Cell micro-injection device and robust impedance control method thereof

[0033] The technical solutions of the present invention will be further described below with reference to the accompanying drawings.

[0034] like Figure 1 to 4 As shown, the cell microspactic apparatus of the present invention includes a connecting rod 1, a package 2, a piezoelectric driver 3, an injector 4, a hub type compliant mechanism 5, a fixing collet 6, a microsuriode 7.

[0035] The connecting rod 1 includes a threaded portion 11, a connecting portion 12, wherein the threaded portion 11 is connected to the fixed collet 6, and the fixing collet 6 is fixed to the outer side of the hub stuff mechanism 5, and there is a threaded portion 11 The nut is adjusted by the rotating nut to adjust the relative position of the connecting rod 1; the pressing portion 13 is abutting at one end of the package 2, and when the nut is tightened, the piezoelectric driver 3 in the package 2 is generated. The action of the preload force, the piezoelectric driver 3 uses piezoelectric ceramics with flexible op amps.

[0036]Injector 4 includes a threaded portion 41, channel 42, mating portion 43. 42 is the inflow passage bore of the injection material, was "L" shaped, bent channel portion 42 is a smooth arc, wherein an injection port located on the side 4 and the other port is connected to the microinjection needle 7; mating portion 43 has a cylindrical shape, one end of the package 2 is fitted to transmit the high-frequency vibration of the piezoelectric actuator 3.

[0037] Wheel compliant mechanism 5 has two concentric hollow cylinders, respectively, within a hollow cylinder threaded portion 53, an outer hollow cylinder 54, wherein the outer hollow cylinder 54 by 6 stationary chuck clamping force, the compliant hub formula mechanism 5 is secured to the fixed chuck 6; wheel compliant mechanism 5 further includes a threaded portion 51, the compliant means 52 reed type. Threaded portion 51 and screwing the threaded portion 41 is formed to transmit a high-frequency vibration of the piezoelectric actuator 3, proper lubrication of the thread portion 51 is connected with the threaded portion 41, reducing wear; Reed unit 52 are compliant with the outer hollow cylinder the inner end surface 54 of the inner hollow cylinder 53 connected to the outer end face, and evenly distributed in the circumferential direction, pliable reed type total six unit 52, is transmitted to the hub of the formula compliant mechanism for axial movement direction of the guide 5 effect; microinjection needle 7 through the inner hollow cylinder 53 and bonded to the inner surface of the hollow cylinder 53, so that the microinjection needle 7 and the wheel hub compliant mechanism 5 is fixedly connected to the microinjection needle 7 follows the wheel hub 5 compliant vibrating mechanism.

[0038] like Figure 5 As shown in the flowchart, the start cell puncture, the signal generator generates a high-frequency sinusoidal signals, and to obtain a piezoelectric actuator fixed within the filtered signal, the package 2 is started by the band rejection filter 3 generates a high frequency signal after receiving the vibration, since the preload force acting connecting rod is connected to the stationary chuck 6 by the screw 1, the vibration is transmitted to the injector 2 is connected to the wrapper 4, the injector 4 and the vibration is transmitted to the hub by screwing the formula compliant mechanism 5, the guide means of the leaf spring 52 is a compliant type axial vibratory motion is transmitted to the microinjection needle 7, so that the microinjection needle tip 7 generates a high frequency axial vibration during lancing cell penetrating cells to complete. Cell injection, the injection liquid to be injected by means external to the liquid to be injected is injected at injector bore 4, the liquid transferred to a microinjection needle communicating with the interior hollow cavity 7 through the channel 42, then through the liquid to be injected microinjection needle 7 into the interior cavity has been completed puncture cells cells cells to complete the injection process.

[0039] like Image 6 , The present invention is robust impedance control method using a single controller and adjusting the position of the piercing needle 7 microinjection; micro force sensor is mounted in the bottom of the microinjection needle 7, in the piezoelectric actuator is integrated inside a displacement sensor to obtain over the desired displacement x d And the ideal force required to puncture f d; Control of the controller frame having two closed-loop control, the position where the inner feedback loop, the position x of the microinjection needle loop control by a feedback controller, microinjection needle position for the position variable x; when the injection needle tip and the object to be injected upon contact, a contact force f, the force f to obtain a contact with the cell microinjection needle by the force sensor, the force f over the demand d After calculating the difference obtained by the impedance model [Delta] x, [Delta] x is fed back to the position feedback loop as an input signal, by adjusting the position input, such that the position of the injection needle and a contact force of the injection needle with the environment over a predetermined trajectory to meet.

[0040] Wherein the contact with the force f over the demand force f Δx obtained by calculating the difference between the impedance model is a dynamic model by using an impedance equation, i.e. (Wherein, m i Is virtual effective quality, B i Is a virtual effective damping coefficient, k i Is a virtual effective stiffness coefficient, k f Is an external force coefficient, e p Is a position error, e f It is a force error, Position error is to time the speed error obtained guide, Is the second position error time required acceleration error conductivity obtained), the process of puncture force error e f Is converted to the position error e p , So as to achieve high robustness controlling penetration force versus position microinjection needle.

[0041] Specifically, the actual process of cell puncture, the position error e p And force error e f Is the relative change value, it is generally in the steady state by using e pss E fss Described, calculated by the respective injection needle expression steady state position of the microscope in the process of cell error e pss Steady state force error e fss. Wherein, e pss E fss Satisfies the expression:

[0042]

[0043] Among them, K i Is a virtual effective stiffness coefficient, k f Is an external force coefficient to adjust the force error E f the weight of, Is external environment effective stiffness coefficient, f d Is ideal, X d Is ideal required, x e Is there a balance position when there is no interaction, E pss Is steady-state position error, E fss It is a coefficient varying impedance model of steady state force error, n according to. In addition, the design impedance model adaptive sliding mode control compensation function to reduce the influence of external disturbances.

[0044] like Figure 7 , The control system of the mouse oocyte to puncture an example graph of input parameters over time. Left is the ideal required force f d - FIG time t, the right is required over the force displacement x d - Time T. For the left, over the force required to puncture mouse oocytes should be maintained at 20 mN; for the right, over the desired displacement versus time slope of k, i.e., the ideal size of the puncture speed should be maintained at 0.7m / s.