| Magnetic tweezer is a common basic tool for the manipulation of biomolecules in single-molecule manipulation technique.The development of single-molecule operation technique has raised the requirements of large output range of magnetic force,high control stability and multi-degree-of-freedom control characteristic,etc.However,most of the existing domestic magnetic tweezers are permanent magnetic tweezers or electromagnetic tweezers with no closed-loop feedback.These magnetic tweezers have problems that the output magnetic force has a single degree of freedom and it is difficult to realize precise control of motion trajectory of the magnetic microsphere.Based on the analysis of domestic and international magnetic tweezer techniques,the key techniques of quadrupole magnetic tweezer are studied in this subject.The main contents are the structure design of magnetic pole and analysis of magnetic field in the quadrupole magnetic tweezer,establishment of current-magnet model,derivation and simplification of the magnet-current inverse model and finally the establishment of an electromagnetic based quadrupole magnetic tweezer and the realization of stable control of the position and trajectory of magnetic microspheres.Compared with the existing domestic magnetic tweezer techniques,the advantage of the quadrupole magnetic tweezer is that it can output magnetic force in any direction in a two-dimensional plane and it realizes high-precision closed-loop control of the position and trajectory of magnetic microspheres.The main research topics of this subject are showing as follows:Firstly,the structure of magnetic pole of the quadrupole magnetic tweezer is designed and the relationship between the applied currents to the coils and the resulting magnetic force on magnetic microspheres is characterized.A lumped parameter model with magnetic monopole approximation is employed to describe the magnetic field generated by the magnetic poles.The current-magnet model is then developed based on this approximation.Then,the magnet-current inverse model of the quadrupole magnetic tweezer is deduced and simplified,which eliminates the computational complexity due to the nonlinearity and position dependency in the output of magnetic force.Secondly,an experimental quadrupole magnetic tweezer is set up.The soft magnetic alloy is chosen as the material of the magnetic pole and yoke to reduce the impact of hysteresis on the performance of the magnetic tweezer.The electromagnetic driving unit of the magnetic tweezer is designed and manufactured.The design and debugging of the master control board and voltage-controlled current source are completed.A fluorescence microscopy and the related software design are completed for monitoring of the position of magnetic fluorescent microspheres.The sampling frequency can reach up to 200 Hz.Thus,a closed-loop feedback unit for the positioning of magnetic microspheres is established.Finally,the experimental quadrupole magnetic tweezer is tested to verify its ability of stable capturing and high-precision control of the position and trajectory of magnetic microspheres.The positioning resolution of magnetic microspheres in the closed-loop feedback unit is tested,which is better than 40 nm.The proportional controller is used and the parameters of the magnetic gain coefficient in addition with the liquid damping coefficient and the time delay of the control system are calculated,which reveals that the output range of the magnetic force in the center of the working area is ±79.2 p N.Then the proportional-integral controller is used to verify the simplified inverse force model of the magnetic tweezer.At last the displacement resolution and motion trajectory control ability of the magnetic tweezer are tested.The results show that the displacement resolution of magnetic microspheres can reach up to 400 nm,and it can realize arbitrary direction motion in a two-dimensional plane.The trajectory error is 5.9 μm while the radius of the circular trajectory is 49.1μm,which indicates that the four-pole magnetic tweezer system has good trajectory control capability for magnetic microspheres. |