscope 26, a microscope camera 27 and a microscopic light source 28. The optical biological microscope 26 is a fluorescence microscope.

[0044] The three-dimensional Helmholtz coil 21 can generate a stable three-dimensional alternating magnetic field. The alternating frequency range can be adjusted to 0-30Hz to meet different experimental requirements. When generating a uniform magnetic field, the coil system can provide a magnetic field strength of up to 20mT in the central area. The uniform magnetic field ensures the uniform distribution of the field and drives the directional rotation of the micro-nano paramagnetic structure in the magnetic field by generating a torque. When generating a gradient magnetic field, the magnetic field gradient can reach 1T / m. In contrast, the gradient magnetic field generates a magnetic force gradient and exerts a translational force, thereby driving the micro-nano paramagnetic structure to achieve linear displacement. Specifically, the three-dimensional Helmholtz coil 21 consists of three orthogonally arranged coils, which control the magnetic fields in the X, Y and Z directions respectively. Each coil consists of two layers of inner and outer coils. Among them, the inner circle diameter of the X-axis coil group is 24cm, and the outer circle diameter is 30cm. The inner circle diameter of the Y-axis coil group is 18cm, and the outer circle diameter is 24cm. The inner circle diameter of the Z-axis coil group is 12cm, and the outer circle diameter is 18cm.

[0045] In order to ensure that a uniform magnetic field is generated in the central area, the three-dimensional Helmholtz coil 21 is arranged on a load-bearing bracket 29. The load-bearing bracket 29 has a height adjustment function, and the position of the coil can be manually adjusted according to needs, and the height adjustment range is 20 cm.

[0046] The first relay and the three coils in the three-dimensional Helmholtz coil 21 are electrically connected through a wire. The signal input end of the first power amplifier 23 is connected to the analog signal output end of the first data acquisition card 22, and the output end of the first power amplifier 23 is connected to the power input end of the first relay through a connecting line. The first data acquisition card 22 is connected to the first computer through a USB communication interface. The first computer is connected to the cell detection module for communication, and displays the detection results of the cell detection module.

[0047] The first data acquisition card 22 can output an analog signal according to preset magnetic field parameters. The preset magnetic field parameters are input by the operator through the first computer. Specifically, the first data acquisition card 22 has six-channel synchronous analog output, supports multi-channel synchronous control, and can accurately adjust the voltage intensity, waveform and frequency of the six Helmholtz coils. The output range is ±10V, thereby achieving all-round control of the magnetic field parameters.

[0048] The first power amplifier 23 can amplify the power of the analog signal output by the first data acquisition card 22 and convert it into a current value required for driving the coil, so as to ensure that the coil generates the required magnetic field strength.

[0049] The first relay is configured to be able to electrically switch the current direction of each coil. By adjusting the digital signal level (high level or low level) output by the acquisition card, the circuit switch of the relay is changed, thereby converting the current flow through the coil, flexibly changing the direction and properties of the magnetic field, and switching to generate a uniform magnetic field or a gradient magnetic field.

[0050] The magnitude of the current is indirectly determined by the signal input from the first computer to the first data acquisition card 22. The first data acquisition card 22 converts the collected computer signal into an analog signal output to adjust the current magnitude of the three-dimensional Helmholtz coil 21. Specifically, the first computer, as the control center of the system, runs the control program, communicates with the first data acquisition card 22 through the USB interface, and adjusts the parameters of the output signal in real time. The first computer can accurately control the key parameters of the magnetic field, such as frequency, intensity, and waveform, and monitor and adjust the image feedback in real time through the microscope camera in the cell detection module, so as to achieve high-precision control and path planning of the micro-clamp operation.

[0051] In order to facilitate the operation and observation of the sample, a sample platform 291 is set in the central area of ​​the three-dimensional Helmholtz coil 21. Specifically, the sample platform 291 is located in the center of the two coils of the Z axis, which is convenient for adjusting the movement of the sample on the XY axis. A three-axis Hall sensor (not shown in the figure) is loaded in the coil, and the signal output end of the sensor is electrically connected to the analog signal input end of the acquisition card through a wire.

[0052] The culture dish for culturing cells to be operated is placed on the sample platform 291. The sample platform 291 is 10 cm long and wide, and is made of a material with low magnetic permeability to minimize interference with the magnetic field. The sample platform 291 is composed of a precision fine-tuning stage, which supports electric movement in three directions of XYZ and has a repeatability accuracy of ±2µm. Through the fine-tuning function of the platform, the sample can be accurately positioned under the microscope, which is convenient for operation and observation. The sample platform also carries a sample tray, which can be replaced with an appropriate model according to the size of the sample culture dish.

[0053] The optical biological microscope 26, the microscope camera 27 and the microscopic light source 28 are also mounted on the load-bearing bracket 29. The optical biological microscope 26 is an inverted fluorescence microscope, and the objective lens is inverted below the sample platform. The microscope camera 27 is connected to the trinocular port of the optical biological microscope 26 to achieve the docking of the optical system of the camera and the microscope.

[0054] The microscope stand provides stability and flexibility, allowing the microscope to work at different heights and angles to suit different observation needs. The optical biological microscope 26 is equipped with multiple sets of lenses, and users can switch between 4X, 10X, 20X, 40X and 63X magnifications by rotating the lens converter to adjust the level of detail of observation as needed. The microscope uses a fluorescent light source that can excite the fluorescent dye in the sample, making cells or other biological samples clearly visible under the microscope.

[0055] The microscope camera 27 has high-resolution imaging capabilities, with a resolution of up to 4096×2160 pixels (4K UHD), which can capture tiny details of cells and ensure the clarity of the image. The signal output end of the microscope camera 27 is connected to the signal input end of the first computer via a USB communication interface. At the same time, the microscope camera 27 also supports high frame rate shooting, and in 1080p full HD mode, the frame rate can reach 60 frames per second. The high frame rate supports real-time dynamic observation of micro-clamps and cell activities in the culture dish, can capture rapidly changing cell behaviors, and improve the accuracy and reliability of detection. As a result, the cell detection module can monitor living tissues and cells in an in vitro environment, and monitor the position of the micron-level magnetically controlled cell micro-clamp 10 in real time.

[0056] Reference Figure 1 and Fig. 9 The in-vivo magnetic control system 30 is a magnetic control system similar to an MR machine, and is specially designed for human body passage and high-precision magnetic field manipulation. The in-vivo magnetic control system 30 includes a magnetic field generator 31, a scanning bed 32, an OCT imaging system 33, a second computer 34, a second data acquisition card 35, a second power amplifier 36, and a second relay 37. The magnetic field generator 31 includes a body 311 and a plurality of groups of superconducting electromagnetic coils 312 arranged on the body 311.

[0057] The main body 311 is an annular or cylindrical structure that can allow the patient's scanning bed to pass through, and is made of materials with excellent magnetic shielding properties to ensure human safety and magnetic field concentration during operation. Specifically, in order to accommodate the passage of the human body, the diameter of the system channel is 80cm and the length is 2.5 meters. The inner wall of the channel is covered with medical silicone flexible material to ensure safety during the passage. The channel is equipped with a human body positioning device to ensure accurate positioning during operation. In order to ensure safety, the system shell is made of high-efficiency magnetic shielding materials to prevent magnetic field leakage, and is equipped with an emergency stop device and a monitoring alarm system to monitor the magnetic field status in real time.

[0058] The superconducting electromagnetic coil 312 is composed of superconducting electromagnets, which can generate high-intensity and stable magnetic fields under the action of cooling liquids such as liquid helium or liquid nitrogen. Multiple groups of superconducting electromagnetic coils 312 are arranged along the X, Y, and Z axis directions. Specifically, the superconducting electromagnetic coil 312 includes an X-axis magnetic control coil, a Z-axis magnetic control coil, and a Y-axis magnetic control coil, which can achieve precise control of the three-dimensional magnetic field. The magnetic field strength can be adjusted in the range of 0.1T to 3T, and the maximum magnetic field gradient can reach 5T / m to achieve precise positioning and manipulation of magnetic micro-clamps or micro-devices in the human body. Each electromagnetic coil of the in-vivo magnetic control system 30 is made of high-conductivity copper wire and powered by a high-voltage AC power supply. The second relay 37 is used to adjust the current size and direction of the electromagnetic coil. The electromagnetic coils are connected in parallel to ensure the uniformity and strength of the magnetic field. The size of each electromagnetic coil is precisely designed to ensure that the required strong magnetic field can be generated. In order to prevent overheating, a cooling pipe surrounds the outside of each electromagnetic coil, and the cooling medium circulates in the pipe to take away the heat generated by the coil through the heat exchange system. The cooling system, including the circulation pump and radiator, is automatically adjustable to ensure optimum cooling at all times.

[0059] The in vivo magnetic control system 30 also integrates a digital control system and a programmable control module, allowing the user to adjust the magnetic field parameters in real time and preset the magnetic field change mode according to the operation requirements. The second computer 34 is responsible for the operation and management of the entire system, and the user can set the target parameters of the magnetic field (such as intensity, direction and gradient) through the interface. The second computer 34 includes a second host 341 and a magnetic field control display 342.

[0060] The second relay 37 and the superconducting electromagnet coil 312 are electrically connected through a wire. The signal input end of the second power amplifier 36 is connected to the analog signal output end of the second data acquisition card 35, and the output end of the second power amplifier 36 is connected to the power input end of the second relay 37 through a connecting line. The second data acquisition card 35 is connected to the second computer 34 through a USB communication interface.

[0061] The second computer 34 sends the preset signal parameters. The second data acquisition card 35 receives the digital signal from the second computer 34 and converts it into analog signals. These analog signals represent the required magnetic field strength and frequency, and are then transmitted to the second signal amplifier.

[0062] The second power amplifier 36 can amplify the power of the analog signal output by the second data acquisition card 35 and convert it into a current value required for driving the coil to ensure that the coil generates the required magnetic field strength.

[0063] The second Hall sensor is connected to the second data acquisition card 35 to provide real-time feedback on the strength and distribution of the magnetic field. All signals are transmitted via optical fiber or highly shielded data lines to avoid electromagnetic interference and ensure the accuracy and stability of the system.

[0064] The OCT imaging system 33 can detect the position of the micron-scale magnetically controlled cell micro-gripper 10 in the body in real time. The specific OCT imaging system 33 can achieve an axial resolution of 1 to 15 microns and a lateral resolution of 10 to 20 microns. The imaging depth depends on the optical properties of the sample and the wavelength of the light source. For biological tissues, the imaging depth of the OCT imaging system 33 is generally in the range of 1 to 3 mm, and it can image deeply into the tissue, thereby providing detailed structural information inside the tissue. The OCT imaging system 33 includes an OCT imager host 331, an OCT imager scanning device 332, and an imaging display screen 333. Fig.10 The imaging display screen 333 can display the blood vessels 7 in the human body and the micron-scale magnetically controlled cell micro-clamp 10 in the blood vessels observed under OCT imaging.

[0065] The specific steps for micro-clamp cell manipulation using an in vitro magnetic control system are as follows:

[0066] The first computer sends a digital signal through USB serial communication. The waveform of the output signal is set in the computer program (generally expressed in mathematical formulas) and transmitted to the first data acquisition card 22 through the software API interface. The digital-to-analog converter (DAC) in the first data acquisition card 22 reads the digital signal sent by the computer as strength and alternating frequency, and converts it into an analog signal. Because the voltage of the analog signal itself is weak and insufficient to drive the three-dimensional Helmholtz coil 21 to generate a magnetic field of the required strength to drive the micro-clamp, the first power amplifier 23 is required to synchronously amplify the analog signal. The amplified voltage signal will be input to the three-dimensional Helmholtz coil 21. Depending on the input signal, magnetic fields of different strengths, gradients, frequencies, and directions are generated. Among them, the magnetic field strength can be generated by changing the amplitude of the signal waveform in the computer program; the magnetic field frequency can be generated by changing the signal period; and the magnetic field direction can be generated by generating different signal strength combinations through the XYZ coil. When the current direction and magnitude of the two coils in a group of coils are consistent (the current direction is switched by a relay), the magnetic field generated in the middle of the coil group can be regarded as a uniform magnetic field with a constant field strength. When the current directions of two coils in a group of coils are inconsistent but the magnitudes are consistent, a gradient magnetic field with a constant gradient can be generated between the coils from the central area to the two ends of the coil group. When a uniform magnetic field is generated, the Hall sensor inside the coil will output the detected magnetic field strength in real time, and generate a signal to be input to the analog input end of the first data acquisition card 22. The computer program can adjust the magnetic field strength in real time based on this signal to achieve closed-loop control. The cell detection module is used to observe samples in real time, including cells or biological tissues in the micro clamp and its surrounding environment. The sample image will be collected by the camera and transmitted back to the user interface of the computer in real time through the USB interface. The experimental operator can control the micro clamp through the computer user interface, and apply different magnetic field control signals according to the posture and morphology of the micro clamp, thereby changing the direction and opening and closing of the micro clamp.

[0067] The micron-scale magnetically controlled cell micro-clamp 10 is made of superelastic photoresist material and Fe3O4 magnetic particles. Since these magnetic particles have superparamagnetism, and the magnetic moments of the magnetic particles in the head-to-tail direction of the micron-scale magnetically controlled cell micro-clamp 10 are arranged along the magnetization axis, their magnetic moments are aligned with the direction of the magnetic field when an external magnetic field exists. When the direction of the magnetic field changes, the magnetic moments of the magnetic particles will realign, driving the micro-clamp to change direction synchronously. After applying a rotating uniform magnetic field with an intensity of 5mT by an in vitro magnetic control system 20, the micro-clamp will rotate synchronously with the magnetic field. In a low Reynolds number environment, the inertia of motion can be ignored, and the movement of the particles is dominated by the viscous resistance of the fluid. The viscous force interacts with the fluid flow generated by the rotation of the micro-clamp, thereby generating a net displacement, causing the micro-clamp to roll and move forward. Due to the constraint of the elastic member 2, the micro-clamp is in a closed state, that is, there is an angle between the two clamp bodies 1.

[0068] When the micro clamp reaches the target position, a rotating uniform magnetic field with an intensity of 15 mT is applied by an in vitro magnetic control system 20. At this time, since the micro clamp is placed in a uniform magnetic field and the intensity of the magnetic field changes, the magnetization intensity and magnetic moment of the magnetic particles will also change. A stronger magnetic field will make the magnetic particles magnetized more strongly, generate a larger magnetic moment, and thus apply a larger torque to drive the structure of the micro clamp to deform. Since the micro clamp is in a closed state before the magnetic field is applied, the direction of its magnetization axis is deflected inward at the clamp mouth, so after the magnetic moment is strengthened, the magnetization axis will be aligned to a greater extent in the direction of the magnetic field. The resulting deflection of the magnetization axis will cause the clamp body 1 to overcome the resistance of the elastic member 2, and the angle between the two clamp bodies 1 will be reduced to near zero degrees. The micro clamp is in an open state. After the cell 3 enters the clamp mouth, a rotating uniform magnetic field of 5 mT is applied again, and the magnetic force on the clamp body 1 is reduced, and it tends to be closed again under the constraint of the elastic member 2, and the micro clamp is in a clamping state. The movement of the micro clamp is achieved by applying a rotating magnetic field, so that the micro clamp moves forward in a spiral motion. After the cell 3 is transported to a designated position, a strong magnetic field is applied to open the jaws and release the cell 3.

[0069] In addition, when the micro-gripper is placed in a gradient magnetic field, the strength of the magnetic field is not uniform in space, and the magnetic moment of the magnetic particles in the micro-gripper will be subjected to a magnetic force in the direction of the gradient in the magnetic field. The stronger the magnetic field, the greater the attraction. When a gradient magnetic field is applied, the movement path of the micro-nano robot can be precisely adjusted by controlling the direction of the magnetic field. By changing the direction of the magnetic field gradient, the robot will move along the new gradient direction. Therefore, cell transport can also be achieved by switching between uniform magnetic field and gradient magnetic field.

[0070] In actual use, in order to prevent the micro-clip from missing the cell when it rolls and approaches the target cell, a gradient magnetic field can be applied to the micro-clip when it approaches the cell to make it move in parallel. Specifically, when clamping the cell, a relatively strong (15mT) rotating uniform magnetic field can be applied to drive the micro-clip to roll and approach the target cell, and the jaws are in an open state. When the distance between the micro-clip and the target cell is close (<100um), the rotating uniform magnetic field is closed and the magnetic field is switched to a gradient magnetic field with a gradient of 500mT / m. The gradient increasing direction of the gradient magnetic field is consistent with the direction in which the micro-clip is driven. When the micro-clip touches the cell, the gradient magnetic field is closed, and the jaws of the micro-clip will close and clamp the cell. After clamping the cell, the magnetic field is switched to a relatively weak (5mT) rotating uniform magnetic field and the cell is transported. Finally, the target position of the transport is reached by controlling the change in the direction of the magnetic field.

[0071] In summary, the operation and movement of the micron-scale magnetically controlled cell micro-gripper 10 in the present application are all controlled by the magnetic field, which can achieve stable cell transportation and triggered release. In addition, by adjusting the opening and closing deformation amplitude of the micro-gripper, it can be used to gently grasp cells or other objects of different geometric shapes and sizes, such as cancer cells, sperm, etc., and can also complete the grasping and removal of tiny condensed foreign bodies.

[0072] The method of using an in vivo magnetic control system to perform micro-clamp cell manipulation is similar to the method of using an in vitro magnetic control system to perform micro-clamp cell manipulation. The only difference is that all magnetic fields are applied by the in vivo magnetic control system 30, and the in vivo magnetic control system 30 has larger uniform magnetic fields and larger gradients than the in vitro magnetic control system because the experiment is conducted in the human body. The samples are observed using OCT imaging rather than microscope imaging, which will not be described in detail here.

[0073] Embodiment 2:

[0074] Reference Fig.11 and Fig.12 The structure of the embodiment 2 is similar to that of the embodiment 1, except that the clamp body 1 is a claw-shaped clamp body, and each clamp body 1 includes four claws 12, so that when the micro clamp is in a clamping state, a spherical jaw consisting of two vertical rings is formed between the two clamp bodies 1. In this way, the claw-shaped clamp body can form a closed contour, which can completely enclose the grasped object in the jaws to prevent it from slipping out when grasping a tiny object (such as sperm).

[0075] The above are only specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis, characterized in that: It comprises a micron-level magnetically controlled cell micro-clamp, an in vitro magnetic control system and an in vivo magnetic control system; the in vitro magnetic control system can generate a first external magnetic field for driving the micron-level magnetically controlled cell micro-clamp to perform cell operations in vitro; the in vivo magnetic control system can generate a second external magnetic field for driving the micron-level magnetically controlled cell micro-clamp to perform cell transport operations in vivo; the micron-level magnetically controlled cell micro-clamp comprises two clamp bodies arranged opposite to each other and an elastic member connected between the clamp bodies; the elastic member can constrain the two clamp bodies in a closed jaw state; the clamp bodies are made of superelastic photoresist material doped with superparamagnetic material; the clamp bodies can be opened or closed under the action of the first external magnetic field or the second external magnetic field to grasp or release cells, and transport cells to a preset position.

2. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 1, characterized in that: When the clamp body is in a closed state, a single cell can be clamped in the jaws.

3. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 2, characterized in that: The clamp body is a sawtooth clamp body or a claw clamp body.

4. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 3 is characterized in that: The fore-and-aft direction of the clamp body is the easy magnetization axis.

5. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 4, characterized in that: The first external magnetic field and the second external magnetic field are both variable magnetic fields that can be transformed between a rotating uniform magnetic field and a gradient magnetic field; the rotating uniform magnetic field is a rotating uniform magnetic field with variable magnetic field strength; when the first external magnetic field is transformed into a rotating uniform magnetic field with a magnetic field strength greater than 7mT, the micron-level magnetically controlled cell micro-clamp is driven to roll forward and open; when the first external magnetic field is transformed into a rotating uniform magnetic field with a magnetic field strength less than 7mT, the micron-level magnetically controlled cell micro-clamp is driven to roll forward and close; when the first external magnetic field is transformed into a gradient magnetic field with a gradient of 0~1T / m or when the second external magnetic field is transformed into a gradient magnetic field with a gradient of 0~5T / m, the micron-level magnetically controlled cell micro-clamp is driven to translate forward.

6. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 5, characterized in that: There is an angle between the two clamp bodies; the easy magnetization axis can be deflected by controlling the strength of the first external magnetic field and the second external magnetic field, thereby controlling the angle between the two clamp bodies.

7. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 1, characterized in that: The in vitro magnetic control system includes a three-dimensional Helmholtz coil, a first data acquisition card, a first power amplifier, a first relay, a first computer and a cell detection module; the three-dimensional Helmholtz coil and the cell detection module are both arranged on a load-bearing bracket; a sample platform is arranged at the center of the three-dimensional Helmholtz coil, and the sample platform is used to place a culture dish for culturing cells to be operated; the cell detection module is communicatively connected to the first computer, and the cell detection module can monitor living tissues and cells, and monitor the position of a micron-level magnetically controlled cell micro-clamp in real time; the first data acquisition card is communicatively connected to the first computer; the first relay is electrically connected to the three-dimensional Helmholtz coil; the signal input end of the first power amplifier is connected to the analog signal output end of the first data acquisition card, and the output end of the first power amplifier is connected to the power input end of the first relay.

8. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 7, characterized in that: The cell detection module includes an optical biological microscope and a microscope camera; the optical biological microscope is an inverted fluorescence microscope, and the objective lens is inverted below the sample platform; the microscope camera is connected to the trinocular port of the optical biological microscope to achieve optical system docking of the microscope camera and the optical biological microscope.

9. The micron-scale magnetically controlled cell micro-clamp system for medical detection and diagnosis according to claim 1, characterized in that: The in vivo magnetic control system includes a magnetic field generator, a scanning bed, an OCT imaging system, a second computer, a second data acquisition card, a second power amplifier and a second relay; the magnetic field generator includes a main body and a plurality of groups of superconducting electromagnetic coils arranged along the X, Y and Z axis directions on the main body; the main body is a ring-shaped or cylindrical structure that can allow the patient scanning bed to pass through; the OCT imaging system can detect the position of the micron-level magnetically controlled cell micro-clamp in the body in real time; the second data acquisition card is communicatively connected to the second computer; the second relay is electrically connected to the superconducting electromagnetic coil; the signal input end of the second power amplifier is connected to the analog signal output end of the second data acquisition card; the output end of the second power amplifier is connected to the power input end of the second relay.

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