A cell precise poking method based on torque balance

Abstract

The present application provides a kind of cell precision dialing method based on moment balance, belongs to the field of micro-operation technology at cell level, comprising the following steps: S1: by analyzing the moment balance condition of cell critical holding state, determine the minimum holding force required for fixed cell not to separate from holding needle;S2: by force analysis to the cell in dialing process, determine the minimum dialing force expression required for cell moment balance;S3: friction push experiment determines the friction coefficient between holding needle-cell and dialing needle-cell;S4: dialing based on moment balance, reduce the damage to cell and improve dialing precision.The present application uses minimum holding force to fix cell, applies minimum dialing force to target cell by force position control of dialing needle, so that cell is in equilibrium state, reduces the average cell deformation in dialing process to less than 15% of artificial operation, reduces cell dialing error to within 1°.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of cell-level micromanipulation technology, and particularly relates to a cell precise dialing method based on torque balance. BACKGROUND

[0002] Cell dialing is a key step to realize cell orientation adjustment and then to perform specific cell structure site operation. In the cell dialing operation, the operator usually uses a holding needle to fix one end of the cell and uses a dialing microneedle to contact and dial the cell from the other end of the cell to make the cell rotate, and then adjusts the cell to the target orientation step by step. During the dialing process, the appropriate dialing force needs to be applied to the cell to make the cell rotate while overcoming the friction force generated by the holding needle and to be in a torque balance state, otherwise the cell is easy to fall off from the holding needle and cause dialing failure. Meanwhile, in order to reduce the mechanical damage to the cell during the dialing process, the dialing force applied to the cell should be as small as possible under the premise of keeping the cell in the torque balance state.

[0003] The current manual operator often designs the contact position and motion trajectory of the dialing needle and the cell according to experience, which is easy to cause the cell to fall off or fail to rotate due to torque imbalance and thus cause dialing failure. We have tried to dial the cell by applying sufficient dialing force in the early stage, but due to the inability to detect the dialing force in real time, the specific friction coefficient of the injection needle and the holding needle cannot be measured online for each cell, and thus the individualized dialing trajectory cannot be designed for the target cell.

[0004] In addition, the dialing force is not controlled during the dialing process, so the dialing force applied to the cell is still significantly greater than the minimum dialing force required for cell dialing, which is easy to cause large cell deformation. Therefore, it is of great significance to develop a dialing method to measure the friction coefficient of the cell and the two microneedles simply, to control the force and position of the dialing needle during the dialing process, to apply the minimum dialing force to the cell, and to keep the cell in the torque balance state, so as to improve the dialing precision and reduce the mechanical damage to the cell during the dialing process. SUMMARY

[0005] The present application is aimed at the problems of dialing error and large mechanical damage to the cell caused by torque imbalance in the current cell dialing operation, sets the holding force based on torque balance, controls the force and position of the dialing needle, provides the minimum dialing force required for dialing the cell, keeps the cell in the torque balance state, and finally realizes a cell precise dialing method based on torque balance, which reduces the cell dialing error and reduces the mechanical damage to the cell.

[0006] The present application adopts the following technical solution to solve the above problems:

[0007] A cell precise dialing method based on torque balance, the method comprising the following steps:

[0008] S1: Determine the minimum holding force required to fix the cell based on the moment balance condition: By analyzing the moment balance condition of the critical holding state of the cell, determine the minimum holding force required to fix the cell so that it does not fall off the holding needle;

[0009] The critical holding state is the state in which the holding pressure is reduced to just enough to maintain the cell from falling off the tube opening of the holding needle. In the process of stress analysis, the deformation of the cell due to holding is ignored, the holding needle is placed horizontally and the tube opening is completely covered by the cell surface, and there is no air leakage phenomenon. At this time, the liquid in the environment is considered as a static fluid, which has no additional fluid force on the cell. At this time, the forces acting on the cell only exist gravity, buoyancy and holding force of the microtube. When the cell is in the critical holding state, the moment of the combined force of gravity and buoyancy that causes the cell to fall off the holding needle is balanced with the fixing moment generated by the holding force, and thus the minimum holding pressure required to fix the cell is calculated.

[0010] S2: Determine the minimum displacement force expression that balances the cell moment: By analyzing the stress of the cell during the displacement process, determine the minimum displacement force expression required to balance the cell moment;

[0011] It is assumed that the friction coefficients of different positions on the cell surface with the holding needle and the injection needle do not change, the holding and contact deformation generated by the holding needle and the injection needle and the cell have reached a stable state, and the displacement process is slow enough to allow the holding needle and the injection needle to have sufficient time to release the force on the cell. Therefore, in the stress analysis of the cell, the related theorem of statics is used to decompose the displacement force into normal pressure pointing to the center of the cell and pushing force along the tangent direction. According to the translation theorem of statics, the displacement force can be translated to the center of the cell and further decomposed into X direction and Y direction two components and a rotational moment, where the two components are balanced with the holding force of the holding needle and the friction resistance between the holding needle and the cell, respectively. According to the balance condition of the resistance moment of the friction resistance and the driving moment of the friction driving force, the expression of the minimum friction driving force and the normal pressure required to displace the cell, i.e. the minimum displacement force, is finally determined.

[0012] S3: Determine the friction coefficients between the holding needle-cell and the displacement needle-cell through friction pushing experiments: Determine the friction coefficients between the holding needle-cell and the displacement needle-cell in the minimum displacement force expression in S2 through friction pushing experiments on the target cell;

[0013] In the friction experiment, the normal extrusion force is exerted on the fixed target cell by the poking needle, and then the tangential movement is measured, the resultant force of the friction force and the extrusion force is calculated, and the friction coefficient between the poking needle and the cell is determined by the ratio of the friction force to the extrusion force. In the pushing experiment, the normal extrusion force is gradually increased by the poking needle, and then the cell is pushed in the tangential direction, and when the cell starts to rotate, the sliding friction force of the holding needle is calculated by using the balance condition of the pushing moment and the friction moment. The friction coefficient between the holding needle and the target cell is determined by the ratio of the sliding friction force to the pressure on the holding needle.

[0014] S4: Poking based on moment balance, reducing the damage to the cell and improving the poking precision: In the poking process, the cell is fixed using the minimum holding force, the force position control of the poking microneedle is performed according to the detected poking force and the contact point position, and the cell is always in the state of moment balance, so that the minimum poking force is exerted on the cell, the mechanical damage to the cell is reduced, and the poking precision is improved.

[0015] Before the poking starts, the minimum holding force required for fixing the cell is calculated according to the cell density and the measured cell geometric parameters, then the minimum poking force is determined according to the minimum holding force, the friction coefficient and the contact point position, the required minimum poking force is exerted on the cell by the force position control of the poking needle, and the cell is separated from the contact after the cell is rotated by a certain angle. In the poking process, the pushing force is detected by the micro force sensor, the depth of the poking needle is adjusted, the minimum poking force is always exerted on the cell to keep the cell moment balance, the cell is rotated smoothly, the actual cell rotation angle is calculated by the angular displacement of the cell edge feature in the focusing state, and the cell deformation amount in the poking process is estimated according to the depth of the microneedle pressed into the cell surface.

[0016] The beneficial effects of the present application are:

[0017] 1. In the present application, the holding force is set based on the moment balance, the minimum holding force is used to fix the cell, the force position control of the poking needle is performed, the minimum poking force is exerted on the target cell by the force position control of the poking needle, the cell is in the balanced state, the average cell deformation in the poking process is reduced to less than 15% of the manual operation, and the cell poking error is reduced to within 1°.

[0018] 2. In the present application, the friction coefficient between the surface of each target cell and the holding needle and the poking needle can be measured online through a simple friction pushing experiment, and then the personalized minimum poking force required for the moment balance of each target cell in the poking process is obtained, so that the mechanical damage to the cell in the poking process is reduced while the poking precision is ensured.

[0019] 3、The holding force applied to the cells by the present application is the minimum holding force required to fix the cells, which reduces the holding damage to the cells and greatly reduces the poking force required to poke the cells, thereby reducing the mechanical damage to the cells during the poking process.

[0020] 4、The present application controls the force position of the poking needle during the poking process according to different contact points and feedback poking force values, ensures that the minimum poking force can be applied to the cells, reduces the control error of the poking force, and guarantees the accuracy of the poking.

[0021] 5、The total cost of the self-made holding needle, poking needle and micro force sensor in the present application is only more than 300 yuan, the operation tool cost is low, and it is conducive to the popularization and application of the cell poking method. BRIEF DESCRIPTION OF DRAWINGS

[0022] In order to more clearly illustrate the specific embodiments of the present application, the drawings needed in the description of the specific embodiments will be briefly introduced below. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0023] Figure 1 is a cell precise poking flowchart based on torque balance;

[0024] Figure 2 is a torque balance schematic diagram of a critical holding state of spherical cells;

[0025] Figure 3 is a schematic diagram of cell stress analysis during the poking process;

[0026] Figure 4 is a friction pushing experiment schematic diagram of the present application;

[0027] Figure 5 is a cell precise poking control block diagram based on torque balance;

[0028] Figure 6 is a cell precise poking experiment diagram based on torque balance;

[0029] Figure 7 is a cell deformation variation diagram during the present poking process. DETAILED DESCRIPTION

[0030] In order to make those skilled in the art better understand the technical solutions of the present application, the present application will be described in detail below with reference to the drawings and specific embodiments.

[0031] As shown in Figure 1 , the present application discloses a cell precise poking method based on torque balance, which comprises the following steps:

[0032] S1: Determine the minimum holding force required to fix cells based on torque balance conditions: By analyzing the torque balance conditions of the critical cell holding state, determine the minimum holding force required to fix cells so that they do not detach from the holding needle;

[0033] S2: Determine the minimum force required to balance the cell's torque: By analyzing the forces acting on the cell during the plucking process, determine the minimum force required to balance the cell's torque.

[0034] S3: Friction-driven experiment to determine the friction coefficient between the holding needle-cell and the plucking needle-cell: By conducting a friction-driven experiment on the target cell, the friction coefficient between the holding needle-cell and the plucking needle-cell in the minimum plucking force expression in S2 is determined;

[0035] S4: Based on torque balance, the agitation reduces damage to cells and improves agitation accuracy: During the agitation process, the cells are fixed with the minimum holding force. The force position of the agitation microneedle is controlled according to the detected agitation force and contact point, so that the cells are always in a torque balance state. This ensures that the minimum agitation force is applied to the cells, thereby reducing mechanical damage to the cells and improving agitation accuracy.

[0036] The operation steps in this embodiment are as follows:

[0037] S0: Preparation of target cells.

[0038] The target cells used in this embodiment were domestic pig oocytes, which were obtained from local slaughterhouses. After the pig ovaries were removed from the slaughterhouse, they were transported to the laboratory within two hours in insulated bottles containing physiological saline at 35°C to 37°C. They were then immediately washed twice with sterile physiological saline containing 100 IU / L penicillin and 50 mg / L streptomycin at 37°C. Oocytes were extracted from follicles with a diameter of 2-6 mm from the ovaries. The extracted cells were washed three times with TL-Hepes-PVA and then cultured in vitro for 42 hours at 39°C and 5% CO2. After IVM, the cells were deovulated using 0.1% hyaluronidase. Finally, the cells were washed three times with M199, and oocytes with polar bodies were selected as the target cells for the experiment.

[0039] S1: Obtaining the minimum holding force based on the torque balance condition of the critical holding state.

[0040] like Figure 2 As shown, a horizontally placed suction device applies a suction force to the target oocyte. When cells are immobilized, because the density of the cells is greater than the density of the culture medium, the gravity of the cells... With buoyancy the resultant direction of the forces will be parallel to the axis, This will cause the deformation of the part of the cell body that is in contact with the lower half of the inner wall of the suction needle (the part close to ) to be greater than that of the upper half (the part close to ). Thus the elastic force exerted by the lower half will be greater than that exerted by the upper half , and the resultant direction of the forces will be biased towards the positive direction of the axis, and the point of action will be biased towards .

[0041] When the cell reaches a state of force equilibrium and the shape no longer changes, according to the rigidification theory of elastic bodies, the cell at this time can be regarded as a rigid body. According to the force equilibrium formula for rigid bodies, we know that

[0042]

[0043] Since the resultant of the forces of gravity and buoyancy is parallel to the axis, parallel to the axis, and both in the plane, according to the three-force equilibrium intersection theorem for rigid bodies, we know that is also in the plane and its action line passes through the intersection point of the action lines of , and . Its size satisfies the following relationship

[0044]

[0045] At this time, since the cell does not rotate, the oocyte, in addition to satisfying force equilibrium, also satisfies moment equilibrium. Let the resultant of the forces of and be . Taking the lowest point of the inner wall of the suction needle as the center of moment, then the moments , and about must be balanced, i.e.

[0046]

[0047] where is the resultant of the forces of and . That is

[0048] ​​​

[0049] When the suction force When it begins to decrease, the elastic force The suction force will also decrease, and its function will gradually shift from preventing cells from entering the holding needle to fixing cells and preventing them from detaching. After being reduced to a certain extent, from Starting at the point, the aspiration needle inner wall applies pressure to the cells. Near zero. With As it continues to decrease, eventually only [the value] remains. The elastic force generated at the edge of the nearby suction pin is greater than zero, therefore at this time The point of application can be approximated as being , about Point torque Approaching zero. For example... Figure 2 As shown, when the cell just barely remains attached to the holding needle, the cell reaches the critical holding state. , and about Torque balance, satisfying

[0050]

[0051] That is to say

[0052]

[0053] like If it continues to shrink, the cells will first and foremost... It detaches, then gradually detaches from the rest of the suction needle opening, and finally detaches from... The cell detaches and eventually slips out of the suction needle. The minimum suction force required to prevent cell detachment can be calculated using equation (6). The expression is as follows

[0054]

[0055] The experiment revealed that when cells are in a critical holding state, the deformation caused by the holding needle is minimal, and the cells can be approximated as spherical. This can be determined from geometric relationships.

[0056]

[0057] S2: Obtaining the minimum triggering force based on torque balance.

[0058] like Figure 3 As shown, the force applied to the cell is... It can be divided into two parts: normal compressive force. and tangential thrust The normal compressive force Pointing to the center of the cell whose action line makes an angle with the axis of , and two components satisfy the following relationship

[0059]

[0060] Let and be the angle between , then according to the geometric relationship

[0061]

[0062] According to the parallel force line theorem, can be equivalent to the force with the same size and direction whose action point is at the center of gravity , and the clockwise force couple on , where the size of satisfies

[0063]

[0064] where is the force arm of on , and only considering the penetration deformation, as shown in Figure 3 . From the geometric relationship, it is not difficult to obtain

[0065]

[0066] Substituting equation (12) into equation (11) gives

[0067]

[0068] where is the component of along the axis and the component of along the axis satisfies the following equation

[0069]

[0070] Similarly, the force applied by the suction needle can be equivalent to two forces perpendicular to each other whose action point is at the intersection of the axis and the suction needle mouth plane: the elastic force parallel to the axis and the friction force parallel to the axis and a force couple that can make the cell rotate clockwise around the center ​​ According to the force balance condition and should be satisfied

[0071]

[0072] In formula (17), because F F is less than G, is positive, and the direction is along the positive direction of the axis, which is consistent with the direction of the friction force resisting the counterclockwise rotation of the cell by the holding needle, so it is possible to keep the cell in a balanced state by counterclockwise poking of the cell by the poking needle.

[0073] When the cell is kept in a balanced state, according to the moment balance condition in statics, it can be known that the additional couple of forces at the center of the cell should satisfy the following relationship

[0074]

[0075] wherein is the distance from the center of the cell to the mouth of the holding needle, and when the deformation of the cell is not obvious, it can be estimated according to the geometric relationship by using the following formula

[0076]

[0077] Formulas (16)-(18) establish the conditions that need to be satisfied by the action force for keeping the cell balanced when the cell rotates counterclockwise. Substituting formulas (9), (12), (14)-(17) into formula (18) can obtain

[0078]

[0079] In fact, in order to balance the action force of , the resultant force of the friction force generated by the holding needle and the newly added elastic force should be on the same straight line as and equal in size, at which time the moment balance condition and the force balance condition are automatically satisfied. In the above formula, actually, according to the force line translation theorem, the additional couple of forces generated by the translation of to the point is

[0080]

[0081] Substituting formula (20) into formula (21) and rearranging can obtain

[0082]

[0083] ​In summary, when the force is applied on the upper part of the cell, the cell needs to be pushed counterclockwise to rotate, and when the applied force satisfies formula (16)-(18), the cell can reach a state of force and torque balance. The condition for the cell to just be able to rotate is that the rotating torque provided by the injection needle equals the maximum resistance provided by the suction needle That is:

[0084]

[0085] And The friction coefficient between the suction needle and the cell satisfies the following relationship:

[0086]

[0087] Substituting formula (15) and formula (21) into formula (24) can obtain:

[0088]

[0089] By combining formula (13), formula (23) and formula (25), the expression of is as follows:

[0090]

[0091] As shown in Figure 3 , the tangential pushing force is generated by the normal pressure . At the same time , the tangential pushing force is also generated by the cell deformation . If the normal pressure is gradually increased first, and then the microneedle is controlled to move along the normal direction, the maximum friction force generated by the microneedle and the cell satisfies the following relationship:

[0092]

[0093] Wherein is the friction coefficient between the injection needle and the oocyte.

[0094] Substituting formula (10) and formula (26) into formula (27) can obtain the expression of the minimum tangential pushing force as follows:

[0095]

[0096] Correspondingly, the normal pressure that can generate the tangential pushing force in formula (28) is as follows:

[0097] ​

[0098] S3: Cell and microneedle friction coefficient acquisition based on friction pushing experiment.

[0099] As shown in Figure 4 , the present application obtains the friction coefficient between the pushing needle and the cell surface through the pushing experiment . First, the cell is subjected to a large enough suction force by the suction needle to ensure that the cell does not rotate in the friction experiment, and the cell is subjected to a normal force by the pushing needle , and then the pushing needle is controlled to move in the tangential direction, so that the pushing needle slides on the cell surface and the pushing force is measured, and according to formula (9), the tangential pushing force and the friction coefficient of the pushing needle and the cell can be calculated by the following formula.

[0100]

[0101] The present application obtains the friction coefficient between the suction needle and the cell through the pushing experiment . First, the target oocyte is sucked using the suction pressure , and the suction force generated can be obtained by the following formula

[0102]

[0103] By gradually increasing and making the pushing needle push the cell along the tangential direction of the cell surface until the cell rotates. At this time, the pushing moment and the friction moment reach equilibrium. The pushing moment can be obtained by formula (33)

[0104]

[0105] The resistance moment is

[0106]

[0107] Substituting (14), formula (19) and formula (32) into formula (34) can obtain

[0108]

[0109] When and reach equilibrium, it can be known from formula (33) and formula (35) that

[0110]

[0111] In the above process, the contact point position of the pushing needle and the cell, and the cell radius , the depth of indentation , obtained by image processing algorithm, and The size of the force is obtained by micro force sensor detection, is calculated by equation (10).

[0112] S4: Precise cell poking process based on torque balance.

[0113] S41: Before the start of the poking, according to the reported cell and liquid density, the cell radius obtained by image processing and the inner diameter of the holding needle, the minimum holding force required to fix the cell is calculated according to equation (8).

[0114] S42: According to the minimum holding force and the friction coefficient of the target cell and the holding needle and the poking needle obtained by the friction pushing experiment detection, the minimum poking force at different contact points is further calculated according to the minimum holding force and the above friction coefficient by equation (28) and equation (29).

[0115] S43: As shown in Figure 5 , the position of the poking needle tip obtained by real-time image processing is controlled to contact the cell surface at the initial point and indent the cell surface to a certain depth until the normal pressure feedback by the micro force sensor reaches the value calculated by equation (29).

[0116] After that, the poking needle moves in the tangential direction to push the cell to rotate, and the indentation depth of the microneedle is controlled according to the calculation result of equation (29) at each point until the pressure reaches the calculated value. By the above force-position cooperative control, the minimum poking force required by the cell is applied, and the cell is rotated by a certain angle and then separated from the cell. In the process of poking, the pushing force is detected by the micro force sensor, the indentation depth of the poking needle is adjusted, and the minimum poking force is always applied to the cell to maintain the torque balance of the cell, ensuring the smooth rotation of the cell. The actual cell rotation angle is calculated by the angular displacement of the cell edge feature in the focusing state, and the cell deformation during the poking process is estimated according to the depth of the microneedle indentation into the cell surface.

[0117] As shown in Figure 6 , by performing the poking experiment on 5 cells, the set poking angle Δ φ is gradually increased from 5° to 40°, with an increase of 5° at each step, and the set and actual average poking angle Δ φ P See Table 1:

[0118]

[0119] As can be seen from Table 1, the average poking error of the cell is only 0.9°, which is much smaller than the average poking error of 8.3° reported in the previous manual poking operation.

[0120] The depth of penetration of the probe needle into the cell surface is determined by the position of the probe needle tip during the poking process D In , and the result is used as an index of the cell deformation.

[0121] As Figure 7 shown, according to the measurement results of one of the cells, the average deformation of the present application is only 4.2 , which is much smaller than the average cell deformation of 28.2 , which is only 15% of the latter.

[0122] The above detailed description of the present application is made through examples, but the content is only the preferred embodiments of the present application, and cannot be considered as limiting the scope of the present application. Any equivalent changes and improvements made according to the scope of the present application should still belong to the scope of the present application.

Claims

1. A method for cell precision dialing based on torque balance, characterized in that: The method comprises the following steps: S1: determining the minimum suction force required for fixing the cell based on the moment balance condition: by analyzing the moment balance condition of the critical suction state of the cell, the minimum suction force required for fixing the cell so that it does not fall off the suction needle is determined, that is, when the force on the cell reaches balance and the shape no longer changes, according to the rigidification theory of the elastic body, the cell at this time can be equivalent to a rigid body, and the force balance formula of the rigid body is known ； in, For elasticity, For holding force, For the cell's gravity, The buoyancy of the cells; when the cells just barely remain attached to the holding needle, the cells reach the critical holding state, at which point... , and Regarding the lower half of the inner wall of the suction needle port The torque is balanced, if As the cell continues to shrink, it will first interact with the upper half of the inner wall of the aspiration needle. It detaches, then gradually detaches from the rest of the suction needle opening, and finally detaches from... The minimum holding force required to prevent cell detachment after the cell slips out of the holding needle. for ； wherein, is the distance from the cell center to the holding needle opening, is the holding needle inner diameter; S2: Determine the minimum expression of the poking force to balance the cell moment: by force analysis on the cell during the poking process, determine the minimum expression of the poking force required to balance the cell moment, the action of the poking needle on the cell Can be divided into two parts: normal extrusion force And tangential pushing force The minimum tangential pushing force expression is: ； In the above equation, is the holding force, is the friction coefficient between the holding needle and the cell, is the friction coefficient between the injection needle and the oocyte, is the normal force of the tangential pushing force is the angle between the action line and the normal force of the tangential pushing force The expression of is as follows: ； S3: Friction push experiment to determine the friction coefficient between the holding needle-cell and the poking needle-cell: through the friction push experiment on the target cell, the friction coefficient between the holding needle-cell and the poking needle-cell in the minimum poking force expression in S2 is determined, and the friction coefficient between the poking needle and the cell surface To ； The friction coefficient between the suction needle and the cell is ； wherein, the inner diameter of the cell when it is approximately spherical, the deformation of the cell, the suction pressure, is and the angle between the two vectors S4: moving based on the moment balance to reduce the damage to the cell and improve the moving precision.

2. The method of claim 1, wherein the method is based on torque balance. In S1, the critical suction state is a state in which the suction pressure is reduced to just maintain the cell from falling off the tube opening of the suction needle, the suction needle is horizontally placed and the tube opening is completely covered by the cell surface, and there is no air leakage phenomenon, and the liquid in the environment is regarded as a static fluid.

3. The method of claim 2, wherein the method is based on torque balance. In the process of stress analysis of the critical suction state, the cell deformation caused by suction is ignored.

4. The method of claim 1, wherein the method is based on torque balance. In S2, it is assumed that the friction coefficients of different positions on the cell surface with the suction needle and the injection needle remain unchanged, the moving process is slow enough, and the forces of the suction needle and the injection needle on the cell have sufficient time to release to the cell, so that the cell deformation has reached stability.

5. The method of claim 1, wherein the method is based on torque balance. In S3, in the friction pushing experiment, a normal extrusion force is applied to the fixed target cell by the moving needle, and then the moving needle is moved tangentially along the cell surface, the resultant force of the friction force and the pressure is measured by a micro force sensor, the friction force is calculated from the resultant force and the extrusion force, and the friction coefficient between the moving needle and the cell is determined from the ratio of the friction force to the extrusion force.

6. The method of claim 5, wherein the method is based on torque balance. In S3, in the friction pushing experiment, the normal extrusion force is gradually increased by the moving needle, and then the cell is pushed in the tangential direction, when the cell starts to rotate, the sliding friction of the suction needle is calculated by using the balance condition of the pushing moment and the friction moment, and the friction coefficient between the suction needle and the cell is determined from the ratio of the sliding friction to the pressure on the suction needle.

7. The method of claim 1, wherein the method is based on torque balance. In S4, the cell is fixed using the minimum suction force during the moving process, the moving microneedle is controlled in force and position according to the detected moving force and the contact point position, so that the cell is always in the state of moment balance, thereby ensuring that the minimum moving force is applied to the cell, reducing the mechanical damage to the cell and improving the moving precision.

8. The method of claim 7, wherein the method is based on torque balance. In S4, the moving process comprises the following steps: S41: calculating the minimum suction force required for fixing the cell before the moving starts; S42: determining the minimum moving force required according to the minimum suction force, the friction coefficients of the cell with the two microneedles, and the initial contact point position; S43: applying the minimum suction force to the cell, and performing force and position coordinated control on the moving needle to apply the minimum moving force required to the cell, and the moving needle is separated from the cell after rotating the cell by a predetermined angle.

9. The method of claim 8, wherein the method is based on torque balance. In S41, the minimum suction force required for fixing the cell is calculated according to the cell density and the measured cell geometric parameters.

10. The method of claim 8, wherein the method is based on torque balance. During the moving process, the pushing force is detected by a micro force sensor, the actual cell rotation angle is calculated from the angular displacement of the cell edge feature relative to the cell center in the focusing state, and the cell deformation amount in the moving process is estimated according to the depth of the microneedle pressed into the cell surface.

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